BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective Exploring the mechanisms of Sanwu Huangqin Decoction in the treatment of liver tumors based on network pharmacology and molecular docking technologies and experimental observations.Methods TCMSP database was used to screen the effective compounds contained in Sanwu Huangqin decoction,Drug bank,Pharm mapper,Uniport,PubMed and other databases were used to obtain the action targets of Sanwu Huangqin decoction,gene cards and TCGA databases were used to obtain the related targets of hepatocellular carcinoma,and the"drug-disease"target genes were obtained after the intersection with the action targets of Sanwu Huangqin decoction,and the protein interaction network was constructed using string database,David and KEGG databases were used for go and KEGG enrichment analysis,Cytoscape software was used to build the corresponding network,and discovery studios software was used for molecular docking to verify the above network pharmacology related results.The effects of Sanwu Huangqin decoction on the proliferation,the metastasis and the expression of IL-6 of cancer cells were observed.Results 81 effective components and 10 key components of Sanwu Huangqin decoction,249 targets,1420 differential targets between tumor samples and normal samples were obtained,and 59 overlapping targets were obtained.Frequency analysis of protein interaction network:the potential mechanism of Sanwu Huangqin Decoction in treating hepatocellular carcinoma is related to ESR1,Myc,Jun,IL-6,MMP9,EGF,etc.Through GO and KEGG enrichment analysis,IL-17 signaling pathway,TNF signaling pathway,Toll like receptor signaling pathway may play important roles.The results of molecular docking showed that acacetin,wogonin,baicalein,oroxylin a,beta sitosterol,8-isoopenenyl-kaempferol,formononetin,luteolin,quercetin,and stigmastrol bound to IL-6 protein,which further confirmed the above results.Animal experiments showed that Sanwu Huangqin decoction could inhibit the tumor size and the pulmonary metastasis,and the content of IL-6 in cancer cells was decreased,which preliminarily verified the anti-tumor effects and mechanism of Sanwu Huangqin decoction.Conclusion In this study,we found that IL-6 was the key target of Sanwu Huangqin decoction by network pharmacology and molecular docking technology.Sanwu Huangqin decoction could reduce the content of IL-6 in tumor tissues to inhibit liver cancer in vivo.These results provided a theoretical basis for the application of Sanwu Huangqin decoction in the treatment of liver cancer.

