Publications by authors named "Xiaohua Chen"

323 Publications

Correlations between Intestinal Microbiota and Clinical Characteristics in Colorectal Adenoma/Carcinoma.

Biomed Res Int 2022 28;2022:3140070. Epub 2022 Jul 28.

Department of Oncology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

Background: Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma.

Aims: To investigate the characteristics of intestinal microbiota in colorectal adenoma and carcinoma patients and the correlations with clinical characteristics.

Methods: Fecal samples were collected from 154 colorectal carcinoma patients (CRC group), 20 colorectal adenoma patients (AD group), and 199 healthy controls (control group). The intestinal microbiota was investigated by 16S rRNA gene sequencing.

Results: Compared to the healthy controls, microbial diversity was dramatically decreased in AD/CRC. At the genus level, significantly decreased with the order of control-AD-CRC ( < 0.05). , , , , , and were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. Combination of the top 10 most important species, including , , , bacterium feline oral taxon 001, , , bacterium LD2013, , bacterium 19gly4, and , showed the best performance in distinguishing AD patients from CRC (AUC = 85.54%, 95% CI: 78.83%-92.25%). The clinicopathologic features, including age, sex, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC.

Conclusion: Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.
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http://dx.doi.org/10.1155/2022/3140070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352470PMC
July 2022

The Activation of the Tumor Suppressor Protein p53 by Acriflavine Leads to Mitochondrial Dysfunction and Improves the Radiosensitivity of Colon Cancer Cells.

J Immunol Res 2022 29;2022:1328542. Epub 2022 Jul 29.

Department of Oncology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

Colon cancer ranks third worldwide, and it has a growing incidence with urbanization and industrialization. Drug resistance in colon cancer is gradually affecting the treatment. This study focused on the mechanisms by which acriflavine (ACF) enhances the radiosensitivity of colon cancer cells. First, the expression and activation levels of tumor suppressor protein p53 were shown high in normal cells and tissues in its detection, which suggests that p53 is likely to be a key factor in colon cancer. Then, the expression of p53 ended up increasing in ACF group after SW620 cells were cultured with ACF. In addition, ACF group had some other changes. The expression of mitochondrial related antiapoptotic protein Bcl-2 increased, while the expression of proapoptotic protein Bax, Bad, cytopigment C, and apoptotic inducer AIF decreased. At the same time, the ability of apoptosis was enhanced, and the ability of proliferation and invasion was decreased. This suggests that ACF can promote p53 expression and affect mitochondrial function and the radiosensitivity of SW620. The luciferase reporting experiment showed that there was a binding site between ACF and p53. Besides, when IR treatment was applied to SW620 with high p53 expression, there was an increase in the expression of Bcl-2 in SW620 and decrease in Bax, Bad, and cytopigment C in AIF. Meanwhile, the cell apoptosis became stronger, and the proliferation and invasion became weaker. The experimental results were similar to those of SW620 cells cultured with ACF, suggesting that p53 is an intermediate factor in the regulation of SW620 by ACF. Finally, in this study, cells were cultured with ACF, and p53 was knocked down at the same time. The experimental results showed that after p53 was knocked down. ACF's ability to regulate SW620 is partially removed. This confirms the view that ACF regulates SW620 cells by regulating p53. In summary, this study found the mechanism by which ACF causes mitochondrial dysfunction and improves the radiosensitivity of colon cancer cells by activating the tumor suppressor protein p53, which may contribute to solving the drug resistance in colon cancer.
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http://dx.doi.org/10.1155/2022/1328542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355786PMC
July 2022

Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.

Emerg Microbes Infect 2022 Aug 4:1-22. Epub 2022 Aug 4.

Department of Infectious Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Omicron variant was featured with high transmissibility and striking antibody evasion. Shanghai has been experiencing Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people was much limited.

Methods: This multicenter cohort study described clinical characteristics of geriatric Omicron infections (aged more than 60), and assessed risk and protective factors for severe infections.

Results: A total of 1377 patients older than 60 were enrolled, with 75.96% had comorbidities. The median viral shedding time and hospitalization time was 9 and 8 days, respectively. Severe/critical were associated with longer virus clearance time (aOR [95%CI]:0.706(0.533-0.935), P=0.015)), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076-1.402], P=0.002; 1.140 [.019-1.274], P=0.022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of progressing to severe/critical. Fully vaccination was a significant protective factor of severe infections (0.237[0.071-0.793], P=0.019). Further, we found patients with more than two comorbidities were more likely to get serious outcome in all age groups.

Conclusion: These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors of severe infection. Patients with more than two comorbidities were more likely to get serious outcome. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking overall spectrum of COVID-19 infections among elders could be compensated in other larger scale studies in the future.
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http://dx.doi.org/10.1080/22221751.2022.2109517DOI Listing
August 2022

Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells.

J Cancer Res Clin Oncol 2022 Jul 27. Epub 2022 Jul 27.

Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

Purpose: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells.

Methods: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis.

Results: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3.

Conclusion: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.
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http://dx.doi.org/10.1007/s00432-022-04170-3DOI Listing
July 2022

Association between Wait Time for Transthoracic Echocardiography and 28-Day Mortality in Patients with Septic Shock: A Cohort Study.

J Clin Med 2022 Jul 16;11(14). Epub 2022 Jul 16.

