ObjectiveTo understand the infection characteristics and drug resistance of carbapenem-resistant Serratia marcescens (CRSM) in a general hospital in Shanghai, and to provide a theoretical basis for clinical anti-infective treatment and prevention of drug-resistant bacteria. MethodsClinical data on cases with CRSM infections detected in clinical specimens at a gradeⅢ level A general hospital in Shanghai from June 2022 to June 2024 were retrospectively collected, and their clinical distributions, factors of hospital-acquired infections, prognosis, and drug-resistant situation were analyzed simultaneously. ResultsA total of 38 cases with CRSM were detected from June 2022 to June 2024, and the number of CRSM strains accounted for 25.00% (38/152) of the number of SM strains. The 38 CRSM infection samples were all derived from sputum. CRSM were distributed in 9 clinical departments, and the top 3 departments having the highest percentages of CRSM among SM strains, were intensive care unit (ICU) (78.79%, 26/33), gastrointestinal surgery department (57.14%, 4/7), and thyroid hernia surgery department (50.00%, 1/2). Among the 38 patients with CRSM infections, 8 cases were identified as hospital-acquired infection, resulting in a hospital-acquired infection rate of 21.05. The mortality rate of the 38 cases of CRSM infected patients within 30 days after detection of CRSM was 23.68% (9/38). The results of multivariate logistic regression analysis showed that sequential organ failure assessment (SOFA) score ≥6.5 points (OR=15.33, P<0.001), septic shock (OR=4.85, P=0.032), and suffering from neoplastic diseases (OR=0.12, P=0.018) were the related factors for death within 30 days after the detection of CRSM in patients with CRSM infection. The results of drug sensitivity test showed that the 38 cases of CRSM exhibited 100.00% (38/38) sensitivity to trimethoprim/sulfamethoxazole, tigecycline, or ceftazidime/avibactam; demonstrated high resistance toβ-lactams except for ceftazidime (18.42%, 7/38), the latter of which was one of the third-generation of cephalosporins; showed elevated resistance to fluoroquinolones [levofloxacin (89.47%, 35/38), ciprofloxacin (94.74%, 36/38)]; maintained good tetracycline sensitivity [doxycycline (97.37%, 37/38), minocycline (76.32%, 29/38)]; and displayed high susceptibility to the aminoglycoside gentamicin (94.74%, 36/38) and elevated resistance to tobramycin (86.84%, 34/38). The detection rate of serine carbapenemase in the 38 strains of CRSM was 100.00%, while all strains tested negative for metallo-β-lactamases. ConclusionFrom June 2022 to June 2024, the detection rate of CRSM in a gradeⅢ level A general hospital in Shanghai was relatively high, especially in the ICU. CRSM has a high resistance rate to commonly used antibacterial drugs such as the first and second-generation cephalosporins, quinolones, and polypeptide antibacterial drugs. Therefore the dynamics of drug-resistant bacteria should be tracked in a timely manner to guide the rational clinical application of antibacterial drugs.

Purpose: This study aimed to evaluate the dietary quality and nutritional status of Chinese adults and investigate the factors related to dietary scores using the Nutrition Quotient (NQ) developed for Korean adults. Methods: An online questionnaire survey including the NQ was administered to 424 Chinese adults residing in Shanghai and parts of the Anhui Province. Multiple linear regression analyses were conducted to identify factors related to NQ scores. Results: The mean NQ scores were as follows: balance (35.9), diversity (61.0), moderation (77.1), and dietary behavior (49.4), with an overall average NQ score of 57.2. Subjects were categorized into three levels of NQ: high 40.1%, middle 43.6%, and low 16.3%. After adjusting for confounding variables, multiple linear regression analyses revealed that age was positively associated with the total and subcomponent NQ scores, while the frequency of eating out was negatively associated with the same. Living alone was negatively related to balance, but positively related to diversity. Singles had lower diversity scores. Compared to the residents of second- or third-tier cities, those living in the countryside or village areas had lower balance scores, whereas the inhabitants of first-tier cities had lower moderation scores but higher dietary behavior scores. Female participants scored lower on dietary behavior. Age and eating out emerged as significant factors related to NQ items. Conclusion Applying the Korean adult NQ to Chinese adults revealed relatively low balance scores, indicating a need for tailored assessment tools and educational programs to enhance the dietary quality and nutritional status among Chinese adults. Further research is warranted to explore the determinants of low dietary balance scores in this population.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Purpose: This study aimed to evaluate the dietary quality and nutritional status of Chinese adults and investigate the factors related to dietary scores using the Nutrition Quotient (NQ) developed for Korean adults. Methods: An online questionnaire survey including the NQ was administered to 424 Chinese adults residing in Shanghai and parts of the Anhui Province. Multiple linear regression analyses were conducted to identify factors related to NQ scores. Results: The mean NQ scores were as follows: balance (35.9), diversity (61.0), moderation (77.1), and dietary behavior (49.4), with an overall average NQ score of 57.2. Subjects were categorized into three levels of NQ: high 40.1%, middle 43.6%, and low 16.3%. After adjusting for confounding variables, multiple linear regression analyses revealed that age was positively associated with the total and subcomponent NQ scores, while the frequency of eating out was negatively associated with the same. Living alone was negatively related to balance, but positively related to diversity. Singles had lower diversity scores. Compared to the residents of second- or third-tier cities, those living in the countryside or village areas had lower balance scores, whereas the inhabitants of first-tier cities had lower moderation scores but higher dietary behavior scores. Female participants scored lower on dietary behavior. Age and eating out emerged as significant factors related to NQ items. Conclusion Applying the Korean adult NQ to Chinese adults revealed relatively low balance scores, indicating a need for tailored assessment tools and educational programs to enhance the dietary quality and nutritional status among Chinese adults. Further research is warranted to explore the determinants of low dietary balance scores in this population.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Purpose: This study aimed to evaluate the dietary quality and nutritional status of Chinese adults and investigate the factors related to dietary scores using the Nutrition Quotient (NQ) developed for Korean adults. Methods: An online questionnaire survey including the NQ was administered to 424 Chinese adults residing in Shanghai and parts of the Anhui Province. Multiple linear regression analyses were conducted to identify factors related to NQ scores. Results: The mean NQ scores were as follows: balance (35.9), diversity (61.0), moderation (77.1), and dietary behavior (49.4), with an overall average NQ score of 57.2. Subjects were categorized into three levels of NQ: high 40.1%, middle 43.6%, and low 16.3%. After adjusting for confounding variables, multiple linear regression analyses revealed that age was positively associated with the total and subcomponent NQ scores, while the frequency of eating out was negatively associated with the same. Living alone was negatively related to balance, but positively related to diversity. Singles had lower diversity scores. Compared to the residents of second- or third-tier cities, those living in the countryside or village areas had lower balance scores, whereas the inhabitants of first-tier cities had lower moderation scores but higher dietary behavior scores. Female participants scored lower on dietary behavior. Age and eating out emerged as significant factors related to NQ items. Conclusion Applying the Korean adult NQ to Chinese adults revealed relatively low balance scores, indicating a need for tailored assessment tools and educational programs to enhance the dietary quality and nutritional status among Chinese adults. Further research is warranted to explore the determinants of low dietary balance scores in this population.

