Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To investigate the prevalence of chronic endometritis(CE)in patients with repeated implantation failure(RIF),and the correlation between diagnostic indexes of CE and classification of peripheral blood immune cells.Methods:A total of 64 patients with RIF who visited Outpatient of Hebei Reproductive Health Hospital from January 2020 to December 2021 were retrospec-tively analyzed.General information of patients,results of hysteroscopy and endometrial immunohistochemistry in the mid luteal phase,the number and percentage of NK cells,Th1 cells,Th2 cells,Th17 cells and Treg cells in peripheral blood,and Th1/Th2,Th17/Treg were collected,and the pregnancy outcome of retransplantation was followed up.To evaluate the consistency of hysteroscopy and endometrial immunohistochemistry CD138 in diagnosis of CE in RIF patients,to analyze whether chronic inflammation of endome-trium was related to classification of peripheral blood immune cells,and to analyze the pregnancy outcome of patients with RIF diag-nosed with CE after retransplantation.Results:Prevalence of CE in RIF patients detected by hysteroscopy was 53.12%,which was sig-nificantly higher than that detected by endometrial immunohistochemistry CD138(25.00%,P<0.05).There was no significant differ-ence in the number and percentage of immune cells in peripheral blood between CE and non CE patients.After antibiotic treatment,the 12-week continuous pregnancy rate and live birth rate in the CD138 positive group were higher than those in negative group,with a statistically significant difference(P<0.05).Conclusion:The combination of hysteroscopy and endometrial CD138 immunohistochem-istry at the right time for RIF patients is beneficial to improve their pregnancy rate and pregnancy outcome.The infiltration of endome-trial plasma cells does not affect the classification of peripheral blood immune cells.

Objective:To investigate the prevalence of chronic endometritis(CE)in patients with repeated implantation failure(RIF),and the correlation between diagnostic indexes of CE and classification of peripheral blood immune cells.Methods:A total of 64 patients with RIF who visited Outpatient of Hebei Reproductive Health Hospital from January 2020 to December 2021 were retrospec-tively analyzed.General information of patients,results of hysteroscopy and endometrial immunohistochemistry in the mid luteal phase,the number and percentage of NK cells,Th1 cells,Th2 cells,Th17 cells and Treg cells in peripheral blood,and Th1/Th2,Th17/Treg were collected,and the pregnancy outcome of retransplantation was followed up.To evaluate the consistency of hysteroscopy and endometrial immunohistochemistry CD138 in diagnosis of CE in RIF patients,to analyze whether chronic inflammation of endome-trium was related to classification of peripheral blood immune cells,and to analyze the pregnancy outcome of patients with RIF diag-nosed with CE after retransplantation.Results:Prevalence of CE in RIF patients detected by hysteroscopy was 53.12%,which was sig-nificantly higher than that detected by endometrial immunohistochemistry CD138(25.00%,P<0.05).There was no significant differ-ence in the number and percentage of immune cells in peripheral blood between CE and non CE patients.After antibiotic treatment,the 12-week continuous pregnancy rate and live birth rate in the CD138 positive group were higher than those in negative group,with a statistically significant difference(P<0.05).Conclusion:The combination of hysteroscopy and endometrial CD138 immunohistochem-istry at the right time for RIF patients is beneficial to improve their pregnancy rate and pregnancy outcome.The infiltration of endome-trial plasma cells does not affect the classification of peripheral blood immune cells.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To evaluate clinical efficacy and safety of immunotherapy by retrospectively analyzing clinical medica-tion of patients with recurrent pregnancy loss(RPL)complicated with abnormal immune factors.Methods:A retrospective cohort study was conducted on RPL cases in outpatient department of Hebei Reproductive Health Hospital from January 2021 to April 2022.Efficacy and safety of immunotherapy were evaluated from pregnancy outcome,adverse reactions and birth defects of offspring.Results:According to guidelines,192 cases with abnormal autoimmunity and/or immune indicators were included.Early abortion rate was 4.16%in group of two lost pregnancies,which was lower than that in group of three lost pregnancies(16.66%).Twelve week sus-tained pregnancy rate was 89.58%in the former group,and 28 week sustained pregnancy rate was 86.45%,which were significantly higher than those in the latter group(75.00%,71.87%).RPL patients were divided into groups according to their exposure to immuno-modulatory drugs before 12 weeks of pregnancy.There was no significant difference in pregnancy outcome,adverse reaction rate and birth defect rate of their offspring(P>0.05).Conclusion:Immunotherapy can effectively reduce risk of recurrent abortion and increase rate of persistent pregnancy in patients with immune RPL.Personalized immunotherapy can make RPL patients with immune factors achieve expected effect of fetal protection.

Objective To assess short-and long-term changes in the upper airway,natural head position and hyoid bone position in skeletal Class Ⅲ patients after bimaxillary surgery.Methods In this retrospective study,the cone-beam computed tomography(CBCT)of skeletal Class Ⅲ patients was taken before surgery(T0),3 months after surgery(T1)and 2 years after surgery(T2).Three-dimensional images were created to assess postoperative changes and the correlation between the upper airway,natural head posi-tion and hyoid bone was analyzed.Results Thirty skeletal Class Ⅲ patients(13 men and 17 women)who underwent bimaxillary sur-gery with a mean(SD)age of 21 years(a range of 17-30 years)were evaluated.A significant decrease was observed in the volume of palatopharynx,glossopharynx and total airway after T1 and T2.There was a significant correlation between changes in the position of the mandible and changes in the volume of the upper airway(P＜0.05).The NSL/OPT angle and the NSL/CVT angle were greater after Tl and T2.The change in the NSL/CVT angle was positively correlated with the change in palatopharyngeal and glossopharyngeal volume(P＜0.05).Conclusion Bimaxillary surgery may cause a decrease in upper airway volume,an increase in the cranio-cervical angle,and a downward and backward movement of the hyoid bone.Changes in the cranio-cervical angle may cause changes in the upper air-way.