Department of Critical Care, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou 510260, China.

the optimal timing of Transthoracic echocardiography (TTE) performance for patients with septic shock remains unexplored. a retrospective cohort study included patients with septic shock in the MIMIC-Ⅲ database. Risk-adjusted restricted cubic splines modeled the 28-day mortality according to time elapsed from ICU admission to receive TTE. The cut point when a smooth curve inflected was selected to define early and delayed group. We applied propensity score matching (PSM) to ensure our findings were reliable. Causal mediation analysis was used to assess the intermediate effect of fluid balance within 72 h after ICU admission. 3264 participants were enrolled and the risk of 28-day mortality increased until the wait time was around 10 h (Early group) and then was relatively flat afterwards (Delayed group). A beneficial effect of early TTE in terms of the 28-day mortality was observed (HRs 0.73-0.78, all < 0.05) in the PSM. The indirect effect brought by the fluid balance on day 2 and 3 was significant (both = 0.006). early TTE performance might be associated with lower risk-adjusted 28-day mortality in patients with septic shock. Better fluid balance may have mediated this effect. A wait time within 10 h after ICU may represent a threshold defining progressively increasing risk.
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http://dx.doi.org/10.3390/jcm11144131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321017PMC
July 2022

The origins of segregation behaviors of solute atoms and their effect on the strength of α-Al//θ'-AlCu interfaces in Al-Cu alloys.

Phys Chem Chem Phys 2022 Aug 3;24(30):18370-18392. Epub 2022 Aug 3.

School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

In many alloy systems, the segregation and strengthening of the solute atoms are caused by mechanical and chemical contributions. To uncover the origins of segregation behaviors and strengthening behaviors of the solute atoms Cd, Si, Sc and Zr at (001)//(001) and (010)//(010) interfaces, first-principles calculations were conducted. Results show that the chemical contribution primarily dominates the oscillatory segregation behaviors of Cd, Si, Sc and Zr on the Al matrix side. The oscillatory segregation behaviors of Cd, Si, Sc and Zr on the θ' side are mainly governed by both chemical and mechanical contributions. The segregation tendency of Cd at the (001)//(001) interface (or (010)//(010) interface) throughout the platelets is small (or strong) because the charge accumulation between Cd and the host atoms is weak (or significant). The segregation trend of Sc (or Zr) on the Al matrix side at the (001)//(001) and (010)//(010) interfaces is strong, which is attributed to significant charge accumulation between Sc (or Zr) and the host atoms. Si exhibits a favorable segregation tendency on the θ' side at both the (001)//(001) and (010)//(010) interfaces, which is ascribed to significant charge accumulation between Si and the host atoms. With the increase of Si, Sc and Zr coverage, the segregation tendencies of Si, Sc and Zr enhance. The segregation tendency of Cd decreases with the increase of Cd coverage. The first-principles tensile test for the interface was conducted. The work of dislocation emission was computed. Results show that the strengthening effects of solute atoms on the interface are primarily dominated by the chemical contribution. Sc (or Zr) segregation leads to an increase in the strength of the interface, which is majorly attributed to a strong electronic interaction between Sc (or Zr) and the host atoms. Cd segregation causes a weakening effect on the interface because of the weak electronic interaction between Cd and the host atoms. The ductility of the (001)//(001) interface with the Sc (or Zr) is more significant than that with the Cd (or Si). This work provides a strategy for improving the mechanical properties of the Al-Cu alloys.
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http://dx.doi.org/10.1039/d2cp01291jDOI Listing
August 2022

Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy.

Microbiol Spectr 2022 Jul 14:e0032422. Epub 2022 Jul 14.

Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and β diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (, , and Roseburia intestinalis) and potential probiotics ( and ) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, sp. 26_22 was negatively associated with serum creatinine ( < 0.05). DN patients could be accurately distinguished from CON by sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by , Fusobacterium varium, and sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.
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http://dx.doi.org/10.1128/spectrum.00324-22DOI Listing
July 2022

Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.

BMC Infect Dis 2022 Jul 19;22(1):630. Epub 2022 Jul 19.

Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice.

Methods: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90.

Discussion: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients.

Trial Registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .
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http://dx.doi.org/10.1186/s12879-022-07557-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295283PMC
July 2022

Differentially expressed genes and miRNAs in female osteoporosis patients.

Medicine (Baltimore) 2022 Jul 15;101(28):e29856. Epub 2022 Jul 15.

Department of Orthopaedics, the First People's Hospital of Fuyang Hangzhou, Hangzhou, Zhejiang Province, PR China.

Osteoporosis is characterized by lowing bone mineral density. This study aimed to investigate the genes, miRNAs, pathways, and miRNA-gene interaction pairs involved in the pathogenesis of female osteoporosis. The differentially expressed genes (DEGs, GSE62402), differentially expressed miRNAs (DEmiRNAs, GSE63446), and differentially methylated genes (GSE62588) between females with low- and high-hip bone mineral density were identified. Genes common to DEGs, differentially methylated genes, DEmiRNAs' targets, and osteoporosis-related genes were retained and used to construct the miRNA-mRNA-pathway regulatory network. The expression of hub nodes was validated in microarray datasets (genes in GSE56116 and miRNAs in GSE93883). Thirty-four DEmiRNAs and 179 DEGs with opposite expression-methylation profiles were identified. Functional enrichment analysis showed that DEGs were associated with pathways including "hsa00380:Tryptophan metabolism," "hsa04670:Leukocyte transendothelial migration," "hsa04630:Jak-STAT signaling pathway," and "hsa04062:Chemokine signaling pathway." The miRNA-mRNA-pathway network included 10 DEGs, 9 miRNAs, and 4 osteoporosis-related pathways. The miRNA-gene-pathway axes including hsa-miR-27b-5p/3p-IFNAR1-hsa04630, hsa-miR-30a-5p/3p-IFNAR1-hsa04630, hsa-miR-30a-5p/3p-ALDH2-hsa00380, and hsa-miR-194-5p/3p-NCF2-hsa04670 were included in the network. Microarray validation showed that IFNAR1, NCF2, and ALDH2 were upregulated, and hsa-miR-30a-3p/5p, hsa-miR-194-3p/5p, hsa-miR-27b-3p/5p, and hsa-miR-34a-3p were downregulated in osteoporotic samples compared with control. Axes including hsa-miR-27b/30a-IFNAR1-Jak-STAT signaling pathway, hsa-miR-30a-ALDH2-Tryptophan metabolism, and hsa-miR-194-NCF2-Leukocyte transendothelial migration were involved in osteoporosis pathogenesis.
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http://dx.doi.org/10.1097/MD.0000000000029856DOI Listing
July 2022

Gold nanocluster adjuvant enables the eradication of persister cells by antibiotics and abolishes the emergence of resistance.

