ObjectiveTo investigate the differences in the risk factors for postoperative pancreatic fistula （POPF） after pancreaticoduodenectomy （PD） between the 2005 and 2016 editions of the definition and classification standards for pancreatic fistula， and to establish a risk prediction model for pancreatic fistula based on the 2016 edition. MethodsA retrospective analysis was performed for the clinical data of 303 patients who were admitted to Tianjin Third Central Hospital and underwent PD from January 2016 to May 2022， and the patients with POPF were identified based on the new and old editions. The independent-samples t test or the non-parametric Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the differences in the risk factors for pancreatic fistula after PD between the two editions； a risk prediction model was established for POPF based on the 2016 edition， and the receiver operating characteristic curve was used to invesitgate the accuracy of this model in predicting POPF and perform model validation. ResultsAccording to the 2005 edition， the univariate analysis showed that the diameter of the main pancreatic duct （χ²=31.641， P<0.001）， main pancreatic duct index （χ²=52.777， P<0.001）， portal vein invasion （χ²=6.259， P=0.012）， intra-abdominal fat thickness （χ²=7.665， P=0.006）， preoperative biliary drainage （χ²=5.999， P=0.014）， pancreatic cancer （χ²=5.544， P=0.019）， marginal pancreatic thickness （t=2.055， P=0.032）， pancreatic CT value （t=-3.224， P=0.002）， and preoperative blood amylase level （Z=-2.099， P=0.036） were closely associated with POPF， and the multivariate logistic regression analysis showed that main pancreatic duct index （odds ratio ［OR］=0.000， 95% confidence interval ［CI］： 0.000‍ ‍—‍ ‍0.011， P<0.05）， pancreatic cancer （OR=4.843， 95%CI： 1.285‍ ‍—‍ ‍18.254， P<0.05）， and pancreatic CT value （OR=0.869， 95%CI： 0.806‍ ‍—‍ ‍0.937， P<0.05） were independent risk factors； based on the 2016 edition， the univariate analysis showed the diameter of the main pancreatic duct （χ²=5.391， P=0.020）， main pancreatic duct index （χ²=11.394， P=0.001）， intra-abdominal fat thickness （χ²=8.899， P=0.003）， marginal pancreatic thickness （t=2.665， P=0.009）， pancreatic CT value （t=-2.835， P=0.004） were closely associated with POPF， and the multivariate logistic regression analysis showed that main pancreatic duct index （OR=0.001， 95%CI： 0.000‍ ‍—‍ ‍0.050， P<0.05） and pancreatic CT value （OR=0.943， 95%CI： 0.894‍ ‍—‍ ‍0.994， P<0.05） were independent risk factors. A risk prediction model was established for POPF after PD， and the ROC curve analysis showed that this model had an area under the ROC curve of 0.788 （95%CI： 0.707‍ ‍—‍ ‍0.870） in the modeling group and 0.804 （95%CI： 0.675‍ ‍—‍ ‍0.932） in the validation group. ConclusionMain pancreatic duct index and pancreatic CT value are closely associated with POPF after PD， and the risk prediction model for pancreatic fistula based on the 2016 edition has a good prediction accuracy.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Objective:To explore the clinical phenotype, diagnosis, treatment and genetic characteristics of infants with lethal mitochondrial trifunctional protein deficiency (MTPD).Methods:The clinical data of one patient with lethal MTPD admitted to the neonatal department of Guilin Maternal and Child Health Hospital were retrospectively analyzed. Relevant literature published up to July 2023 were retrieved from the Chinese Science and Technology Journal database, CNKI, Wanfang Database, Chinese Medical Journal Full-text Database, Chinese Biomedical Journal Literature Database, China Biomedical Literature Database, PubMed, Elsevier ScienceDirect, Embase and BIOSIS Previews with the terms of "mitochondrial trifunctional protein deficiency", "mitochondrial trifunctional protein", "HADHA", "HADHB", "newborn", "infant" and "lethal". Then the characteristics of clinical phenotypes and genetic variations about MTPD infants were summarized.Results:This patient was a 33 +3 week premature male infant who developed symptoms 9 d after birth. The main manifestations were metabolic acidosis, recurrent apnea, shock, cardiomyopathy and heart failure. Blood tandem mass spectrometry reported an increased levels of multiple acylcarnitines, and genetic testing indicated that the patient's HADHB gene had maternal c.527C>G missense mutation and de novo c.1148C>T missense mutation. The infant was diagnosed with lethal MTPD and died 12 d after birth after his family gave up the treatment. There were 29 cases in the total 13 publications that were retrieved. Together with this case, there were 30 cases involved. Among the 16 cases with relatively complete data, 10 cases were male and 15 cases developed symptoms in neonatal period. The main clinical phenotypes were cardiomyopathy, abnormal myocardial enzyme