Publications by authors named "Gang Ji"

158 Publications

Germline and tumor mutations in Chinese high grade serous ovarian cancer patients.

Ann Transl Med 2021 Mar;9(6):453

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Studies on the prevalence of mutations in ovarian cancer mainly focused on germline single-nucleotide variant (SNV)/insertion/deletion (indel). The status of large genomic rearrangement (LRG) and somatic mutation were poorly investigated.

Methods: Paired blood and tumor DNA from an unselected cohort of 115 Chinese high grade serous ovarian cancer (HGSOC) patients were collected and analyzed for SNV and indel by NGS. LRG was detected by MLPA. Clinicopathological characteristics including age at diagnosis, FIGO stage, family history and follow-up data were collected for further analysis.

Results: A total of 115 HGSOC patients were screened. Among them, 30 (26.1%) had germline mutations, including 19 (16.5%) SNV/indels, 5 (4.3%) LGRs in , and 6 (5.2%) SNV/indels in . Ten (8.7%) had somatic mutations, including 5 (4.3%) in and 5 (4.3%) in . The entire tumor mutation frequency was 34.8%. No patients were found with two or more deleterious mutations. The proportion of germline (66.7%) and tumor (75%) mutation carriers was significantly increased for patients with family history when compared with those without (P<0.05). Patients with germline mutation appeared to be younger than non-carriers (mean age, 50.9 54.4 years, P=0.004) and somatic mutation carriers (mean age, 50.9 58.7 years, P=0.009). No significant association was found between status and clinicopathological characteristics including stage and family history of other cancer than breast and ovarian cancer. In univariate and Cox regression analysis, patients with tumor mutations had significant improvements than non-carriers in overall survival in the first two years after surgery (P<0.05). No significant impacts were found between various mutation status in PFS.

Conclusions: There is a high germline and tumor mutation incidences in Chinese HGSOC patients. Germline mutations were associated with family history and age at diagnosis, whereas somatic mutations were not. In our study, tumor mutations showed a time-depended improved survival outcome. A larger cohort should be examined to clarify the relation between mutation and survival outcomes.
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http://dx.doi.org/10.21037/atm-20-6827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039691PMC
March 2021

Impact of Laparoscopic Converted to Open Gastrectomy on Short- and Long-Term Outcomes of Patients with Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis.

J Gastrointest Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127 Changle West Road, 710032, Xi'an, China.

Background: It remains unclear whether laparoscopic conversation to open gastrectomy causes higher morbidity and has an adverse effect on the long-term survival outcomes of patients with gastric cancer. This study was designed to evaluate the impact of the conversion on short and long-term outcomes of patients with locally advanced gastric cancer (AGC).

Methods: We retrospectively investigated 871 patients who initially underwent laparoscopic gastrectomy (LG) for pathologically confirmed diagnosis of AGC between February 2009 and April 2018. The patients were grouped as the conversion (CONV) group and completed laparoscopic (LAP) group. The 1:2 propensity score matching was performed to reduce the effect of bias due to the imbalanced baseline features between the two groups. Multivariate analyses were performed to identify risk factors for conversion and poor survival.

Results: After propensity-score matching, 168 patients (56 in the CONV group and 112 in the LAP group) were studied. The CONV group was associated with significantly longer operation time (252.4 vs. 216.7 min, P < 0.001) and greater estimated blood loss (234.8 vs. 171.2 ml, P < 0.001) as compared with the LAP group. The time to first flatus (3.8 vs. 3.3 days, P = 0.043), time to start a liquid diet (4.1 vs. 3.5 days, P = 0.021), and postoperative hospital stay (8.7 vs. 7.6 days, P = 0.020) were significantly longer in the CONV group than that in the LAP group. The overall complication rate did not differ significantly between the CONV group and the LAP group (16.1% vs. 12.5%, P = 0.692). Both 5-year overall survival (OS) and 5-year disease-free survival (DFS) did not differ significantly between the CONV group and the LAP group (P = 0.805, P = 0.945, respectively). Multivariate analysis showed that lymphovascular invasion and stage III were independent prognostic factors for poor OS and DFS, whereas conversion was not.

Conclusions: The conversion from laparoscopic to open gastrectomy had no negative impact on morbidity and long-term survival outcomes for patients with locally AGC.
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http://dx.doi.org/10.1007/s11605-021-04975-6DOI Listing
April 2021

Medial Plication Using an Arthroscopic All-Inside Technique for Treatment of Patellar Instability in Adolescents.

J Knee Surg 2021 Mar 2. Epub 2021 Mar 2.

Department of Joint Surgery, Orthopedic, Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.

The purpose of this study was to present a medial plication using an arthroscopic all-inside technique for the treatment of patellar instability in adolescents. From July 2009 to June 2012, 19 patients with acute patellar dislocation were operated by this technique. Of these patients, follow-up was available in 17 patients at an average of 3 years (range: 1.5-4 years). At the follow-up, we evaluated the patients with physical examinations, radiographs, computed tomography scan, as well as the Lysholm and Kujala scoring scales. No recurrence of patellar instability has been found. The recovery of knee mobilization resulted to be good. We think this could be a valid technique to treat patellar instability in adolescents with less associated morbidity and good cosmetic results.
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http://dx.doi.org/10.1055/s-0041-1723978DOI Listing
March 2021

Reprint of "Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation".

Prog Biophys Mol Biol 2021 Mar 26;160:5-15. Epub 2021 Feb 26.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
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http://dx.doi.org/10.1016/j.pbiomolbio.2021.02.001DOI Listing
March 2021

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Cancer Biol Med 2021 Feb;18(1):283-297

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Medical University of PLA, Xi'an 710032, China.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.

Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m.

Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight ( neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy.

Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877168PMC
February 2021

Comparison of Outcomes of Totally Laparoscopic Total Gastrectomy (Overlap Reconstruction) versus Laparoscopic-Assisted Total Gastrectomy for Advanced Siewert III Esophagogastric Junction Cancer and Gastric Cancer of Upper and Middle Third of Stomach: Study Protocol for a Single-Center Randomized Controlled Trial.

Cancer Manag Res 2021 22;13:595-604. Epub 2021 Jan 22.

Department of Digestive Surgery, Xi Jing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.

Background: Totally laparoscopic total gastrectomy (TLTG) using the overlap reconstruction method is associated with fewer postoperative complications and fast recovery than laparoscopic-assisted radical total gastrectomy (LATG). However, evidence on the safety and feasibility of TLTG (overlap reconstruction) in patients with advanced Siewert III esophagogastric junction cancer and gastric cancer of the upper and middle third of the stomach is scarce.

Methods: This study is a prospective, single-center, single-blind, two-arm randomized controlled trial designed to include 292 patients with advanced Siewert III esophagogastric junction cancer and gastric cancer of the upper and middle third of the stomach who will be randomly assigned to two groups: a TLTG overlap group (n=146) and an LATG group (n=146). The patients' demographics, pathological characteristics, intraoperative variables, postoperative complications, postoperative recovery variables, 3-year disease-free survival and 3-year overall survival will be collected and analyzed. The primary outcome is the postoperative complications within 30 days after surgery including intra-abdominal hemorrhage, anastomotic leakage, duodenal stump fistula, pancreatic fistula, chyle leakage, abdominal infection, intestinal obstruction, wound complications, pulmonary infection, pleural effusion, pulmonary embolism, cardiovascular and cerebrovascular complications, and deep vein thrombosis. The secondary outcomes are the 3-year disease-free survival and 3-year overall survival.

Discussion: This trial will provide high-level evidence for the safety and feasibility of TLTG (overlap reconstruction) compared with LATG in advanced Siewert III esophagogastric junction cancer and the upper and middle third of gastric cancer.

Trial Registration: This trial has been registered at the Chinese Clinical Trial Registry: ChiCTR1900025667 (registration date: September 4, 2019).
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http://dx.doi.org/10.2147/CMAR.S285598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837541PMC
January 2021

Assessment of Patellar Morphology in Trochlear Dysplasia on Computed Tomography Scans.

Orthop Surg 2021 Apr 24;13(2):458-465. Epub 2021 Jan 24.

Department of Orthopaedic Surgery, Third Hospital, Shijiazhuang, China.

Objective: To evaluate the patellar morphology of trochlear dysplasia and normal knees in different genders and in different severities of trochlear dysplasia on CT scans.

Methods: A total of 75 patients with trochlear dysplasia (110 knees) treated at the Third Hospital of Hebei Medical University from December 2013 to December 2018 were included in an experimental group, and an age-matched and sex-matched cohort of 46 patients with normal trochlear shape (61 knees) were randomly selected into a control group. The experimental group was divided into a female experimental group (Group FE, 47 patients, 72 knees) and a male experimental group (Group ME, 28 patients, 38 knees); the control group was divided into a female control group (Group FC, 31 knees, 24 female patients) and a male control group (Group MC, 30 knees, 22 male patients). Furthermore, according to the severity of trochlear dysplasia, Group FE was divided into a female low-grade dysplasia group (Group FL, 20 knees) and a female high-grade dysplasia group (Group FH, 52 knees); Group ME was divided into a male low-grade dysplasia group (Group ML, 16 knees) and a male high-grade dysplasia group (Group MH, 22 knees). All participants had undergone CT scans in the supine position; the patellar width and thickness, the lateral patellar facet angle, the Wiberg angle, and the Wiberg index were measured and compared.

Results: In trochlear dysplasia knees, the mean patellar width and thickness and the lateral patellar facet angle were significantly smaller; the mean Wiberg index was significantly larger than in normal knees, regardless of gender (P < 0.05); and there was no statistically significant difference in the mean Wiberg angle (P > 0.05). In the female groups, the mean patellar width and thickness and the Wiberg angle were significantly smaller; the mean lateral patellar facet angle was significantly larger than those in the male groups (P < 0.05); and there was no significant difference in the mean Wiberg index (P > 0.05). In the low-grade dysplasia group, the mean Wiberg index was smaller than that in the high-grade dysplasia group (P < 0.05), regardless of gender; however, there was no significant difference in the mean patellar width and thickness, the lateral patellar facet angle, and the Wiberg angle in low-grade and high-grade dysplasia (P > 0.05).

Conclusion: On CT scans, the patella in trochlear dysplasia had a smaller width, a thinner thickness, a lengthened lateral facet, and a more flattened articular facet. In addition, the patellar articular facet was more prominent in female patients. With the severity of trochlear dysplasia increased, the lateral patellar facet became longer. In addition, the abnormal stress distribution on the patella influenced the patellar morphology in trochlear dysaplasia.
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http://dx.doi.org/10.1111/os.12825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957432PMC
April 2021

Down-regulation of miR-let-7e attenuates LPS-induced acute lung injury in mice via inhibiting pulmonary inflammation by targeting SCOS1/NF-κB pathway.

Biosci Rep 2021 Jan;41(1)

Burn Center of Yunnan Province, Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.
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http://dx.doi.org/10.1042/BSR20201089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785041PMC
January 2021

Connectome-Based Prediction of Optimal Weight Loss Six Months After Bariatric Surgery.

Cereb Cortex 2021 Mar;31(5):2561-2573

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China.

