Objective To compare the serological and pathological characteristics of 3 nonalcoholic steatohepatitis(NASH)models:high-fat diet(HFD)with carbon tetrachloride(CCl4)injection,methionine and choline deficient diet(MCD),and Aymlin liver NASH(AMLN)diet-induced NASH models.Methods 3 NASH models were established by feeding mice an HFD with CCl4 injection for 10 weeks,MCD for 8 weeks and NASH for 26 weeks.After feeding,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glucose(GLU),liver triglyceride(TG),total cholesterol(TC),and malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were measured.Insulin levels were measured by enzyme-linked immunosorbent assay(ELISA)and the homeostasis model assessment of insulin resistant(HOMA-IR)index was calculated.Hematoxylin-eosin(HE),Sirius red,and oil red staining were used to indicate pathological changes to the liver.The NAS score was used to grade the pathology.Results Compared to each normal control(NC)group mice,all mice in the 3 model groups had an obvious increase in serum transaminase and liver TG,TC,MDA levels and SOD activity.The levels of serum FINS,GLU and the HOMA-IR index were significantly increased in the AMLN and CCl4+HFD model groups but decreased in the MCD model group.According to the HE,oil red staining and NAS score,mice in all 3 groups had NASH phenotypic changes.Liver collagen deposition was most obvious in mice in theCCl4+HFD model group.Liver lipid droplets were most abundant in the AMLN model group.Conclusions All the above 3 animal models can stably simulate the serological and pathological changes of NASH in human.The AMLN model can simulate the progress and mechanism of the disease,as well as systemic metabolic disorders such as insulin resistance and oxidative stress.However,it is time-consuming and the fibrosis progression rate is slow.The MCD diet can simulate the serological and pathological features of NASH in 8 weeks,but no obesity or insulin resistance occurred.The CCl4 combined with HFD model can induce NASH model in 10 weeks,which can simulate its serological and pathological changes,and the liver has obvious fibrous deposition and oxidative stress damage.

Objective To investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

Objective To compare the serological and pathological characteristics of 3 nonalcoholic steatohepatitis(NASH)models:high-fat diet(HFD)with carbon tetrachloride(CCl4)injection,methionine and choline deficient diet(MCD),and Aymlin liver NASH(AMLN)diet-induced NASH models.Methods 3 NASH models were established by feeding mice an HFD with CCl4 injection for 10 weeks,MCD for 8 weeks and NASH for 26 weeks.After feeding,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glucose(GLU),liver triglyceride(TG),total cholesterol(TC),and malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were measured.Insulin levels were measured by enzyme-linked immunosorbent assay(ELISA)and the homeostasis model assessment of insulin resistant(HOMA-IR)index was calculated.Hematoxylin-eosin(HE),Sirius red,and oil red staining were used to indicate pathological changes to the liver.The NAS score was used to grade the pathology.Results Compared to each normal control(NC)group mice,all mice in the 3 model groups had an obvious increase in serum transaminase and liver TG,TC,MDA levels and SOD activity.The levels of serum FINS,GLU and the HOMA-IR index were significantly increased in the AMLN and CCl4+HFD model groups but decreased in the MCD model group.According to the HE,oil red staining and NAS score,mice in all 3 groups had NASH phenotypic changes.Liver collagen deposition was most obvious in mice in theCCl4+HFD model group.Liver lipid droplets were most abundant in the AMLN model group.Conclusions All the above 3 animal models can stably simulate the serological and pathological changes of NASH in human.The AMLN model can simulate the progress and mechanism of the disease,as well as systemic metabolic disorders such as insulin resistance and oxidative stress.However,it is time-consuming and the fibrosis progression rate is slow.The MCD diet can simulate the serological and pathological features of NASH in 8 weeks,but no obesity or insulin resistance occurred.The CCl4 combined with HFD model can induce NASH model in 10 weeks,which can simulate its serological and pathological changes,and the liver has obvious fibrous deposition and oxidative stress damage.

