ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

Objective To investigate the expression levels of microRNA-34a(miR-34a),β-catenin and pro-grammed death receptor-1(PD-L1)in cancer tissues of patients with cervical cancer(CC)and their correla-tion with patients' prognosis.Methods A total of 83 patients with CC admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University from June 2021 to January 2024 were selected as the research objects.General data,CC tissue and adjacent normal tissue samples of all patients were collected.The mRNA expres-sion levels of miR-34a,β-catenin and PD-L1 in CC tissues and adjacent normal tissues were detected by fluo-rescence quantitative PCR and compared.The expression levels of β-catenin and PD-L1 in CC tissues and adja-cent normal tissues were detected by immunohistochemistry.Multivariate Logistic regression analysis was used to analyze the influencing factors of prognosis in CC patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of miR-34a,β-catenin and PD-L1 expression levels in CC pa-tients with poor prognosis.Results Compared with adjacent normal tissues,the expression level of miR-34a of the CC tissues was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).The positive expression rates of β-catenin and PD-L1 protein in CC tissues were higher than those of adjacent nor-mal tissues(89.16％vs.10.84％,78.31％vs.20.48％,x2=101.807,55.526,P＜0.05).There were no sig-nificant differences in age and body mass index(BMI)between the good prognosis group and the poor progno-sis group(t=1.508,1.820,both P＞0.05),while there were significant differences in International Federa-tion of Gynecology and Obstetrics(FIGO)stage and differentiation degree between the two groups(x2=8.451,9.115,both P＜0.05).Compared with the good prognosis group,the expression level of miR-34a of the poor prognosis group was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).Multivariate Logistic regression analysis showed that increased expression of miR-34a was an protective factor for poor prognosis in CC patients,while the increased expression levels of β-catenin and PD-L1,Ⅱ a and Ⅱ b FIGO staging and low differentiation were independent risk factors for poor prognosis in CC patients(P＜0.05).ROC curve analysis showed that miR-34a,β-catenin and PD-L1 all had certain predictive value for the poor prognosis of CC patient,and the area under the curve(AUC)of the single detection was 0.765,0.836 and 0.797,respectively.The AUC of the combined detection was 0.914(Z=2.631,2.331,2.571,P=0.009,0.020,0.010).Conclusion The expression levels of miR-34a,β-catenin and PD-L1 mRNA affect the prognosis of CC patients.Increased expression of miR-34a is an protective factor for poor prognosis in CC patients,in-creased β-catenin and PD-L1 expressions are independent risk factors for poor prognosis in CC patients,and all three factors can be used as biomarkers to predict poor prognosis in CC patients,and the combined detection of the three has the highest prognostic value.

Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl₄)-induced hepatic fibrosis mouse model in vivo. METHODS: For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl₄ (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot. RESULTS: EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl₄-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05). CONCLUSIONS EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.
Acetates ; Animals ; Autophagy ; Carbon Tetrachloride ; Hepatic Stellate Cells ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Ribosomal Protein S6 Kinases, 70-kDa ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

Objective:To investigate the therapeutic value of modified multipoint drainage for biliary complications after liver transplantation.Methods:A total of 125 patients treated by endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications after liver transplantation in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2018 to May 2020 were enrolled. Patients were divided into endoscopic retrograde biliary drainage (ERBD) group ( n=67, treated with multiple drainage of bile duct stent) and modified multipoint drainage group [ n=58, treated with ERBD combined with endoscopic nasobiliary drainage (ENBD)] by random number table. Modified multipoint drainage group were further randomly divided into two groups, modification group 1, 31 cases, where nasobiliary ducts were cut proximal to duodenal papilla after one week under endoscopy and modification group 2, 27 cases, where they were cut proximal to duodenal papilla after two weeks under endoscopy. The changes of serological indexes in 2 weeks after the operation in three groups were compared, and the incidence of short-term and long-term complications were analyzed. Results:The serological indexes were improved in patients at 1 d, 7 d and 14 d after ERCP, especially in modified multipoint drainage groups. Two weeks after the operation, the improvement of serological indexes in modification group 2 was better than that in modification group 1. Incidence of recent complications including cholangitis, hyperamylasinemia, and pancreatitis in the ERBD group were higher than those in modification group 1 [32.84% (22/67) VS 12.90% (4/31), 46.27% (31/67) VS 19.35% (6/31), 20.90% (14/67) VS 3.23% (1/31), all P<0.05] and modification group 2 [32.84% (22/67) VS 11.11% (3/27), 46.27% (31/67) VS 22.22% (6/27), 20.90% (14/67) VS 3.70% (1/27), all P<0.05]. ERBD group had a higher incidence of long-term complications including recurrent biliary infection and jaundice than modification group 1 [ 58.21% (39/67) VS 35.48% (11/31), P=0.036; 49.25% (33/67) VS 25.81% (8/31), P=0.027] and modification group 2 [58.21% (39/67) VS 11.11% (3/27), P<0.001; 49.25% (33/67) VS 25.93% (7/27), P=0.038]. The incidence of recurrent biliary infection in modification group 1 was higher than that in modification group 2 [35.48% (11/31) VS 11.11% (3/27), P=0.030]. Conclusion:Multiple drainage with indwelling nasal bile duct by ERCP can effectively reduce the short-term and long-term complications and improve the recovery of serological indexes for patients with biliary complications after liver transplantation. It is suggested that the nasobiliary duct should be retained for 2 weeks and then transformed into a built-in tube to continue drainage.

