Publications by authors named "Dongliang Wang"

213 Publications

Structure, Antigenic Properties, and Highly Efficient Assembly of PCV4 Capsid Protein.

Front Vet Sci 2021 24;8:695466. Epub 2021 Aug 24.

Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, Laboratory of Functional Proteomics, Research Center of Reverse Vaccinology, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China.

Porcine circovirus type 4 (PCV4), a recently reported circovirus, was first identified in pigs with clinical signs similar to porcine dermatitis nephropathy syndrome (PDNS), in Hunan province, China, in 2019. More knowledge regarding the assembly of capsid protein (Cap) into virus-like particles (VLPs), their structure and antigenic properties, are needed to provide new knowledge for diagnosis and further characterization of PCV4. In this study, high-level expression of PCV4 Cap was achieved in with purified Cap self-assembling into VLPs (~20 nm) . Furthermore, these VLPs were internalized by PK15 and 3D4/21 cell lines. Significant structural differences between PCV4 and PCV2 capsids were demonstrated among loops (loop BC, CD, DE, EF, and GH), based on comparisons of 3D structures. In addition, five potential B cell epitopes identified were mostly located in surface-exposed loops of PCV4 capsid. Cross-reaction between PCV4 and PCV2 or PCV3 conferred by humoral immune responses was deemed unlikely on the basis of ELISA and Western blotting for assessment of VLPs and using PCV4 or PCV2 VLPs. In conclusion, these studies provided new knowledge regarding PCV4 capsid surface patterns. It is noteworthy that the PCV4 VLPs prepared in our study have much potential for development of serological diagnostics for PCV4 and to further characterize this virus.
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http://dx.doi.org/10.3389/fvets.2021.695466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421537PMC
August 2021

Establishing the Minimum Intensity of Transcranial Magnetic Stimulation Superconditioning Pulses to Effect Inhibition and Facilitation of Motor Evoked Potentials.

J Clin Neurophysiol 2021 Aug 19. Epub 2021 Aug 19.

Department of Neurosurgery, Upstate Medical University, Syracuse, New York, U.S.A.; College of Medicine, Upstate Medical University, Syracuse, New York, U.S.A.; and Department of Public Health and Preventive Medicine, Upstate Medical University, Syracuse, New York, U.S.A.

Purpose: Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses-a superconditioning (SC) train-when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles.

Methods: We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalized to test input responses and were compared within and between subjects.

Results And Conclusions: For inhibition, the minimum intensity of SC pulses needed to influence the follow-on MEP was found to be 60% of the target muscle's resting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse-often reported as 80% of the single-pulse threshold-typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.
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http://dx.doi.org/10.1097/WNP.0000000000000891DOI Listing
August 2021

High Co-infection Status of Novel Porcine Parvovirus 7 With Porcine Circovirus 3 in Sows That Experienced Reproductive Failure.

Front Vet Sci 2021 29;8:695553. Epub 2021 Jul 29.

Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, Laboratory of Functional Proteomics (LFP), Research Center of Reverse Vaccinology (RCRV), College of Veterinary Medicine, Hunan Agricultural University, Changsha, China.

Porcine parvoviruses (PPVs) and porcine circoviruses (PCVs) infect pigs worldwide, with PPV1-7 and PCV2 infections common in pigs. Although PPV7 was only identified in 2016, co-infection of PPV7 and PCV2 is already common, and PPV7 may stimulate PCV2 replication. PCV3, a novel type of circovirus, is prevalent in pig populations worldwide and considered to cause reproductive disorders and dermatitis nephrotic syndrome. In recent studies, pigs were commonly infected with both PCV3 and PPV7. Our objective was to investigate the co-infections between PPV7 and PCV3 in samples from swine on farms in Hunan, China, and assess the potential impacts of PPV7 on PCV3 viremia. A total of 209 samples, known to be positive (105) or negative (104) for PCV3, were randomly selected from serum samples that were collected from commercial swine herds in seven regions from 2016 to 2018 in our previous studies; these samples were subjected to real-time PCR to detect PPV7. Of these samples, 23% (48/209) were positive for PPV7. Furthermore, the PPV7 positive rate was significantly higher in PCV3 positive serum (31.4%, 33/105) than in PCV3 negative serum (14.4%, 15/104). Another 62 PCV3 positive sow serum samples and 20 PCV3 positive aborted fetuses were selected from 2015 to 2016 in our other previous study. These samples were designated as being from farms with or without long-standing histories of reproductive failure (RF or non-RF), respectively, and they were also subjected to real-time PCR to detect PPV7 and to determine whether PPV7 affected PCV3 viremia. Among the 62 serum samples (39 PCV3 positive RF-serum and 23 PCV3 positive non-RF-serum), 45.1% (28/62) were positive for PPV7 and PCV3, and the PPV7 positive rate was significantly higher in PCV3 positive RF-serum (51.2%, 20/39) than in PCV3 positive non-RF-serum (34.8%, 8/23). In addition, there was a higher positive rate of PPV7 (55%, 11/20) in PCV3 positive aborted fetus samples. In addition, the copy number of PCV3 in PPV7 positive samples was significantly higher than that in PPV7 negative serum samples. Based on these findings, we concluded that PPV7 may stimulate PCV3 replication.
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http://dx.doi.org/10.3389/fvets.2021.695553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358293PMC
July 2021

Identification of a Novel Immune-Related CpG Methylation Signature to Predict Prognosis in Stage II/III Colorectal Cancer.

Front Genet 2021 28;12:684349. Epub 2021 Jun 28.

Department of Radiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training ( = 127) and test groups ( = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan-Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training ( = 0.000296) and test groups ( = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.
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http://dx.doi.org/10.3389/fgene.2021.684349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273301PMC
June 2021

Exosomal IDH1 increases the resistance of colorectal cancer cells to 5-Fluorouracil.

J Cancer 2021 11;12(16):4862-4872. Epub 2021 Jun 11.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.

