ObjectiveTo systematically evaluate the efficacy and safety of omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy. MethodsThis study was conducted according to the PRISMA guideline. English and Chinese databases including CNKI， Wanfang Data， VIP， CBM， the Cochrane Library， PubMed， Embase， and Web of Science were searched for clinical studies on omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy published up to November 2022， and Stata 16 and Review Manager 5.4 were used to perform the meta-analysis. ResultsA total of 15 studies with 1 830 patients were included in this study. The meta-analysis showed that the omental wrapping group had a significantly lower overall incidence rate of postoperative pancreatic fistula （POPF） than the non-omental wrapping group （odds ratio ［OR］=0.30， 95% confidence interval ［CI］： 0.22‍ ‍—‍ ‍0.41， P<0.001）， and the subgroup analysis showed that the omental wrapping group had a significantly lower incidence rate of grade B/C POPF than the non-omental wrapping group （OR=0.29， 95%CI： 0.21‍ ‍—‍ ‍0.39， P<0.001）. Compared with the non-omental wrapping group， the omental wrapping group had significantly lower incidence rates of postoperative bile leakage （OR=0.30， 95%CI： 0.16‍ ‍—‍ ‍0.56， P<0.001）， postoperative hemorrhage （OR=0.35， 95%CI： 0.24‍ ‍—‍ ‍0.53， P<0.001）， delayed gastric emptying （OR=0.45， 95%CI： 0.31‍ ‍—‍ ‍0.64， P<0.001）， abdominal infection （OR=0.55， 95%CI： 0.40‍ ‍—‍ ‍0.75， P<0.001）， reoperation （OR=0.31， 95%CI： 0.18‍ ‍—‍ ‍0.54， P<0.001）， and death within 30 days after surgery （OR=0.42， 95%CI： 0.22‍ ‍—‍ ‍0.80， P=0.009）， a significantly earlier time to diet （mean difference ［MD］=-0.98， 95%CI： -1.84 to -0.11， P=0.03）， and a significantly shorter length of postoperative hospital stay （MD=-2.44， 95%CI： -4.10 to -0.77， P=0.004）. There were no significant differences between the two groups in the time of operation （MD=-13.68， 95%CI： -28.31 to -0.95， P=0.07） and intraoperative blood loss （MD=-17.26， 95%CI： -57.55 to -23.03， P=0.40）. ConclusionOmental wrapping can reduce the incidence rates of postoperative complications such as pancreatic fistula， bile leakage， postoperative hemorrhage， abdominal infection， and delayed gastric emptying， improve the prognosis of patients， and shorten the length of hospital stay， without increasing surgical difficulty or time of operation.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To explore the safety and effectiveness of transvaginal ischia spinous fascia fixation for pelvic organ prolapse.Methods The retrospective analysis of 124 patients who underwent surgical treatment for stage Ⅲ-Ⅳ pelvic organ prolapse was conducted.Among them, 53 cases of transvaginal ischia spinous fascia fixation (IS-FF) were performed as a study group (ISFF group) while 71 cases of transvaginal sacrospinous ligament fixation (SSLF) were performed as a control group (SSLF group) .The operation time, postoperative hospitalization days, preoperative and postoperative hemoglobin values, indwelling urinary catheter time, postoperative pain scores, and the occurrence of complications were compared between the two groups, and the efficacy of the operation was objec-tively evaluated by using the staging method of pelvic organ prolapse (POP-Q) .Also the scores of the pelvic floor impact questionnaire-7 (PFIQ-7) , the pelvic floor dysfunction questionnaire-20 (PFDI-20) , and the questionnaire of quality of life12 (PISQ-12) were used to evaluate the patients' postoperative quality of life.Results The oper-ation time and postoperative hospitalization days of patients in the ISFF group were less than those in the SSLF group , and the differences were statistically significant (P<0.05) .The preoperative and postoperative hemoglobin values, retention time of urinary catheter, postoperative pain scores, and hospitalization costs of patients in the two groups were compared, and the differences were not statistically significant.At the 3-month postoperative outpatient follow-up, the objective success rate was 100％ in two groups.The median follow-up time of patients in both groups was 24 months (12-41 months) , and there were 2 cases of recurrence in the ISFF group, with a recurrence rate of 3.77％ and a subjective success rate of 96.23％.While there were 3 cases of recurrence in the SSLF group and 2 cases of loss of visit, with a recurrence rate of 4.34％ and a subjective success rate of 95.65％.1 patient in the SSLF group presented with a pelvic hematoma with a diameter of about 5 cm after surgery.The hematoma disap-peared after hemostasis and other symptomatic treatment.There was no organ injury or blood transfusion in both groups.Conclusion Transvaginal ischia spinous fascia fixation is a safe and effective treatment for pelvic organ prolapse, and it has the advantages of short operation time, fast postoperative recovery, fewer complications, and improvement of patients' quality of life.

Objective:To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods:According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results:Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects ( t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group ( F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group ( F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation ( F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group ( F=88.24, P<0.001). Conclusions:Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To explore the predicting value of quantitative CT features of peritumoral nodules for the risk of thymic epi-thelial tumors(TETs).Methods A total of 108 patients with TETs confirmed by pathology were analyzed retrospectively.Accord-ing to the WHO classification of thymic tumors,the patients were divided into high-risk group and low-risk group.The quantitative CT features included the long diameter,volume,mass,and distance between peritumoral nodules and main tumor.The values of these features were assessed using the Mann-Whitney U test,and the thresholds were determined using the receiver operating characteristic(ROC)curve.Results Among 108 TETs patients,there were 45 patients with peritumoral nodules on chest CT,including 30 high-risk group and 15 low-risk group,respectively.Interobserver consistencies were well with intraclass correlation coefficient(ICC)between 0.886 and 0.907.The long diameter,volume,and mass of peritumoral nodules were greater in the high-risk group than in the low-risk group(P＜0.05),and there was no significant difference in the distance to the main tumor(P＞0.05).The mass of peritumoral nodules had the best diagnostic performance in predicting TETs risk,and the thresholds was 27.84 mg with the area under the curve(AUC)of 0.889,sensitivity of 83.3％,specificity of 87.5％,and accuracy of 85.3％,respectively.Conclusion The quantitative CT features of peritumoral nodules especially mass can be useful in predicting the risk of TETs.

