ObjectiveBased on the regulation of macrophage M2 polarization， this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis， thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl₄， followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining， the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry， the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β （TGF-β）， platelet derived growth factor subunit B （PDGFB）， interleukin-10 （IL-10）， phosphorylated Janus kinase 1 （p-JAK1）， and phosphorylated signal transducer and activator of transcription 6 （p-STAT6）. Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1， STAT6， Arginase 1（Arg1）， and Fizz1. Based on the theory of serum pharmacology， liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ， as well as collagen fiber content （P<0.05）. It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10， TGF-β and PDGFB， and up-regulated the levels of p-JAK1 and p-STAT6 （P<0.05）. A total of 1 214 compounds were identified from Qijia Rougan prescription， medicated serum and blank serum， and 29 ingredients were finalized by Venn analysis， including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1， with binding free energies of -9.6 kcal·mol^-1（1 cal≈4.184 J） and -9.1 kcal·mol^-1， respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns， with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol^-1 and -27.39 7.0.85 kcal·mol^-1， respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5， and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels （P<0.05）. ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway， thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization， clinical application and new drug development， as well as a reference for monolithic anti-hepatic fibrosis research.

OBJECTIVES: To elucidate the molecular mechanism by which villin-like protein VILL (VILL) inhibits proliferation of nasopharyngeal carcinoma (NPC) cells. METHODS: Co-immunoprecipitation (CO-IP) assay, mass spectrometry, Western blotting, immunofluorescence staining, and GST pull-down assay were employed to identify and confirm the protein interacting with VILL that had the highest abundance in NPC cell lines. Transgenic experiments were conducted in both NPC cell lines and nude mice to validate the regulatory role of VILL and its target protein in NPC proliferation. Immunohistochemistry was utilized to assess the correlation of the expression levels of VILL and its target protein in clinical tissue specimens of NPC with the clinical features of the patients. RESULTS: In NPC cell lines (HONE1 EBV and S18), VILL was found to interact most abundantly with the E3 ubiquitin ligase LMO7, and both proteins co-localized in the cytoplasm with direct interactions. Overexpression of LMO7 partially counteracted the inhibitory effect of VILL on NPC cell proliferation. The expression of VILL was significantly downregulated in 136 NPC tissue samples compared to 67 non-cancerous nasopharyngeal tissues (P<0.00001) with close correlation with clinical T stage (P=0.04), N stage (P=0.01), and M stage (P=0.013), whereas LMO7 was highly expressed in all the NPC tissues. CONCLUSIONS VILL overexpression inhibits NPC proliferation probably by suppressing the oncogenic function of LMO7.
Nasopharyngeal Neoplasms/metabolism* ; Humans ; LIM Domain Proteins/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Animals ; Mice ; Nasopharyngeal Carcinoma ; Mice, Nude ; Transcription Factors/metabolism* ; Carcinoma ; Female ; Microfilament Proteins/genetics* ; Male ; Middle Aged

This study was aimed at investigating infections with Giardia and Cryptosporidium in Ochotona curzoniae in Zoige County,Sichuan Province.O.curzoniae were captured in five townships of Zoige County(Dazhasi,Axi,Hongxing,Tangke,and Maixi)between March and December of 2023.DNA from the gastrointestinal contents was subjected to nested PCR to amplify Giardia bg,gdh,and tpi genes,and the Cryptosporidium SSU rRNA gene.The sequences of PCR-PCR products were analyzed and compared.Phylogenetic trees were constructed to determine the protozoa species and genotypes.A total of 114 O.curzoniae animals were captured,among which 44 samples showed bg gene positivity,and 14 samples showed gdh gene positivity for Giardia.The total detection rate was 43.9％(50/114),and two assemblages were detected(assem-blage E and a new assemblage tentatively termed assemblage OC1);the positivity rate for Cryptosporidium was 7.0％(8/114),and three new genotypes were observed.Mixed infection with Cryptosporidium and Giardia was present in some sam-ples,with a detection rate of 3.5％(4/114).Giardia lamblia and Giardia sp.(REG-1,REG-2)were prevalent in O.curzoni-ae in Zoige County in Sichuan province;assemblage E was the dominant assemblage,and the new assemblage OC1 was pres-ent;and Cryptosporidium sp.(REG-1,REG-2,and REG-3)were identified.In summary,future monitoring of Giardia and Cryptosporidium should be further strengthened in Zoige to provide detailed data for promoting local public health.