Chemoresistance challenges the clinical treatment of colorectal cancer and requires an urgent solution. Isocitrate dehydrogenase 1 (IDH1) is a key enzyme involved in glucose metabolism that mediates the malignant transformation of tumors. However, the mechanisms by which IDH1 is involved in colorectal cancer cell proliferation and drug resistance induction remain unclear. In this study, we found that IDH1 was highly expressed in human colorectal cancer tissues and could be used to indicate a high-grade tumor. gene overexpression and knockdown were used to determine whether IDH1 promoted the proliferation of the colorectal cancer cell line HCT8 and resistance to 5-Fluorouracil (5FU). Further studies have shown that the 5FU-resistant cell line, HCT8FU, secreted exosomes that contained a high level of IDH1 protein. The exosomal IDH1 derived from 5FU-resistant cells enhanced the resistance of 5FU-sensitive cells. Metabolic assays revealed that exosomes derived from 5FU-resistant cells promoted a decrease in the level of IDH1-mediated NADPH, which is associated with the development of 5FU resistance in colorectal cancer cells. Therefore, exosomal IDH1 may be the transmitter and driver of chemoresistance in colorectal cancer and a potential chemotherapy target.
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http://dx.doi.org/10.7150/jca.58846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247374PMC
June 2021

Experience to prevent wire tethering in deep brain stimulation from a single center.

Neurol Res 2021 Jul 1:1-7. Epub 2021 Jul 1.

Department of Neurosurgery, Peking University People's Hospital, Beijing, China.

Objective: To analyze the causes of wire tethering in deep brain stimulation (DBS) and propose ways to prevent it.

Methods: A total of 70 consecutive patients (140 electrodes) operated for DBS in our department from September 2017 to December 2019 were analyzed to document wire tethering, respectively, in the initial period (September 2017-June 2018) and the late period (July 2018-December 2019). The patients come back to our clinic 1 month postoperatively to turn on the equipment and followed up any time postoperatively face to face.

Results: Wire tethering was divided into mild, moderate and severe. The frequency of mild wire tethering was 12.5% (2/16) in the initial period and 9.3% (5/54) in the late period. The frequency of moderate wire tethering was 12.5% (2/16) in the initial period and 3.7% (2/54) in the late period. There was only one patient suffered from severe wire tethering in the initial period and none in the late period. There was a significant difference between the initial (31.3%) and the late (13%) periods in the frequency of total wire tethering.

Conclusions: Wire tethering is a rare but serious hardware complication in DBS which should be noteworthy. Improving surgical skill when implanted the extension wire and inventing new material covering extension wire can prevent wire tethering.
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http://dx.doi.org/10.1080/01616412.2021.1948737DOI Listing
July 2021

Association between plasma S-adenosylmethionine and risk of mortality in patients with coronary artery disease: A cohort study.

Am J Clin Nutr 2021 Jun 30. Epub 2021 Jun 30.

Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Background: S-adenosylmethionine (SAM) as methyl donors participates in methylation and is converted into S-adenosylhomocysteine (SAH), which is a precursor of homocysteine. Increased plasma SAH and homocysteine are associated with increased risk of cardiovascular disease. However, the relation of plasma SAM with cardiovascular risk is still unclear.

Objectives: To determine the relation between plasma SAM and risk of mortality among patients with coronary artery disease (CAD).

Methods: Baseline plasma SAM concentrations were measured in 1553 patients with CAD from the Guangdong Coronary Artery Disease Cohort between October 2008 and December 2011. Proportional hazards Cox analyses were performed to ascertain associations between SAM and risk of all-cause and cardiovascular mortality.

Results: After a median follow-up of 9.2 (IQR: 8.5-10.2) y, of 1553 participants, 321 had died, including 227 deaths from cardiovascular diseases. Patients in the lowest quartile of SAM concentrations had a higher risk of all-cause death (HR, 1.59; 95% CI: 1.14, 2.21) and cardiovascular death (HR, 2.14; 95% CI: 1.41, 3.27) than those in the highest quartile in multivariable adjusted analysis. Each 1-SD decrease in the SAM concentration remained associated with a 42% greater risk of total death (HR, 1.42; 95% CI: 1.23, 1.64) and a 66% higher risk of cardiovascular death (HR, 1.66; 95% CI: 1.37, 2.01) after fully adjusting for other cardiovascular risk factors. Furthermore, each 1-SD decrease in plasma SAM/SAH ratio, as the methylation index, was also inversely associated with the risk of all-cause (HR, 1.80; 95% CI: 1.42, 2.29) and cardiovascular mortality (HR, 1.68; 95% CI: 1.29, 2.19) in fully adjusted analyses.

Conclusions: Our data show a significant inverse relation between plasma SAM and risk of mortality in patients with CAD after adjustment for homocysteine, SAH, and other cardiovascular disease risk factors.
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http://dx.doi.org/10.1093/ajcn/nqab210DOI Listing
June 2021

Long term outcomes in fellow eyes comparing DSAEK and DMEK for treatment of Fuchs Corneal Dystrophy.

Am J Ophthalmol 2021 Jun 19. Epub 2021 Jun 19.

Department of Surgery, Ophthalmology Division Michigan State University College of Human Medicine Eye Grand Rapids Michigan Verdier Center, Grand Rapid, MI, USA. Electronic address:

Purpose: To compare the long term results of Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK) in fellow eyes for treatment of Fuchs endothelial corneal dystrophy (FED).

Methods: Two-centered, retrospective case series of 64 patients (128 eyes) with DSAEK followed by DMEK. The main outcomes measured were BSCVA and duration of time to achieve BSCVA as well as eye preference.

