OBJECTIVE: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. METHODS: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. RESULTS: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). CONCLUSION The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
Animals ; Toll-Like Receptor 4/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Aquaporin 5/metabolism* ; Sjogren's Syndrome/genetics* ; Signal Transduction ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Interleukin-1beta/metabolism* ; Female

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors

Objective:To investigate knowledge, attitude and practice intention of medical students on advance care planning (ACP) and to analyze the relevant influencing factors.Methods:This study was a cross-sectional study. From April to May 2019, the convenience sampling method was used to select medical students who were interning in 3 medical schools and affiliated hospitals in Guangdong Province as the research objects. General information questionnaire and self-designed ACP Knowledge, Attitude and Practice Intention Questionnaires were uesd to investigate. Multiple linear regression analysis was used to influencing factors. A total of 276 questionnaires were recovered in this survey, of which 274 were valid, the effective response rate was 99.3%.Results:The average accuracy rate of the ACP Knowledge Questionnaire for medical students was 48.75%. The average score of items of the ACP Attitude Questionnaire was (4.00±0.53) . The average score of items of the ACP Practice Intention Questionnaire for medical students was (3.94±0.59) . The results of multiple linear regression analysis showed that the attitude toward the major they studied, whether they had the part-time social experience, whether they heard of ACP and whether they received ACP training or courses were influencing factors of ACP knowledge for medical students ( P<0.05) . Whether they had clinical practice and whether they had the treatment experience of patients' death were the influencing factors of ACP attitude of medical students ( P<0.05) . Attitudes towards the major they learned and whether they had any experience in the treatment of patients' death were the influencing factors of ACP practice intention of medical students ( P<0.05) . Conclusions:Medical students have a certain acceptance of ACP, but the awareness rate of ACP is generally low. Consideration should be given to improving the relevant education methods and content to prepare for the role adaptation of medical students in future clinical work, improving the humanistic care literacy of medical students and promotion of ACP in the clinical practice.

Objective:To test whether the constructed intervention model of advance care planning (ACP) for patients with advanced cancer can be successfully implemented and the preliminary intervention effect, which provides reference for empirical research.Methods:32 cases of advanced cancer patients and 25 cases of their families at the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai were selected. The patients were subdivided into the experimental group and the control group by random number table method. The control group received routine nursing, while the experimental group adopted the intervention model of "VIP for future care" on the basis of customary nursing. We measured the main outcome indicators: enrollment rate, consent rate, completion rate and loss of follow-up rate and secondary outcome indicators: decision-making certainty, end-of-life care preference and post-intervention satisfaction of patients and their families, within 1 week and 1 month after intervention.Results:The enrollment rate, consent rate and loss of follow-up rate were 74.6% (206/276), 36.9% (76/151)and 15.6% (5/32), respectively. After intervention, the completion rates of the experimental group and the control group were 16/16 and 15/16 within one week, and 14/16 and 13/16 within one month. All of the family members were conducted during the follow-up period. The intervention mode of "VIP for future care" had a statistically significant difference in decision-making certainty between the two groups of patients ( β=0.63, 95% CI 0.08-1.18, P<0.05), no statistically significant difference in end-of-life care preference between the two groups of patients and their families ( P>0.05), and had a statistically significant difference in "whether to recommend this project to others" between the two groups ( χ2 value was 4.167 , P<0.05). Conclusions:On the premise of sufficient preparation, the "VIP for future care" intervention mode can be successfully implemented in advanced cancer patients in mainland China, can improve the decision-making certainty of patients and the satisfaction of patients and their families, and it is recommended. And should be applied to ACP intervention for patients with advanced cancer.

ObjectiveTo systematically evaluate the clinical effect of epidermal growth factor receptor (EGFR)-targeted agents in the treatment of advanced pancreatic cancer. MethodsEMbase, PubMed, Cochrane Library, Clinical Trials, CNKI, Wanfang Data, and VIP were searched for randomized controlled trials (RCTs) of EGFR-targeted therapies for advanced pancreatic cancer. Eligible RCTs were screened out based on quality and related criteria, and RevMan 5.3 and STATA 12.0 were used to perform the meta-analysis. ResultsA total of 8 RCTs were included, with 2382 patients in total. The results of the meta-analysis showed that compared with the control group, the experimental group had no increases in overall survival time (hazard ratio ［HR］=0.86, 95% confidence interval ［CI］: 0.74-1.02, P＞0.05) and objective response rate (risk ratio ［RR］=1.00, 95%CI: 0.76-1.32, P＞0.05), but had significant increases in progression-free survival time (HR=0.78, 95%CI: 0.62-0.98, P＜0.05) and disease control rate (RR=1.22, 95%CI: 1.04-1.43, P＜0.05). The subgroup analysis showed that after the source of heterogeneity was identified and the studies with high heterogeneity were excluded, the experimental group had a significant increase in overall survival time (HR=0.85, 95%CI: 0.77-0.94, P＜0.05), and the patients with rash appeared to be more sensitive to the therapies (HR=0.70, 95%CI: 0.54-0.92, P＜0.05). ConclusionFor patients with advanced pancreatic cancer, EGFR-targeted therapies can effectively prolong overall survival time and improve quality of life.