Despite bariatric surgery being the most effective treatment for obesity, a proportion of subjects have suboptimal weight loss post-surgery. Therefore, it is necessary to understand the mechanisms behind the variance in weight loss and identify specific baseline biomarkers to predict optimal weight loss. Here, we employed functional magnetic resonance imaging (fMRI) with baseline whole-brain resting-state functional connectivity (RSFC) and a multivariate prediction framework integrating feature selection, feature transformation, and classification to prospectively identify obese patients that exhibited optimal weight loss at 6 months post-surgery. Siamese network, which is a multivariate machine learning method suitable for small sample analysis, and K-nearest neighbor (KNN) were cascaded as the classifier (Siamese-KNN). In the leave-one-out cross-validation, the Siamese-KNN achieved an accuracy of 83.78%, which was substantially higher than results from traditional classifiers. RSFC patterns contributing to the prediction consisted of brain networks related to salience, reward, self-referential, and cognitive processing. Further RSFC feature analysis indicated that the connection strength between frontal and parietal cortices was stronger in the optimal versus the suboptimal weight loss group. These findings show that specific RSFC patterns could be used as neuroimaging biomarkers to predict individual weight loss post-surgery and assist in personalized diagnosis for treatment of obesity.
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http://dx.doi.org/10.1093/cercor/bhaa374DOI Listing
March 2021

Comparing the Impact of Laparoscopic Sleeve Gastrectomy and Gastric Cancer Surgery on Resting-State Brain Activity and Functional Connectivity.

Front Neurosci 2020 26;14:614092. Epub 2020 Nov 26.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Laparoscopic sleeve gastrectomy (LSG) is one of the most performed bariatric surgeries in clinical practice. Growing neuroimaging evidence shows that LSG induces brain functional and structural alterations accompany with sustained weight-loss. Meanwhile, for clinical treatment of gastric cancer, stomach removal surgery is a similar procedure to LSG. It is unclear if the gastric cancer surgery (GCS) would induce the similar alterations in brain functions and structures as LSG, and it would help to clarify the specificity of the LSG. We recruited 24 obese patients who received LSG in the LSG group and 16 normal weight patients with gastric cancer who received GCS as the control group. Functional magnetic resonance imaging was employed to investigate the differences and similarity of surgery's impact on resting-state brain activity and functional connectivity (RSFC) between LSG and GCS groups. Both LSG and GCS groups showed increased activities in the posterior cingulate cortex (PCC) and supplementary motor area (SMA) as well as the decreased RSFC of PCC- dorsomedial prefrontal cortex and SMA- dorsolateral prefrontal cortex. There were decreased resting-state activity of hippocampus and putamen in LSG group and increases in GCS group. In LSG group, resting-state activities of hippocampus and putamen were correlated with craving for high-caloric food and body mass index after surgery, respectively. These findings suggest LSG induced alterations in resting-state activity and RSFC of hippocampus and putamen specifically regulate the obese state and overeating behaviors in obese patients.
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http://dx.doi.org/10.3389/fnins.2020.614092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726325PMC
November 2020

Polygalacin D suppresses esophageal squamous cell carcinoma growth and metastasis through regulating miR-142-5p/Nrf2 axis.

Free Radic Biol Med 2021 Feb 8;164:58-75. Epub 2020 Dec 8.

Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China. Electronic address:

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with poor survival. High expression of nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant transcript factor that protects malignant cells from death. Polygalacin D (PGD), a bioactive compound isolated from Platycodongrandiflorum (Jacq.), has recently been reported to be an anti-tumor agent. This study aimed to investigate the anti-cancer effects of PGD and its underlying molecular mechanisms in human ESCC. Here, we confirmed that Nrf2 was over-expressed in clinical ESCC tissues and cell lines. PGD treatments markedly reduced Nrf2 expression in a dose- and time-dependent manner in ESCC cell lines. Importantly, we found that PGD significantly reduced proliferation, and induced G2/M cell cycle arrest and apoptosis in ESCC cells. Also, PGD dramatically triggered autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 (BafA1) greatly abrogated the inhibitory role of PGD in cell viability and apoptosis. In addition, PGD evidently provoked reactive oxygen species (ROS) accumulation in ESCC cells, and pre-treatment of ROS scavenger N-acetyl-l-cysteine (NAC) markedly abolished PGD-triggered cell death. PGD also dramatically repressed migration and invasion in ESCC cells. Mechanistic investigation revealed that Nrf2 gene was directly targeted by miR-142-5p. MiR-142-5p negatively regulated Nrf2 expression in ESCC cells. We notably found that PGD-inhibited proliferation, migration and invasion in ESCC were considerably rescued by miR-142-5p knockdown; however, ROS production, apoptosis and autophagy induced by PGD were almost eliminated when miR-142-5p was silenced. On the contrast, over-expressing miR-142-5p could remarkably promote the anti-ESCC effects of PGD. Experiments in vivo by the tumor xenograft model confirmed that miR-142-5p effectively improved the activity of PGD to repress tumor growth and lung metastasis. Both in vitro and in vivo studies showed that PGD had few side effects on normal cells and major organs. Collectively, our findings provided the first evidence that PGD could be an effective therapeutic strategy for ESCC treatment by regulating miR-142-5p/Nrf2 axis with few adverse effects.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.029DOI Listing
February 2021

Risk Factors and Clavien-Dindo Classification of Postoperative Complications After Laparoscopic and Open Gastrectomies for Gastric Cancer: A Single-Center, Large Sample, Retrospective Cohort Study.

Cancer Manag Res 2020 23;12:12029-12039. Epub 2020 Nov 23.

Department of Digestive Surgery, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, People's Republic of China.

Background: Laparoscopy has been increasingly used for the surgery of gastric cancer. However, the postoperative complications are still under-investigated and the short-term results of laparoscopic gastrectomy remain controversial. This study aimed to explore the differences of postoperative complications between laparoscopic and open radical gastrectomies in patients with gastric cancer through the large sample size, retrospective cohort study, and evaluate the safety of laparoscopy in patients who underwent radical gastrectomy.