Results: Preoperative median logarithm of the minimum angle of resolution (logMAR) BSCVA was similar in eyes receiving DMEK 0.36±0.26 and DSAEK 0.42±0.34 (P = 0.266). Average follow up time needed for the DMEK eyes to achieve BSCVA was faster than that of DSAEK (277 days versus 490 days, P = 0.0014). With long term follow-up BSCVA of the DMEK eyes [0.09±0.10 logMAR and DSAEK eyes 0.11 ±0.16 logMAR did not show a statistically significant difference (P = 0.069). Twenty two of the 64 preferred the DMEK eye, 17 patients preferred the DSAEK eye (P= 0.423) while 25 patients did not have a preference. In the DMEK group the average spherical equivalent was -0.08 compared to DSAEK group at 0.06. [P = 0.2854].

Conclusion: In our fellow eye study with long term follow-up DMEK and DSAEK had comparable levels of BSCVA and patient satisfaction. The DMEK eyes reached their BSCVA sooner, however the DSAEK eyes improved over a longer time frame. A greater number of patients had 20/25 and 20/20 vision in the DMEK group, however the difference was not statistically significant.
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http://dx.doi.org/10.1016/j.ajo.2021.06.013DOI Listing
June 2021

Nonampullary Duodenal Adenomas in Familial Adenomatous Polyposis and Sporadic Patients Lack the DNA Content Abnormality That is Characteristic of the Adenoma-Carcinoma Sequence Involved in the Development of Other Gastrointestinal Malignancies.

Am J Surg Pathol 2021 Jun 17. Epub 2021 Jun 17.

Department of Pathology, University of California at San Francisco, San Francisco, CA Department of Pathology, University of Washington, Seattle, WA Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL.

Nonampullary duodenal adenomas (NADAs) develop sporadically or in the setting of a hereditary syndrome such as familial adenomatous polyposis (FAP). Although they are thought to progress into duodenal adenocarcinomas via an adenoma to carcinoma sequence similar to colorectal cancer, limited data suggested that they may be biologically dissimilar to colorectal adenomas. The clinicopathologic features of 71 patients diagnosed with NADAs (37 FAP and 34 sporadic) were analyzed. From the 71 patients, 89 NADA biopsies (42 FAP and 47 sporadic) were evaluated by DNA flow cytometry. Eighty-two samples showed low-grade dysplasia, and 7 demonstrated high-grade dysplasia (HGD). Twenty-one low-grade adenomas of the ileal pouch (n=19) and jejunum (n=2) from 15 FAP patients who underwent total proctocolectomy were also analyzed by DNA flow cytometry. The FAP patients were more likely to be younger (mean: 28 y) and have multifocal disease (92%) than the sporadic patients (66 y and 24%, respectively) (P<0.001). Most NADAs presented as polypoid lesions (87%) in the duodenal bulb and/or second portion of the duodenum (94%). Sporadic NADAs (mean: 2.4 cm) were significantly larger than FAP-related NADAs (1.3 cm) (P=0.005). Three (4%) patients (2 sporadic and 1 FAP) had high-grade NADAs at the first endoscopy, while the remaining 68 (96%) patients had low-grade dysplasia. Two additional sporadic and 1 FAP patients developed HGD on follow-up. Although the overall detection rate of advanced neoplasia (either HGD or adenocarcinoma) was similar between the FAP (n=5; 14%) and sporadic groups (n=4; 12%) (P=1.000), 3 FAP patients (all with Spigelman stage III to IV) developed adenocarcinoma in the duodenum (n=2) or in the ileal pouch (n=1) within a mean follow-up time of 76 months, while no adenocarcinoma was found in the sporadic group. Of the 37 FAP patients, 29 (78%) had a history of total proctocolectomy, and 15 (52%) developed low-grade adenomas in the ileal pouch with (n=2) or without (n=13) jejunal involvement (vs. 0% in the sporadic patients, P<0.001). All 15 patients had ≥Spigelman stage II. Aneuploidy was detected in only 1 (1%) sporadic NADA with HGD, whereas the remaining 109 duodenal, ileal pouch, and jejunal adenomas showed normal DNA content. The overall 3-, 9-, and 15-year detection rates of adenocarcinoma (in the duodenum and ileal pouch) in all NADA patients were 1.4%, 7.2%, and 18.8%, respectively. Three-, 9-, and 15-year detection rates of adenocarcinoma in the FAP patients were 2.7%, 9.7%, and 22.6%, respectively, while these rates remained at 0% in the sporadic patients. In conclusion, FAP-related NADAs have distinct clinicopathologic features compared with their sporadic counterpart. However, the vast majority of both FAP-related and sporadic NADAs (99%) lack the DNA content abnormality that is characteristic of the typical adenoma-carcinoma sequence involved in other gastrointestinal carcinogenesis. Although adenocarcinoma is more likely to develop in FAP patients with a high adenoma burden, probably due to the higher likelihood that some advanced lesions are missed endoscopically, FAP-related and sporadic NADAs may have a comparable risk of developing advanced neoplasia on a per-adenoma basis.
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http://dx.doi.org/10.1097/PAS.0000000000001754DOI Listing
June 2021

A Methylene Blue Assisted Electrochemical Sensor for Determination of Drug Resistance of .

Front Chem 2021 31;9:689735. Epub 2021 May 31.

Department of Food and Drugs, Shandong Institute of Commerce and Technology, Jinan, China.

Due to the abuse of antibiotics in clinical, animal husbandry, and aquaculture, drug-resistant pathogens are produced, which poses a great threat to human and the public health. At present, a rapid and effective drug sensitivity test method is urgently needed to effectively control the spread of drug-resistant bacteria. Using methylene blue as a redox probe, the electrochemical signals of methylene blue in drug-resistant strains were analyzed by a CV method. Graphene ink has been used for enhancing the electrochemical signal. Compared with the results of the traditional drug sensitivity test, we proposed a rapid electrochemical drug sensitivity test method which can effectively identify the drug sensitivity of . The sensitivity of four isolates to ciprofloxacin, gentamicin, and ampicillin was tested by an electrochemical drug sensitivity test. The respiratory activity value %RA was used as an indicator of bacterial resistance by electrochemical method.
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http://dx.doi.org/10.3389/fchem.2021.689735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201616PMC
May 2021

Persistent or recurrent Barrett's neoplasia after an endoscopic therapy session is associated with DNA content abnormality and can be detected by DNA flow cytometric analysis of paraffin-embedded tissue.

