Objective:To investigate the role of the IgG subtypes (IgG1 and IgG2a) in anti-glycoprotein (GP) Ⅰbα antibody-induced platelet clearance.Methods:Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells (THP-1 cells) induced by different anti-GPⅠbα antibodies (AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2) was detected by flow cytometry. The effects of the AN51 full-length antibody, F (ab') 2, and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. Results:Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro ( P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F (ab') 2 nor the Fab fragment could induce THP-1 cells to phagocytose platelets ( P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2 ( P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a ( P<0.05) . Conclusion:IgG2a plays an important role in anti-GPⅠbα-induced clearance.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Objective:To investigate the role of the IgG subtypes (IgG1 and IgG2a) in anti-glycoprotein (GP) Ⅰbα antibody-induced platelet clearance.Methods:Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells (THP-1 cells) induced by different anti-GPⅠbα antibodies (AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2) was detected by flow cytometry. The effects of the AN51 full-length antibody, F (ab') 2, and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. Results:Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro ( P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F (ab') 2 nor the Fab fragment could induce THP-1 cells to phagocytose platelets ( P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2 ( P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a ( P<0.05) . Conclusion:IgG2a plays an important role in anti-GPⅠbα-induced clearance.

This study investigated the perceptions and medical history of third molars (M3s) and assessed the prevalence of visible M3s (V-M3s) among 904 Chinese adults. The enrolled participants were interviewed to complete a structural questionnaire focused on sociodemographic information and their understanding of, attitudes toward, behaviors regarding, and medical history with respect to M3s. In addition, the number of V-M3s in the cohort was determined by oral examination. Logistic regression analysis was performed to explore the association between individuals' sociodemographic characteristics and their perception of M3s or the presence of V-M3s. The Chi-square test was used to compare the actions taken against symptomatic M3s and the corresponding outcomes among different groups divided according to respondents' sociodemographic factors. In total, 904 completed questionnaires were gathered and analyzed. Nearly half (43.9%) of the respondents knew nothing about M3s, and only 12.7% provided correct answers to all the questions asked. Male sex, older age, occupation involving physical labor, and no previous dental experience were active factors in unawareness of M3s. Male sex was also significantly associated with the presence of at least one V-M3 and negative behavior about symptomatic M3s. In terms of medical history, 192 participants reported having had at least one M3 extracted (438 in total), and 72.6% of the M3s were removed due to the presence of related symptoms or pathologies. In conclusion, the population investigated had a shortage of knowledge about M3s and adopted negative attitudes and actions about M3-related problems.

Objective To investigate the changes and clinical significance of bile acid spectrum levels in patients with early non-alcoholic fatty liver disease(NAFLD).Methods A total of 149 patients with early NAFLD(NAFLD group)and 140healthy controls(healthy group)who underwent physical examinations at the Physical Examination Center,the Fourth Affiliated Hospital of Zhejiang Uni-versity School of Medicine from July 2021 to February 2022 were selected,and liver function test,bile acid spectrum detection and con-trolled attenuation parameter test were performed on all patients,the differences in liver function and bile acid spectrum between the two groups were compared,and the risk factors of early NAFLD and the efficacy of bile acid subgroups in diagnosing early NAFLD were ana-lyzed.Results The levels of aspartate transaminase(AST),alanine aminotransferase(ALT),and γ-glutamyl transpeptidase(r-GT)in the NAFLD group were higher than those in the healthy group(P<0.05).cholic acid(CA),glycocholic acid(GCA),tauro-cholic acid(TCA),glycodeoxycholic acid(GDCA),chenodeoxycholic acid(CDCA),glycochenodeoxycholic acid(GCDCA),tauro-chenodeoxycholic acid(TCDCA),glycineursodeoxycholic acid(GUDCA),tauroursodeoxycholic acid(TUDCA)and taurolithocholic acid(TLCA)were higher than those in the healthy group(P<0.05),and the level of lithocholic acid(LCA)was lower than the healthy group(P<0.05);Logistic regression analysis showed that AST,GCA,TCA,CDCA,GCDCA,TCDCA,GUDCA and TLCA were inde-pendent risk factors in NAFLD patients;receiver operating characteristic curve shows that AST,GCA,TCA,CDCA,GCDCA,TCDCA,GUDCA and TLCA could predict the occurrence of NAFLD to a certain extent,among which AST had the best comprehensive prediction effect(AUC =0.750),and GCA had the highest sensitivity(77.2%),and TLCA had the strongest specificity(88.6%);the levels of GCA and TCA in the severe group were significantly higher than those in the mild group(P<0.05),the concentration of serum TCA in-creased gradually increased with the aggravation of NAFLD severity,and there was a linear correlation between them(r = 0.52,P<0.05).Conclusion The bile acid spectrum components of patients with early NAFLD was changed,mainly primary bile acids and con-jugated bile acids.The level of TCA can not only predict the occurrence of NAFLD to a certain extent,but also has a positive correlation with the severity of NAFLD,which is expected to become a serological marker of NAFLD.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