Objective: The objective of the study was to compare the effects of long-term and short-term embryo culture to assess whether there is a correlation between culture duration and clinical outcomes. Methods: Embryos were divided into two study groups depending on whether their post-warming culture period was long-term (20–24 hours) or short-term (2–4 hours). Embryo morphology was analyzed with a time-lapse monitoring device to estimate the appropriate timing and parameters for evaluating embryos with high implantation potency in both groups. Propensity score matching was performed to adjust the confounding factors across groups. The grades of embryos and blastoceles, morphokinetic parameters, implantation rate, and ongoing pregnancy rate were compared. Results: No significant differences were observed in the implantation rate or ongoing pregnancy rate between the two groups (56.3% vs. 67.9%, p=0.182; 47.3% vs. 53.6%, p=0.513). After warming, there were more expanded and hatching/hatched blastocysts in the long-term culture group than in the short-term culture group, but there was no significant between-group difference in embryo grade. Regarding pregnancy outcomes, the completion of re-expansion was faster in women who became pregnant than in those who did not for both culture durations (long-term: 2.19±0.63 vs. 4.11±0.81 hours, p=0.003; short-term: 1.17±0.29 vs. 1.94±0.76 hours, p=0.018, respectively). Conclusion The outcomes of short-term culture and long-term culture were not significantly different in vitrified-warmed blastocyst transfer. Regardless of the post-warming culture time, the degree of blastocyst re-expansion 3–4 hours after warming is an important marker for embryo selection.

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.
Clinical Protocols ; Clinical Trials as Topic ; Humans ; Medicine, Chinese Traditional ; Research Design

BACKGROUND/AIMS: This study was aimed to investigate the current clinical status of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in Korea based on a National Health Insurance (NHI) database between 2011 and 2014. METHODS: The claims data of ESD for EGC in Korean NHI were reviewed using material codes of Health Insurance Review and Assessment Service between November 2011 and December 2014. The current clinical status was analyzed in terms of treatment pattern, in-hospital length of stay (LOS), total medical costs, and en bloc resection rate according to the hospital type. RESULTS: A total of 23,828 cases of ESD for EGC were evaluated. ESD was performed in 67.4% of cases in tertiary care hospitals, 31.8% in general hospitals, and 0.8% in hospitals, respectively. The median LOS was 5 days, and total median medical costs was approximately 1,300 US dollars. En bloc resection rate was 99%; 8.5% of cases underwent additional treatment within 90 days ESD, and 5.5% in 91 to 365 days after ESD. The clinical status was not significantly different according to the year and hospital type. CONCLUSIONS A majority of ESD for EGC were performed in tertiary care hospitals in Korea. The clinical status showed excellent clinical outcomes and did not differ by the year and between the types of hospitals in Korea.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been regarded as a curative treatment for early gastric cancer (EGC) in indicated cases. The aim of this study was to evaluate the nationwide long-term clinical outcomes of ESD for EGC in Korea. METHODS: A prospective multicenter cohort study was performed to evaluate the long-term efficacy of ESD for EGC within pre-defined indications at 12 institutes in Korea. The cases that met the expanded criteria upon pathological review after ESD were followed for 5 years. The primary outcome was 5-year disease specific free survival. RESULTS: Six hundred ninety-seven patients with 722 EGCs treated with ESD were prospectively enrolled and followed for 5 years. Complete resection was achieved in 81.3% of the cases, and curative resection was achieved in 86.1%. During the 5-year follow-up, the overall survival rate was 96.6%, and the disease specific free survival rate was 90.6%. Local recurrence developed in 0.9%, and metachronous tumor development occurred in 7.8%; both conditions were treated by endoscopic or surgical treatment. Distant metastasis developed in 0.5% during follow-up. CONCLUSIONS: ESD showed excellent long-term clinical outcomes and can be accepted as a curative treatment for patients with EGC who meet the expanded criteria in final pathology studies.
Academies and Institutes ; Cohort Studies* ; Follow-Up Studies ; Humans ; Korea ; Neoplasm Metastasis ; Pathology ; Prospective Studies* ; Recurrence ; Stomach Neoplasms* ; Survival Rate