Nanoscale 2022 Jul 21;14(28):10016-10032. Epub 2022 Jul 21.

Department of Otolaryngology, Head and Neck Surgery, Stanford University, 801 Welch Road, Stanford, CA 94305-5739, USA.

Persister cells are responsible for relapses of infections common in cystic fibrosis and chronic suppurative otitis media (CSOM). Yet, there are no Food and Drug Administration (FDA) approved antibiotics to eradicate persister cells. Frustratingly, the global preclinical bacterial pipeline does not contain antibacterial agents targeting persister cells. Therefore, we report a nontraditional antimicrobial chemotherapy strategy based on gold nanoclusters adjuvant to eradicate persister cells by existing antibiotics belonging to that different class. Compared to killing with antibiotics alone, combining antibiotics and [email protected] sterilizes persister cells and biofilms. Enhanced killing of up to 4 orders of magnitude in a validated mouse model of CSOM with infection was observed when combining antibiotics and [email protected], informing a potential approach to improve the treatment of CSOM. We established that the mechanism of action of [email protected] is due to disruption of the proton gradient and membrane hyperpolarization. The method presented here could compensate for the lack of new antibiotics to combat persister cells. This method could also benefit the current effort to slow resistance development because [email protected] abolished the emergence of drug-resistant strains induced by antibiotics.
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http://dx.doi.org/10.1039/d2nr01003hDOI Listing
July 2022

An ultrasonication-aided self-assembly strategy toward a PTCDA/RGO film cathode for organic K-ion full batteries.

Chem Commun (Camb) 2022 Jul 26;58(60):8348-8351. Epub 2022 Jul 26.

Joint School of National University of Singapore and Tianjin University International Campus of Tianjin University, Binhai New City, Fuzhou 350207, China.

A free-standing PTCDA/RGO film was synthesized by an ultrasonication-aided self-assembly strategy to alleviate the solubility of PTCDA in organic electrolytes. The PTCDA/RGO-50% film cathode exhibits a high capacity of 135.1 mA h g at 0.05 A g and excellent cycling stability (capacity retention of 85% after 200 cycles) for potassium ion batteries.
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http://dx.doi.org/10.1039/d2cc02600gDOI Listing
July 2022

Pattern and prognostic value of lymph node metastasis in sinonasal mucosal melanoma.

Ear Nose Throat J 2022 Jul 5:1455613221112350. Epub 2022 Jul 5.

Department of Otorhinolaryngology Head and Neck Surgery, 373651The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objective: To analyze the pattern of lymph node (LN) metastasis and its effect on prognosis in sinonasal mucosal melanoma (SNMM).

Methods: This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) Program data. Survival outcomes were analyzed using the Kaplan-Meier method. Factors were compared between groups using log-rank test and Fisher's exact test, and prognostic factors were screened using the Cox proportional hazards model. Propensity score matching (PSM) was conducted to examine the treatment differences after accounting for sex, age, race, T stage, N stage, and M stage.

Results: Level I (57.1%) and level II (53.6%) nodes were the most common sites of lymph node metastasis, followed by level III (17.9%) and IV (17.9%) nodes. T stage, M stage, and tumor size were associated with LN metastasis. The 5-year overall survival rates for patients without and with LN metastasis were 35.2% and 5.3%, respectively.

Conclusions: Level I and II lymph nodes may be the sentinel nodes of SNMM, Advanced T stage and increasing tumor size could promote LN metastasis. LN metastasis may promote distant metastasis and remains an important prognostic factor for patients with SNMM.
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http://dx.doi.org/10.1177/01455613221112350DOI Listing
July 2022

A Novel Approach Combined with MIPO Technique for the Treatment of Type C Pilon Fractures.

Oxid Med Cell Longev 2022 14;2022:7427255. Epub 2022 Jun 14.

Department of Orthopedics, Chongqing University Three Gorges Hospital, Chongqing 404000, China.

Objective: Type C fracture is a complete intra-articular fracture, and the mainstay of treatment remains open reduction and internal fixation. The purpose of the study is to observe the clinical effect of an anterior ankle C approach (ankle-C) combined with minimal invasive plate osteosystems (MIPO) for tibial pilon fractures (AO/OTA 43C, combined with fibula fractures).

Methods: A retrospective comparative analysis was performed on the clinical data of 33 patients with C-type pilon fractures (combined fibula fractures) admitted to our department from July 2018 to July 2021, including 12 cases treated with ankle-C (a-C) approach and 21 cases with conventional approach (including combined approach). All patients were followed up for over 6 months. Visual Analogue Scale (VAS), AOFAS Ankle-Hindfoot Scale (AOFAS-AHS), wound healing time, fracture healing time, and complications were used to evaluate the clinical efficacy.

Results: The scores of VAS and AOFAS in the a-C group scored better than the conventional group ( < 0.05), especially in the extent of limited range of motion (LROM) of ankle dorsiflexion-plantarflexion in 1 month after operation and at the last follow-up ( < 0.01). Bone healing was achieved in both groups 6 months after operation, with no implant exposure or infection. Among them, 4 cases in the conventional approach group had wound healing time exceeding 2 weeks.

