ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Objective:To explore the distribution of HIV-1 genetic subtypes and drug resistance profiles among HIV-1 infected patients with antiretroviral treatment (ART) failure in Henan Province and to provide evidence for optimizing ART regimens.Methods:HIV-1 infected patients who had received ART for at least 6 months with viral loads (VL) ≥200 copies/ml in 18 cities of Henan from January to December 2023. The plasma samples were collected, and partial pol gene sequences and full-length integrase ( int) gene sequences of HIV-1 were amplified using nested RT-PCR. HIV-1 subtypes were determined using the REGA HIV-1 subtyping tool, and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/). Chi-square tests and multivariate logistic regression were used to identify risk factors associated with drug resistance of HIV-1 infected patients. Results:Among 697 HIV-1 infected patients with ART failure, 14 HIV-1 genetic subtypes were identified. Subtype B was predominant (58.68%, 409/697), followed by CRF01_AE (21.95%, 153/697) and CRF07_BC (12.91%, 90/697). The overall drug resistance rate was 72.31% (504/697), with CRF55_01B exhibiting a resistance rate of 91.30% (21/23). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) had the highest resistance mutation rate (67.29%, 469/697), followed by nucleoside reverse transcriptase inhibitors (NRTIs)(56.81%, 396/697), protease inhibitors (PIs)(5.74%, 40/697), and integrase strand transfer inhibitors (INSTIs)(2.75%, 19/691). The results of multivariate analysis showed that the positive correlation factor for drug resistance in HIV-1 infected individuals with failed ART was baseline CD4 +T lymphocyte counts <200 cells/μl (a OR=3.84, 95% CI: 1.69-8.72), and the negative correlation factor was ART duration of 3-5 years (a OR=0.32, 95% CI: 0.13-0.77), the initial treatment ART protocol used two types of NRTIs plus one type of PIs (a OR=0.14, 95% CI: 0.05-0.43) and two types of NRTIs plus one type of INSTIs protocol (a OR=0.12, 95% CI: 0.03-0.57). Conclusions:The drug resistance rate of HIV-1 infected patients with ART failure was relatively higher in Henan Province in 2023. Strengthening the monitoring of HIV-1 drug resistance is of great significance to improve the ART effect of HIV-1 infected patients.

Objective To investigate the effect of different radiotherapy doses on the prognosis of patients with stage cT1-4N0M0 esophageal squamous cell carcinoma(ESCC)who received radical radio(chemo)therapy categorized into subgroups with different tumor local factors.Methods A retrospective analysis was conducted on 256 patients with clinically nonmetastatic esophageal squamous cell carcinoma.The optimal cutoff for tumor local factors was determined.The relationship between latest treatment efficacy and tumor local factors was analyzed,and independent indicators affecting patient overall survival(OS)were examined using multivariate analysis.The subgroup analysis was performed to determine the correlation between selected factors and radiation therapy doses.Results The shorter the X-ray length of esophageal tumor lesion and the smaller the lesion canal wall thickness and gross tumor volume(GTV),the better the latest treatment efficacy of the patients(χ2=9.066,10.310,15.661,respectively,P=0.011,0.006,P＜0.001).Multivariate analysis results showed that GTV(P＜0.001),radiation dose(P=0.038),and latest treatment efficacy(P＜0.001)were independent predictors of the patients'OS,and the latter two were also independent predictors of the patients'progression-free survival(PFS)(P=0.033,＜0.001).Subgroup analysis further showed that high doses of radiotherapy(over 60 Gy)resulted in good OS(χ2=5.040,4.588,5.400,P=0.025,0.032,0.020)and PFS(χ2=6.089,4.353,6.459,P=0.014,0.037,0.011)in the subgroup with maximum wall thickness below 3.7 cm,with esophageal lesions with GTV below 37.34 cm3,or not receiving simultaneous chemotherapy.Conclusion Local tumor factors are important prognostic factors of ESCC patients treated with radical radio(chemo)therapy.Patients with thin lesion walls and small tumor volumes may greatly benefit from high doses of radiation(over 60 Gy).

