OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae （CRKP） infection， develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae （CSKP） during the same period as the modeling group. Using the same criteria， data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis， LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling， and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic （ROC） curves and calibration plots. RESULTS A total of 530 patients were enrolled， with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection （P＜0.05）. The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations， respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Background Staff in biosafety laboratories (BSL) are more likely to experience occupational burnout and other psychological issues due to their unique working environment and high job demands. However, current research in this field tends to focus on overall analyses, overlooking the internal differences within this group. Objective To explore latent profiles of occupational burnout among BSL workers and their influencing factors, providing a reference for targeted burnout interventions. Methods In 2022, cluster random sampling was used to select 8023 BSL workers in Xinjiang. Data were collected via a questionnaire survey, including a self-designed general information questionnaire, the Maslach Burnout Inventory-General Survey (MBI-GS), and the Effort-Reward Imbalance (ERI) scale, to analyze demographic characteristics, occupational burnout, and job stress status. After data cleaning, latent profile analysis (LPA) was applied to identify burnout profiles, followed by K-means clustering for verification. Logistic regression was used to analyze influencing factors with burnout profiles as the dependent variable. Results After excluding invalid questionnaires, 7924 valid questionnaires were retained, with an recovery rate of 98.77%. The LPA results indicated that occupational burnout among BSL staff was categorized into three latent profiles: a low burnout profile (2208 individuals, 27.86%), a moderate burnout profile (4636 individuals, 58.51%), and a high burnout profile (1080 individuals, 13.63%). A similar grouping was derived from K-means clustering analysis (28.71%, 53.37%, and 17.92%), and a Sankey diagram demonstrated significant overlap between the two classification results. Statistically significant differences were observed across the three latent profiles in all three dimensions of burnout: emotional exhaustion, cynicism, and reduced personal accomplishment. The final logistic regression model revealed that the influencing factors exhibited characteristics of partial overlap and partial differentiation. Among the common influencing factors, the shared protective factors included: age ≥50 years (OR_{moderate burnout}=0.42, OR_{high burnout}=0.45), monthly income of 4000-6000 RMB (OR_{moderate burnout}=0.83, OR_{high burnout}=0.71), good sleep quality (OR_{moderate burnout}=0.70, OR_{high burnout}=0.13) and very good sleep quality (OR_{moderate burnout}=0.51, OR_{high burnout}=0.12), and engaging in physical exercise ≥5 times per week (OR_{moderate burnout}=0.74, OR_{high burnout}=0.48). The protective effects were more pronounced for the high burnout profile. The common risk factors included: 21–30 years of service (OR_{moderate burnout}=1.38, OR_{high burnout}=3.00), ≥31 years of service (OR_{moderate burnout}=1.47, OR_{high burnout}=3.39), working in "other positions" (OR_{moderate burnout}=1.46, OR_{high burnout}=1.56), and occupational stress (ERI>1) (OR_{moderate burnout}=2.62, OR_{high burnout}=3.25), with the risk effects being more significant for the high burnout profile. Regarding differentiated influencing factors, protective factors exclusively associated with the moderate burnout profile included having an associate degree (OR=0.70) and engaging in physical exercise 3-4 times per week (OR=0.74). For the high burnout profile, exclusive protective factors included age 40-50 years (OR=0.56), while exclusive risk factors included having a senior professional title (OR=1.85), holding a managerial role (OR=1.78), a high number of night shifts per month (OR=2.66), and a very high number of night shifts per month (OR=3.93). Conclusion BSL workers exhibit three distinct latent burnout profiles. Occupational burnout requires greater attention, and targeted prevention and intervention strategies should be developed based on worker subtypes.

AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

[Objective] To explore the efficacy and safety of retrograde intrarenal surgery (RIRS) using a flexible negative pressure suction sheath in the treatment of upper urinary tract stones >2 cm in diameter, to provide reference for the diagnosis and treatment of such disease. [Methods] Clinical data of 155 patients who underwent surgery for upper urinary tract stones during Nov.2022 and Nov.2023 at the Second Affiliated Hospital of Shaanxi University of Chinese Medicine were retrospectively analyzed.The patients were divided into 3 groups: percutaneous nephrolithotripsy (PCNL) group (n=54), conventional sheath RIRS group (n=41), and flexible sheath RIRS group (n=60). The general and clinical data of the 3 groups were compared. [Results] The PCNL group had more patients with severe hydronephrosis (22.22% vs. 4.88%, 5.00%, P=0.027) and smaller IPA involving the lower calyx [(36.17±17.6)° vs. (48.57±17.56)°, (47.41±10.82)°, P=0.014] than the conventional sheath RIRS group and flexible sheath RIRS group.Three days after operation, the stone-free rate (SFR) was 90.74%, 53.66% and 78.33% in the PCNL, conventional sheath RIRS, and flexible sheath RIRS groups, respectively (P<0.05). At 1 month postoperatively, the SFR was 92.59%, 73.17%, and 81.67%, with no statistically significant difference between the PCNL and flexible sheath RIRS groups (P>0.05), but was higher than that in the conventional sheath RIRS group (P<0.05). The PCNL group had shorter operation time than the two RIRS groups [(65.22±17.67) min vs. (91.73±20.57) min, (94.38±24.75) min, P<0.001], longer postoperative hospital stay [(5.0(4.0, 7.0) d vs.3.0(2.0, 4.0) d, 3.0(2.0, 4.0) d, P<0.001], greater decrease in hemoglobin level [(18.00±5.78) g/L vs. (5.57±5.16) g/L, (7.42±5.09) g/L, P<0.001], and higher visual analogue scale (VAS) score [(4.83±1.48) min vs. (2.95±1.07) min, (3.05±1.21) min, P<0.001], while there was no difference between the two RIRS groups (P>0.05). The costs were lower in the flexible sheath RIRS group than in the conventional sheath RIRS group but higher than in the PCNL group [(23 311.19±1 341.20)yuan vs.(24 550.49±1 172.51)yuan, (15 351.97±1 101.4)yuan, P<0.001]. The overall incidence of complications was similar among the three groups, but stone street occurred only in the conventional sheath RIRS group. [Conclusion] For the treatment of patients with upper urinary tract stones >2 cm, RIRS has shorter postoperative hospital stay, lower hemoglobin decrease, and lower VAS score compared to PCNL; the early postoperative SFR of flexible sheath RIRS is superior to that of conventional sheath RIRS, and the 1-month SFR is comparable to that of PCNL, with a low incidence of stone street.

Objective To explore the value of lipoprotein-associated phospholipase A2(Lp-PLA2)in the diagnostic grading and prog-nostic assessment of pneumonia-associated acute respiratory distress syndrome(p-ARDS).Methods The study was a prospective ob-servational study.Fifty-seven patients with p-ARDS admitted to the ICU ward of Tianjin Hospital from January 2022 to August 2023 were included as the research subjects.Twenty-six pneumonia patients admitted to the general respiratory ward during the same period and 10 healthy individuals undergoing medical examinations were selected as the control group.Their serum samples were collected,and the samples from p-ARDS and pneumonia patients were obtained within 24 hours of admission.The levels of serum Lp-PLA2,in-terleukin 6(IL-6),and IL-8 were detected using the Luminex? multiplex test kit.The baseline data and laboratory test results,inclu-ding routine blood parameters,biochemical markers,C-reactive protein(CRP),procalcitonin(PCT),and D-dimer at admission,were collected from the patients with p-ARDS or pneumonia.The levels of serum Lp-PLA2 were compared by grouping based on clinical diagnosis,severity of ARDS,and clinical outcomes on day 28 after admission.The diagnostic and prognostic value of serum Lp-PLA2 in p-ARDS was evaluated by plotting the receiver operating characteristic(ROC)curve,Spearman correlation analysis,and Logistic regression analysis.Results The levels of serum Lp-PLA2 in the p-ARDS group([233.67±83.49]ng/mL)were significantly higher than that in the pneumonia group([150.86±39.48]ng/mL,P＜0.05),while those in the pneumonia group were significantly higher than that in the healthy control group([150.86±39.48]ng/mL vs[92.07±12.89]ng/mL,P＜0.05).The analysis results of the ROC curve showed that serum Lp-PLA2 had a better ability to distinguish p-ARDS from pneumonia than indicators such as IL-6,IL-8,CRP,and PCT,with an area under the ROC curve(AUCROC)of 0.781(95％CI:0.685-0.878).The diagnostic value of serum Lp-PLA2 combined with D-dimer was higher,with an AUCROC of 0.897(95％CI:0.832-0.963).Subgroup analysis found that as lung inju-ry worsened,the levels of serum Lp-PLA2 increased,and that serum Lp-PLA2 levels were negatively correlated with the PaO2/FiO2 ra-tio in p-ARDS patients(r=-0.549)and positively correlated with the sequential organ failure assessment(SOFA)scores at admission(r=0.412).The levels of serum Lp-PLA2 in the death group of p-ARDS were significantly higher than that in the survival group([314.5±43.1]ng/mL vs[174.9±48.9]ng/mL,P＜0.001).Logistic regression analysis showed that after adjusting for the SOFA score,serum Lp-PLA2 was independently associated with the mortality risk on day 28 after admission(OR=1.099,95％CI:1.026-1.178,P=0.007).Similar results were obtained after adjusting for IL-8 or the PaO2/FiO2 ratio.Conclusion Serum Lp-PLA2 may be used as a biomarker to aid in the diagnostic grading and prognostic assessment of p-ARDS.