Conclusions: For type C pilon fractures (combined with fibula fractures), ankle-C approach combined with MIPO technique has certain advantages in ankle function recovery and soft tissue repair, which provides an alternative for the treatment of type C pilon fractures.
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http://dx.doi.org/10.1155/2022/7427255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213148PMC
June 2022

The Temporal Impact of Prosthesis Implantation and Semi-Quantitative Criteria on the Diagnostic Efficacy of Triple-Phase Bone Scanning for Periprosthetic Joint Infection.

Orthop Surg 2022 Jul 14;14(7):1438-1446. Epub 2022 Jun 14.

Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: To evaluate the diagnostic efficacy of triple-phase bone scanning and the temporal impact of prosthesis implantation on the diagnostic efficacy of triple-phase bone scanning for periprosthetic joint infection (PJI).

Methods: Patients who were admitted to our hospital for joint pain and dysfunction after total joint arthroplasty between 2014 and 2020 were retrospectively included. Triple-phase bone scanning was performed, and the blood pool images were evaluated to obtain the semi-quantitative criteria. The patients were then grouped into six groups according to the time interval from index primary arthroplasty to triple-phase bone scanning. We examined whether there were significant differences in sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy between the groups.

Results: Overall, 66 patients who underwent total hip arthroplasty (THA) and 74 patients who underwent total knee arthroplasty (TKA) were analyzed. No significant differences were observed between visual analysis and semi-quantitative measurement in terms of sensitivity, specificity, PPV, NPV, and accuracy. For patients with a time interval from prosthesis implantation to bone scanning of >1 year, visual analysis had a higher PPV (100%) in patients who underwent THA and the use of semi-quantitative criteria had a higher NPV (85.7%) in patients who underwent TKA.

Conclusion: The semi-quantitative criteria showed no advantages in the diagnosis of PJI. In addition, triple-phase bone scanning demonstrated good clinical diagnostic efficacy when the time interval from prosthesis implantation to bone scanning was >1 year.
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http://dx.doi.org/10.1111/os.13278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251298PMC
July 2022

Modulation of proton-coupled electron transfer reactions in lysine-containing alpha-helixes: alpha-helixes promoting long-range electron transfer.

Phys Chem Chem Phys 2022 Jun 15;24(23):14592-14602. Epub 2022 Jun 15.

School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, P. R. China.

The proton-coupled electron transfer (PCET) reaction plays an important role in promoting many biological and chemical reactions. Usually, the rate of the PCET reaction increases with an increase in the electron transfer distance because long-range electron transfer requires more free energy barriers. Our density functional theory calculations here reveal that the mechanism of PCET occurring in lysine-containing alpha(α)-helixes changes with an increasing number of residues in the α-helical structure and the different conformations because of the modulation of the excess electron distribution by the α-helical structures. The rate constants of the corresponding PCET reactions are independent of or substantially shallower dependent on the electron transfer distances along α-helixes. This counter-intuitive behavior can be attributed to the fact that the formation of larger macro-cylindrical dipole moments in longer helixes can promote electron transfer along the α-helix with a low energy barrier. These findings may be useful to gain insights into long-range electron transfer in proteins and design α-helix-based electronics the regulation of short-range proton transfer.
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http://dx.doi.org/10.1039/d2cp00666aDOI Listing
June 2022

The Aging Trend of Insureds and Stochastic Evaluation of Financial Sustainability of Basic Pension in China.

Authors:
Xiaohua Chen

Front Public Health 2022 19;10:911535. Epub 2022 May 19.

School of Finance, Jiangxi University of Finance and Economics, Nanchang, China.

The document, points out that in order to actively respond to the aging population in China, it is necessary to steadily increase the endowment wealth reserves. To achieve this goal, it is urgent to stochastically assess the future financial situation of the basic pension insurance in China, grasp its various possible conditions, trends, and corresponding confidence intervals, so that the government can take targeted measures to gradually consolidate the wealth reserves for this basic insurance first, and then steadily increase the social wealth reserves for the elderly. Thus, this paper first analyzes the characteristics of the aging population of insureds participating in basic pension insurance, and then randomly simulates the long-term financial situation of the basic pension insurance. The study found that the aging of the insureds has the characteristics of "fierce coming and slow decline" and "long-term seriousness." Among the six indicators of the financial situation of basic pension insurance, Indicator 1 (the current year's expenditures as a proportion of current year's contributions), Indicator 2 (current year's balance of contributions and expenditures), Indicator 3 (current year's payment gap as a proportion of current year's contributions), Indicator 4 (accumulated balance), Indicator 5 (fund ratio), and Indicator 6 (accumulated payment gap as a proportion of current year's contributions) are respectively in the range of [0.73%, 1.80%], [-12.05, -0.12] trillion yuan, [0.29%, 3.89%], [-133.39, -5.62] trillion yuan, [2032, 2043] years and [6.72%, 215.63%] with a probability of 95%. We analyzed the influence direction and degree of main parameters on the financial situation of the fund and analyzed the impact of parameter value paths on the final financial status of the fund to improve the ability to strengthen fund reserve. The backtracking found that if the value path of the average salary growth rate shows a trend of rising first and then falling, then the final financial situation at the end of the period will be "worse." If it shows a trend of falling first and then rising, the final financial situation will be "better."
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http://dx.doi.org/10.3389/fpubh.2022.911535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162449PMC
June 2022

Metabolomics Reveals 5-Aminolevulinic Acid Improved the Ability of Tea Leaves ( L.) against Cold Stress.

Metabolites 2022 Apr 26;12(5). Epub 2022 Apr 26.