OBJECTIVES: The aims of this study were to update the latest data on the prevalence of hypertension (HTN) in the elderly Chinese population and to assess relationships between new anthropometric indices and HTN. METHODS: Data were obtained from the Basic Public Health Service (BPHS) survey for Jiangsu Province, China. A total of 944,760 people aged 65 years and older were included in this study. Blood pressure was measured by trained investigators. Body weight, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), conicity index (COI), body roundness index (BRI), and a body shape index (ABSI) were included in the analysis as anthropometric indices. Logistic regression analysis and restricted cubic splines were used to evaluate the association of anthropometric indices with HTN. RESULTS: The prevalence of HTN among elderly residents of Jiangsu Province was 64.7% (95% confidence interval, 64.6 to 64.8). After adjusting for multiple covariates, all anthropometric indices except ABSI showed significant non-linear positive dose-response associations with HTN across sex (pnonlinear<0.001). Among participants with BMI <28 kg/m2, abnormal weight, WC, WtHR, BRI, COI, and ABSI were positively associated with HTN. CONCLUSIONS The prevalence of HTN in the elderly in Jiangsu Province is gradually increasing. It is necessary to consider the combination of ABSI and COI with BMI for screening elderly individuals for HTN in follow-up prospective studies.

Objective:To evaluate the role of small ubiquitin-associated modifier (SUMO) E3 ligase (PIAS)-regulated SUMOylation of peroxisome proliferator-activated receptor γ (PPARγ) in the endogenous protective mechanism against endotoxin-induced acute lung injury (ALI) in mice.Methods:Experiment Ⅰ Twenty-four clean-grade wild type male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ PPARγ inducer TZD group (ALI+ T group) and ALI+ TZD+ SUMOylation inhibitor anacardic acid group (ALI+ T+ A group). Lipopolysaccharide (LPS) 15 mg/kg was injected into the tail vein to develop the ALI model. In ALI+ T+ A group, anacardic acid 5 mg/kg was intraperitoneally injected at 1 h before LPS administration. In ALI+ T group and ALI+ T+ A group, TZD 50 mg/kg was intraperitoneally injected at 30 min before LPS administration. The mice were sacrificed at 12 h after LPS administration, and the lung tissues were obtained to examine the pathological changes which were scored and to determine the wet/dry (W/D) weight ratio, and expression of PIAS1, PIAS2, PIAS3 and PIASy protein and mRNA (by Western blot or polymerase chain reaction). Experiment Ⅱ Mouse alveolar macrophages (MH-S cells) were cultured in vitro and divided into 4 groups ( n=5 each) using a random number table method: control group (C group), LPS group, LPS+ PIAS2 siRNA group (L+ P group) and LPS+ Con siRNA group (L+ C group). Cells were routinely cultured in group C. Cells were stimulated with 10 μg/ml LPS to develop the model of endotoxin challenge. PIAS2 siRNA 50 nmol/L and Con siRNA 50 nmol/L were transfected at 48 h before LPS was added in L+ P group and L+ C group, respectively. The cells were collected at 24 h of incubation with LPS to determine the cell viability, levels of M1 and M2 alveolar macrophages (by flow cytometry), expression of PIAS2 and PPARγ (by Western blot), co-expression of PPARγ-SUMO1 (by immunoprecipitation) and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) mRNA (by polymerase chain reaction). The ratio of M1/M2 was calculated. Results:Experiment Ⅰ Compared with C group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was up-regulated in the other three groups ( P<0.05). Compared with ALI group, the lung injury scores and W/D ratio were significantly decreased, and the expression of PIAS2 protein and mRNA was up-regulated in ALI+ T group and ALI+ T+ A group ( P<0.05). Compared with ALI+ T group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was down-regulated in ALI+ T+ A group ( P<0.05). There was no significant difference in the expression of PIAS1, PIAS3 and PIASy protein and mRNA in lung tissues among the four groups ( P>0.05). Experiment Ⅱ Compared with C group, the cell viability was significantly decreased, the expression of PPARγ and co-expression of PPARγ-SUMO1 was up-regulated, the levels of M1 and M2 macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was up-regulated, and the expression of IL-10 mRNA was down-regulated in the other three groups, and PIAS2 expression was significantly up-regulated in L group and L+ C group ( P<0.05). Compared with L group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and PPARγ-SUMO1 co-expression were down-regulated, the M1 macrophage level and M1/M2 ratio were increased, TNF-α mRNA expression was up-regulated, and the expression of IL-10 mRNA was down-regulated in L+ P group ( P<0.05), and no significant change was found in the parameters mentioned above in L+ C group ( P>0.05). Compared with L+ C group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and co-expression of PPARγ-SUMO1 were down-regulated, the level of M1 alveolar macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was down-regulated, and the expression of IL-10 mRNA was up-regulated in L+ P group ( P<0.05). Conclusions:PIAS2-regulated SUMOylation of PPARγ is the endogenous protective mechanism against endotoxin-induced ALI in mice, which may be related to inhibition of macrophage polarization into M1 type and alleviation of inflammatory responses.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.
Child, Preschool ; Exchange Transfusion, Whole Blood/adverse effects* ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant ; Infant, Newborn ; Kernicterus/therapy* ; Phototherapy/methods* ; Retrospective Studies