Objective To analyze drug resistance and clustering of environmental and clinical isolates of Acinetobacter baumannii (A. baumannii) in ICU of a medical institution in Shanghai. Methods The isolates of A. baumannii from ICU environments and clinic were used to analyze the contamination and distribution in 2021-2024. Antimicrobial susceptibility testing was carried out with microbroth dilution method. Whole genome sequencing was performed out of strains for MLST typing and SNP clustering. Results The detection rate of contamination in ICU environment was 7.67%, and the most serious contamination was found in pillows, bedding, hospital gowns and other items that patients directly contacted. Clinical isolates were predominantly from sputum specimens. The environmental and clinical isolates had a high level of resistance to third generation cephalosporins, third generation quinolones and carbapenems (more than 85%). Environmental isolates had a low level of resistance to polymyxin B, but none of the clinical isolates were resistant. MLST typing showed that ST2 was the dominant clone (66.67%), and SNP clustering found that isolates from different sources but with the same ST type were clustered together. Conclusion ST2 is the dominant clone of A. baumannii isolates in this medical institution, and there is cross-contamination between different samples. Monitoring of drug resistance and disinfection should be further strengthened to prevent the emergence and spread of pan-resistant or even fully resistant strains.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective:To investigate the effects of smoking cessation on lung function improvement in patients with chronic obstructive pulmonary disease (COPD) and the related mechanisms.Methods:A case-control study was conducted involving 184 patients with COPD admitted to the Department of Respiratory and Critical Care Medicine at Lishui Central Hospital from January 2022 to May 2023. Based on smoking behavior following 6-month smoking cessation intervention, the patients were categorized into three groups: 56 patients who continued to smoke (control group), 63 patients who completely quit smoking (observation group), and the remaining 65 patients who were partial quitters. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1), and peak expiratory flow rate were monitored before and after the intervention in both the control and observation groups. Additionally, serum levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor alpha, nuclear factor kappa B (NF-κB), malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Western blotting was performed to detect the protein levels of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (Akt), Forkhead box protein O1 (FoxO1), IL-6, IL-1β, NF-κB, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 in peripheral blood cells. FoxO1 chromatin immunoprecipitation sequencing was performed to analyze FoxO1-bound chromatin. Results:After smoking cessation intervention, the FEV 1, FVC, FEV 1/FVC ratio, and peak expiratory flow rate in the observation group were (1.29 ± 0.32) L, (1.96 ± 0.36) L, (71.81 ± 8.57)%, and (2.58 ± 0.72) L/s, respectively, which were significantly higher than those in the control group [(1.10 ± 0.37) L, (1.72 ± 0.34) L, (63.17 ± 8.82)%, (2.20 ± 0.71) L/s, t = -3.00, -3.73, -5.42, -2.89, all P < 0.01]. The serum levels of IL-6, NF-κB, IL-1β, and tumor necrosis factor alpha in the observation group were (21.67 ± 3.25) ng/L, (19.58 ± 4.02) ng/L, (24.30 ± 4.03) ng/L, and (270.14 ± 32.49) ng/L, respectively, which were significantly lower than those in the control group [(39.18 ± 4.34) ng/L, (35.48 ± 4.17) ng/L, (34.42 ± 4.05) ng/L, (445.04 ± 39.12) ng/L, t = 25.08, 21.16, 13.64, 26.63, all P < 0.001]. Additionally, the serum malondialdehyde level in the observation group was significantly lower than that in the control group ( t = 29.08, P < 0.001). In contrast, the levels of superoxide dismutase and glutathione peroxidase in the observation group were significantly higher than those in the control group ( t = -9.21, -9.59, both P < 0.001). The phosphorylation levels of PI3K, Akt, and FoxO1 in peripheral blood cells were significantly lower in the observation group compared with the control group ( t = 6.64, 9.35, 7.12, all P < 0.001). FoxO1 bound to genes involved in inflammation and oxidative stress signaling pathways. The levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in the observation group were significantly higher than those in the control group ( t = -4.97, -10.49, both P < 0.05). Conclusions:Smoking cessation intervention can inhibit PI3K/Akt phosphorylation in patients with COPD, and then activate FoxO1, exert anti-inflammatory and antioxidant effects, and inhibit the deterioration of lung function in patients with COPD who smoke.

Objective To observe the changes of left ventricular systolic function in children with sepsis by two-dimensional speckle tracking imaging(2D-STI).Methods A total of 29 children with sepsis were retrospectively enrolled and divided into severe sepsis group(n=10)and non-severe sepsis group(n=19)according to relevant diagnostic criteria,while 21 healthy children were taken as controls(control group).Conventional echocardiographic parameters and 2D-STI parameters were compared among 3 groups and between each 2 groups.Results Significant differences of left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and right atrial diameter(RAD)were found among 3 groups(all P＜0.05),while no significant difference of right ventricular end-diastolic diameter(RVEDD)nor left ventricular ejection fraction(LVEF)was noticed(both P＞0.05).Meanwhile,significant differences of left ventricular global longitudinal strain(LVGLS)and basal anterior(BA),basal anterolateral(BAL),basal inferolateral(BIL),mid-anterior(MA),mid-anterolateral(MAL),mid-inferolateral(MIL),apical anterior(APA),apical lateral(APL),apical inferior(API)and apex cap(APEX)segment longitudinal strain(LS)were found among 3 groups(all P＜0.05),also of LVGLS between each 2 groups,of LS in BAL,BIL,MA,MAL,MIL,APA,APL,API and APEX segments between severe sepsis group and control group,of LS in BAL and MAL segments between non-severe sepsis group and control group,and of LS in BA,M A,APL,API and APEX segments between severe sepsis group and non-severe sepsis group(all P＜0.05).Conclusion Left ventricular 2D-STI parameters in children with sepsis changed when LVEF was still in normal range,and some parameters were related to the severity of disease.