Shaanxi Provincial Bioresource Key Laboratory, College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China.

Tea is an important woody crop whose cultivation is severely limited by cold stress. Although 5-aminolevulinic acid (ALA) is known to be effective in alleviating abiotic stresses in plants, knowledge of the detailed metabolic response of tea plants to exogenous ALA-induced cold resistance is still limited-a lack which restricts our ability to protect tea plants from cold stress. In the present study, we performed an in-depth metabolomics analysis to elucidate the metabolic responses of tea plants to cold stress and explore the role of ALA in improving tea plants' cold-resistance capability. Metabolic profiles showed that cold stress altered various metabolisms in tea plants, especially galactose composition and flavonoid contents. Furthermore, exogenous ALA application altered a series of metabolisms associated with cold stress. Importantly, increases in metabolites, including catechin, 3,4-dihydroxyphenylacetic acid and procyanidin B2, involved in the mechanisms of ALA improved tea plants' cold resistance. Overall, our study deciphered detailed metabolic responses of tea plants to cold stress and elucidated the mechanisms of ALA in enhancing cold resistance through rebuilding compositions of soluble carbohydrates and flavonoids. Therefore, we have provided a basis for exogenous usage of ALA to protect tea plants from cold stress.
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http://dx.doi.org/10.3390/metabo12050392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144897PMC
April 2022

Postoperative analgesic effectiveness of quadratus lumborum block: systematic review and meta-analysis for adult patients undergoing hip surgery.

J Orthop Surg Res 2022 May 19;17(1):282. Epub 2022 May 19.

Department of Orthopedics, Chongqing General Hospital, Chongqing, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, People's Republic of China.

Background: Quadratus lumborum block is a truncal block with several technique variations. It has been reported as providing effective analgesia for postoperative pain. The aim of this study is to determine the efficacy of the QL block in providing postoperative analgesia for hip surgery when compared with placebo or no block or other analgesic techniques.

Methods: Randomized trials evaluating quadratus lumborum block benefits in elective hip surgery were sought. The primary outcome was the 24 h opioid requirement after surgery. Two independent reviewers selected the studies and extracted the data.

Results: Thirteen randomized-controlled trials were included in this study. The included studies had significant heterogeneity regarding comparator groups; therefore, a limited quantitative analysis was undertaken for the comparison of QL block versus no block or placebo only. QL block reduced the opioid use by 15.78 (95% CI, 2.31 to 29.26) mg IME in the first postoperative 24 h compared with no block or placebo with no difference in static pain scores, pain grade was reduced by 2.95 (95% CI, 2.40 to 3.60) in the QL block group compared with placebo or no block in the first postoperative 24 h during movement.

Conclusions: Our meta-analysis indicates that QL block may be effective for analgesia in patients after hip surgery compared with placebo or no block. There is currently limited evidence comparing QL block with other analgesic techniques for hip surgery.
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http://dx.doi.org/10.1186/s13018-022-03172-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118859PMC
May 2022

A revision of the genus Hübner, 1825 from China based on morphology and molecular data, with descriptions of five new species (Lepidoptera, Crambidae, Pyraustinae).

Zookeys 2022 23;1090:1-44. Epub 2022 Mar 23.

School of Ecology, Sun Yat-sen University, Guangzhou, Guangdong 510275, China Sun Yat-sen University Guangzhou China.

The genus Hübner, 1825 is revised. Most type materials were examined, and a preliminary phylogeny is presented based on a combined dataset of COI, 16S rRNA, 28S rRNA and EF-1α gene regions. The tree topology and morphological characters suggest that Moore, 1886 is a new synonym of , and Munroe & Mutuura, 1969 is restored as a valid genus. According to the morphological evidence and tree topology, 17 species are recorded, including five new species described from China: Zhang & Xiang, , Xiang & Zhang, , Zhang & Xiang, , Zhang & Xiang, and Zhang & Xiang, Seven new combinations are created, (Walker, 1859), , (Pryer, 1877), , (Moore, 1888), , (Butler, 1880), , (Moore, 1886), , (Walker, 1859), , and (Snellen, 1890), , as well as eight new synonyms, namely Warren, 1895, , Strand, 1918, , Warren, 1896, , Gao, Zhang & Wang, 2013, , South, 1901, , Gao, Zhang &Wang, 2013, , Gao, Zhang & Wang, 2013, , and Zhang, Li & Wang, 2004, All adults and their genital structures are illustrated and an identification key based on adult external morphology and genitalia is provided.
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http://dx.doi.org/10.3897/zookeys.1090.78442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967814PMC
March 2022

[Relationship of in-hospital mortality and using intra-aortic balloon pump with extracorporeal cardiopulmonary resuscitation in patients with cardiac arrest: a secondary analysis based on literature data].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Mar;34(3):269-273

Department of Intensive Care Unit, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong, China. Corresponding author: Xiong Xuming, Email:

Objective: To assess the effect of intra-aortic balloon pump (IABP) on in-hospital mortality in patients with cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation (ECPR).

Methods: A retrospective study was performed on 696 patients with intra-hospital cardiac arrest undergoing ECPR from Samsung Medical Center in Korea between January 2004 and December 2013. According to whether IABP was used, the patients were divided into ECPR group and ECPR+IABP group. Cox regression and propensity score matching (PSM) were used to examine the correlation between IABP usage and in-hospital mortality, and standardized mean difference (SMD) was used to check the degree of PSM. Survival analysis of in-hospital mortality was performed by the Kaplan-Meier method, and further analyzed by the Log-Rank test. Using the propensity score as weights, multiple regression model and inverse probability weighting (IPW) model were used for sensitivity analysis. In-hospital mortality, extracorporeal membrane oxygenation (ECMO) withdrawal success rate and neurological function prognosis were compared between the two groups.