Objective:To explore the distribution of HIV-1 genetic subtypes and drug resistance profiles among HIV-1 infected patients with antiretroviral treatment (ART) failure in Henan Province and to provide evidence for optimizing ART regimens.Methods:HIV-1 infected patients who had received ART for at least 6 months with viral loads (VL) ≥200 copies/ml in 18 cities of Henan from January to December 2023. The plasma samples were collected, and partial pol gene sequences and full-length integrase ( int) gene sequences of HIV-1 were amplified using nested RT-PCR. HIV-1 subtypes were determined using the REGA HIV-1 subtyping tool, and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/). Chi-square tests and multivariate logistic regression were used to identify risk factors associated with drug resistance of HIV-1 infected patients. Results:Among 697 HIV-1 infected patients with ART failure, 14 HIV-1 genetic subtypes were identified. Subtype B was predominant (58.68%, 409/697), followed by CRF01_AE (21.95%, 153/697) and CRF07_BC (12.91%, 90/697). The overall drug resistance rate was 72.31% (504/697), with CRF55_01B exhibiting a resistance rate of 91.30% (21/23). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) had the highest resistance mutation rate (67.29%, 469/697), followed by nucleoside reverse transcriptase inhibitors (NRTIs)(56.81%, 396/697), protease inhibitors (PIs)(5.74%, 40/697), and integrase strand transfer inhibitors (INSTIs)(2.75%, 19/691). The results of multivariate analysis showed that the positive correlation factor for drug resistance in HIV-1 infected individuals with failed ART was baseline CD4 +T lymphocyte counts <200 cells/μl (a OR=3.84, 95% CI: 1.69-8.72), and the negative correlation factor was ART duration of 3-5 years (a OR=0.32, 95% CI: 0.13-0.77), the initial treatment ART protocol used two types of NRTIs plus one type of PIs (a OR=0.14, 95% CI: 0.05-0.43) and two types of NRTIs plus one type of INSTIs protocol (a OR=0.12, 95% CI: 0.03-0.57). Conclusions:The drug resistance rate of HIV-1 infected patients with ART failure was relatively higher in Henan Province in 2023. Strengthening the monitoring of HIV-1 drug resistance is of great significance to improve the ART effect of HIV-1 infected patients.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Objective To investigate mortality risk factors and characterize pathogen distribution and antimicrobial resistance patterns in intensive care unit(ICU)patients with suspected infection following surgery.Methods A total of 65 hospitals in 16 provinces in China from July 1,2021,to December 31,2022.Clinical data were collected for surgical patients transferred to the ICU with suspected infection.Data included demographics[sex,age,underlying conditions(hypertension,diabetes,cardiovascular/cerebrovascular disease,hematologic disease)],surgical site,infection site,microbiological results with susceptibility testing,drug resistance and acute physiology and chronic health evaluationⅡ(APACHEⅡ)scores and the length of hospital stays.Patients were stratified by prognosis into death group and survial group,by drug resistance status into resistant and non-resistant groups.Univariate and multivariate Logistic regression identified risk factors for mortality and antimicrobial resistance.Draw the receiver operator characteristic curve(ROC curve)to evaluate the predictive value of each risk factor for patient prognosis and drug resistance occurrence.Results A total of 677 patients with suspected postoperative infection in the ICU were enrolled.There were 96 deaths and 591 survivors.① Analysis of risk factors affecting prognosis:univariate analysis showed that compared with the survival group,the patients in the had a higher APACHEⅡscore,the proportion of patients with previous cerebrovascular disease,surgery sites in the abdomen,chest,brain,pelvis,limbs,other areas,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,Gram-positive bacterial infection(Candida),fungal infection,multi-drug resistant bacterial infection was higher,and the length of hospital stay was shorter(all P<0.05).Multivariate Logistic regression analysis identified higher APACHEⅡscore[odds ratio(OR)=1.15,95%confidence interval(95%CI)was 1.11-1.20],pulmonary infection(OR=4.07,95%CI was 2.05-8.11),bloodstream infection(OR=2.61,95%CI was 1.52-4.51),and urinary tract infection(OR=2.20,95%CI was 1.01-4.42)were independent risk factors for prognosis(all P<0.05).The ROC curve analysis showed that the death risk prediction model established based on the above independent risk factors had certain predictive value for the prognosis of ICU postoperative patients with suspected infection,area under the curve(AUC)=0.820,95%CI was 0.770-0.860,P<0.05.