Objective To preliminarily investigate the effects of estradiol on retinal microglia and retinal ganglion cells(RGCs)in rats with glucocorticoid-induced ocular hypertension(OHT).Methods Thirty-six male SD rats(36 eyes)were randomly divided into a control group,an OHT group,and an OHT estradiol-treated group(E2-OHT group),with 12 rats in each group.Among them,the rats in the OHT group and the E2-OHT group were given dexamethasone sodi-um phosphate injection under the conjunctiva,and the rats in the control group were injected with the same volume of ster-ile normal saline.Two weeks after modeling,the rats in the E2-OHT group were treated with estradiol eye drops in addition to subconjunctival injection of dexamethasone sodium phosphate.The eyeballs of all rats were removed 4 weeks after mod-eling.The changes in the number of RGCs and the activation of microglia were observed after immunofluorescence stai-ning,the expression levels of Brn3a and Iba1 proteins in the retina were detected by Western blot,and the relative expres-sion levels of tumor necrosis factor α(TNF-α)and interleukin 1 β(IL-1 β)mRNA were detected by real-time quantitative polymerase chain reaction.Results Among the three groups,the intraocular pressure(IOP)of rats showed no signifi-cant difference before modeling(all P＞0.05),but showed a significant difference at 1 week,2 weeks,3 weeks and 4 weeks after modeling(all P＜0.01).Compared with the control group,the IOP of rats in the OHT group at 1 week,2 weeks,3 weeks and 4 weeks after modeling increased significantly(all P＜0.01).Compared with the OHT group,the IOP of rats in the E2-OHT group showed no significant difference at 1 week and 2 weeks after modeling(both P＞0.05),but decreased significantly at 3 weeks and 4 weeks after modeling(both P＜0.01).The immunofluorescence staining results showed that the retinal microglia of rats in the control group were mainly concentrated in the inner plexiform layer,while the retinal microglia of rats in the OHT group migrated to the ganglion cell layer and had morphological changes(amoebic activation state).The morphology and distribution of rat retinal microglia in the E2-OHT group were basically the same as the retinal staining results of rats in the control group.Compared with the control group,the number of RGCs in the OHT group decreased,the relative expression levels of TNF-α and IL-1β mRNA and Iba1 protein increased,while the expression level of Brn3a protein decreased,and the differences were statistically significant(all P＜0.05).Compared with the OHT group,the rats in the E2-OHT group had an increased number of RGCs,a decreased relative expression level of TNF-α and IL-1 β mRNA and Ibal protein,and an increased expression level of Brn3a protein(all P＜0.05).Conclusion Estradiol can inhibit the activation of microglia,reduce the expression of TNF-α and IL-1β in the retina of rats with OHT,and reduce the damage to RGCs.

Objective To explore the mechanism of butylphthalide(NBP)in regulating microglia acti-vation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy af-ter carbon monoxide poisoning(DEACMP).Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized in-to three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegeta-ble oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-bind-ing adapter molecule 1(IBA1)was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA.Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency(P=0.001,P=0.029),reduced nerve cells(P=0.001,P=0.035),up-regulated expression of IBA1(P=0.001,P=0.042),increased mean fluorescence intensity of IBA1(P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α(TNF-α)(P=0.002,P=0.024),inter-leukin(IL)-6(P=0.001,P=0.015),and IL-1β(P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency(P=0.025),increased nerve cells(P=0.039),down-regulated expression of IBA1(P=0.035),decreased average fluorescence intensity of IBA1(P=0.031),and lowered levels of TNF-α(P=0.028),IL-6(P=0.037),and IL-1 β(P=0.034).Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cog-nitive dysfunction and brain tissue damage caused by DEACMP.