Objective:To evaluate the associations of COVID-19 vaccination during pregnancy with the risk of pregnancy complications and neonatal adverse birth outcomes, and to provide evidence for improving strategies for COVID-19 vaccination during pregnancy.Methods:"covid-19 vaccines" "covid19" "covid 19" "vaccin*" "neonatal outcomes" "perinatal outcomes" "pregnancy outcomes" "premature birth" were used as the main search terms. Articles published from January 1st 2020 to May 27th 2022 were searched in PubMed, Web of Science, Scopus, Cochrane library, CNKI, Wanfang Database, VIP Database and Chinese Biomedical Literature Database by adopting the method of the combination of MeSH words and free words. Stata16.0 software was used to calculate pooled effect values, perform heterogeneity test and sensitivity analysis and assess publication bias.Results:According to the inclusion and exclusion criteria, a total of 12 English papers were included from 482 relevant literatures retrieved, with 88 682 pregnant women vaccinated during pregnancy. Meta-analysis results showed that COVID-19 vaccination in pregnancy did not increase the risk of gestational hypertension, postpartum hemorrhage, neonatal preterm birth, small-for-gestational-age infants, and 5 min Apgar score<7, with pooled relative risk ( RR) and 95% confidence interval (95% CI) of 0.97 (0.91-1.05), 1.01 (0.83-1.23), 0.92 (0.77-1.10), 0.97 (0.90-1.04) and 0.93 (0.87-1.00), respectively. There was no significant difference in neonatal birth weight between the two groups of pregnant women who received COVID-19 vaccine or not, and the combined mean difference (MD) and 95% CI was -18.26 (-40.39-3.87) g. However, COVID-19 vaccination in pregnancy may increase the risk of gestational diabetes and the combined RR (95% CI) was 1.14 (1.03-1.26). In addition, sensitivity analysis showed that the results were stable and reliable. Egger's test and Begg's test showed that there was no publication bias among the included studies. Conclusion:This study does not support the increased risk of pregnancy complications and neonatal adverse birth outcomes for pregnant women vaccinated against COVID-19, but more researches are still needed to provide evidence of the safety of COVID-19 vaccination in pregnancy.

Objective:To evaluate the associations of COVID-19 vaccination during pregnancy with the risk of pregnancy complications and neonatal adverse birth outcomes, and to provide evidence for improving strategies for COVID-19 vaccination during pregnancy.Methods:"covid-19 vaccines" "covid19" "covid 19" "vaccin*" "neonatal outcomes" "perinatal outcomes" "pregnancy outcomes" "premature birth" were used as the main search terms. Articles published from January 1st 2020 to May 27th 2022 were searched in PubMed, Web of Science, Scopus, Cochrane library, CNKI, Wanfang Database, VIP Database and Chinese Biomedical Literature Database by adopting the method of the combination of MeSH words and free words. Stata16.0 software was used to calculate pooled effect values, perform heterogeneity test and sensitivity analysis and assess publication bias.Results:According to the inclusion and exclusion criteria, a total of 12 English papers were included from 482 relevant literatures retrieved, with 88 682 pregnant women vaccinated during pregnancy. Meta-analysis results showed that COVID-19 vaccination in pregnancy did not increase the risk of gestational hypertension, postpartum hemorrhage, neonatal preterm birth, small-for-gestational-age infants, and 5 min Apgar score<7, with pooled relative risk ( RR) and 95% confidence interval (95% CI) of 0.97 (0.91-1.05), 1.01 (0.83-1.23), 0.92 (0.77-1.10), 0.97 (0.90-1.04) and 0.93 (0.87-1.00), respectively. There was no significant difference in neonatal birth weight between the two groups of pregnant women who received COVID-19 vaccine or not, and the combined mean difference (MD) and 95% CI was -18.26 (-40.39-3.87) g. However, COVID-19 vaccination in pregnancy may increase the risk of gestational diabetes and the combined RR (95% CI) was 1.14 (1.03-1.26). In addition, sensitivity analysis showed that the results were stable and reliable. Egger's test and Begg's test showed that there was no publication bias among the included studies. Conclusion:This study does not support the increased risk of pregnancy complications and neonatal adverse birth outcomes for pregnant women vaccinated against COVID-19, but more researches are still needed to provide evidence of the safety of COVID-19 vaccination in pregnancy.