Patients And Methods: A total of 2,966 patients with gastric cancer (TNM I~III) who underwent laparoscopy or open gastrectomy from February 2009 to March 2016 were enrolled in this study. Complications were categorized according to the Clavien-Dindo classification. The incidence and severity of complications between laparoscopic and open gastrectomy were compared using one-to-three propensity score matching (PSM) analysis. Logistic regression analyses were performed to identify risk factors related to postoperative complications.

Results: A total of 2,966 patients were included in the study, including 687 (23.2%) in the LG (Laparoscopy gastrectomies) group and 2,279 (76.8%) in the OG (open gastrectomies) group. After PSM, a well-balanced cohort of 2,373 patients (676 cases in the LG group and 1,697 cases in the OG group) was further analyzed. The results showed that the incidence of overall complications in the LG group was significantly less than the OG group (15.4% vs 20.8%, =0.003). However, the severe complications of the LG group showed no difference towards the OG group (5.8% vs 5.8%, =0.952). Multivariate analysis revealed that laparoscopic surgery is a protective factor for the reduction of postoperative complications. Age ≥60 years, ASA classification IIIc and estimated blood loss ≥200 mL were confirmed as independent risk factors of overall complications.

Conclusion: Compared with traditional open gastrectomy, LG is safe and feasible with less trauma and fewer complications for patients with gastric cancer.
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http://dx.doi.org/10.2147/CMAR.S275621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700075PMC
November 2020

Resting activity of the hippocampus and amygdala in obese individuals predicts their response to food cues.

Addict Biol 2021 05 21;26(3):e12974. Epub 2020 Oct 21.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China.

Obese individuals exhibit brain functional abnormalities in multiple regions implicated in reward/motivation, emotion/memory, homeostatic regulation, and executive control when exposed to food cues and during rest. However, it remains unclear whether abnormal brain responses to food cues might account for or relate to their abnormal activity in resting state. This information would be useful for understanding the neural mechanisms behind hyperactive responses to food cues, a critical marker of obesity. Resting-state functional magnetic resonance imaging (RS-fMRI) and a cue-reactivity fMRI task with high- (HiCal) and low-caloric (LoCal) food cues were employed to investigate brain baseline activity and food cue-induced activation differences in 44 obese participants (OB), in 37 overweight participants (OW), and in 37 normal weight (NW) controls. One-way analyses of variance showed there was a group difference in the left hippocampus/amygdala activity during resting state and during food-cue stimulation (p < 0.05); post-hoc tests showed the OB group had both greater basal activity and greater food cue-induced activation than the OW and NW groups; OW had higher activity in the hippocampus/amygdala than the NW group, which was only significant during resting state. In the OB group, resting-state activity in the left hippocampus/amygdala was positively correlated with activation induced by HiCal food cues, and both of these measures correlated with body mass index (BMI). Mediation analysis showed that the relationship between BMI and hippocampus/amygdala response to HiCal food cues was mediated by their resting-state activity. These findings suggest a close association between obesity and brain functional abnormality in the hippocampus/amygdala. They also indicate that resting-state activity in the hippocampus/amygdala may impact these regions' responses to food cues.
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http://dx.doi.org/10.1111/adb.12974DOI Listing
May 2021

Beware Pathological Findings of the Stomach in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Obes Surg 2021 01 12;31(1):337-342. Epub 2020 Oct 12.

Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Changlexi St. 127#, Xi'An City, Shaanxi Province, China.

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.
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http://dx.doi.org/10.1007/s11695-020-05029-7DOI Listing
January 2021

Brain Connectivity, and Hormonal and Behavioral Correlates of Sustained Weight Loss in Obese Patients after Laparoscopic Sleeve Gastrectomy.

Cereb Cortex 2021 Jan;31(2):1284-1295

Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.
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http://dx.doi.org/10.1093/cercor/bhaa294DOI Listing
January 2021

Cytoplasmic Cargo Receptor p62 Inhibits Avibirnavirus Replication by Mediating Autophagic Degradation of Viral Protein VP2.

J Virol 2020 11 23;94(24). Epub 2020 Nov 23.

MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China

Selective autophagy regulates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and aggregated proteins. Furthermore, autophagy is capable of degrading avibirnavirus, but the mechanism responsible for this process is unclear. Here, we show that autophagy cargo receptor p62 regulates the degradation of the avibirnavirus capsid protein VP2. Binding of p62 to VP2 enhances autophagic induction and promotes autophagic degradation of viral protein VP2. Further study showed that the interaction of p62 with viral protein VP2 is dependent on ubiquitination at the K411 site of VP2 and the ubiquitin-associated domain of p62. Mutation analysis showed that the K411R mutation of viral protein VP2 prohibits its p62-mediated degradation. Consistent with this finding, p62 lacking the ubiquitin-associated domain or the LC3-interacting region no longer promoted the degradation of VP2. Virus production revealed that the knockout of p62 but not the overexpression of p62 promotes the replication of avibirnavirus. Collectively, our findings suggest that p62 mediates selective autophagic degradation of avibirnavirus protein VP2 in a ubiquitin-dependent manner and is an inhibitor of avibirnavirus replication. Avibirnavirus causes severe immunosuppression and mortality in young chickens. VP2, the capsid protein of avibirnavirus, is responsible for virus assembly, maturation, and replication. Previous study showed that avibirnavirus particles could be engulfed into the autophagosome and degradation of virus particles took apart. Selective autophagy is a highly specific and regulated degradation pathway for the clearance of damaged or unwanted cytosolic components and superfluous organelles as well as invading microbes. However, whether and how selective autophagy removes avibirnavirus capsids is largely unknown. Here, we have shown that selective autophagy specifically clears ubiquitinated avibirnavirus protein VP2 by p62 recognition and that p62 is an inhibitor of avibirnavirus replication, highlighting the role of p62 as a potential drug target for mediating the removal of ubiquitinated virus components from cells.
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http://dx.doi.org/10.1128/JVI.01255-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925189PMC
November 2020

Alendronate enhances osseointegration in a murine implant model.

