ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

ObjectiveTo investigate the impact of hepatocellular carcinoma （HCC） on the prognosis of patients with liver cirrhosis undergoing emergency endoscopic therapy for esophagogastric variceal bleeding， as well as independent influencing factors for the prognosis of liver cirrhosis patients without HCC after emergency endoscopic therapy for esophagogastric variceal bleeding. MethodsA total of 117 liver cirrhosis patients without HCC and 119 liver cirrhosis patients with HCC who underwent emergency endoscopic therapy for esophagogastric variceal bleeding in Renmin Hospital of Wuhan University from January 2017 to July 2023 were enrolled. Basic information including age and sex was collected from all patients， as well as the presence or absence of chronic diseases such as hypertension， diabetes， and coronary heart disease， the time of emergency endoscopy after admission， and liver function parameters including international normalized ratio， albumin， creatinine， sodium， total bilirubin， alanine aminotransferase， and aspartate aminotransferase （AST）. The independent-samples t test was used for comparison of normally distributed continuous variables between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous variables between two groups； the chi-square test was used for comparison of categorical variables between groups. The covariance analysis and the multivariate logistic regression analysis were used for comparison of outcome variables after control of baseline variables， and the Kaplan-Meier survival curve was plotted for each group. The univariate and multivariate Cox regression analyses were performed for survival time in the non-HCC group to investigate the independent influencing factors for survival time， and then the Kaplan-Meier curve analysis and the log-rank test were performed to validate such independent influencing factors and analyze the independent influencing factors for secondary outcomes. ResultsCompared with the non-HCC group， the HCC group had significantly higher red blood cell transfusion units （6.00［2.00～9.00］ vs 4.00［1.75～7.00］， Z=-2.050， P=0.040， F=4.869， adjusted P=0.028）， a significantly shorter survival time （29.77±16.01 days vs 38.07±11.43 days， t=4.574， P<0.001， F=17.294， adjusted P<0.001）， and a significantly higher 5-day rebleeding rate （22.69% vs 6.84%， χ²=11.736， P<0.001， adjusted P=0.021）. The Kaplan-Meier curve analysis showed that the risk of 42-day mortality in the HCC group was 3.897 （95% confidence interval ［CI］： 2.338 ‍— 6.495， P<0.001） times that in the non-HCC group. The multivariate Cox regression analysis of the non-HCC group showed that the total length of hospital stay （hazard ratio ［HR］=0.793， 95%CI： 0.644 ‍— ‍0.976， P=0.029） was an independent protective factor for 42-day survival. The Kaplan-Meier curve analysis showed that a length of hospital stay of >9 days was beneficial for the prognosis of patients （HR=4.302， 95%CI： 1.439 — 12.870， P=0.037）. Blood sodium level （odds ratio ［OR］=0.523， 95%CI： 0.289 ‍— ‍0.945， P=0.032） and MELD-Na score （OR=0.495， 95%CI： 0.257 ‍— ‍0.954， P=0.036） were independent protective factors against 5-day rebleeding， while AST level was an independent risk factor for 5-day rebleeding （OR=1.023， 95%CI： 1.002 ‍— ‍1.043， P=0.028） and in-hospital death （OR=1.036， 95%CI： 1.001‍— ‍1.073， P=0.045）. ConclusionLiver cirrhosis patients with variceal bleeding and HCC tend to have a worse prognosis， and for the non-HCC group， in-hospital mortality rate increases with the increase in AST level. The total length of hospital stay is an independent protective factor for survival time in the non-HCC group， and it is recommended to appropriately prolong the length of hospital stay for such patients.