Objective:To investigate neuroprotective effect of alpinetin on ischemic stroke(IS)rats by regulating Shh/Gli1 signaling pathway.Methods:Fifteen rats were randomly collected as control group,remaining rats were used to construct an IS model.Rats that successfully modeling were randomly grouped into model group,alpinetin group(5 mg/kg),Shh/Gli1 signaling pathway inhibitor cycloparamide group(15 mg/kg)and alpinetin+cycloparamide group(5 mg/kg alpinetin+15 mg/kg cycloparamide),with 15 rats in each group,and administered once a day for two consecutive weeks,control group and model group were given equal amounts of physiological saline.Zea-Longa scoring method was applied to evaluate neural function;ELISA was applied to detect inflammatory factors levels;mass of brain tissue was weighed and water content of brain tissue was calculated;TTC staining was applied to measure volume of cerebral infarction;HE staining was applied to observe nerve cell damage;TUNEL staining was applied to detect neuronal apoptosis;qRT-PCR and Western blot were used to detect mRNA and protein expressions of Shh and Gli1.Results:There were no abnormalities in hippocampal tissue of control group,while hippocampal tissue structure of model group rats was abnor-mal,with disordered cell arrangement and nuclear pyknosis of nerve cells,cell damage rate,Zea-Longa score,infarct volume,IL-1β,IL-6,TNF-α,brain tissue water content,and cell apoptosis rate in model group were obviously higher than control group(P<0.05),mRNA and protein levels of Shh and Gli1 were obviously decreased(P<0.05);compared with model group,cells in alpinetin group were arranged more neatly,and phenomenon of neuronal cell nucleus pyknosis was improved,cell damage rate,Zea-Longa score,infarct volume,IL-1β,IL-6,TNF-α,brain tissue water content,and cell apoptosis rate were obviously decreased(P<0.05),mRNA and protein levels of Shh and Gli1 were obviously increased(P<0.05),trend of above indicators in cyclophosphamide group was opposite,ciclopramide reversed neuroprotective effect of alpinetin on IS rats.Conclusion:Alpinetin may exert neuroprotective effects on IS rats by activating Shh/Gli1 signaling pathway.

This article reported a case of hypertrophic pyloric stenosis after neonatal esophageal atresia repair. The mother of the child did not have regular prenatal care. The child was born at a gestational age of 40 weeks and 2 days of gestation, with polyhydramnios at birth, and was diagnosed with esophageal atresia and cleft palate after birth and underwent thoracoscopic esophageal-esophageal end-to-end anastomosis and esophageal-tracheal fistula ligation and was given nasogastric feeding after surgery. At four months of age, the child vomited a lot of coffee-like material after nasogastric feeding, and the ultrasonographic and upper gastroenterography findings suggested hypertrophic pyloric stenosis, which was treated surgically with good results. This case suggests that hypertrophic pyloric stenosis should be considered in children with unexplained non-bilious vomiting/feeding difficulties after esophageal atresia repair. After definitive diagnosis, laparoscopic pyloromyotomy is feasible.

Objective Meta-analysis was used to summarize the current status of medication adherence in patients with type 2 diabetes mellitus and to clarify the characteristics of people with low medication adherence.Methods Relevant literatures were searched in Pubmed,Cochrane Library,Web of Science,Embase,CINAHL,CBM,China National Knowledge Infrastructure,Wanfang Data,and VIP.Two researchers conducted literature screening,data extraction and quality evaluation.Stata 16.0 software was used for subgroup analysis,sensitivity analysis,offset analysis.Results A total of 42 papers were included,and the overall medication adherence of middle-aged and elderly type 2 diabetes patients ranged from 18.37%-96.53%.The medication adherence was higher among those with high education level(63%),married(61%),not living alone(50%),monthly income>3000 RMB/month(64%),having medical insurance(49%),good psychological status(61%),no chronic co-morbidities(66%),having knowledge about the disease(53%),taking≤3 types of medication(58%),convenient access to medical care(58%),and good doctor-patient relationship(50%).Conclusion The medication adherence of patients with type 2 diabetes mellitus varies greatly among different subgroups.In the future,the specific influencing factors should be further explored to formulate targeted policies and intervention measures to improve patients'medication adherence and improve their health and quality of life.

Objective To systematically evaluate the efficacy and acceptability of non-pharmaceutical intervention(NPI)for depression in patients with mild cognitive impairment(MCI).Methods Randomized controlled trials of NPI in treatment of depression patients with MCI published in PubMed,Embase,Web of Science,CINAHL,Cochrane Library,CNKI,Wanfang Data,VIP and CBM databases were searched from self-built databases to January 6,2024,and performed a network Meta-analysis using Stata 14.0 software.Results A total of 55 literatures were included,involving 10 NPIs.According to the surface under the cumulative ranking curve(SUCRA),the top 3 curative effects were cognitive behavioral therapy(CBT),Chinese traditional sport(CTS)and art therapy,the top 3 acceptability were CBT,CTS,and health education.Conclusion CBT and CTS may be effective and acceptable NPI for improving depression in patients with MCI,and individualized interventions can be tailored to the patient's situation to achieve the best results.