Mod Pathol 2021 Oct 9;34(10):1889-1900. Epub 2021 Jun 9.

University of California at San Francisco, Department of Pathology, San Francisco, CA, USA.

Endoscopic therapy is currently the standard of care for the treatment of high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) in patients with Barrett's esophagus (BE). Visible lesions are treated with endoscopic mucosal resection (EMR), which is often coupled with radiofrequency ablation (RFA). However, endoscopic therapy may require multiple sessions (one session every 2-3 months) and does not always assure complete eradication of neoplasia. Furthermore, despite complete eradication, recurrences are not uncommon. This study assesses which potential risk factors can predict a poor response after endoscopic sessions. Forty-five BE patients who underwent at least one endoscopic session (EMR alone or ablation with or without preceding EMR) for the treatment of HGD/IMC, low-grade dysplasia (LGD), or indefinite for dysplasia (IND) were analyzed. DNA flow cytometry was performed on 82 formalin-fixed paraffin-embedded samples from the 45 patients, including 78 HGD/IMC, 2 LGD, and 2 IND. Eight non-dysplastic BE samples were used as controls. Three to four 60-micron thick sections were cut from each tissue block, and the area of HGD/IMC, LGD, or IND was manually dissected. Potential associations between clinicopathologic risk factors and persistent/recurrent HGD/IMC following each endoscopic session were examined using univariate and multivariate Cox models with frailty terms. Sixty (73%) of the 82 specimens showed abnormal DNA content (aneuploidy or elevated 4N fraction). These were all specimens with HGD/IMC (representing 77% of that group). Of these 60 HGD/IMC samples with abnormal DNA content, 42 (70%) were associated with subsequent development of persistent/recurrent HGD/IMC (n = 41) or esophageal adenocarcinoma (EAC; n = 1) within a mean follow-up time of 16 months (range: 1 month to 9.4 years). In contrast, only 6 (27%, all HGD/IMC) of the 22 remaining samples (all with normal DNA content) were associated with persistent/recurrent HGD/IMC. For outcome analysis per patient, 11 (24%) of the 45 patients developed persistent/recurrent HGD/IMC or EAC, despite multiple endoscopic sessions (mean: 3.6, range: 1-11). In a univariate Cox model, the presence of abnormal DNA content (hazard ratio [HR] = 3.8, p = 0.007), long BE segment ≥ 3 cm (HR = 3.4, p = 0.002), endoscopic nodularity (HR = 2.5, p = 0.042), and treatment with EMR alone (HR = 2.9, p = 0.006) were significantly associated with an increased risk for persistent/recurrent HGD/IMC or EAC. However, only abnormal DNA content (HR = 6.0, p = 0.003) and treatment with EMR alone (HR = 2.7, p = 0.047) remained as significant risk factors in a multivariate analysis. Age ≥ 60 years, gender, ethnicity, body mass index (BMI) ≥ 30 kg/m, presence of hiatal hernia, and positive EMR lateral margin for neoplasia were not significant risk factors for persistent/recurrent HGD/IMC or EAC (p > 0.05). Three-month, 6-month, 1-year, 3-year, and 6-year adjusted probabilities of persistent/recurrent HGD/IMC or EAC in the setting of abnormal DNA content were 31%, 56%, 67%, 79%, and 83%, respectively. The corresponding probabilities in the setting of normal DNA content were 10%, 21%, 28%, 38%, and 43%, respectively. In conclusion, in BE patients with baseline HGD/IMC, both DNA content abnormality and treatment with EMR alone were significantly associated with persistent/recurrent HGD/IMC or EAC following each endoscopic session. DNA content abnormality as detected by DNA flow cytometry identifies HGD/IMC patients at highest risk for persistent/recurrent HGD/IMC or EAC, and it also serves as a diagnostic marker of HGD/IMC with an estimated sensitivity of 77%. The diagnosis of HGD/IMC in the setting of abnormal DNA content may warrant alternative treatment strategies as well as long-term follow-up with shorter surveillance intervals.
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http://dx.doi.org/10.1038/s41379-021-00832-8DOI Listing
October 2021

Identification of a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma: A case report.

Medicine (Baltimore) 2021 May;100(19):e25957

Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing.

Rationale: Gallbladder carcinoma is a malignant biliary tract tumor which is characterized by poor prognosis. Recent advances in genomic medicine have identified a few novel germline mutations that contribute to the increased risk of gallbladder carcinoma. RAD52 is a crucial human deoxyribonucleic acid (DNA) repair gene involved in maintaining genomic stability and preventing tumor occurrence.

Patient Concerns: A 57-year-old man was hospitalized for space-occupying lesions in the gallbladder.

Diagnosis: A diagnosis of gallbladder adenocarcinoma was made based on computed tomography, B-ultrasound, blood tests, and postoperative pathology.

Interventions: Next-generation sequencing using a 599-gene panel and Sanger sequencing were performed to validate the mutation in the proband and his family members, respectively.

Outcomes: A novel potentially pathogenic heterozygous germline RAD52 missense mutation (c.276T > A: p.N92K) was identified in the patient. Sanger sequencing revealed that this variation was not observed in unaffected family members.

Lessons: We identified a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma. Our results added to the current body of knowledge. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with gallbladder carcinoma.
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http://dx.doi.org/10.1097/MD.0000000000025957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133115PMC
May 2021

Effect of meteorological factors and lunar phases on occurrence of psychogenic nonepileptic seizures.

Epilepsy Behav 2021 08 30;121(Pt A):108070. Epub 2021 May 30.

Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, 766 Irving Ave., Syracuse, NY 13210, United States.