J Orthop Res 2021 04 19;39(4):719-726. Epub 2020 Sep 19.

Arthroplasty Research Laboratory, Hospital for Special Surgery, New York, New York, USA.

Administration of bisphosphonates following total joint arthroplasty might be beneficial to reduce aseptic loosening. However, their effects on peri-implant bone formation and bone-implant interface strength have not been investigated yet. We used a physiologically loaded mouse implant model to investigate the short-term effects of postoperative systemic alendronate on osseointegration. A titanium implant with a rough surface was inserted in the proximal tibiae of 17-week-old female C57BL/6 mice (n = 44). Postimplantation mice were given alendronate (73 μg/kg/days, n = 22) or vehicle (n = 22) 5 days/week. At 7- and 14-day postimplantation, histology and histomorphometry were conducted. At 28 days, microcomputed tomography and biomechanical testing were performed (n = 10/group). Postoperative alendronate treatment enhanced osseointegration, increasing maximum pullout load by 45% (p < .001) from 19.1 ± 4.5 N in the control mice to 27.6 ± 4.9 N in the treated mice, at day 28 postimplantation. Alendronate treatment increased the bone volume fraction by 139% (p < .001) in the region distal to the implant and 60% (p < .05) in the peri-implant region. At 14-day postimplantation, alendronate treatment decreased the number of osteoclasts per bone perimeter (p < .05) and increased bone volume fraction (p < .01) when compared with the control group. Postimplantation, short-term alendronate treatment enhanced osseointegration as demonstrated by increased bone mass, trabecular bone thickness, and maximum pullout load. Alendronate decreased peri-implant osteoclasts while preserving peri-implant osteoblasts and endothelial cells, in turn, increasing bone volume fraction. This data supports the postoperative clinical use of bisphosphonates, especially in patients with high risks of aseptic loosening.
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http://dx.doi.org/10.1002/jor.24853DOI Listing
April 2021

Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation.

Prog Biophys Mol Biol 2020 10 3;156:3-13. Epub 2020 Aug 3.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
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http://dx.doi.org/10.1016/j.pbiomolbio.2020.07.009DOI Listing
October 2020

Inactivation of fungal spores in water using ozone: Kinetics, influencing factors and mechanisms.

Water Res 2020 Oct 22;185:116218. Epub 2020 Jul 22.

Key Laboratory of Northwest Water Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China. Electronic address:

Fungal contamination of drinking water sources is increasingly threatening the environment and human health. In this study, the inactivation of three genera of dominant fungi in drinking water sources using ozone was first reported. The inactivation of the fungal spores by ozone could be divided into two distinct stages: first a rapid reduction in survival, and then the inactivation at a slower rate. The secondary stage inactivation fitted the Chick-Watson model well, and there was no significant difference in the second-order inactivation rate constants of the three fungal spores (0.199-0.209 L mg min). The inactivation rate constants of fungal spores by molecular ozone were much lower than those of viruses, which were equivalent to that of Cryptosporidium. The increase in pH and temperature showed a positive effect on the inactivation rate. Damage to cell membranes, leakage of intracellular compounds, and changes of reactive oxygen species and esterase activity in the spores were detected after inactivation. The results indicated that ozone inactivated fungal spores by firstly destroying cell walls and membranes and then causing the release of intracellular compounds. The fungicidal efficiency of ozone was superior to those of chlorine and chlorine dioxide. In addition, the inactivation efficiency of ozone on fungal spores in real water matrices was reduced to 50.7-91.2% of the efficiency in phosphate buffer. In conclusion, ozone showed high efficiency in the inactivation of fungal spores and could be used as an alternative disinfectant for fungal contamination in drinking water sources.
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http://dx.doi.org/10.1016/j.watres.2020.116218DOI Listing
October 2020

Development and Clinical Validation of a 90-Gene Expression Assay for Identifying Tumor Tissue Origin.

J Mol Diagn 2020 09 28;22(9):1139-1150. Epub 2020 Jun 28.

Cancer of Unknown Primary Group, Pathology Committee, Chinese Research Hospital Association, Shanghai, People's Republic of China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. Electronic address:

The accurate identification of tissue origin in patients with metastatic cancer is critical for effective treatment selection but remains a challenge. The aim of this study is to develop a gene expression assay for tumor molecular classification and integrate it with clinicopathologic evaluations to identify the tissue origin for cancer of uncertain primary (CUP). A 90-gene expression signature, covering 21 tumor types, was identified and validated with an overall accuracy of 89.8% (95% CI, 0.87-0.92) in 609 tumor samples. More specifically, the classification accuracy reached 90.4% (95% CI, 0.87-0.93) for 323 primary tumors and 89.2% (95% CI, 0.85-0.92) for 286 metastatic tumors, with no statistically significant difference (P = 0.71). Furthermore, in a real-life cohort of 141 CUP patients, predictions by the 90-gene expression signature were consistent or compatible with the clinicopathologic features in 71.6% of patients (101/141). Findings suggest that this novel gene expression assay could efficiently predict the primary origin for a broad spectrum of tumor types and support its diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer. Additional studies are ongoing to further evaluate the clinical utility of this novel gene expression assay in predicting primary site and directing therapy for CUP patients.
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http://dx.doi.org/10.1016/j.jmoldx.2020.06.005DOI Listing
September 2020

In situ transformations during SLM of an ultra-strong TiC reinforced Ti composite.

Sci Rep 2020 Jun 29;10(1):10523. Epub 2020 Jun 29.