Results: A total of 199 patients with cardiac arrest undergoing ECPR were included, including 120 males and 79 females, and the average age was (60.0±16.8) years. Thirty-one patients (15.6%) were treated with ECPR and IABP, and 168 patients (84.4%) only received ECPR. The total hospitalized mortality was 68.8% (137/199). The 1 : 1 nearest neighbor matching algorithm was performed with the 0.2 caliper value. The following variables were selected to generate propensity scores, including age, gender, race, marital status, insurance, admission type, service unit, heart rate, mean arterial pressure, respiratory rate, pulse oxygen saturation, white blood cell count. After the propensity score matching, 24 pairs of patients were successfully matched, with the average age of (63.0±12.8) years, including 31 males and 17 females. The in-hospital mortality was 72.6% (122/168) and 48.4% (15/31) in the ECPR group and the ECPR+IABP group [hazard ratio (HR) = 0.48, 95% confidence interval (95%CI) was 0.28-0.82, P = 0.007]. Multiple regression model, adjusted propensity score, PSM and IPW model showed that the in-hospital mortality in the ECPR+IABP group was significantly lower compared with the ECPR group (HR = 0.44, 0.50, 0.16 and 0.49, respectively, 95%CI were 0.24-0.79, 0.28-0.91, 0.06-0.39 and 0.31-0.77, all P < 0.05). The combined application of IABP could improve the ECMO withdrawal success rate [odds ratio (OR) = 8.95, 95%CI was 2.72-29.38, P < 0.001] and neurological prognosis (OR = 4.06, 95%CI was 1.33-12.40, P = 0.014) in adult cardiac arrest patients.

Conclusions: In patients with cardiac arrest using ECPR, the combination of IABP was independently associated with lower in-hospital mortality, higher ECMO withdrawal success rate and better neurological prognosis.
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http://dx.doi.org/10.3760/cma.j.cn121430-20211014-01492DOI Listing
March 2022

A microarray expression profile and bioinformatic analysis of circular RNA in human esophageal carcinoma.

J Gastrointest Oncol 2022 Apr;13(2):510-526

Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Background: Recent studies indicate that non-coding circular RNAs (circRNAs) are involved in the development of esophageal carcinoma (EC). This study aimed to identify differential expression of circRNAs in EC, which can provide potential biomarkers and therapeutic targets for EC treatment and improve the understanding of tumorigenesis mechanism.

Methods: First, samples (n=5) of EC tissues and adjacent normal tissue were sent for circRNA microarray detection, Second, further bioinformatic analysis was performed, including circRNA-microRNA (miRNA), co-expression network analysis, Spearman correlation test, and cancer-related circRNA-miRNA axis analysis. Finally, the expression of circRNA that our analysis predicted to be hub genes was verified in samples (n=15) of EC tissues and adjacent normal tissue by real-time polymerase chain reaction (RT-PCR).

Results: Microarray identified 102 upregulated and 67 significantly downregulated circRNAs were in EC patients' tumors relative to adjacent normal tissue. One upregulated circRNA () showed the most connection with MREs, therefore was regarded as the hub gene by the Spearman correlation test. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that four primary pathways (mRNA surveillance, cytoskeleton actin regulation, spliceosome, and the NOD-like receptor signaling pathway) were predicted in the hub circRNA's five connected miRNA response elements (MREs). Furthermore, cancer-related circRNA-miRNA axis analyses showed that and its four connected MREs participated in the cancer-related pathway. RT-PCR showed that and were significantly increased in the tumor tissues of EC patients.

Conclusions: Abnormal expression of circRNAs was involved in the tumorigenesis of EC. Key circRNAs, namely and , may be as potential biomarkers and therapeutic targets for the treatment of EC.
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http://dx.doi.org/10.21037/jgo-22-137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086029PMC
April 2022

An interesting possibility of forming special hole stepping stones with high-stacking aromatic rings in proteins: three-π five-electron and four-π seven-electron resonance bindings.

RSC Adv 2021 Aug 4;11(43):26672-26682. Epub 2021 Aug 4.

Chongqing Key Laboratory of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Chongqing University Chongqing 401331 P.R. China

Long-range hole transfer of proteins plays an important role in many biological processes of living organisms. Therefore, it is highly useful to examine the possible hole stepping stones, which can facilitate hole transfer in proteins. However, the structures of stepping stones are diverse because of the complexity of the protein structures. In the present work, we proposed a series of special stepping stones, which are instantaneously formed by three and four packing aromatic side chains of amino acids to capture a hole, corresponding to three-π five-electron (π:π∴π↔π∴π:π) and four-π seven-electron (π:π∴π:π↔π:π:π∴π) resonance bindings with appropriate binding energies. The aromatic amino acids include histidine (His), phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp). The formations of these special stepping stones can effectively reduce the local ionization potential of the high π-stacking region to efficiently capture the migration hole. The quick formations and separations of them promote the efficient hole transfer in proteins. More interestingly, we revealed that a hole cannot delocalize over infinite aromatic rings along the high π-π packing structure at the same time and the micro-surroundings of proteins can modulate the formations of π:π∴π↔π∴π:π and π:π∴π:π↔π:π:π∴π bindings. These results may contribute a new avenue to better understand the potential hole transfer pathway in proteins.
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http://dx.doi.org/10.1039/d1ra05341hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037495PMC
August 2021

Optimizing the Microstructure of SnO-CeO Binary Oxide Supported Palladium Catalysts for Efficient and Stable Methane Combustion.

ACS Appl Mater Interfaces 2022 Apr 4;14(14):16233-16244. Epub 2022 Apr 4.

