Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Primary intrahepatic stones(PIS)is a refractory disease with a high incidence rate in Southwest China,which greatly affects the life of patients.Metabolites,such as β-glucuronidase produced by chronic biliary tract infection,play an important role in the formation of pigmented stones.In addition to exogenous β-glucuronidase produced by bacteria,endogenous β-glucuronidase produced by intrahepatic bile duct cells also plays an important role in the formation of stones.This article analyzes the research advances in the role of β-glucuronidase in the pathogenesis of PIS,in order to provide a possible method for the prevention and treatment of PIS.

Objective:To analyze the clinical efficacy of arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip.Methods:A total of 30 patients (12 males and 18 females) with bilateral external snapping hip underwent arthroscopic transverse release of the iliotibial band through peritrochanteric space in Department of Sports Medicine, Senior Department of Orthopaedics, the Fourth Medical Center, Chinese PLA General Hospital were retrospectively analyzed from May 2021 and June 2022. The average age was 32.5±8.2 years (range, 17-51 years). At the same time, 30 patients who underwent arthroscopic external release of the iliotibial band through the external surface of the iliotibial band (external iliotibial band group) were selected as control group, including 13 males and 17 females, aged 29.5±6.8 years (range, 11-45 years). The visual analogue scale (VAS), modified Harris hip score (mHHS), and gluteal muscle contracture disability scale (GDS) were compared between the two groups at preoperative, 6 months postoperative, and final follow-up.Results:All patients successfully completed the operation and were followed up for 17.5±3.3 months (range, 12-25 months). The VAS scores of the two groups at the last follow-up were lower than those before operation ( P<0.05). The mHHS scores before operation, 6 months after operation and at the last follow-up in the peritrochanteric space group were 76.5 (67.0, 85.5), 98.5 (94.8, 100.0) and 100.0 (97.0, 100.0), respectively, and those in the external iliotibial band group were 80.5 (70.0, 86.0), 100.0 (96.0, 100.0) and 100.0 (99.5, 100.0). The differences in mHHS scores between the two groups were statistically significant for intragroup comparisons ( P<0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in mHHS scores between groups at different time points ( P>0.05). The GDS before operation, at 6 months after operation and at the last follow-up were 47.0 (35.8, 64.5), 90.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the peritrochanteric space group, and 51.0 (38.0, 64.5), 50.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the external iliotibial band group, respectively. The differences in GDS between the two groups were statistically significant for intragroup comparisons ( P< 0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in GDS between groups at different time points ( P>0.05). Conclusion:Arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip can effectively reduce hip pain and improve hip function, with satisfactory clinical results, and can be used as an alternative treatment to transverse release through the external surface of the iliotibial band.

[Purpose]To analyze the compliance and influencing factors of endoscopic screening in high-risk population of upper gastrointestinal cancer(UGC)in Chongqing Municipality.[Methods]Risk assessment of UGC was conducted among residents aged 40～74 years old in the areas covered by the Chongqing Urban Cancer Early Diagnosis and Treatment Program from 2012 to 2019.The residents with high risk of UGC were advised to receive free endoscopic screening in designated hospitals.The compliance and influencing factors of endoscopic screening among high-risk sub-jects were analyzed.[Results]There were 266 611 residents who completed the questionnaires and UGC risk assessment,among whom 48 000(18.00％)were assessed as high risk.A total of 9 162 high-risk individuals received the following endoscopic screening with a compliance rate of 19.09％.Multivariate Logistic regression analysis showed that residents aged 45～64 years old,with high school or above education,divorced or widowed status,occupational exposure to haza-rdous substances,hot food preference,high fat diet,frequent consumption of pickled and dried food,exposure to kitchen fume,psychic trauma or depression,upper gastrointestinal disease his-tory and family history of UGC were likely to accept endoscopic screening;while those aged 70 years old and above,current smokers,and having regular physical exercise were likely to have low compliance.[Conclusion]Among high-risk residents of UGC in Chongqing,the compliance to endoscopic screening needs be improved,health education and management should be targeted to those likely to have low compliance.

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC₅₀ value of 12.88 ± 0.11 μmol·L^-1.
Humans ; Polycyclic Sesquiterpenes ; Sesquiterpenes/chemistry* ; Aspergillus/chemistry* ; Magnetic Resonance Spectroscopy ; Molecular Structure