Objective To investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

Objective To investigate the effects of cultured mycelium Cordyceps sinensis(CMCS)on the AMPK/SirT1 signaling pathway in carbon tetrachloride(CCl4)-induced liver fibrosis in mice.Methods Forty male SPF-grade C57BL/6 mice were divided randomly into a normal control group,CMCS control group(3.0 g/kg),model control group,CMCS1.5 g/kg group,and CMCS 3.0 g/kg group.Mice were injected intraperitoneally with 10%CCl4(2 mL/kg)to induce liver fibrosis.Two weeks later,serum levels of alanine transaminase(ALT),aspartate transaminase(AST),and total bilirubin(TBil)were measured.Inflammation and collagen deposition in liver tissue were observed by hematoxylin and eosin(HE)and Sirius red staining,respectively.The content of hydroxyproline in liver tissue was detected by Jamall's hydrochloric acid hydrolysis method.Levels of interleukin(IL)-6,monocyte chemoattractant protein-1(MCP-1),interferon,tumor necrosis factor(TNF),IL-10,and IL-12p70 in liver tissue were detected using a cytometric bead array analysis system.Collagen Ⅰ and SirT1 expression in liver tissue were detected by immunohisotochemistry,and Prkaa1,Prkaa2,Lkb1,and p53 gene expression were detected by real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction.Results Serum levels of ALT,AST,and TBil were significantly increased in the model control group compared with those in the normal control group(P＜0.05).HE and Sirius red staining showed extensive inflammatory cell infiltration and collagen deposition in the liver,respectively.Hydroxyproline content and expression levels of IL-6,MCP-1,and TNF in the liver were significantly increased(P＜0.05),while IL-10 and IL-12p70 levels were significantly decreased(P＜0.01).Immunohistochemical staining revealed an increase in Collagen Ⅰ expression and SirT1 staining was decreased in the hepatic sinusoidal space,while collagen deposition was increased.Prkaa1,Prkaa2,and Lkb1 gene expression levels were decreased and p53 was increased in liver tissue(P＜0.05).CMCS significantly reduced serum ALT and AST levels,decreased IL-6,MCP-1,and TNF expression in liver tissue(P＜0.05),up-regulated IL-10 and IL-12p70(P＜0.05),alleviated liver inflammation,collagen deposition,and hydroxyproline content,up-regulated the expression of SirT1 in the hepatic sinusoidal space,enhanced Prkaa1,Prkaa2,and Lkb1 expression(P＜0.05),and down-regulated Collagen Ⅰ and p53(P＜0.05)in the liver.Compared with CMCS 1.5 g/kg,CMCS 3.0 g/kg significantly inhibited liver inflammation and collagen deposition and up-regulated AMPK/SirT1 expression(P＜0.05).Conclusions CMCS could improve CCl4-induced liver fibrosis via up-regulation of the AMPK/SirT1 signaling pathway.