PMA, Department of Mechanical Engineering, KU Leuven and Member of Flanders Make, 3001, Leuven, Belgium.

This work demonstrates a successful in situ method capable of producing an ultra-strong novel Ti composite without aluminium and vanadium. In this method, selective laser melting is used to conduct in situ alloying and reinforcing of a Ti/10.5 wt% MoC powder mixture. It is shown that this leads to a metastable β-Ti matrix homogeneously reinforced by high aspect ratio, 50-200 nm wide and up to several micrometre long TiC whiskers. The transformations of the phases are controlled by decomposition, dissolution, diffusion, and reformation of constituents. The whisker morphology of in situ formed TiC particles is associated with directional crystal growth along the TiC direction. The developed TiC reinforced β-Ti alloy combines a hardness over 500 HV, a Young's modulus of 126 GPa, and an ultimate compressive strength of 1642 MPa. Improving the ductility of this composite is the subject of another work.
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http://dx.doi.org/10.1038/s41598-020-67434-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324562PMC
June 2020

Total Laparoscopic Uncut Roux-en-Y for Radical Distal Gastrectomy: An Interim Analysis of a Randomized, Controlled, Clinical Trial.

Ann Surg Oncol 2021 Jan 18;28(1):90-96. Epub 2020 Jun 18.

Department of Digestive Surgery, State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Background: The traditional Billroth II and Roux-en-Y anastomosis after laparoscopic distal gastrectomy for gastric cancer are associated with bile reflux gastritis and roux stasis syndrome, respectively. The uncut Roux-en-Y gastrojejunostomy can decrease the incidence of these complications by blocking the entry of bile and pancreatic juice into the residual stomach and retaining the impulses originating from the duodenum. The purpose of the present study was to compare the short-term outcomes of uncut Roux-en-Y (URY) and Billroth II combined Braun (BB) anastomosis.

Methods: In this prospective, multi-center, two-arm randomized controlled trial, 124 patients with advanced distal gastric cancer were randomized into two groups: URY (n = 62) and BB (n = 62) groups.

Results: The mean gastric juice pH was significantly lower in the URY group compared with the BB group (3.94 ± 0.71 vs. 5.83 ± 0.91, P < 0.0001). The bile reflux gastritis at 3 months (P < 0.0001) and 6 months (P = 0.002) was significantly more frequent in the BB group. No recanalization occurred in the URY group, and no significant difference was found between the two groups in terms of mean operative time (P = 0.69), mean time to perform anastomosis (P = 0.86), mean estimated blood loss (P = 0.77), mean number of harvested lymph nodes (P = 0.90), time to first passage of flatus or defecation (P = 0.87), postoperative hospital stay (P = 0.83), and the incidence of postoperative complications (P = 0.70).

Conclusions: URY anastomosis is associated with a significantly lower incidence of bile reflux gastritis and roux stasis syndrome compared with BB anastomosis.
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http://dx.doi.org/10.1245/s10434-020-08710-4DOI Listing
January 2021

Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial.

BMJ Open 2020 06 3;10(6):e034685. Epub 2020 Jun 3.

Department of Digestive Surgery, Xi Jing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China

Introduction: Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.

Methods And Analysis: This study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients' demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.

Ethics And Dissemination: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.

Trial Registration Number: ChiCTR1900026291 (registration date: 29 September 2019).
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http://dx.doi.org/10.1136/bmjopen-2019-034685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279648PMC
June 2020

Comparison of outcomes between nonsurgical and surgical treatment of distal radius fracture: a systematic review update and meta-analysis.

Arch Orthop Trauma Surg 2020 Aug 28;140(8):1143-1153. Epub 2020 May 28.

The Central Hospital of Wuhan, Achao Han, 26 Shengli Road, Wuhan, 430014, Hubei, China.

Introduction: This study was a systematic review comparing the clinical outcomes of nonsurgical and surgical management for distal radius fractures.

Materials And Methods: A comprehensive literature search was conducted using multiple databases, including Medline, Embase, and Cochrane. All databases were searched from the earliest records through June 2019 using the following Boolean operators: distal radius fracture, conservative treatment, nonoperative treatment, nonsurgical treatment, surgical treatment, and operative. All prospective and retrospective controlled trials were retrieved that directly compared the functional outcomes between the nonsurgical and surgical groups.

Results: Five prospective studies and six retrospective comparative studies were retrieved. A total of 1049 patients were included: 529 in the nonsurgical group and 520 in the surgical group. Both types of treatment led to similar results with respect to DASH and grip strength, as well as and most other functional assessments. However, there was significant difference in radial inclination, radial length, ulnar variance and range of wrist flexion.

Conclusions: No significant differences in most functional assessments were found when comparing surgical and nonsurgical management of distal radius fractures. Although there were significant differences in radial inclination, radial deviation, ulnar variance, and wrist flexion, they did not seem to have impacts on the quality of wrist. Nonsurgical treatment for the distal radius fractures should be considered firstly. Indications for operative fixation should be considered carefully in the treatment of DRFs.

Level Of Evidence: Therapeutic study (systematic review), Level III.
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http://dx.doi.org/10.1007/s00402-020-03487-3DOI Listing
August 2020

Evaluation of the application of laparoscopy in enhanced recovery after surgery (ERAS) for gastric cancer: a Chinese multicenter analysis.

Ann Transl Med 2020 Apr;8(8):543

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Background: Enhanced recovery after surgery (ERAS) has been successfully applied in general surgery, especially in colorectal resection. However, the effect of ERAS in gastric cancer resection in current studies are inconsistent and most of which were single center retrospective ones. Thus, our study was aimed to evaluate the application of laparoscopy in ERAS for gastric cancer based on Chinese multicenter data.