Background: Psychogenicnonepilepticseizures (PNES) lack the abnormal electrographical discharges in electroencephalogram seen in epileptic seizures. The notion of the effects of meteorological factors and lunar phases onoccurrence of seizures in patients with PNES has been the subject of very few research studies and the available evidence in the literature is equivocal. In this study, we aimed to study the influence oflunarphases and meteorological factors on the frequency of PNES and its semiological categories.

Methods: We retrospectively reviewed the medical records of patients discharged with a diagnosis of PNES from our epilepsy monitoring unit in a 3-year period. The 119 patients who met the inclusion criteria were categorized into hypermotor, hypomotor, or intact sensorium based on semiology of their seizures. The occurrence of PNES, in total and in each semiological category, was correlated with the daily average temperature, atmospheric pressure, and the 4 lunar phases.

Results: There were 31.8% and 11.1% more-than-expected captured seizures when the average daily atmospheric pressure was lower or higher, respectively, of what is generally considered a comfortable atmospheric pressure. No consistent relation was found between the full moon phases and occurrence of PNES.

Conclusion: A significant association between atmospheric pressure and the occurrence of nonepileptic seizures was found, whereas no consistent increase in PNES was observed during the full moon phases. There is still an open debate about the effect of the lunar phases on human behavior and neurological disorders such as PNES.
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http://dx.doi.org/10.1016/j.yebeh.2021.108070DOI Listing
August 2021

Genetic alteration of Chinese patients with rectal mucosal melanoma.

BMC Cancer 2021 May 27;21(1):623. Epub 2021 May 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, Peking, 100142, Beijing, People's Republic of China.

Background: Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy.

Methods: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance.

Results: BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005].

Conclusions: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
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http://dx.doi.org/10.1186/s12885-021-08383-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161925PMC
May 2021

Smooth ROC curve estimation via Bernstein polynomials.

PLoS One 2021 25;16(5):e0251959. Epub 2021 May 25.

Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, United States of America.

The receiver operating characteristic (ROC) curve is commonly used to evaluate the accuracy of a diagnostic test for classifying observations into two groups. We propose two novel tuning parameters for estimating the ROC curve via Bernstein polynomial smoothing of the empirical ROC curve. The new estimator is very easy to implement with the naturally selected tuning parameter, as illustrated by analyzing both real and simulated data sets. Empirical performance is investigated through extensive simulation studies with a variety of scenarios where the two groups are both from a single family of distributions (symmetric or right skewed) or one from a symmetric and the other from a right skewed distribution. The new estimator is uniformly more efficient than the empirical ROC estimator, and very competitive to eleven other existing smooth ROC estimators in terms of mean integrated square errors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251959PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148335PMC
May 2021

Study on the reaction strategy of directional alkylation fulfilled by controlling the adsorption pose of benzene and methanol in space with Ru/HZSM-5.

BMC Chem 2021 May 21;15(1):35. Epub 2021 May 21.

College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou, 730050, People's Republic of China.

Background: The alkylation of benzene with methanol is an important synthetic method that is widely used in various chemical production processes. However, obtaining a high selectivity for xylene and annihilating the MTO side reaction remain challenges.

Results: In this work, a Ru/HZSM-5 catalyst was prepared using ZSM-5 as the precursor by a chemical precipitation method. Both XRD and TEM confirmed that Ru nanoparticles were evenly dispersed on the surface of the ZSM-5. The catalytic performance of benzene alkylation with methanol on the Ru/HZSM-5 catalyst was investigated. The results showed that the Ru/HZSM-5 catalyst could completely annihilate the MTO side reaction with a high conversion efficiency of benzene and selectivity for xylene, which resulted from the large gap between the transgression energy value of Ru and the ionization potential value of benzene, and the acidity of the catalyst changed greatly.

Conclusion: These findings may offer not only a new and efficient multifunctional catalyst for benzene alkylation but also fundamental insight into the catalytic mechanism of the Ru/HZSM-5 catalyst.
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http://dx.doi.org/10.1186/s13065-021-00761-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140447PMC
May 2021

A seq2seq model to forecast the COVID-19 cases, deaths and reproductive R numbers in US counties.

Res Sq 2021 Apr 26. Epub 2021 Apr 26.

The global pandemic of coronavirus disease 2019 (COVID-19) has killed almost two million people worldwide and over 400 thousand in the United States (US). As the pandemic evolves, informed policy-making and strategic resource allocation relies on accurate forecasts. To predict the spread of the virus within US counties, we curated an array of county-level demographic and COVID-19-relevant health risk factors. In combination with the county-level case and death numbers curated by John Hopkins university, we developed a forecasting model using deep learning (DL). We implemented an autoencoder-based Seq2Seq model with gated recurrent units (GRUs) in the deep recurrent layers. We trained the model to predict future incident cases, deaths and the reproductive number, . For most counties, it makes accurate predictions of new incident cases, deaths and R values, up to 30 days in the future. Our framework can also be used to predict other targets that are useful indices for policymaking, for example hospitalization or the occupancy of intensive care units. Our DL framework is publicly available on GitHub and can be adapted for other indices of the COVID-19 spread. We hope that our forecasts and model can help local governments in the continued fight against COVID-19.
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http://dx.doi.org/10.21203/rs.3.rs-456641/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132245PMC
April 2021

Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer.

Diagn Pathol 2021 May 1;16(1):38. Epub 2021 May 1.

Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, Beijing, 100142, People's Republic of China.

Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients.

Methods: The data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS).

Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%).

Conclusions: Using IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.
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http://dx.doi.org/10.1186/s13000-021-01099-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088709PMC
May 2021

A seq2seq model to forecast the COVID-19 cases, deaths and reproductive numbers in US counties.

medRxiv 2021 Apr 20. Epub 2021 Apr 20.