②Regarding antimicrobial resistance:250 patients developed resistance and 427 did not.Univariate analysis showed compared with the non-resistant group,the APACHEⅡscore,the proportion of patients with cerebrovascular diseases,hematological diseases,surgeries at chest,brain,limbs,other sites,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,intracranial infection,Gram-negative bacillus infection,and Gram-positive cocci infection(Staphylococcus epidermidis,Staphylococcus aureus,Enterococcus faecalis),and the mortality rate in the resistant group were significantly higher,the proportion of patients with surgeries at abdominal cavity,pelvic cavity and abdominal cavity infection were significantly lower,and the length of hospital stay was significantly longer(all P<0.05).Multivariate Logistic regression analysis bloodstream infection(OR=4.00,95%CI was 2.22-7.19),urinary tract infection(OR=3.25,95%CI was 1.47-7.17),Klebsiella pneumoniae infection(OR=2.23,95%CI was 11.22-44.02),Acinetobacter baumannii infection(OR=48.12,95%CI was 20.10-115.17),Pseudomonas aeruginosa infection(OR=34.06,95%CI was 13.00-89.25),Escherichia coli infection(OR=24.97,95%CI was 10.55-59.13),Stenotrophomonas maltophilia infection(OR=19.04,95%CI was 3.30-109.96),and Staphylococcus aureus infection(OR=13.48,95%CI was 4.57-39.78)were independent risk factors for resistance(all P<0.01).The ROC curve analysis showed that the predictive model for drug resistance established based on the above independent risk factors had certain predictive value for drug resistance in adult patients with suspected infections after surgery in the ICU.The AUC=0.920,95%CI was 0.890-0.940,P<0.05.Conclusion Higher APACHEⅡscores and the presence of pulmonary,bloodstream,or urinary tract infections were associated with increased mortality in ICU patients with suspected postoperative infection.Patients with bloodstream or urinary tract infections,or infections caused by Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Escherichia coli,Stenotrophomonas maltophilia,or Staphylococcus aureus,had significantly higher odds of developing antimicrobial resistance.

Objective:To analyze the drug resistance characteristics and influencing factors in human immunodeficiency virus (HIV)-1 treated patients in Henan Province.Methods:HIV-1 treated patients who had received anti-retroviral therapy (ART) for more than six months and had a viral load >200 copies/mL in the Zhengzhou Sixth People′s Hospital from January to December 2024 were enrolled. Plasma samples were collected. Partial pol region gene sequences and integrase gene sequences of HIV-1 were amplified by reverse transcription nested polymerase chain reaction. The REGA HIV-1 subtype analysis tool was used to determine the subtypes of HIV-1 isolates, and the HIV drug resistance database of Stanford University in the United States was used to analyze the genetic drug resistance mutations and antiviral drug susceptibility. The multivariate logistic regression analysis was used to analyze the factors related to drug resistance. Results:Among 933 HIV-1 treated patients with ART failure, 825 samples were successfully amplified, with the amplification success rate of 88.42%. The overall drug resistance rate was 70.06%(578/825), among which the drug resistance rates of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), and integrase inhibitor (INSTI) were 55.15%(455/825), 64.36%(531/825), 5.70%(47/825), and 2.31%(19/821), respectively. The most common drug resistance mutations included M184I/V (47.88%(395/825)), K103N/S (38.18%(315/825)), and K70E/G/N/Q/R/S/T/del (16.61%(137/825)). Multivariate analysis showed that the baseline CD4 + T cell count <200 cells/μL (adjusted odds ratio ( OR)=2.239, 95% confidence interval ( CI)1.011 to 4.960), an initial 2NRTI+ NNRTI-based treatment regimen (adjusted OR=44.332, 95% CI 5.191 to 378.593), initial 2NRTI+ PI/r (r means ritonavir)-based regimen (adjusted OR=14.391, 95% CI 1.304 to 158.805) and a change in the ART regimen (adjusted OR=5.941, 95% CI 2.373 to 14.878) were independent risk factors for drug resistance (all P<0.05). Conclusions:The drug resistance rate after virological failure in HIV-1 treated patients in Henan Province is relatively high, which is mainly characterized by NNRTI resistance. The baseline immune status and the choice of the initial treatment regimen are important factors affecting the occurrence of drug resistance. The treatment monitoring and drug resistance monitoring should be strengthened.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

At present, the da Vinci surgical system, recognized as the most advanced minimally invasive surgical system, has been garnering growing attention in its application within the field of breast surgery. This article provides a comprehensive review of the development trajectory of the da Vinci surgical system in breast surgery, its indications and contraindications, as well as the common surgical modalities of da Vinci robotic-assisted breast surgery. Additionally, it offers a prospective outlook on the future development directions of da Vinci robotic-assisted breast surgical procedures.