Methods: The clinical and pathological data of patients who underwent radical gastric cancer resection at three Chinese medical centers between January, 2015 and December, 2017 were retrospectively analyzed. The current application of laparoscopy in ERAS for gastric cancer was evaluated.

Results: A total of 1,434 patients were involved in the final analysis. The operation time was 265.7±79.1 min, blood loss was 200 [5-1,300] mL, and the number of lymph nodes dissected was 26.4±12.9. Time to first ambulation, flatus, and liquid food intake were 2.1±1.3, 4.4±2.7, and 6.1±3.6 days, respectively, and postoperative hospital stay was 9.0±1.5 days. The incidence of postoperative complications, Clavien-Dindo score ≥ II, was 10.0%, and the rate of readmission within 30 days of discharge was 1.4%. Of the patients who underwent total gastrectomy, those in the laparoscopic group had a higher number of lymph nodes retrieved than those in the open group (P<0.05), and also had earlier ambulation, oral intake and first flatus, as well as a shorter postoperative hospital stay time than the open group. There were no significant differences in intraoperative blood loss or postoperative complications between the two groups (P>0.05). Of the patients who underwent distal gastrectomy, the laparoscopic group had a lower volume of blood loss, shorter postoperative hospital stay time, and earlier ambulation, oral intake, and first flatus than the open group, and had a similar number of lymph nodes dissected compared to the open group (P>0.05).

Conclusions: Laparoscopic surgery combined with ERAS can shorten the time to early ambulation, oral intake, and first flatus, and shorten the length of hospital stay. Laparoscopic surgery can achieve the same oncological outcomes as open surgery and is safe and feasible without increasing the incidence of postoperative complications.
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http://dx.doi.org/10.21037/atm-20-2556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214879PMC
April 2020

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration.

Oncol Rep 2020 Jun 30;43(6):1975-1985. Epub 2020 Mar 30.

State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Air Force Medical University, Xi'an, Shaanxi 710032, P.R. China.

Circulating tumor cells (CTCs) or CTC clusters are considered as suitable and relevant targets for liquid biopsy as they more accurately indicate cancer progression, the therapeutic effects of treatment and allows for monitoring of cancer metastasis in real‑time. Among the various methods for isolating CTCs, size‑based filtration is one of the most convenient methods. However, cell clogging makes the filtration process less efficient. In the present study, an electromagnetic vibration‑based filtration (eVBF) device was developed that efficiently isolated rare CTCs and CTC clusters from clinical blood samples of patients with gastric cancer. Using human blood samples spiked with human gastric cancer cells, the parameters of this device such as vibrating amplitude and flow rate were optimized. Putative CTCs were detected using a conventional filtration method and the eVBF device from the peripheral blood samples of patients with gastric cancer. Continuous flow isolation of CTCs was evaluated by a simulated blood flow system. The eVBF device utilized the electromagnetic force to generate a periodic vibration that prevented the cell clogging and improved the filtering efficiency. The optimized eVBF device with the high‑amplitude vibration exhibited a recovery efficiency of 80‑90% from whole blood samples spiked with 100 or 1,000 gastric cancer cells per ml. Using the eVBF device, CTCs were detected in 100% of patients (10/10) with gastric cancer, and the positive detection rate of the eVBF device was 30% higher compared with the conventional filtration method. Furthermore, CTC clusters were detected in 40% (4/10) of CTC‑positive patient samples, and the integrity of CTC clusters was preserved using the eVBF device. The eVBF device allowed for high‑throughput (1 ml/min) and continuous flow isolation of CTCs without the addition of any antibodies, any chemical reagents or any pretreatment processes. Thus, the eVBF device provides an efficient tool for isolating rare CTCs and CTC clusters from patients with cancer, highlighting its potential for use in cancer diagnosis, treatment and cancer biology research.
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http://dx.doi.org/10.3892/or.2020.7567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160539PMC
June 2020

Laparoscopic sleeve gastrectomy improves brain connectivity in obese patients.

J Neurol 2020 Jul 13;267(7):1931-1940. Epub 2020 Mar 13.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710071, Shaanxi, China.

Objective: Obese individuals have shown functional abnormalities in frontal-limbic regions, and bariatric surgery is an effective treatment for morbid obesity. The aim of the study was to investigate how bariatric surgery modulates brain regional activation and functional connectivity (FC) to food cues, and whether the underlying structural connectivity (SC) alterations contribute to these functional changes as well as behavioral changes.

Methods: A functional magnetic resonance imaging cue-reactivity task with high- (HiCal) and low-calorie (LoCal) food pictures and diffusion tensor imaging (DTI) with deterministic tractography were used to investigate brain reactivity, FC and SC in 28 obese participants tested before and 1 month after laparoscopic sleeve gastrectomy (LSG). Twenty-two obese controls (Ctr) without surgery were also tested at baseline and 1 month later.

Results: LSG significantly decreased right dorsolateral prefrontal cortex (DLPFC) activation to HiCal versus LoCal cues and increased FC between DLPFC and ventral anterior cingulate cortex (vACC), which are regions involved in self-regulation of feeding behaviors. LSG also increased SC between DLPFC and ACC as quantified by fractional anisotropy. Increases in SC and FC between DLPFC and ACC were associated with greater reductions in BMI, and SC changes were positively correlated with FC changes. Increased SC between right DLPFC and ACC mediated the relationship between reduced BMI and increased right DLPFC-vACC FC; likewise, increases in right DLPFC-vACC FC mediated the relationship between increased right DLPFC-ACC SC and reduced BMI.

Conclusion: LSG might induce weight loss in part by increasing SC and FC between DLPFC and ACC, and thus strengthening top-down control over food intake.
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http://dx.doi.org/10.1007/s00415-020-09780-wDOI Listing
July 2020

Acute and long-term effects of electroacupuncture alter frontal and insular cortex activity and functional connectivity during resting state.