This study was aimed at investigating infections with Giardia and Cryptosporidium in Ochotona curzoniae in Zoige County,Sichuan Province.O.curzoniae were captured in five townships of Zoige County(Dazhasi,Axi,Hongxing,Tangke,and Maixi)between March and December of 2023.DNA from the gastrointestinal contents was subjected to nested PCR to amplify Giardia bg,gdh,and tpi genes,and the Cryptosporidium SSU rRNA gene.The sequences of PCR-PCR products were analyzed and compared.Phylogenetic trees were constructed to determine the protozoa species and genotypes.A total of 114 O.curzoniae animals were captured,among which 44 samples showed bg gene positivity,and 14 samples showed gdh gene positivity for Giardia.The total detection rate was 43.9％(50/114),and two assemblages were detected(assem-blage E and a new assemblage tentatively termed assemblage OC1);the positivity rate for Cryptosporidium was 7.0％(8/114),and three new genotypes were observed.Mixed infection with Cryptosporidium and Giardia was present in some sam-ples,with a detection rate of 3.5％(4/114).Giardia lamblia and Giardia sp.(REG-1,REG-2)were prevalent in O.curzoni-ae in Zoige County in Sichuan province;assemblage E was the dominant assemblage,and the new assemblage OC1 was pres-ent;and Cryptosporidium sp.(REG-1,REG-2,and REG-3)were identified.In summary,future monitoring of Giardia and Cryptosporidium should be further strengthened in Zoige to provide detailed data for promoting local public health.

Splicing factors(SFs)are a type of protein that serves as an integral component of the dynamic spliceosome complex. The spliceosome, similar to “scissors”, has the ability to accurately process precursor RNA(pre-mRNA)in eukaryotes and generate a diverse range of mRNA sequences. This process is important for gene regulation and protein expression. Pre-mRNA processing factor 31(PRPF31)is a widely expressed SFs in various biological tissues. However, mutations in PRPF31 are specifically linked to the development of autosomal dominant retinitis pigmentosa(adRP), known as PRPF31-RP. Currently, the pathogenesis of PRPF31-RP is still unclear. This article reviews the research progress on the molecular mechanism of PRPF31 in the development of adRP and the progress in PRPF31-RP treatment from the perspective of tissue damage and impairment of biological processes caused by PRPF31 mutation or deletion, in order to provide new ideas on the pathogenesis and treatment of PRPF31-RP.

Objective:To evaluate the effects of intensive intervention on negative spouses in sero-discordant couples.Methods:From December 2019 to December 2020, all HIV sero-discordant couples in seven townships in Butuo County of Liangshan were enrolled and divided into intensive intervention group and routine intervention group. Both intensive intervention and routine intervention were conducted for one year. Baseline survey and follow-up were conducted respectively with a questionnaire survey and a serological testing in HIV sero-discordant couples in the two groups at 6 th month before and after the interventions. Multivariable Cox proportional hazards model and difference-in-difference model were used to evaluate the effect of the intensive intervention. Results:A total of 899 sero-discordant couples were enrolled (393 of intensive intervention group and 506 of routine intervention group), in whom 806 completed the follow up survey (349 of intensive intervention group and 457 of routine intervention group). Compared with routine intervention, intensive intervention had no effect to improve the correct answer rate of an AIDS related question in negative spouses ( P>0.05), but could improve their awareness of AIDS related knowledge ( β=1.40, P=0.008). Compared with routine intervention, intensive intervention could reduce the frequency of sex between HIV sero-discordant couples ( β=-0.73, P=0.021), and increase the frequency of condom use ( β=0.19, P=0.007), but had no effect to decrease the positive conversion rate in negative spouses ( β=-0.61, OR=0.55,95% CI:0.18-1.66, P=0.294). Conclusions:The intensive interventions could improve the awareness of AIDS related knowledge in negative spouses in sero-disordant couples and promote their safe sexual behavior, but had no effect to decrease the positive conversion in negative spouses. It is necessary to continue the intensive intervention and follow up to evaluate the effects of the intervention.

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4⁺T lymphocytes (CD4) counts >500 cells/μl (compared with having recent CD4 counts <200 cells/μl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adolescent ; Adult ; Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; HIV Infections/epidemiology* ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Marriage ; Young Adult