Objective: To investigate the genetic characteristics of VP1 genes carried by coxsackievirus A16 strains isolated from cases of hand foot and mouth disease (HFMD) in Shenzhen during 2016 to 2017. Methods: Fecal and anal swab specimens were collected from patients with mild HFMD in four sentinel hospitals and the Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, China during 2016 to 2017. All specimens were tested for CVA16 viral RNA using real-time RT-PCR. The VP1 genes of 51 randomly selected CVA16 strains were amplified by RT-PCR and then sequenced using TaKaRa Biomedical Technology (Dalian). Bioinformatics software, including Mega6.02, BioEdit and DNAStar, was used for comparison and analysis of the VP1 genes. Results: CVA16 strains in Shenzhen during 2016 to 2017 mainly belonged to B1a and B1b subtypes as well as an emerging subtype B3. The epidemic of B1b subtype was found in both 2016 (28 strains) and 2017 (19 strains), while the B1a subtype (two strains) was only detected in 2017. Two B3 subtype strains were detected in 2017. The strains of B1b subtype were closely related to the strains isolated in Shanghai (JQ314149), Wenzhou (KP289416) and Beijing (KU254598), while the B1a subtype strains were closely related to the strains isolated in Kunming (JQ316639) and Tailand (GQ184139). The B3 subtype strain was an emerging CVA16 epidemic strain in mainland China. Further comparison of the CVA16 epidemic strains in Shenzhen area during 2016 to 2017 with the CVA16 strains causing severe neurological symptoms showed that two amino acid mutations (S14N and M23L) were found in VP1 protein. Conclusions The epidemic strains of CVA16 were B1b subtype in Shenzhen area in 2016. However, B1a, B1b and the emerging B3 subtype strains were prevalent in 2017. Compared with the CVA16 strains causing severe neurological symptoms, the CVA16 strains circulating in Shenzhen during 2016 to 2017 carried two amino acid mutations inVP1 protein.

Objective To analyze the genetic characteristics of VP1-VP4 genes carried by cox-sackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015. -ethods The VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6. 0 and MEGA6. 02 software packages. Results Four cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98. 8％-98. 9％ homology in nucleotide sequences and 99. 3％-99. 8％ in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95. 0％ homology in nucleotide sequences and 99. 3％ homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785). Conclusions All CVA6 strains causing severe HFMD ca-ses in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.

The foreign body reaction refers to a chronic inflammatory reaction and a wound-healing reaction that mainly involve macrophages and foreign body giant cells, which occur after a biological material is implanted into the body. Since macrophages in the foreign body reaction are recruited to the surface of the material after implantation of the material, subsequent secretion of a series of inflammatory factors and fusion into foreign body giant cells may lead to the degradation of the biological materials and environmental stress cracking. Moreover, the prolongation of macrophage polarization and the influence of related receptors may also lead to the phenomenon of fiber encapsulation, resulting in poor prognosis. Some scholars are committed to reducing the response of foreign bodies from the perspective of macrophages and foreign body giant cells, specifically by regulating the secretion of related inflammatory factors, reducing the subtypes of M1 macrophages, promoting their polarization to M2 macrophages, and regulating the fusion of macrophages and selective expression of macrophage-associated receptors to regulate fibrosis. The new immunological view holds that macrophages have the potential to repair bone tissue via angioplasts and osteogenesis in foreign body reactions. Therefore, the gold standard that has long been considered in regenerative medicine, which is that an inert material does not cause a foreign body reaction, is expected to be gradually replaced by tissue engineering that regulates tissue activity and function.

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.
Acoustic Stimulation ; Analysis of Variance ; Animals ; Dose-Response Relationship, Drug ; Electroencephalography ; Excitatory Amino Acid Antagonists ; pharmacology ; Gamma Rhythm ; drug effects ; Ketamine ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sensory Gating ; drug effects ; Sleep Stages ; drug effects ; Statistics as Topic ; Time Factors ; Wakefulness ; drug effects