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Background:Doxycycline can be used in the eradication of Helicobacter pylori(Hp)infection,but there is a lack of large sample study to confirm its efficacy and safety.Aims:To explore the efficacy and safety of doxycycline in the eradication of Hp infection.Methods:Literatures on doxycycline and other antibiotics in the eradication of Hp infection were retrieved from CNKI,Wanfang data,VIP,PubMed,Embase,Web of Science,and Cochrane Library from the date of database establishment to October 2023.Meta-analysis was conducted by RevMan 5.3 software.Results:Nineteen literatures including 3 686 patients with Hp infection were enrolled.Both intention-to-treat(ITT)eradication rate(82.51%vs.73.65%;OR=1.72,95%CI:1.42-2.07,P<0.000 01)and per-protocol(PP)eradication rate(88.96%vs.78.06%;OR=1.63,95%CI:1.28-2.06,P<0.000 1)of doxycycline-based regimen were significantly higher than those of non-doxycycline regimens.The adverse reaction rate of doxycycline-based regimen was significantly lower than that of non-doxycycline regimens(8.35%vs.15.01%;OR=0.55,95%CI:0.42-0.71,P<0.000 01).Subgroup analysis showed that Hp eradication rate of doxycycline-based regimen was significantly higher than that of clarithromycin-based regimen(OR=2.67,95%CI:1.84-3.88,P<0.000 01)and levofloxacin-based regimen(OR=2.20,95%CI:1.50-3.22,P<0.000 1),however,no significant difference in Hp eradication rate was found between doxycycline-based regimen and amoxicillin-based regimen(OR=1.09,95%CI:0.78-1.52,P=0.61)and tetracycline-based regimen(OR=0.87,95%CI:0.33-2.26,P=0.77).Conclusions:The eradication rate of doxycycline-based regimen in the eradication of Hp is significantly higher than that of non-doxycycline regimens,and the adverse reaction rate is low,which is worthy of clinical application.

Due to the diverse application forms of Chinese herbal medicine products,the wide range of users,and the complex conditions of medication in China,adverse events including herb-induced liver injury(HILI)occur frequently in recent years.In order to further understand HILI and standardize its risk management and prevention and treatment measures,this article discusses the risk management,clinical evaluation,prevention,and treatment of HILI based on related clinical research advances and experience in recent years.In the multiple links of traditional Chinese medicine including production and clinical application after marketing,the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events,involving product quality control,patient safety education,rational drug use by clinicians,regular monitoring,and graded and classified treatment,which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future.

Purpose: Recently, totally laparoscopic gastrectomy has been gradually accepted by surgeons worldwide for gastric cancer treatment. Complete dissection of the lymph nodes and the establishment of the surgical margin are the most important considerations for curative gastric cancer surgery. Previous studies have demonstrated that indocyanine green (ICG)-traced laparoscopic gastrectomy significantly improves the completeness of lymph node dissection. However, it remains difficult to identify the tumor location intraoperatively for gastric cancers that are staged ≤T3. Here, we investigated the feasibility of ICG fluorescence for lymph node mapping and tumor localization during totally laparoscopic distal gastrectomy. Materials and Methods: Preoperative and perioperative data from consecutive patients with gastric cancer who underwent a totally laparoscopic distal gastrectomy were collected and analyzed. The patients were categorized into the ICG (n=61) or the non-ICG (n=75) group based on whether preoperative endoscopic mucosal ICG injection was performed. Results: The ICG group had a shorter operation time and less intraoperative blood loss.Moreover, significantly more lymph nodes were harvested in the ICG group than the non-ICG group. No pathologically positive margin was found and there was no significant difference in either the proximal or distal surgical margins between the 2 groups. Conclusions Near-infrared fluorescence imaging with ICG can be successfully used in totally laparoscopic distal gastrectomy, and it contributes to both the completeness of D2 lymph node dissection and confirmation of the gastric transection line. Well-designed prospective randomized studies are needed in the future to fully validate our findings.