Psychiatry Res Neuroimaging 2020 04 20;298:111047. Epub 2020 Feb 20.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China. Electronic address:

Electroacupuncture (EA) is a safe method for treating obesity; however, its underlying neural mechanisms remain unclear. We employed resting-state-functional-magnetic-resonance-imaging (RS-fMRI) and amplitude-of-low-frequency-fluctuation (ALFF) to investigate acute/long-term effects of EA on brain activity and resting-state-functional-connectivity (RSFC) in overweight/obesity subjects who received real/Sham stimulation. For acute effects, 26 and 19 overweight/obesity subjects were included in EA and Sham groups respectively. There were significant time effects on ALFF in the right insula (INS) and left dorsolateral-prefrontal-cortex (DLPFC) due to decreases/increases in INS/DLPFC in both groups. There were weaker positive RSFC between INS and supplementary-motor-area (SMA)/right DLPFC and weaker negative RSFC between INS and precuneus (PCUN); stronger negative RSFC between DLPFC and dorsomedial-prefrontal-cortex (DMPFC) in both groups. For long-term study, body-mass-index (BMI) had significant reduction in EA (n = 17) and Sham (15) groups; EA had higher BMI reduction than in Sham. There were significant time effects on ALFF in right ventrolateral-prefrontal-cortex (VLPFC) due to significant increases in EA group, and stronger positive RSFC between VLPFC and orbitofrontal-cortex and negative RSFC between VLPFC and left thalamus (THA) in both groups after long-term treatment. These findings suggest that changes in resting-activity and RSFC implicated in inhibitory-control, gastric-motility and satiety-control are associated with EA-induced weight-loss.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111047DOI Listing
April 2020

Altered Interactions Among Resting-State Networks in Individuals with Obesity.

Obesity (Silver Spring) 2020 03;28(3):601-608

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China.

Objective: The aim of this study was to investigate alterations in functional connectivity (FC) within and interactions between resting-state networks involved in salience, executive control, and interoception in participants with obesity (OB).

Methods: Using resting-state functional magnetic resonance imaging with independent component analysis and FC, alterations within and interactions between resting-state networks in 35 OB and 35 normal-weight controls (NW) were investigated.

Results: Compared with NW, OB showed reduced FC strength in the ventromedial prefrontal cortex and posterior cingulate cortex/precuneus within the default-mode network, dorsal anterior cingulate cortex within the salience network (SN), bilateral dorsolateral prefrontal cortex-angular gyrus within the frontoparietal network (FPN), and increased FC strength in the insula (INS) (P  < 0.0125). The dorsal anterior cingulate cortex FC strength was negatively correlated with craving for food cues, left dorsolateral prefrontal cortex FC strength was negatively correlated with Yale Food Addiction Scale scores, and right INS FC strength was positively correlated with craving for high-calorie food cues. Compared with NW, OB also showed increased FC between the SN and FPN driven by altered FC of bilateral INS and anterior cingulate cortex-angular gyrus.

Conclusions: Alterations in FC within and interactions between the SN, default-mode network, and FPN might contribute to the high incentive value of food (craving), lack of control of overeating (compulsive overeating), and increased awareness of hunger (impaired interoception) in OB.
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http://dx.doi.org/10.1002/oby.22731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098432PMC
March 2020

Changes in Cartilage and Subchondral Bone of Femoral Trochlear Groove After Patellectomy in Growing Rabbits.

Orthop Surg 2020 Apr 19;12(2):653-660. Epub 2020 Feb 19.

Department of Joint Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Objective: To explore the effects of patellectomy on the bony and cartilaginous morphology of the trochlear groove in growing rabbits.

Methods: Forty-eight 4-week-old New Zealand white rabbits were randomly assigned to two groups. The control group underwent a sham surgical procedure, whereas the patellectomy group underwent patella excision surgery. Half of the rabbits in each group were sacrificed 3 months postoperatively; the rest were sacrificed 6 months postoperatively. Hematoxylin and eosin staining was performed on collected samples. Measurements included the bony and cartilaginous sulcus angles of the trochlear groove. In addition, the thickness of the articular cartilage at the deepest sulcus position (central thickness) and at the mid-position of the medial and lateral facets was measured and compared between groups.

Results: Three months after surgery, histological images revealed significant differences between the control group and the patellectomy group in cartilaginous sulcus angle (144.2° ± 1.5° vs 151.9° ± 2.4°, respectively; P < 0.001). No obvious difference in bony sulcus angle was found between the groups. Six months after surgery, significant between-group differences were observed in cartilaginous sulcus angle (136.3° ± 2.5° in control group vs 160.7° ± 3.0° in patellectomy group, P < 0.001) and bony sulcus angle (136.2° ± 2.2° in control group vs 160.4° ± 2.6° in patellectomy group, P < 0.001). However, there were no significant intra-group differences between cartilaginous and bony sulcus angles in either group. Three months after surgery, significant between-group differences were detected in articular cartilage thickness at the three different positions (medial facet: 324.3 ± 14.0 μm in control group vs 391.7 ± 98.8 μm in patellectomy group, P = 0.029; central position: 362.1 ± 13.6 μm in control group vs 730.3 ± 76.8 μm in patellectomy group, P < 0.001; lateral facet: 324.6 ± 12.7 μm in control group vs 358.5 ± 38.7 μm in patellectomy group, P = 0.009). No between-group differences in cartilage thickness were found at 6 months.

Conclusions: Abnormal mechanical stress (patellectomy) during a rabbit's development can cause flattening of the femoral trochlear cartilage, followed by changes in the subchondral osseous layer. Abnormal mechanical stress is a crucial factor in the development of trochlear groove dysplasia.
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http://dx.doi.org/10.1111/os.12631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189040PMC
April 2020