Objective To investigate the effect of upstream transcription factor 2 (USF2) on the proliferation and apoptosis of human gastric cancer BGC-823 cells. Methods Lipofectamine?3000 transfection reagent was used to transfect USF2 siRNA into BGC-823 cells (siRNA-USF2 group). Blank control and negative control (siRNA-NC) groups were also prepared. The mRNA and protein expression levels of USF2 in transfected BGC-823 cells were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The proliferation and clone formation abilities of BGC-823 cells in each group were investigated by CCK-8 and plate cloning assay. The apoptosis of gastric cancer cells was examined by flow cytometry. The expression levels of PCNA and apoptosis-related proteins Bax and Bcl-2 in BGC-823 cells were measured by Western blot. Results Compared with those in the blank control and siRNA-NC groups, the mRNA and protein expression levels of USF2 significantly decreased in the siRNA-USF2 group (P < 0.05). At 72 h after transfection, the absorbance in the siRNA-USF2 group was lower than that in the blank control group (P < 0.05). Compared with that in the blank control and siRNA-NC groups, the number of BGC-823 cell clones significantly decreased in the siRNA-USF2 group (P < 0.05). The apoptosis rate of BGC-823 cells significantly differed among the blank control, siRNA-NC, and siRNA-USF2 groups (P < 0.05). Compared with those in the blank control and siRNA-NC groups, the expression of PCNA and Bcl-2 protein decreased and that of Bax protein increased in the siRNA-USF2 group (P < 0.05). Conclusion Inhibiting USF2 expression can suppress the proliferation of human gastric cancer cells and induce their apoptosis. USF2 inhibitors may have important value in the treatment of gastric cancer.

Modular scientific research teaching is an open teaching mode for undergraduates in medical colleges and universities. Under the premise of students' own choice, the lab-based training was performed for 15 teaching weeks, with three modular scientific research courses. Meanwhile, with the help of a series of scientific research lectures, literature reports, and discussions of experimental results, the teachers guided the students to carry out modular scientific research training and taught related theoretical knowledge during experimental teaching. The modular scientific research teaching for undergraduates in medical colleges and universities helps to enhance their knowledge of life science and basic medical knowledge, cultivate basic experimental abilities, and make them fully prepared for clinical research or postgraduate study.

Objective To evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitor,linagliptin,in subjects aged 60 years or older with type 2 diabetes mellitus (T2DM).Methods Data from eight 24-week,multinational,multicenter,randomized,double-blind,placebo-controlled,parallel-group studies were analyzed.Patients aged 60 years or older with T2DM were received oral linagliptin (5 mg/d) or placebo in combination with mefformin,or metformin plus sulfonylurea.Efficacy was assessed by the changes in glycosylated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) from baseline to 24 weeks of treatment.Safety endpoint included the frequency and intensity of adverse events.Results A total of 1 421 patients (placebo 429,linagliptin 992) were included in the full analysis set (FAS).Mean ages of the subjects were (67.4 ± 5.6) years in the linagliptin group and (66.7-± 5.6) years in the placebo group.Baseline HbA1c was (8.0 ±0.8) ％ in the linagliptin group and (8.1 ±0.9) ％ in the placebo group.At the end of 24-week,placebo-adjusted reduction in HbAlc in subjects with linagliptin was (0.7 ±0.1)％ (95％ CI 0.6-0.8,P ＜0.000 1),and placebo-adjusted reduction in FPG in subjects with linagliptin was (0.88 ±0.12) mmol/L(95％ CI 0.65-1.11,P ＜0.000 1).Overall safety and tolerability in the two groups were similar.Adverse events occurred in 57.1％ of patients in the placebo group and 61.1％ of patients in the linagliptin group,and the incidence of adverse events leading to discontinuation was 3.2％ in the placebo group and 3.8％ in the linagliptin group.Serious adverse events occurred in 1.6％ of patients in the placebo group and 2.8％ of patients in the linagliptin group.Investigator-defined hypoglycaemia occurred in 7.3％ of patients in the placebo group and 11.9％ of patients in the linagliptin group.Among them,most were mild or moderate hypoglycaemia,and severe hypoglycaemia only occurred in 0.2％ of patients in the placebo and 0.5％ in the linagliptin groups.Overall incidence of hypoglycaemia in linagliptin group was slightly higher than that in placebo group,which might be due to the fact that more patients were taking sulfonylureas in linagliptin group than in placebo group (26.8％ linagliptin;18.4％ placebo).No difference could be viewed in hypoglycaemia between the two groups in patients without sulfonylureas (1.2％ linagliptin,1.1％ placebo)Moreover,no severe hypoglycaemia was reported in subjects without sulfonylureas.The incidences of other adverse events were similar in both groups.Conclusion Linagliptin was efficacious in lowering glucose with a safety profile similar to placebo in type 2 diabetic patients aged 60 years or older.

Child ; Diagnostic Errors ; Foreign Bodies ; diagnosis ; Humans ; Trachea ; Tracheal Stenosis ; diagnosis

To investigate the chemical constituents of the endophytic fungus Penicillium sp. FJ-1 of Ceriops tagal, the chemical constituents were isolated by column chromatography on silica gel and Sephadex LH-20. Their structures were elucidated on the basis of spectroscopic analysis. Their antibacterial activity was tested by paper disco diffusion method. Two compounds were isolated and identified as 7-hydroxy-deoxytalaroflavone (1), and deoxytalaroflavone (2). Compound 1 is a new compound, and compounds 1 and 2 showed weak activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.