Objective:To investigate the anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics of patients with warfarin-related major bleeding in the emergency department of a general hospital.Methods:In a registry study from January 2017 to February 2020, 114 cases of warfarin-related major bleeding patients admitted to Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University were enrolled. The descriptive methods were used to analyze anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics. Patients were divided into the international normalized ratio (INR) overrange group and the INR non-overrange group according to INR value during bleeding. The Chi-square test, Student’s t test, and Wilcoxon rank sum test were used to compare the differences between the INR overrange group and the INR non-overrange group. The Wilcoxon rank sum test and Student’s t test were used to analyze the characteristics of gastrointestinal tract bleeding and cerebral hemorrhage. Results:Warfarin-related major bleeding accounted for 0.36% (114/32 040) of first aid cases and 9.84% (114/1 158) of warfarin-taking cases, respectively. Seventy-seven cases (67.5%) of anticoagulant causes were related to atrial fibrillation (AF) and 32 cases (28.1%) were related to post-operative cardiac valve replacement. Of the bleeding susceptibility factors, HAS-BLED scored at 4.0 (3.0, 5.0), 84 cases (73.7%) had a history of drug use, 77 cases (67.5%) aged older than 65 years old, 65 cases (57.0%) had irregular INR monitoring, and 29 cases (25.4%) had recent increase in dose. Forty cases (35.1%) were gastrointestinal tract bleeding with the lowest hemoglobin (Hb) value and the highest score of HAS-BLED. Twenty-one cases (18.4%) were cerebral hemorrhage with the shortest prothrombin time (PT), the lowest INR value, the highest Hb, and the lowest score of HAS-BLED. Twelve cases (10.5%) died or gave up treatment in critical condition, including 6 cases of cerebral hemorrhage, 5 cases of gastrointestinal tract bleeding, and 1 case of hemoptysis. There were statistically significant differences in previous history of antiplatelet therapy, recent increase in dose, HAS-BLED score and bleeding site between the INR overrange group and the INR non-overrange group (all P<0.05). Conclusions:Among patients with warfarin-related major bleeding, AF and post-operative cardiac valve replacement are the main causes of warfarin anticoagulation. INR overrange is related to the previous history of antiplatelet therapy, recent increase in dose, and the high score of HAS-BLED. The gastrointestinal tract bleeding is the most common, with the lowest Hb value and the highest score of HAS-BLED. Cerebral hemorrhage is the second common, with the shortest PT, the lowest INR value, and the highest Hb. The incidence and mortality rates of warfarin-related major bleeding are relatively high.

Objective:To investigate and compare the therapeutic effect of Foley catheter balloon dilation and the traditional open reduction in the treatment of intussusception in children.Methods:A total of 68 children with intussusception treated by Foley catheter balloon dilatation by laparoscopic surgery or traditional open reduction in Department of Pediatric Surgery, the Second Hospital of Lanzhou University from August 2015 to July 2019 were retrospectively analyzed.Among them, there were 32 cases in the Foley catheter group and 36 cases in the traditional laparotomy group.Foley catheter group were treated with laparoscopic Foley catheter balloon dilatation, while the traditional open group were treated with traditional open surgery which was performed with finger dilatation.The results of surgical treatment, postoperative recovery, short-term complications, patient satisfaction and long-term complications were compared between the two groups.Results:Among the indexes of surgical treatment effect, the operation time[(0.4±1.1) h], intraoperative bleeding volume[(10.2±3.4) mL], incision size[(0.5±0.4) cm] and incidence of the rupture of intestine[6.3%(2/32 cases)] in the Foley catheter group were significantly lower than those in the traditional open group[(1.3±2.9) h, (40.5±2.1) mL, (5.1±0.7) cm, 30.6%(11/36 cases)], and the differences were statistically significant (all P< 0.05). Among the indexes of postoperative recovery and short-term complications, recovery time of gastrointestinal function[(1.2±3.1) d], length of hospital stay[(6.7±1.8) d], incidence of incision infection[9.4%(3/32 cases)]and incidence of incisional hernia(0) in the Foley catheter group were significantly lower than those in the traditional open group[(3.3±6.4) d, (7.3±0.9) d, 36.1%(13/36 cases), 16.7%(6/36 cases)], and the differences were statistically significant (all P<0.05). Among the indexes of family satisfaction and long-term complications, the score of family satisfaction in the Foley catheter group [(8.7±1.2) scores]was significantly higher than that in the traditional open group[(6.6±3.1) scores], and the incidence of adhesive intestinal obst-ructionin the Foley catheter group (0)was significantly lower than that in the traditional open group[0 vs.19.4%(7/36例)], and the differences were statistically significant(all P<0.05). Conclusions:Compared with traditional open reduction in the treatment of intussusception in children, Foley catheter balloon dilation has the advantages of short operation time, safe operation, low incidence of intestinal injury, less bleeding, and so on, and also has the advantages of small incision, fast recovery, short hospitalization time, high satisfaction of parents.In addition, the Foley catheter balloon dilation has a lower incidence of incisional infection, incisional hernia, postoperative intestinal adhesion and other complications.

The anoikis resistance confers the ability of cancer cells to survive and metastasize in the blood circulation without adhesion,but its effect and mechanism in intrahepatic and distant metastasis of hepatocellular carcinoma has not been fully elucidated.Recent studies have shown that certain factors or drugs may inhibit anoikis of hepatoma cells through some signaling pathways.These signaling pathways are not completely separated,they are interconnected to promote metastasis of hepatocellular carcinoma.Liver is the metabolic center of many substances,and many related factors can promote metastasis of hepatocellular carcinoma through inhibiting anoikis.In this review,we summarized the signaling pathways of anoikis resistance of hepatocellular carcinoma.