Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.

Objective To investigate the effects of different depth of anesthesia on ScvO2 and ABL in elderly patients with gastrointestinal cancer. Methods Totally 55 elderly patients undergoing gastrointestinal sur-gery were randomly divided into deep anesthesia group(BIS40-49)(group D,n=27)and light anesthesia group (BIS50-59)(group S,n = 28). While SVV value was fixed,fluid management was conducted while monitoring CVP. HR,MAP,the change of central venous oxygen saturation and lactic acid index were recorded in different time points. Results Propofol dosage in group D and group S indicated statistical significance(P<0.05). ScvO2 in group S in T3~T5 was higher than that in T0 and the difference was statistically significant(P < 0.05). Com-pared with ScvO2 in T3 in group D,that in group S was significantly higher and the difference was statistically sig-nificant(P<0.01),but no significant difference was found in other time point in 2 groups(P>0.05). There was no significant difference between and within ABL groups in each time period(P>0.05). There was no significant difference in terms of other indicators between 2 groups. Conclusions For elderly patients with gastrointestinal surgery,shallow anesthesia can improve tissue oxygenation and reduce the amount of anesthetics.

Objective To understand the genotype distribution of Mycobacterium tuberculosis and the drug susceptibility of M.tuberculosis with different genotypes in Changping district of Beijing and evaluate the application of genotyping of M.tuberculosis in local tuberculosis (TB) prevention and control.Methods A total of 1 099 M.tuberculosis strains isolated in Changping from 2011 to 2015 were used.Spoligotyping and 12-locus VNTR recommended by Gao were used for the genotyping of these isolates.In addition,the susceptibility of the M.tuberculosis isolates to rifampin (RFP),isoniazid (INH),ethambutol (EMB),streptomycin (SM),amikacin (AMK) and ofloxcin (OFX) were detected by using conventional drug susceptibility test.Results From 2011 to 2015,the detection rate of OFX-resistance increased from 2.9％ to 8.9％ (P=0.01).Of all the M.tuberculosis isolatcs,976 belonged to Beijing genotype (88.8％),and the other 123 belonged to non-Beijing genotype (11.2％).In addition,there were 189 ancient Beijing genotype isolates and 787 modern Beijing genotype isolates,respectively.The proportion of Beijing genotype strains showed no significant increase in the past five years (81.1％ in 2011 vs.82.0％ in 2015).On the basis of VTNR genotyping,only 2 isolates belonged to one cluster (0.1％).In addition,the AMK resistant rate of Beijing genotype strains (1.7％)was significantly lower than that of non-Beijing genotype strains (4.9％,P=0.02).Compared with modern Beijing genotype strains,the SM resistant rate of ancient Beijing genotype strains was significantly higher (28.0％ vs.15.7％,P=0.01).Conclusions In the past five years,the OFX-resistant rate of M.tuberculosis in Changping was in increase.There was no significant difference in the detection of Beijing genotype strains during this period.In addition,the low clustering rate indicated that the TB transmission rate was low in Changping.

Objective To compare the complication and long-term efficacy of standard and extended pancreaticoduodenectomy for carcinoma of the head of pancreas by meta-analysis.Methods A literature search was performed of PubMed,Web of Science,Springer,WanFang,CNKI and CBMDisc databases from January 1990 to August 2014.Qualitative analysis of these literatures was conducted using Jadad evaluation.Patients with pancreatic head carcinoma undergoing extended radical resection and standard radical resection were divided into treatment group (extended pancreaticoduodenectomy group,EPD) and control group (standard pancreaticoduodenectomy group,SPD),respectively.Based on the heterogeneity test,meta-analysis of a fixed-or random-effect model were used.Results A total of 5 studies suitable for the selection criteria were chosen,involving 597 patients (299 in EPDs and 298 in SPDs).The results of meta-analysis showed that the EPDs have significantly longer operative time (MD =64.36,95％ CI =23.88-104.85,P =0.002) and more dissected lymph nodes (MD =16.45,95％ CI =9.61-23.29,P ＜ 0.000 01) than SPDs.There was no statistical difference (OR =1.76,95 ％ CI =0.66-4.65,P =0.26) in postoperative complications (46.3％ vs 36.0％) mortality (OR =1.31,95％ CI =0.47-3.69,P =0.61),1-year survival rate (OR =0.70,95 ％ CI =0.49-0.99,P =0.05),3-year survival rate (OR =0.79,95％ CI =0.55-1.15,P =0.22),and 5-year survival rate (OR =-0.02,95％ CI =-0.17-0.12,P =0.77).Conclusions Compared with standard radical resection,extended radical resection for pancreatic head carcinoma does not prolong the postoperative 1-,3-,and 5-year survival rates with comparable postoperative mortality and morbidity and prolonged operative time.

OBJECTIVETo investigate and analysis the clinical and pathological characteristic of gastrointestinal stromal tumor (GIST) patients, and to clarify the factors that effect on prognosis.

METHODSThe clinical and pathological features and follow-up of GIST patients who received surgery in Peking Union Medical College Hospital from May 2002 to December 2013 were analyzed retrospectively. The prognosis was evaluated by univariate and multivariate analysis. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model.

RESULTSA total of 558 GIST patients were collected, including 284 males and 272 females. The high incidence was in the elderly and age of 50 to 70 years. Most of the primary tumors are located in stomach (303 cases), followed by the small intestine (118 cases). Surgical procedures included R0 resection in 517 cases, R1 resection in 4 cases, R2 or palliative resection in 37 cases. The recurrence risk was very low in 102 cases, low in 156 cases, moderate in 67 cases and high in 233 cases. Of all the patients, 495 cases completed the follow-up, the follow-up rate was 88.7%. Five year survival rate was 87.4%. Patients who took targeted therapy with moderate and high risk of recurrence had a better prognosis compared with not taking the drug. Univariate analysis revealed that the factors impacting the prognosis were age, tumor size, tumor site and mitotic count. Multivariate analysis showed that tumor size (P=0.01, RR=1.562, 95% CI: 1.452 to 15.664), location (P=0.01, RR=1.552, 95% CI:1.324 to 12.225), mitotic figures (P<0.01, RR=1.415, 95% CI: 2.126 to 7.968) and tumor rupture (P=0.01, RR=1.578, 95% CI: 1.543 to 15.892) were independent prognostic factors.

CONCLUSIONR0 resection combined with targeted therapy is the best treatment of GIST. Tumor size, location, mitosis count and tumor rupture are independent prognostic factors of GIST patients.

Aged ; Beijing ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; Humans ; Intestine, Small ; pathology ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach ; pathology ; Survival Rate