The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurode-generative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for in-flammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effec-tively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC50)of 0.478 μM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective:To investigate the feasibility and clinical effects of ultra early enteral nutrition (≤24 h) in critically ill children supported by extracorporeal membrane oxygenation (ECMO).Methods:A retrospective cohort study was conducted. Clinical data of 43 critically ill children who received ECMO support in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2016 to December 2023 were collected, including general information, nutritional support modalities, and enteral nutrition tolerance. Based on the timing of enteral nutrition initiation, patients were divided into the within 24 h enteral nutrition group and the after 24 h enteral nutrition group. Nutritive indicators, nutritional intake, duration of ECMO support, duration of mechanical ventilation duration, and mortality rates were compared between the 2 groups using the two independent sample t test, Mann-Whitney U test, χ2 test and Fisher′s exact test. Results:Among the 43 children, 25 were male and 18 were female, with an age of 47 (18, 97) months. There were no statistically significant differences between the within 24 h enteral nutrition group (21 cases) and the after 24 h enteral nutrition group (22 cases) in terms of age, body mass index Z score, total protein, albumin, hemoglobin levels before ECMO support, duration of ECMO support, duration of mechanical ventilation, length of PICU stay, number of enteral nutrition intolerance events, number of enteral nutrition interruption, or mortality rate (all P>0.05). The protein intake adequacy rate during ECMO support was higher in the within 24 h enteral nutrition group than in the after 24 h enteral nutrition group (0 (0, 21%) vs. 0 (0, 0), U=175.00, P<0.05). Conclusions:Ultra early enteral nutrition is safe for children supported by ECMO. Initiating enteral nutrition within 24 h can increase the proportion of days with adequate protein intake in ECMO children without increasing the occurance of enteral nutrition intolerance or interruptions.

Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.

Objective To explore the correlation between fasting blood glucose(FBG)level and fractional flow reserve(FFR)in patients with borderline coronary artery disease,and to clarify its potential influence on FFR measurement.Methods From August 2020 to August 2023,the data of 135 patients with coronary atherosclerotic heart disease who received coronary angiography and FFR evaluation in the Fourth Affiliated Hospital of Harbin Medical University were retrospectively collected.According to the exclusion and inclusion criteria,85 cases of borderline diseased vessels of single coronary artery with stenosis degree of 50％-80％were screened out,and they were divided into FBG≥6.1 mmol/L group(47 cases)and FBG＜6.1 mmol/L group(38 cases).The baseline data,angiographic and functional indexes of the two groups were compared,and the correlation between FBG and FFR was analyzed.Results Compared with the FBG＜6.1 mmol/L group,the FBG≥6.1 mmol/L group had a higher proportion of FFR negative results(72.3％vs.23.7％,P＜0.001),and the FFR measurement values were generally increased[0.84(0.80,0.90)vs.0.75(0.68,0.80),P＜0.001],with statistically significant differences.Pearson correlation analysis was performed on all lesions,and FFR＞0.80(negative result)was positively correlated with FBG≥6.1 mmol/L(r=0.484,P＜0.001).Conclusions Among the patients with borderline coronary artery disease(50％-80％stenosis)included in this study,FBG≥6.1 mmol/L is significantly correlated with FFR＞0.80.For patients with borderline coronary lesions with elevated FBG,the influence of blood glucose factors should be carefully considered in clinical interpretation of FFR results.