College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University, Fuzhou 350007, Fujian, P. R. China.

The preparation of palladium-based catalysts with both high catalytic activity and hydrothermal stability currently appears as a critical topic in methane combustion. Herein, we propose a facile strategy to boost the performance of SnO-CeO binary oxide supported palladium catalysts by tuning the composition of supports. The coexistence of SnO and CeO phases in an appropriate ratio is favorable for the formation of both PdCeO and PdSnO solid solutions due to the reduced crystallite size. This unique microstructure could enhance the metal-support interaction to stabilize the active PdO phase and promote its reoxidation, meanwhile generating more oxygen vacancies to improve the reducibility of PdO. On account of the facilitated conversion of PdO ↔ Pd, coupled with the low-temperature dissociation of methane promoted by abundant active oxygen species, the Pd/5Sn5Ce catalyst exhibits a superior catalytic activity with a of ca. 360 °C, a robust stability under both dry and wet conditions, and an excellent thermal stability during heating-cooling light-off tests.
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http://dx.doi.org/10.1021/acsami.2c01420DOI Listing
April 2022

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis.

J Bone Miner Res 2022 05 28;37(5):1044-1055. Epub 2022 Mar 28.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, School of Stomatology, the Fourth Military Medical University, Xi'an, PR China.

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4542DOI Listing
May 2022

The Impact and Clinical Prediction of Hyperglycemia During Parenteral Nutrition for Nondiabetic Patients After Gastrectomy for Gastric Cancer.

Front Nutr 2022 14;9:807841. Epub 2022 Feb 14.

Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou, China.

Background And Purpose: Hyperglycemia (HG) is associated with increased postoperative complications. This study aims to evaluate the effect of HG during supplemental parenteral nutrition (SPN) on short-term prognosis in non-diabetic patients undergoing gastrectomy for cancer and to analyse the risk factors and prevention methods for HG.

Methods: A total of 359 patients were divided into three groups according to blood glucose (BG) during SPN: normoglycemic patients ( ≤ 125 mg/dL), mild HG (125~200 mg/dL), and severe HG (>200 mg/dL). The effect of BG on postoperative short-term outcomes was analyzed. Multivariate regression was performed to investigate influencing factors for severe HG. The safety and efficacy of insulin addition to total nutrient admixture (TNA) for the prevention and management of HG were assessed by propensity score matching (PSM). In addition, regression analysis was performed in the noninsulin group to investigate the predictive factors of severe HG, and a nomogram was plotted.

Results: The postoperative complication rate was 18.9%, but it was significantly higher in patients with severe HG than in mild HG and normoglycemic patients (25.2, 15.0, and 10.0%, respectively, < 0.05). Multivariate logistic regression analysis showed that anemia, myosteatosis, higher postoperative capillary blood glucose (CBG) before TNA infusion, and insulin in the TNA were independent influencing factors for severe HG. Based on the above factors, 75 pairs of patients (insulin group and non-insulin group) with comparable baseline data were successfully matched by PSM. The HG incidence and the glycemic fluctuation were significantly improved through 1 U insulin/6 g glucose (1/6 scheme) to TNA. A nomogram containing hemoglobin, skeletal muscle radiodensity, pre-SPN CBG, and pTNM stage with good predictive efficacy (C-index: 0.750) was constructed based on the noninsulin group.

Conclusion: Poor postoperative glycemic control was related to worse outcomes in non-diabetic patients undergoing gastrectomy for cancer. Pre-operative anemia, myosteatosis, and high postoperative CBG before TNA infusion are risk factors for severe HG. Insulin in TNA can improve the blood glucose control of patients. Our proposed nomogram rendered an individualized predictive tool for HG during SPN, which helps screen high-risk patients requiring insulin therapy. Future studies with larger samples are needed to develop a complete insulin application protocol for SPN.
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http://dx.doi.org/10.3389/fnut.2022.807841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882839PMC
February 2022

The Risk of Hippocampal Metastasis and the Associated High-Risk Factors in 411 Patients With Brain Metastases.

Front Oncol 2022 14;12:808443. Epub 2022 Feb 14.

Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou, China.

Background And Aims: To retrospectively analyze the incidence of hippocampal metastasis and the associated high-risk factors in patients with brain metastases and evaluate the safety of hippocampal avoidance whole-brain radiation therapy (HA-WBRT).

Methods: We retrospectively analyzed the data of patients with brain metastases diagnosed by contrast-enhanced cranial Magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The boundaries of the hippocampus, hippocampus + 5 mm area, hippocampus + 10 mm area, and hippocampus + 20 mm area were delineated, and the distances from the brain metastases to the hippocampus were measured. Univariate and multivariate logistic regressions were adopted to analyze the high-risk factors of hippocampal metastasis.

Results: A total of 3,375 brain metastases in 411 patients were included in the analysis. The metastasis rates in the hippocampus and surrounding areas of the entire group were as follows: 7.3% (30/411) in the hippocampus, 16.5% (68/411) in the hippocampus + 5 mm area, 23.8% (98/411) in the hippocampus + 10 mm area, and 36.5% (150/411) in the hippocampus + 20 mm area. Univariate logistic regression showed that the pathological type, the number of metastases, the maximum diameter of metastases, and the volume of brain metastases were all correlated with hippocampal metastasis. Multivariate logistic regression showed that the pathological type, the number of metastases, and the total volume of metastases were correlated with hippocampal metastasis.