The global pandemic of coronavirus disease 2019 (COVID-19) has killed almost two million people worldwide and over 400 thousand in the United States (US). As the pandemic evolves, informed policy-making and strategic resource allocation relies on accurate forecasts. To predict the spread of the virus within US counties, we curated an array of county-level demographic and COVID-19-relevant health risk factors. In combination with the county-level case and death numbers curated by John Hopkins university, we developed a forecasting model using deep learning (DL). We implemented an autoencoder-based Seq2Seq model with gated recurrent units (GRUs) in the deep recurrent layers. We trained the model to predict future incident cases, deaths and the reproductive number, . For most counties, it makes accurate predictions of new incident cases, deaths and R values, up to 30 days in the future. Our framework can also be used to predict other targets that are useful indices for policymaking, for example hospitalization or the occupancy of intensive care units. Our DL framework is publicly available on GitHub and can be adapted for other indices of the COVID-19 spread. We hope that our forecasts and model can help local governments in the continued fight against COVID-19.
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http://dx.doi.org/10.1101/2021.04.14.21255507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077584PMC
April 2021

Pallidal versus subthalamic deep-brain stimulation for meige syndrome: a retrospective study.

Sci Rep 2021 Apr 22;11(1):8742. Epub 2021 Apr 22.

Department of Neurosurgery, Peking University People's Hospital, 11th Xizhimen South St., Beijing, 100044, China.

Deep-brain stimulation (DBS) is an effective treatment for patients with Meige syndrome. The globus pallidus interna (GPi) and the subthalamic nucleus (STN) are accepted targets for this treatment. We compared 12-month outcomes for patients who had undergone bilateral stimulation of the GPi or STN. Forty-two Asian patients with primary Meige syndrome who underwent GPi or STN neurostimulation were recruited between September 2017 and September 2019 at the Department of Neurosurgery, Peking University People's Hospital. The primary outcome was the change in motor function, including the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) at 3 days before DBS (baseline) surgery and 1, 3, 6, and 12 months after surgery. Secondary outcomes included health-related quality of life, sleep quality status, depression severity, and anxiety severity at 3 days before and 12 months after DBS surgery. Adverse events during the 12 months were also recorded. Changes in BFMDRS-M and BFMDRS-D scores at 1, 3, 6, and 12 months with DBS and without medication did not significantly differ based on the stimulation target. There were also no significant differences in the changes in health-related quality of life (36-Item Short-Form General Health Survey) and sleep quality status (Pittsburgh Sleep Quality Index) at 12 months. However, there were larger improvements in the STN than the GPi group in mean score changes on the 17-item Hamilton depression rating scale (- 3.38 vs. - 0.33 points; P = 0.014) and 14-item Hamilton anxiety rating scale (- 3.43 vs. - 0.19 points; P < 0.001). There were no significant between-group differences in the frequency or type of serious adverse events. Patients with Meige syndrome had similar improvements in motor function, quality of life and sleep after either pallidal or subthalamic stimulation. Depression and anxiety factors may reasonably be included during the selection of DBS targets for Meige syndrome.
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http://dx.doi.org/10.1038/s41598-021-88384-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062505PMC
April 2021

Comprehensive review and evaluation of computational methods for identifying FLT3-internal tandem duplication in acute myeloid leukaemia.

Brief Bioinform 2021 Sep;22(5)

Computer Network Information Center, Chinese Academy of Sciences. His research interests include cancer genomics, metagenomics, and the development of computational tools for working with data from next-generation sequencing technologies. His affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.

Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3-ITD) constitutes an independent indicator of poor prognosis in acute myeloid leukaemia (AML). AML with FLT3-ITD usually presents with poor treatment outcomes, high recurrence rate and short overall survival. Currently, polymerase chain reaction and capillary electrophoresis are widely adopted for the clinical detection of FLT3-ITD, whereas the length and mutation frequency of ITD are evaluated using fragment analysis. With the development of sequencing technology and the high incidence of FLT3-ITD mutations, a multitude of bioinformatics tools and pipelines have been developed to detect FLT3-ITD using next-generation sequencing data. However, systematic comparison and evaluation of the methods or software have not been performed. In this study, we provided a comprehensive review of the principles, functionality and limitations of the existing methods for detecting FLT3-ITD. We further compared the qualitative and quantitative detection capabilities of six representative tools using simulated and biological data. Our results will provide practical guidance for researchers and clinicians to select the appropriate FLT3-ITD detection tools and highlight the direction of future developments in this field. Availability: A Docker image with several programs pre-installed is available at https://github.com/niu-lab/docker-flt3-itd to facilitate the application of FLT3-ITD detection tools.
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http://dx.doi.org/10.1093/bib/bbab099DOI Listing
September 2021

Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma.

BMC Cancer 2021 Mar 31;21(1):331. Epub 2021 Mar 31.

Department of Hepatobiliary and Pancreatic Surgery, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong Province, 266000, People's Republic of China.

Background: The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression.

Methods: In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA).

Results: Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored.

Conclusion: The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.
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http://dx.doi.org/10.1186/s12885-021-08052-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011181PMC
March 2021

Feasibility of Adjunctive Bright Light Therapy for Depressive Symptoms on an Acute Psychiatric Floor.

Cureus 2021 Mar 17;13(3):e13945. Epub 2021 Mar 17.

Psychiatry, State University of New York Upstate Medical University, Syracuse, USA.

Background: Bright light therapy (BLT) has been increasingly used as an experimental treatment in non-seasonal unipolar depression. While clinical trials have demonstrated the efficacy of BLT in ameliorating depression for outpatients, studies examining BLT in the psychiatric inpatient setting are currently lacking.

Aim: The purpose of this study is to explore whether BLT as adjunctive treatment for depressive symptoms on an acute psychiatric floor is feasible and explore associated changes in depressive symptoms.

