ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

To investigate the prevalence and associated factors of fall risk among Chinese older adults, and to examine the roles of urban-rural differences, regional disparities, physical health status, and psychosocial factors in falls among this population, thereby providing evidence for tailored fall prevention strategies.

Objective To investigate the frequency and dose of X-ray computed tomography (CT) medical exposure in Shantou City, and to evaluate the collective effective dose burden of residents caused by CT medical exposure. Methods The study subjects were selected using the stratified random sampling method from CT scanners in all medical institutions in Shantou City in 2020. CT application units were divided into the four tiers of municipal hospitals, district hospitals, subdistrict hospitals, and private hospitals, and 50% of the hospitals in each tier were randomly selected according to the number of hospitals in the tier. The study analyzed CT dose index results, CT scanning standard conditions, and the distribution of characteristic doses of medical exposure to evaluate the dose burden of residents in Shantou City caused by CT medical exposure. Results There were 51 CT scanners in medical institutions in Shantou City. By the end of 2020, the average number of CT scanners per million population was 9.30, and the frequency of CT medical exposure was 135.24 per 1000 population. Jinping District had the highest number of CT scanners per million population (23.2), while Chaoyang District had the lowest number of CT scanners per million population (3.6). The median and range of effective doses for different scan regions were 1.65 (0.76, 4.49) mSv in the head, 4.12 (1.90, 53.21) mSv in the chest, 5.96 (2.68, 10.25) mSv in the abdomen, and 10.30 (4.12, 12.67) mSv in the lumbar spine. By the end of 2020, the effective dose to the public in Shantou City was 6080.67 Sv·person, and the average annual effective dose per person was 1.10 mSv. Conclusion Medical exposure is the most important factor affecting resident dose burden, particularly the overuse of medical exposure examinations. CT examination is the most significant component of medical exposure causing resident dose burden. Reducing unnecessary medical exposure, ensuring the rational use of CT examination, and properly utilizing personal protective equipment are effective measures to minimize the dose burden on examinees.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS).Methods:This retrospective cohort study enrolled patients aged ≥45 years who were diagnosed with ACAOS by coronary computed tomography angiography (CTA) at the Affiliated Hospital of Xuzhou Medical University between January 1, 2011, and December 31, 2018. Baseline clinical data and coronary CTA images were collected. Anatomic imaging features were extracted, including ACAOS subtype, course of the anomalous vessel, and ostial angle. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac death, and coronary revascularization. The Maxstat method was used to determine the cut-off values of specific anatomical features for predicting MACE risk. Cox proportional hazards models were employed to analyze the impact of these imaging features on MACE in middle-aged and elderly ACAOS patients.Results:A total of 203 patients were enrolled, aged (60.0(51.0, 66.0)) years, including 119 (58.6%) males. Over a follow-up of (98.2±30.9) months, 39 patients experienced MACE. Maxstat identified an optimal cut-off value of 34.3° for the ostial angle of the anomalous vessel. Multivariable Cox proportional hazards regression analysis revealed that the following factors were independent risk factors for MACE: left-sided ACAOS subtype ( HR=4.35, 95% CI 2.17-8.73, P<0.001), an interarterial course between the aorta and pulmonary artery ( HR=3.21, 95% CI 1.23-8.37, P=0.017), an anomalous vessel ostial angle <34.3° ( HR=2.62, 95% CI 1.18-5.77, P=0.017), and concomitant coronary artery disease ( HR=2.92, 95% CI 1.49-5.73, P=0.002). Conclusion:In middle-aged and elderly patients with ACAOS, the imaging anatomical features of a left-sided ACAOS subtype, an interarterial course, and an ostial angle <34.3° are independent risk factors for MACE.

Objectives:We evaluated the clinical significance of unipolar electrogram and bipolar electrogram in guiding radiofrequency ablation for outflow tract ventricular premature contractions(PVC).Methods:Data were collected from 78 patients who underwent successful radiofrequency ablation of PVC.Pre-procedure electrocardiogram showed a LBBB morphology on inferior leads.In the included patients,the right-side ablation was performed at first,and if the ablation failed,the left-side ablation was then performed.According to the location of the successful ablation target,they were divided into unilateral ablation successful group and bilateral ablation successful group.The differences in the earliest bipolar local activation to QRS(LATBi),unipolar-dV/dTmax to QRS(LATUni),and local activation time were compared between the two groups.Furthermore,the electrogram characteristics predicting bilateral ablation were explored.Results:Patients were divided into unilateral ablation group(n=57)and bilateral ablation group(n=21)according to the ablation site.There were statistically significant differences in LATBi(25[21,30]ms vs.14[10,24]ms),LATUni(7[0,17]ms vs.-23[-41,-11]ms),and ΔLATBi-Uni(15[11,25]ms vs.44[25,56]ms)between the unilateral ablation group and the bilateral ablation group(all P<0.05).Multivariate regression analysis suggested that LATBi,LATUni,and ΔLATBi-Uni were independent predictors of the need for bilateral ablation.There was no significant difference between left and right LATBi,LATUni and ΔLATBi-Uni in the bilateral ablation group.LATUni≤-1 was the most accurate parameter for predicting the need for bilateral ablation(AUC=0.941;specificity 80.7%;sensitivity 100%).Conclusions:LATUni≤-1ms is a useful indicator for predicting the need for bilateral PVC ablation in this patient cohort.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.