Conclusion: The pathological type, the number of metastases, and the total volume of metastases are the high-risk factors associated with hippocampal metastasis. Small cell lung cancer (SCLC) has a significantly higher rate of hippocampal metastasis than other tumor types. The greater the number and total volume of metastases, the more likely the hippocampal metastasis. For patients with SCLC or a greater number and total volume of brain metastases, the implementation of HA-WBRT may bring a higher risk of tumor recurrence.
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http://dx.doi.org/10.3389/fonc.2022.808443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882759PMC
February 2022

Dual-RNA controlled delivery system inhibited tumor growth by apoptosis induction and TME activation.

J Control Release 2022 04 18;344:97-112. Epub 2022 Feb 18.

Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People's Republic of China. Electronic address:

Drug-controlled release is recognized as effective for improving compliance with treatment and obtaining better therapeutic efficacy with less toxicity in cancer treatment. However, few reports in this area are involved in nucleic acids delivery, especially in RNA therapeutics delivery. In this study, an injectable hydrogel Methacrylated gelatin (GM) scaffold was introduced into a dual-RNA hybrid delivery complex hybrid lipid particle (HLP) to form a G-HLP/RNAs system. This system can control the release of both siRNA and mRNA and was found to be efficient for protecting these RNAs from biodegradation and retaining their therapeutic effect over 7 days. Further, a tumor environment (TME)-activation function after peritumoral injection of mocked GM scaffold was observed. Then, matured DC cells and activated T-cells were detected by the addition of HLP/RNAs complex, thus verifying the immunoactivation function of GM scaffold and its ability to reserve immune cells and antigens. Finally, two doses of G-HLP/RNAs treatment efficiently suppressed C26 tumor growth in mice with a tumor weight inhibition rate of 71.9%. Owing to its ability to achieve RNA drug-controlled release, alter TME, and induce tumor apoptosis, the G-HLP/RNAs system may become a valuable tool for cancer gene therapy.
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http://dx.doi.org/10.1016/j.jconrel.2022.02.022DOI Listing
April 2022

Multi-Institutional Validation of Two-Streamed Deep Learning Method for Automated Delineation of Esophageal Gross Tumor Volume Using Planning CT and FDG-PET/CT.

Front Oncol 2021 24;11:785788. Epub 2022 Jan 24.

Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

Background: The current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation with high labor costs and inter-user variability.

Purpose: To validate the clinical applicability of a deep learning multimodality esophageal GTV contouring model, developed at one institution whereas tested at multiple institutions.

Materials And Methods: We collected 606 patients with esophageal cancer retrospectively from four institutions. Among them, 252 patients from institution 1 contained both a treatment planning CT (pCT) and a pair of diagnostic FDG-PET/CT; 354 patients from three other institutions had only pCT scans under different staging protocols or lacking PET scanners. A two-streamed deep learning model for GTV segmentation was developed using pCT and PET/CT scans of a subset (148 patients) from institution 1. This built model had the flexibility of segmenting GTVs only pCT or pCT+PET/CT combined when available. For independent evaluation, the remaining 104 patients from institution 1 behaved as an unseen internal testing, and 354 patients from the other three institutions were used for external testing. Degrees of manual revision were further evaluated by human experts to assess the contour-editing effort. Furthermore, the deep model's performance was compared against four radiation oncologists in a multi-user study using 20 randomly chosen external patients. Contouring accuracy and time were recorded for the pre- and post-deep learning-assisted delineation process.
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http://dx.doi.org/10.3389/fonc.2021.785788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820194PMC
January 2022

Neuron-derived neuropeptide Y fine-tunes the splenic immune responses.

Neuron 2022 04 8;110(8):1327-1339.e6. Epub 2022 Feb 8.

State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

The nervous and immune systems are closely entwined to maintain the immune balance in health and disease. Here, we showed that LPS can activate suprarenal and celiac ganglia (SrG-CG) neurons and upregulate NPY expression in rats. Single-cell sequencing analysis revealed that knockdown of the NPY gene in SrG-CG altered the proliferation and activation of splenic lymphocytes. In a neuron and splenocyte coculture system and in vivo experiments, neuronal NPY in SrG-CG attenuated the splenic immune response. Notably, we demonstrated that neuronal NPF in Drosophila exerted a conservative immunomodulatory effect. Moreover, numerous SNPs in NPY and its receptors were significantly associated with human autoimmune diseases, which was further supported by the autoimmune disease patients and mouse model experiments. Together, we demonstrated that NPY is an ancient language for nervous-immune system crosstalk and might be utilized to alleviate inflammatory storms during infection and to modulate immune balance in autoimmune diseases.
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http://dx.doi.org/10.1016/j.neuron.2022.01.010DOI Listing
April 2022

TRIM32 promotes radioresistance by disrupting TC45-STAT3 interaction in triple-negative breast cancer.

Oncogene 2022 03 28;41(11):1589-1599. Epub 2022 Jan 28.

Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, 730000, P.R. China.

Radioresistance is common in the treatment of triple-negative breast cancer (TNBC), but the molecular mechanisms involved remain unclear. Herein, we reveal that tripartite motif-containing protein 32 (TRIM32) is upregulated in TNBC and is negatively associated with survival of TNBC patients. Radiotherapy resulted in enhanced expression of TRIM32, whereas TRIM32 depletion reduced TNBC radioresistance in vitro and in vivo. Mechanistically, radiotherapy promoted the association between TRIM32 and nuclear STAT3, which suppressed TC45-induced dephosphorylation of STAT3, resulting in increased STAT3 transcriptional activation and TNBC radioresistance. Finally, we demonstrated that TRIM32 and STAT3 phosphorylation are co-expressed in TNBC tissues. Moreover, high expression of TRIM32 and STAT3 phosphorylation is positively linked to poor prognosis of TNBC patients. Our study demonstrates that TRIM32 is a novel target for predicting radioresistance in TNBC patients.
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http://dx.doi.org/10.1038/s41388-022-02204-1DOI Listing
March 2022
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