Objective:To explore the clinical value of syndecan-1 (SDC1), asymmetric dimethylarginine (ADMA) assessment in the early diagnosis and course monitoring of patients with type 2 diabetic kidney disease (DKD).Methods:This is a cross-sectional study. A total of 232 patients with type 2 diabetes admitted to the Department of Endocrinology of Kailuan General Hospital from December 2020 to December 2021 were included. The general biochemical indexes, SDC1 and ADMA were detected. According to urinary albumin/creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), patients were divided into simple diabetes group (50 cases) and DKD group (182 cases). According to the risk of progression of DKD, the DKD group was further divided into low-progression diabetic nephropathy (LDKD) subgroup (90 cases), medium-progression diabetic nephropathy(MDKD)subgroup (55 cases), and high-progression diabetic nephropathy(HDKD) subgroup (37 cases). Forty healthy people undergoing physical examination during the same period in our hospital were selected as the healthy control group. According to the quartile value of N-acetyl-β-D-glucosaminase/urinary creatinine (NAG/Ucr), the DKD group was divided into Q1- Q4 subgroups, with 45, 45, 46 and 46 cases, respectively. Spearman correlation was used to analyze the correlation between SDC1, ADMA and glomerular and renal tubule injury indexes in DKD patients. Multifactor ordered Logistic regression was used to analyze the influencing factors of the progression risk of DKD and renal tubular injury. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of SDC1 and ADMA for DKD. Results:The levels of systolic blood pressure, diastolic blood pressure, triglyceride (TG), serum creatinine (Scr), uric acid (UA), NAG/Ucr, SDC1 and ADMA in DKD group were higher than those in SDM group and healthy control group (all P<0.05). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and hemoglobin A1c (HbA 1c) in DKD group were higher than those in healthy control group, and the level of high density lipoprotein cholesterol (HDL-C) was lower than that in healthy control group (all P<0.05). The SDC1 level in HDKD subgroup was higher than that in SDM group and LDKD subgroup, and the ADMA level was higher than that in SDM group and lower than that in LDKD subgroup (all P<0.05). SDC1 level in MDKD subgroup was higher than that in SDM group and LDKD subgroup, ADMA level was higher than that in SDM group, but lower than that in LDKD subgroup (all P<0.05).The levels of SDC1 and ADMA in LDKD subgroup were higher than those in SDM group (all P<0.05). The levels of TC, AporB, HbA 1c, Scr, UACR and SDC1 in NAG/Ucr Q4 subgroup were higher than those in Q1 subgroup, the levels of Scr, UACR and SDC1 were higher than those in Q2 subgroup, and the levels of HbA 1c, Scr, UACR and SDC1 in Q3 subgroup were higher than those in Q1 subgroup (all P<0.05). Spearman correlation analysis showed that SDC1 was positively correlated with UACR, NAG/Ucr ( r=0.757, 0.566, all P<0.05),and was negatively correlated with eGFR ( r=-0.337, P<0.05). ADMA was positively correlated with UACR, NAG/Ucr ( r=0.197, 0.142, all P<0.05). Multifactor ordered Logistic regression analysis showed that SDC1, NAG/Ucr and Scr were the independent influencing factors of progression risk in DKD patients ( OR=2.043, 1.067, 1.047, 0.660, 1.394, all P<0.05), while SDC1, HbA 1c and ACR were the independent influencing factors of renal tubule injury in DKD patients ( OR=1.177, 1.193, 1.002,all P<0.05). ROC curve showed that the area under the curve (AUC) of SDC1 for DKD diagnosis was 0.979, the sensitivity was 92.31%, and the specificity was 92.22%, while the AUC of ADMA for DKD diagnosis was 0.745, the sensitivity was 81.32%, and the specificity was 60.00%. The AUC, sensitivity and specificity of the combined diagnosis of DKD were 0.981, 90.66% and 95.66%. Conclusions:SDC1 is an independent risk factor of DKD progression and tubular injury in DKD patients, which can be used to diagnose early DKD and monitor the progression of DKD. ADMA is suitable for early screening of DKD.

Objective To investigate the effect of genistein on the proliferation,migration and invasion of prostate cancer cells and its molecular mechanism.Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group(conventional culture)and the experimental group(50μmol/L genistein treatment).The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay.The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay.The protein levels of epithelial interstital transformation(EMT)intermediate markers E-Cadherin,N-Cadherin,Vimentin,and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay.Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells.The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group,and the number of cells passing through the Transwell membrane was significantly reduced(P＜0.05).Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin,Vimentin,CD44 and Oct4 in prostate cancer cells,and up-regulate the expression of E-Cadherin in epithelial cells(P＜0.01).Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process,thus reducing the proliferation,migration and invasion of prostate cancer cells.