Objective To investigate the effects of long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) on the proliferation, migration, and angiogenesis of gastric cancer cells. Methods The expression levels of LncRNA TUG1 in gastric cancer tissues and adjacent non-cancerous tissues were analyzed based on public databases. The expression of lncRNA TUG1 in gastric cancer cell lines was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). SGC-7901 gastric cancer cells were transfected with si-TUG1 and si-NC, and the effects of knocking down lncRNA TUG1 on cell proliferation, colony formation, migration, and angiogenesis were analyzed using the Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Transwell assay, and Matrigel tube formation assay. The correlation between alkB homolog 5 (ALKBH5) gene and lncRNA TUG1 was analyzed based on public databases. The regulatory relationship between ALKBH5 and lncRNA TUG1 was verified using Actinomycin D experiments. The effects of knocking down ALKBH5 on the proliferation, colony formation, migration, and angiogenesis of gastric cancer cells were analyzed through cell function experiments. Results LncRNA TUG1 was up-regulated in gastric cancer tissues and cell lines. After knocking down lncRNA TUG1, the proliferation, colony formation, migration, and angiogenesis abilities of SGC-7901 cells were lower than those of control cells(P < 0.05). Database analysis results showed that ALKBH5 was positively correlated with lncRNA TUG1 expression in gastric cancer (r=0.37, P < 0.05). Compared with control cells, the RNA stability of lncRNA TUG1 in SGC-7901 cells with knocked-down ALKBH5 decreased, and the cell proliferation, colony formation, migration, and angiogenesis abilities were also reduced (P < 0.05). Conclusion ALKBH5 promotes the proliferation, colony formation, migration, and angiogenesis of gastric cancer cells by inducing the expression of lncRNA TUG1.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To investigate the efficacy and safety of posaconazole in the prevention of invasive pulmonary aspergillosis (IPA) in patients with liver failure treated with glucocorticoids (GC).Methods:The study was an observational study. Patients with early and middle stages of liver failure hospitalized in the Department of Infectious Diseases of Hebei Medical University Third Hospital, who received GC treatment between February 2016 and February 2022 were included. The patients were divided into trial group (with posaconazole suspension (200 mg each time, three times daily)) and control group (without posaconazole) according to whether posaconazole was used during treatment. Two groups of patients were matched of 1∶2 ratio according to age, gender and baseline model for end-stage liver disease (MELD) score. The basic information, laboratory examination results, adverse reactions of posaconazole, incidence of invasive Aspergillus infection and therapeutic effect of patients were collected. Statistical analysis was performed using the chi-square test, logistic regression analysis was used to screen risk factors for IPA, the receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the risk factors, Kaplan-Meier survival curves was used to analyze patient′s survival, and Log-rank test was used to compare the survival rates between the trial group and control group. Results:A total of 108 patients (36 in trial group and 72 in control group) were enrolled. There were no statistical differences between the two groups in terms of the etiology of liver diseases, baseline laboratory findings and risk factors for invasive Aspergillus infection (all P>0.05). There were 21 cases of IPA during hospitalization, with a total infection rate of 19.4%(21/108), including 5.6%(2/36) in the trial group and 26.4%(19/72) in the control group. The difference of IPA incidences between the two groups was statistically significant ( χ2=6.65, P=0.010). Logistic regression analysis suggested that elevated C-reactive protein, GC application more than seven days and cumulative dose of GC were independent risk factors for IPA in patients with liver failure treated with GC (odds ratio ( OR)=1.080, 15.266, 1.004, respectively, all P<0.05). The ROC curve showed that the cut-off value of C-reactive protein was 6.00 mg/L, and cumulative dose of GC was 490 mg. There were no statistical differences between the two groups in terms of adverse effects such as neutropenia, thrombocytopenia, gastrointestinal bleeding, nausea and vomiting rates (all P>0.05), and there were no patients with visual disturbances or discontinuation of medication. Cumulative deaths were 20(18.5%), and 88(81.5%) patients survived in this study. There were 11(52.4%) deaths among 21 patients with IPA and nine (10.3%) deaths among 87 patients without IPA. The difference of survival rates between patients who developed and did not develop IPA was statistically significant ( χ2=21.31, P<0.001). Conclusions:Posaconazole may be helpful in reducing the incidence of concurrent IPA morbidity in patients with liver failure treated with GC, thereby improving survival rates with few adverse effects.

A clinical data, laboratory examination, genetic test results, diagnose and treatment of a patient with 46, XY disorders of sexual development (46, XY DSD) from a family of the Asp-Glu-Ala-His-box helicase 37 ( DHX37) gene mutation were retrospectively analyzed.The child was admitted in the Department of Genetics, Endocrinology and Metabolism, Jiangxi Children′s Hospital in June 2021.The DHX37 gene mutation was confirmed as a new pathogenic gene leading to 46, XY DSD in 2019.It is featured as autosomal dominant inheritance with incomplete externality.Its clinical manifestations are abnormal external genitalia, testicular degeneration insufficiency syndrome and gonadal insufficiency.This patient is the first 46, XY DSD case caused by the heterozygous variation of DHX37 gene c. 2020C>T (p.R674W) in China.This study can provide new ideas for diagnosis and treatment of 46, XY DSD children and reliable genetic evidence for family reproduction.

Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.

Acute abdomen is often a general term for abdominal diseases with acute abdominal pain as the main manifestation. Common clinical acute abdomen includes acute appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, gastrointestinal perforation, intestinal obstruction and other diseases, its characteristics are great changes, rapid progress, high misdiagnosis rate, high postoperative complication rate and high mortality rate, accurate diagnosis and early treatment can obtain a good prognosis. With our in-depth understanding of the occurrence and development of acute abdomen diseases and the development of evidence-based medicine, minimally invasive technology plays a pivotal role in the diagnosis and treatment of common acute abdomen. Laparoscopy on diagnosis can clarify disease diagnosis to a large extent. For those who cannot undergo surgery, decompression and drainage under endoscopy provides a diversified plan for treatment decisions. In addition, minimally invasive techniques are also used in etiological treatment and complications. Disease, prevention of recurrence in all aspects, Minimally invasive technology is beneficial to the etiological treatment of biliary pancreatitis, appendicitis and cholangitis, and endoscopic technology is more consistent with the minimally invasive concept in the treatment of complications.