OBJECTIVE: To analyze the clinical characteristics, microbiological analysis, and drug resistance patterns of intensive care unit (ICU) bloodstream infection. METHODS: A prospective cohort study method was employed to collect clinical data from patients suspected of bloodstream infection (BSI) during their stay in ICUs across 67 hospitals in 16 provinces and cities nationwide, from July 1, 2021, to December 31, 2022. Electronic data collection technology was used to gather general information on ICU patients, including gender, age, length of hospital stay, as well as diagnostic results, laboratory tests, imaging studies, microbiological results (including smear, culture results, and pathogen high-throughput testing), and prognosis. Patients were divided into a BSI group and a non-BSI group based on the presence or absence of BSI; further, patients with BSI were categorized into a drug-resistant group and a non-drug-resistant group based on the presence or absence of drug resistance. Differences in the aforementioned indicators between groups were analyzed and compared; variables with P < 0.10 in the univariate analysis were included in a multivariate Logistic regression analysis to identify risk factors for mortality and drug resistance in ICU patients with BSI. RESULTS: A total of 2 962 ICU patients suspected of BSI participated in the study, including 790 in the BSI group and 2 172 in the non-BSI group. Patients in the BSI group were mainly from East China and Southwest China, with significantly higher age and mortality rates than those in the non-BSI group. Among ICU patients with BSI, Staphylococcus had the highest detection rate (8.10%), followed by Klebsiella pneumoniae (7.47%); there were 169 cases in the drug-resistant group and 621 cases in the non-drug-resistant group; 666 cases survived, and 124 cases died (mortality was 15.70%). There were statistically significant differences between the death group and the survival group in terms of age, regional distribution, and bloodstream infections caused by Gram negative (G^-) bacilli, Enterococcus faecium, Aspergillus, and Klebsiella pneumoniae; multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.01, 95% confidence interval (95%CI) was 1.00-1.03], regional distribution (OR = 4.07, 95%CI was 1.02-1.34), Enterococcus faecium infection (OR = 3.64, 95%CI was 1.16-11.45), and Klebsiella pneumoniae infection (OR = 2.64,95%CI was 1.45-4.80) were independent risk factors for death in ICU patients with BSI (all P < 0.05). There were statistically significant differences between the drug-resistant group and the non-drug-resistant group in terms of age and bloodstream infections caused by Gram positive (G⁺) cocci and G^- bacilli; multivariate Logistic regression analysis showed that age (OR = 1.01,95%CI was 1.00-1.03), G^- bacilli infection (OR = 2.18, 95%CI was 1.33-3.59), Escherichia coli infection (OR = 0.28,95%CI was 0.09-0.84), and Enterococcus faecium infection (OR = 3.35, 95%CI was 1.06-10.58) were independent risk factors for drug resistance in ICU patients with BSI (all P < 0.05). CONCLUSIONS Bloodstream infections may increase the mortality of ICU patients. Older age, regional distribution, Enterococcus faecium infection and Klebsiella pneumoniae infection can increase the mortality rate of ICU patients with BSI; bloodstream infections caused by G^- bacilli are prone to drug resistance, but have no significant impact on the mortality of ICU patients with BSI.
Adult ; Humans ; Bacteremia/microbiology* ; China/epidemiology* ; Cohort Studies ; Cross Infection/microbiology* ; Drug Resistance, Bacterial ; Intensive Care Units/statistics & numerical data* ; Prospective Studies ; Risk Factors ; Sepsis/microbiology*