spectrum, heart failure and lactic acidosis or metabolic acidosis. Among the 15 cases with clear age of death, 14 died within 3 months of life. Of the reported patients, only one survived at 8 years of age. 29 cases were confirmed through genetic test, 10 infants had HADHA gene variations and 19 had HADHB gene variations. Only one patient was confirmed by pathological detection and mass spectrometry analysis. Conclusions:MTPD is a rare autosomal recessive genetic disease. Lethal MTPD has an early onset with high mortality. Severe acidosis and heart failure are the most common symptoms in neonatal period. Early detection of acylcarnitine and HADHB, HADHA gene should be performed in highly suspected infants to help early genetic diagnosis and intervention.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China,and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990,the national KBD detectable rate was 21.01％. X-ray detection decreased to below 10％ in 2003 and below 5％ in 2007. Between 2010 and 2018,the prevalence of KBD in children was less than 0.4％,which fluctuated at a low level,and has decreased to 0％ since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Objective To investigate the effect of nobiletin on platelet-activating factor(PAF)metabolism in diabetic rats with renal injury.Methods Totally 72 rats were randomly divided into control group(n=10)and modeling group(n=62).The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group,aspirin group(20 mg/kg),and nobiletin low(50 mg/kg),medium(100 mg/kg),and high-dose(200 mg/kg)groups,each with 10 rats.After continuous oral administration for 6 weeks,rat body weight,kidney weight,and kidney index were measured.Histopathological assessments were conducted by using HE,periodic acid-Schiff staining(PAS),Masson staining,and transmission electron microscopy.Blood glucose levels,renal function,inflammatory factors,PAF and its regulatory factors were detected.Expression levels of PAF metabolism-related proteins,PAF-acetylhydrolase(PAFAH),PAF receptor(PAFR),and cholinephosphotransferase 1(CHPT1)in kidney tissues were assessed using Western blotting and immunohistochemistry.Results Following nobiletin intervention,rat body weight increased while kidney weight and kidney index decreased.Improvement in renal tissue pathology was observed,with reduced interstitial fibrosis and thinner basement membrane.Fasting blood glucose and glycated hemoglobin decreased,while fasting insulin showed no significant improvement.Urea nitrogen,blood creatinine,cystatin C,and 24-hour urinary protein excretion were reduced.Levels of interleukin(IL)-1α,IL-6,IL-8,and tumor necrosis factor(TNF-α)were lowered.PAF and its regulatory factors decreased.PAFR and CHPT1 expression decreased,while PAFAH increased.Conclusion Nobiletin can alleviate renal injury in diabetic rats with renal injury,improve kidney function,regulate blood glucose,and mitigate inflammatory response.Its mechanism may be associated with the modulation of platelet-activating factor metabolism.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(Ⅳ)prodrug(C8Pt(Ⅳ))and Cet.The so-called antibody-platinum(Ⅳ)prodrugs conjugates,named Cet-C8Pt(Ⅳ),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(Ⅳ)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(Ⅳ)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(Ⅳ)prodrugs conjugates.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:This study investigates the conditional combination paths of different types of patient demands in Internet hospitals,aiming to optimize service utilization.Methods:The Andersen's model research framework and fuzzy set qualitative comparative analysis(fsQCA)are used to construct a causal chain including predisposing characteristics,enabling resources and demand factors.Results:The study proposes six condition combination paths for the three service stages of pre-diagnosis,consultation and follow-up from the user's perspective.Factors such as economy,professionalism and guidance were examined comprehensively to analyze the demands of different age and disease groups.The study found that there are significant differences across the factors in the user demands of Internet hospitals at different service stages and under different condition combination paths.Conclusions and Suggestions:Internet hospitals should provide differentiated services to meet diversified user demands according to representative user groups in different paths,such as"lower age groups+pre-diagnosis","lower age groups+consultation experience"and"higher age groups+follow-up".At the same time,it is recommended to establish Internet diagnosis and treatment services covering the whole service chain,and improve the related regulatory and policy framework to enhance the utilization of Internet hospital services.