OBJECTIVE: To investigate the risk factors of postoperative pulmonary infection (PPI) in patients over 60 years of age with gastric cancer after radical gastrectomy. METHODS: Clinicopathological data of 373 patients over 60 years of age who underwent radical gastrectomy at Department IV of Gastrointestinal Cancer Center, Peking University Cancer Hospital, from April 2009 to December 2016 were retrospectively collected in this case-control study. The clinicopathological characteristics of patients with postoperative pulmonary infection (including postoperative atelectasis) and those without pulmonary infection were compared. A Student t-test (reported as Mean±SD if data matching normal distribution) or Mann-Whitney U test [reported as median (quartile) if data did not conform to normal distribution] was used to analyze continuous variables. A χ² test or Fisher exact tests (reported as number and percentage) was used for categorical variables. Multivariable logistic regression was used to analyze the risk factors for pulmonary infection after operation of gastric cancer.PPI was defined as postoperative patients with elevated body temperature (>38.0 degrees centigrade) for more than 24 hours; cough and expectoration; positive sputum bacteria culture;recent infiltration, consolidation or atelectasis confirmed by chest imaging examination. RESULTS: Among 373 patients, 50 cases had PPI(13.4%, PPI group), 323 cases had no PPI(86.6%, non-PPI group). There were 39 (78.0%) and 178(55.1%) patients with comorbidities (including hypertension, diabetes and cardiopulmonary disease) preoperatively in PPI and non-PPI group, respectively. The difference between two groups was statistically significant (χ²=9.325,P=0.002). The incidence of preoperative hypoalbuminemia in PPI group was also significantly higher than that in non-PPI group [10.0%(5/50) vs. 3.1% (10/323),χ²=4.098, P=0.048]. Compared to non-PPI group, the rate of total gastrectomy [54.0%(27/50) vs. 34.4% (111/323), χ²=12.501, P=0.002], postoperative wound pain [34.0%(17/50) vs. 11.8% (38/323),χ²=16.928, P<0.001], secondary operation [6.0%(3/50) vs. 0.6% (2/323), χ²=6.032, P=0.014] and the rate of gastric tube removal later than 7 days postoperatively [96.0%(48/50) vs. 84.5%(273/323),χ²=4.811, P=0.028] were significantly higher in PPI group, respectively. The postoperative hospital stay was also prolonged in PPI group [16.0(9.5) days vs. 12.0(5.0) days, U=4 275.0, P<0.001]. Multivariate logistic regression analysis showed that preoperative comorbidities (OR=4.008, 95%CI:1.768-9.086, P=0.001), abdominal infection (OR=3.164, 95%CI:1.075-9.313, P=0.037), and wound pain (OR=3.428, 95%CI:1.557-7.548, P=0.002) were independent risk factors for PPI in patients over 60 years of age with gastric cancer. Furthermore, 50 patients with pulmonary infection were classified according to the length of latency and the type of infection. The patients with PPI latency ≤ 3 days were classified as early onset (34 cases, 68.0%), and those with latency ≥ 4 days as delayed onset (16 cases, 32.0%); PPI combined with surgical infection (including anastomotic leakage, abdominal infection, duodenal stump leakage, wound infection, etc.) was classified into mixed infection group (13 cases, 26.0%), with non-surgical infection as simple infection group (37 cases, 74.0%). The results showed that the pulmonary infection occurred 0 to 12 days (median 3 days) before surgical infection in mix infection group. The incidence of previous chronic obstructive pulmonary disease (COPD) in patients with early onset was significantly higher than that in patients with delayed onset [17.6%(6/34) vs. 0, χ²=5.005, P=0.025], and the incidence of mixed infection in patients with delayed onset was significantly higher than that in patients with early onset [50%(8/16) vs. 14.7%(5/34), χ²=6.730, P=0.009],but there was no significant difference in postoperative hospital stay between the two groups[17.0(9.8) days vs. 14.0(9.5) days, U=224.0, P=0.317]. CONCLUSIONS Postoperative pulmonary infection is common in gastric cancer patients over 60 years of age. Preoperative comorbidities, abdominal infection and wound pain are independent risk factors for postoperative pulmonary infection. Pulmonary infection within 3 days after operation is associated with preoperative COPD. For patients suffering from PPI after the 4th day,attentions should be paid to abdominal infection and anastomotic leakage.
Age Factors ; Anastomotic Leak ; etiology ; Case-Control Studies ; Gastrectomy ; adverse effects ; methods ; Humans ; Intraabdominal Infections ; etiology ; Middle Aged ; Pneumonia ; etiology ; Pulmonary Atelectasis ; etiology ; Pulmonary Disease, Chronic Obstructive ; complications ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; complications ; surgery