BACKGROUND:It has been shown that Gushukang affects bone metabolism by regulating nucleotide and amino acid metabolism and immune mechanisms.Current research on the mechanism of Gushukang in the treatment of osteoporosis primarily focuses on osteoblast regulation and requires further improvement from the perspective of osteoclasts. OBJECTIVE:To investigate the mechanism by which Gushukang interferes with osteoclasts in the treatment of osteoporosis using RAW264.7 cells as the research model. METHODS:Twenty-four 8-week-old female Sprague-Dawley rats were randomly divided into four groups(n=6 per group):the three experimental groups were given 1,2 and 4 g/kg osteoporosis solution by gavage(2 times per day),and the control group was given an equal amount of distilled water by gavage(2 times per day).After 7 days of intragastric administration,aortic blood samples were extracted to collect serum samples using centrifugation,and serum samples from the same groups were combined to obtain the low-,medium-,and high-concentration Gushukang-containing and normal sera for the subsequent experiments.(1)RAW264.7 cells were cultured in six groups:normal serum was added to the control group;low,medium,and high concentration groups were added with low,medium,and high concentrations of Gushukang-containing serum,respectively;ML385,a nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor was given in the Nrf2 inhibitor group;and t-BHQ,a Nrf2 activator,was added in the Nrf2 activator group.Cell viability was detected using the cell counting kit-8 assay.(2)The 3rd generation RAW 264.7 cells were cultured and divided into five groups:the blank control group was added with normal serum,the osteoclast group was added with receptor activator of nuclear factor κB ligand(RANKL),and the low-,medium-,and high-concentration groups were added with low-,medium-,and high-concentration Gushukang-containing serum based on the addition of RANKL.Tartrate-resistant acid phosphate staining was performed after 5 days of culture.(3)RAW264.7 cells were cultured and divided into five groups:blank control group was cultured with normal serum,osteoclast group cultured with normal serum and RANKL,high concentration+osteoclast group cultured with RANKL+high concentration Gushukang-containing serum,osteoclast+Nrf2 agonist group cultured with RANKL+t-BHQ,and high concentration+osteoclast+Nrf2 inhibitor group cultured with RANKL+high concentration Gushukang-containing serum+ML385.Western blot assay and determination of reactive oxygen content were performed after 5 days of culture. RESULTS AND CONCLUSION:The cell counting kit-8 results indicated that Gushukang-containing serum,NRF2 inhibitor or agonist had no significant effect on RAW264.7 cell viability.Tartrate-resistant acid phosphate staining results demonstrated that Gushukang-containing serum exhibited a concentration-dependent inhibitory effect on osteoclast differentiation.Western blot analysis and determination of reactive oxygen species revealed that compared with the blank control group,Nrf2 protein expression was decreased in the osteoclast group(P<0.05),while c-Fos and NFATc1 protein expression and reactive oxygen species content were elevated(P<0.05);compared with the osteoclast group,Nrf2 protein expression was elevated and reactive oxygen species content was decreased in the high-concentration+osteoclast group,osteoclast+Nrf2 agonist group,and high-concentration+osteoclast+Nrf2 inhibitor group(P<0.05),while c-Fos and NFATc1 protein expression was decreased in the high concentration+osteoclast group and osteoclast+Nrf2 agonist group(P<0.05);compared with the high concentration+osteoclast group,Nrf2 protein expression was decreased(P<0.05)and reactive oxygen species content was elevated(P<0.05)in the high concentration+osteoclast+Nrf2 inhibitor group.To conclude,Gushukang reduces reactive oxygen species production by activating Nrf2,thereby inhibiting downstream of the c-Fos/NFATc1 pathway and suppressing osteoclast differentiation.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Aim To observe the effect of lipopolysac-charide(LPS)induced supernatant of BV-2 cells on the inflammatory response and apoptosis of HT22 neu-rons.Methods After the concentration and time of LPS were determined by CCK-8 method,BV-2 cells were cultured with medium without LPS and medium containing LPS,the morphological changes of BV-2 microglia were observed by inverted microscope,and the CD86/CD206 ratio of BV-2 microglia was detected by immunofluorescence.Subsequently,BV-2 cell cul-ture supernatants were isolated and added to HT22 neuronal culture to observe the effect on the inflamma-tory response of HT22 neurons.The proliferation of HT22 neurons was detected by CCK-8 method and EdU method.The structural changes of HT22 neurons were observed under the microscope and examined by urani-um-lead staining.The levels of cytokines interleukin-1β(IL-1β),interleukin-10(IL-10),nuclear factor kappa-B(NF-κB)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent as-say(Elisa).Neuronal apoptosis was detected by the TUNEL method.The protein expressions of Bax,Bcl-2 and inflammatory factors were detected by Western blot.Results After induction with 1 mg·L-1 LPS,BV-2 cells exhibited increased cell body size,thicker protrusions on both side,and some cells showed de-formed protrusions,the CD86/CD206 ratio in BV-2 cells decreased,promoting the transformation of BV-2 cells from M2 type to M1 type.After treating with the culture supernatant of BV-2 cells,HT22 neuronal cell activity and proliferation were reduced,axons short-ened,and the number of cells decreased.Neuronal cell bodies were enlarged and some cells were de-formed,with damaged cell membranes,round cell nu-clei but displaced nucleoli from the normal position,swollen mitochondria with vacuoles,reduced internal ridge structures,and increased levels of inflammatory factors NF-κB,IL-1 β,and TNF-α(P＜0.05 or P＜0.01),while the anti-inflammatory factor IL-10 de-creased(P＜0.05),protein expression of the pro-apoptotic indicator Bax increased(P＜0.01),and the protein expression of the anti-apoptotic indicator Bcl-2 decreased(P＜0.05).Conclusion After induction of BV-2 cell polarization by LPS,the supernatant could inhibit HT22 neuronal cell viability,upregulate inflam-matory factor expression and promote apoptosis.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.