Methods: An observational, cross-sectional study was conducted at State University of New York (SUNY) Upstate 4B acute inpatient psychiatric unit. BLT was administered to participating patients as adjunctive therapy to their psychopharmacological and psychotherapy treatments on a daily basis throughout their hospitalization. Beck Depression Inventory-II (BDI-II), Hamilton Rating Scale for Depression (HAM-D), and Outcome Questionnaire-45.2 (OQ-45.2) were administered before commencing BLT and after their last BLT session. Changes to the aforementioned measures before and after BLT treatment, the dose response of measure changes based on number of sessions, and the hospital length of stay along with the secondary factors such as age, gender, other psychiatric comorbidities, social factors, and psychiatric medications were analyzed.

Results:  BLT is feasible on acute psychiatric inpatient floor with adherence of 94% and has very few side effects. The repeated measures of depression and functioning demonstrated significant decrease in depression and improvement in functioning. Although not statistically significant, clinical meaningful dose-response relationship was found between a number of BLT sessions and improvement in depressive symptoms with five BLT sessions being an optimal amount for depression amelioration.

Conclusion: BLT combined with the ongoing psychopharmacological treatment was well tolerated and easy to administer. It offers a simple, safe, and cost-effective approach to augmenting depressive treatment on an acute psychiatric floor.
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http://dx.doi.org/10.7759/cureus.13945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968349PMC
March 2021

Effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction.

Braz J Med Biol Res 2021 15;54(5):e10000. Epub 2021 Mar 15.

Department of Neurology, The People's Hospital of Beilun District, Beilun Branch Hospital of The First Affiliated Hospital, Zhejiang University School of Medicine, Ningbo, Zhejiang Province, China.

This study aimed to explore the effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction. A total of 120 patients with acute cerebral infarction were divided into two groups by the random number table method, with 60 patients in each group: observation group (intravenous thrombolysis with alteplase) and control group (intravenous thrombolysis with batroxobin). The clinical efficacy after a 14-day treatment was observed. Serum C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), CD62p, GMP-140, and neuron-specific enolase (NSE) were measured. Scores of National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) were determined. The total effective rate in the observation group was 81.67%, which was higher than the 61.67% in the control group (P<0.05). The improvement of inflammatory factors (CRP, TNF-α, IL-6, CD62p, GMP-140, and NSE), NIHSS, MMSE, and MoCA in the observation group was superior to that in the control group (all P<0.05). The modified Rankin scale at three months after hospital discharge in the observation group was lower than that in the control group (P<0.01). Intravenous thrombolysis with alteplase for acute cerebral infarction can enhance the clinical efficacy, alleviate inflammatory response and brain injury, and improve cognitive function, which is worthy of further clinical application and study.
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http://dx.doi.org/10.1590/1414-431X202010000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959170PMC
March 2021

Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice.

Biochem Pharmacol 2021 04 6;186:114501. Epub 2021 Mar 6.

Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China; Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China; Guangdong Engineering Technology Research Center for Nutrition Translation, Guangzhou 510080, China. Electronic address:

Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-κB (NF-κB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-α-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-κB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion. The lactucopicrin effect was not due to modulation of inhibitor of NF-κB kinases (IKK) α/β/γ, inhibitor of NF-κB alpha (IκBα), and NF-κB/p65 DNA binding activity. Instead, lactucopicrin inhibited importin-α3 expression by destabilization of its mRNA, an effect mediating the lactucopicrin effect on NF-κB activity. More importantly, in lipopolysaccharide (LPS)-elicited septic mice, oral gavage with lactucopicrin decreased mortality by 30.5% as compared with the control treatment. This effect was associated with inhibited importin-α3 expression, suppressed NF-κB activation and VCAM-1/ICAM-1 expression, and inhibited leukocyte influx in the vascular endothelium of both lung and aorta. Collectively, our novel data suggest that dietary supplementation with lactucopicrin inhibits endothelial NF-κB activation by down-regulation of importin-α3 and thereby improves sepsis.
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http://dx.doi.org/10.1016/j.bcp.2021.114501DOI Listing
April 2021

Improving recovery after microvascular decompression surgery for hemifacial spasm: experience from 530 cases with enhanced recovery after surgery (ERAS) protocol.

Br J Neurosurg 2021 Mar 2:1-6. Epub 2021 Mar 2.

Department of Neurosurgery, Peking University People's Hospital, Beijing, China.

Objective: To assess the efficacy of microvascular decompression (MVD) for hemifacial spasm with an enhanced recovery after surgery (ERAS) protocol.

Methods: 984 hemifacial spasm patients who underwent MVD from Jan 2017 to Dec 2017 were analyzed. They were divided into the conventional treatment group (control;  = 453) and the later ERAS group ( = 531). The multimodal ERAS protocol consists of 23 perioperative elements. Time to feeding, mobilization, and urinary catheter removal, wound pain, postoperative nausea and vomiting (PONV), and total, preoperative, and perioperative hospital length of stay (LOS), along with outcomes and complications, were analyzed.

Results: The patients in both groups had similar clinical characteristics. Patients in the ERAS group had significantly higher rates of early feeding (469 [88.5%], ERAS, vs. 183 [40.6%], control;  < 0.05), early mobilization (497 [93.7%], ERAS, vs. 215 [47.7%], control;  < 0.05), and early removal of urinary catheter (458 [86.4%], ERAS, vs. 175 [38.8%], control;  < 0.05). The ERAS group also had a significantly lower incidence of wound pain (135 [25.5%], ERAS, vs. 348 [77.2%], control) and PONV (173 [32.6%], ERAS, vs. 251 (55.7%), control) ( < 0.05) and significantly shorter preoperative (0.9 ± 0.3 d, ERAS, vs. 2.3 ± 0.6 d, control), postoperative (4.1 ± 0.4 d, ERAS, vs. 5.8 ± 0.7 d, control), and total LOS (5.2 ± 0.3 d, ERAS, vs. 8.8 ± 0.6 d, control) ( < 0.05). There was no significant difference in outcomes or surgical complication rates between two groups.