Objective:To explore the clinical effect of nerve-containing free latissimus dorsi myocutaneous flap in emergency treatment to repair the severe wound of the upper limb and restore the function of elbow flexion or extension.Methods:Retrospective analysis of the clinical data of patients with upper limb composite tissue defects treated in the Department of Joint Trauma Orthopedics of the Yidu Central Hospital of Weifang from March 2013 to November 2019, all of whom were repaired with nerve-containing free latissimus dorsi myocutaneous flap in an emergency. The patients were followed up for 12-24 months, and the patient’s satisfaction with the myocutaneous flap was investigated by questionnaire. The upper limb motor nerve function was evaluated by the upper limb function evaluation standard of the Chinese Society of Hand Surgery. The Mayo Elbow Performance Score was used to evaluate the effect of elbow repair. At 12 months after the operation, the flexion and extension of the elbow joint on the affected side and the healthy side, and the pronation angle and supination angle of the forearm were measured. Observe the shape and function of the donor area. SPSS 23.0 software was used for statistical analysis. Measurement data conforming to normal distribution were expressed as Mean±SD. An independent sample t-test was used to compare the differences in flexion and extension of the elbow between the affected side and the healthy side and the pronation and supination angles of the forearm. The difference is statistically significant if the P value is less than 0.05. Results:A total of 21 cases were included, including 15 males and 6 females. The age ranged from 18 to 60 years old, with an average of 37 years old. Causes of injury: traffic injury in 14 cases, machine injury in 7 cases. All of them were severe composite tissue defects of the upper limb, accompanied by elbow flexion or elbow extension function damage. The area of soft tissue defect is 15 cm × 6 cm-33 cm × 12 cm, and the area of the myocutaneous flap is 17 cm × 8 cm-35 cm × 15 cm. Time from injury to operation: 2-5 h. All the myocutaneous flaps of 21 patients survived. The patients were followed up for 12-24 months. The satisfaction rate of patients with myocutaneous flap healing was 100%(21/21); the satisfaction rate of morphology was 100% (21/21); the satisfaction rate of temperature was 90.48% (19/21); the satisfaction rate of sensation was 85.71%(18/21); the satisfaction rate of function was 95.24% (20/21). Motor nerve function examination and evaluation grading, 12 cases M3+ , 8 cases M3, and 1 case M2. The Mayo Elbow Performance Score, excellent in 11 cases, good in 8 cases, fair in 2 cases. Twelve months after the operation, the elbow flexion, extension, forearm pronation angle, and supination angle of the affected side and the healthy side were compared (134.73°±7.41°, 6.28°±2.16°, 78.59°±3.72°, 79.28°±3.59° respectively for the affected side and 139.37°±9.13°, 5.91°±1.95°, 80.26°±3.94°, 81.02°±3.81° for the healthy side). There was no statistical significance between the data ( t=1.81, 0.58, 1.41, 1.52; P=0.078, 0.563, 0.166, 0.136). There was no obvious scar contracture in the skin grafting area of the donor area, and there was no significant effect on the shape and function. Conclusions:Latissimus dorsi myocutaneous flap for emergency repair of severe tissue defects of the upper limb not only covers the defect wound but also reconstructs the function of the affected limb. It has the advantage that other myocutaneous flaps cannot replace and effectively shortens the recovery cycle of patients. It is one of the effective method for emergency repair of severe trauma of the upper limb with elbow function injury.