Conclusions: Implementation of the ERAS protocol for patients undergoing MVD procedures for the treatment of HFS improved the quality of perioperative care without an increase in adverse events.
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http://dx.doi.org/10.1080/02688697.2021.1888876DOI Listing
March 2021

Silencing long non-coding RNAs nicotinamide nucleotide transhydrogenase antisense RNA 1 inhibited papillary thyroid cancer cell proliferation, migration and invasion and promoted apoptosis via targeting miR-199a-5p.

Endocr J 2021 May 20;68(5):583-597. Epub 2021 Mar 20.

Department of Head and Neck Surgery, Jilin Cancer Hospital, Changchun 130012, China.

The increasing incidence of papillary thyroid cancer (PTC) has attracted many researchers to investigate the mechanism underlying PTC progression. This study explored the growth and apoptosis of PTC cells based on an lncRNA regulatory mechanism. The expression of nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in PTC cell lines and PTC tissues was analyzed by qRT-PCR. The mutual binding site between NNT-AS1 and miR-199a-5p was predicted by starBase and confirmed by dual-luciferase reporter assay. The correlation between NNT-AS1 and miR-199a-5p was shown by Pearson correlation test. The viability, clone formation, migration, invasion and apoptosis of TPC-1 and IHH-4 cells were examined by CCK-8, colony formation, wound-healing, transwell, and flow cytometry assays, respectively. The expressions of Bax, cleaved Caspase-3, Bcl-2, E-Cadherin, N-Cadherin and SNAIL in TPC-1 and IHH-4 cells were determined by Western blot or qRT-PCR. NNT-AS1 expression was upregulated in PTC cells and tissues. In TPC-1 cells, silencing NNT-AS1 inhibited viability, clone formation, migration, and invasion as well as the expressions of N-Cadherin, SNAIL and Bcl-2, but promoted the expressions of E-Cadherin, Bax, and cleaved caspase-3. The effects of NNT-AS1 overexpression on IHH-4 cells were opposite to those of silencing NNT-AS1. In PTC tissues, miR-199a-5p was low-expressed and targeted by NNT-AS1, and it was negatively correlated with NNT-AS1. MiR-199a-5p inhibitor promoted TPC-1 cell progression, but miR-199a-5p mimic inhibited IHH-4 cell progression. NNT-AS1 and miR-199a-5p exerted opposite effects on PTC cells. Silencing NNT-AS1 inhibited PTC cell proliferation, migration and invasion, but promoted apoptosis via upregulation of miR-199a-5p.
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http://dx.doi.org/10.1507/endocrj.EJ20-0353DOI Listing
May 2021

Degradation of refractory organics in dual-cathode electro-Fenton using air-cathode for HO electrogeneration and microbial fuel cell cathode for Fe regeneration.

J Hazard Mater 2021 06 1;412:125269. Epub 2021 Feb 1.

School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China; Hubei Provincial Engineering Laboratory of Solid Waste Treatment, Disposal and Recycling, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China.

The electrogeneration of HO and electro-regeneration of ferrous are conflicting matters in electro-Fenton system. In this research, the degradation of Rhodamine B, methyl orange (MO) and 4-chlorophenol (4-CP) was investigated using a novel dual-cathode microbial fuel cell (MFC) electro-Fenton (EF) hybrid system. An air-cathode of an EF system was used for HO electrogeneration and a carbon felt cathode of a MFC was used to accelerate Fe regeneration. Synergistic improvement of MFC power generation and the degradation of the above refractory organics through EF reaction was achieved. The EF air-cathode was fabricated by adopting activated carbon/graphite powder mixture and PVDF binder, which showed higher HO generation but slower Fe reduction rate than MFC carbon felt cathode. The Rhodamine B removal rate constant and mineralization current efficiency of the MFC coupled EF were 64% and 42% higher than that of uncoupled EF, respectively. The MFC-EF coupled system also exhibited significantly higher removal efficiency for MO and 4-CP than that of un-coupled EF system. Moreover, the power density of MFC was greatly enhanced by coupling EF due to higher Fe/Fe redox potential than oxygen reduction.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125269DOI Listing
June 2021

Associated factors and outcomes of delaying adjuvant chemotherapy in breast cancer by biologic subtypes: a National Cancer Database study.

J Cancer Res Clin Oncol 2021 Aug 31;147(8):2447-2458. Epub 2021 Jan 31.

Department of Hematology-Oncology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.

Purpose: Several studies have evaluated the role of delayed initiation of adjuvant chemotherapy (AC) in breast cancer (BC), but the results have remained controversial and an optimal time has not been defined. Our aim was to determine the effect of time to starting AC from the date of surgery on survival of BC patients, based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, using data from the National Cancer Database (NCDB).

Methods: A total of 332,927 Stage I-III BC patients who received AC from 2010 to 2016 were analyzed. We included all ER, PR and HER2 statuses and excluded patients with stage 4 and stage 0 (DCIS) disease. The cohort was divided into five groups based on the time of initiating AC from the date of the most definitive surgery i.e., ≤ 30 days, 31-60 days, 61-90 days, 91-120 days and > 120 days. They were further divided into five subgroups based on the receptor status.

Results: Hazard ratio (HR) estimates and Kaplan-Meier (KM) analysis shows that starting AC by 31-60 days shows the best survival outcome in all the subtypes, except in hormone positive/HER2 negative BC in which 31-60 days and 61-90 days have similar outcomes.

Conclusions: After surgery for BC, it takes around 4-6 weeks to begin AC and delay in initiating the same leads to poor outcomes. Our results are particularly significant in triple-negative breast cancer (TNBC), similar to prior studies showing a benefit to starting AC as early as possible after surgery.
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http://dx.doi.org/10.1007/s00432-021-03525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847714PMC
August 2021

MSIsensor-ct: microsatellite instability detection using cfDNA sequencing data.

Brief Bioinform 2021 Sep;22(5)

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.

Motivation: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.

Results: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines.

Availability: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct.

Supplementary Information: Supplementary data are available at Briefings in Bioinformatics online.
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http://dx.doi.org/10.1093/bib/bbaa402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424396PMC
September 2021
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