ObjectiveTo clarify the application value of nutritional scoring in patients with sepsis and explore the impact of the modified Nutritional Risk in Critically Ill （mNUTRIC） score on the in-hospital fatality of sepsis patients in the emergency intensive care unit （EICU）. MethodsA retrospective analysis was conducted on the clinical data and laboratory examination results of 436 sepsis patients treated in the EICU of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2021 to May 2024. The patients were divided into survival group （298 cases） and death group （138 cases） according to whether they died or not during hospital treatment， and then compared the two groups’ data. Logistic multi-factor regression analysis was used to analyze the risk factors for in-hospital death and the ROC curve to evaluate the predictive value of each risk factor for the prognosis of sepsis patients. ResultsThe death group exhibited higher Acute Physiology and Chronic Health EvaluationⅡ（APACHE Ⅱ） score， Nutritional Risk Screening 2002 （NRS 2002） score， mNUTRIC score， Sequential Organ Failure Assessment （SOFA） score， Padua Prediction Score for Venous Thromboembolism， the proportions of chronic kidney failure and pneumonia patients， C-reactive protein （CRP） level， lactate concentration and neutrophil count， but lower prognostic nutritional index， cholinesterase level， cholinesterase-albumin ratio and lymphocyte count than the survival group， with statistical significance （all P<0.05）. Logistic regression analysis revealed that the mNUTRIC score ［OR=1.254， 95%CI （1.109，1.417）］， CRP ［OR=1.004， 95%CI （1，1.007）］， and pneumonia ［OR=1.82， 95%CI （1.017， 3.257）］ were independent risk factors for in-hospital death in sepsis patients. ROC curve analysis showed that the area under the curve （AUC） of the mNUTRIC score for predicting in-hospital death in sepsis patients was 0.683 ［95%CI （0.623，0.742）］， with a sensitivity of 83% and a specificity of 49.3%. The AUC for CRP and pneumonia were 0.602 ［95%CI （0.533， 0.671）］， and 0.582 ［95%CI （0.516，0.647）］. ConclusionThe mNUTRIC score is an independent predictive indicator for in-hospital death in sepsis patients in the EICU.

Objective : To analyze the trends in mortality and life lost due to bladder cancer in Suzhou City, Jiangsu Province from 2003 to 2022, so as to provide the reference for prevention and treatment strategy of bladder cancer. Methods: The data of bladder cancer death in Suzhou City from 2003 to 2022 were collected through Suzhou Residents' Death Registration System, including age, gender, date of death and underlying cause of death. The crude mortality, standardized mortality, years of potential life lost (PYLL), standardized years of potential life lost (SPYLL), years of potential life lost rate (PYLLR), standardized years of potential life lost rate (SPYLLR) and average years of life lost (AYLL) were calculated. The average annual percent change (AAPC) was used to analyze the trends in bladder cancer death and life lost. Results: Totally 2 978 deaths occurred due to bladder cancer in Suzhou City from 2003 to 2022. The crude mortality was 2.22/105, which appeared a tendency towards a rise (AAPC=4.271%, P<0.05). The standardized mortality was 0.91/105, which appeared no significant changing trend (P>0.05). The standardized mortality was 1.58/105 in males and 0.37/105 in females, which appeared no significant tendency in males (P>0.05) and appeared a tendency towards a decline in females (AAPC=-2.331%, P<0.05). The age-specific crude mortality was low among people who aged under 45 years, began to rise among people aged over 45 years and peaked among people aged 60 years and older. The crude mortality of bladder cancer in males aged 60 years and older showed an increasing trend (AAPC=2.864%, P<0.05), but there was no significant tendency in females aged 60 years and older (P>0.05). The PYLL, SPYLL, PYLLR, SPYLLR and AYLL of bladder cancer were 5 020.00 person-years, 2 945.14 person-years, 0.04‰, 0.03‰ and 9.07 years per person. SPYLL, SPYLLR and AYLL showed an decreasing trend (AAPC=-2.867%, -3.321%, -3.738%, P<0.05). Conclusions The mortality of bladder cancer in Suzhou City appeared a tendency towards a rise from 2003 to 2022. The PYLL appeared a downward trend. Males aged 60 years and older are the key groups for the prevention and control of bladder cancer.

Objective: To evaluate the risk of fine particulate matter (PM2.5) on excess mortality among residents. Methods: The data of residential mortality in Yangzhou City, Jiangsu Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The average daily mass concentration of PM2.5 and meteorology data were collected from the Yangzhou Environmental Monitoring Station and Yangzhou Meteorological Bureau, respectively. The effects of PM2.5 on non-accidental mortality, morality of respiratory diseases and mortality of circulatory diseases were evaluated using a generalized additive model. The risk of excess mortality was evaluated using excess risk (ER) and the number of excess mortality. Results: The median average annual mass concentration of PM2.5 was 38.00 (interquartile range, 31.95) µg/m3 in Yangzhou City from 2015 to 2021, decreasing from 51.75 (interquartile range, 32.82) µg/m3 in 2015 to 28.00 (interquartile range, 23.42) µg/m3 in 2021. The median average annual number of non-accidental mortality, mortality of respiratory diseases and mortality of circulatory diseases were 96 (interquartile range, 22), 9 (interquartile range, 5) and 38 (interquartile range, 13) cases, respectively. The greatest effects of per 10 μg/m3 increase in PM2.5 mass concentration on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases were seen at a cumulative lag of 1 day (ER=0.528%, 95%CI: 0.293%-0.763%), a cumulative lag of 2 days (ER=0.917%, 95%CI: 0.125%-1.714%) and a cumulative lag of 1 day (ER=0.595%, 95%CI: 0.232%-0.961%), respectively. The number of excess mortality caused by PM2.5 on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases in Yangzhou City from 2015 to 2021 were 2 125, 412 and 977 cases, respectively; compared with 2015, the number of excess mortality in 2021 decreased by 66.95%, 75.53% and 64.42%, respectively. Conclusions An increase in the mass concentration of atmospheric PM2.5 may elevate the risk of excess mortality among residents. Compared to 2015, the number of excess deaths attributed to exposure to atmospheric PM2.5 declined in 2021.

OBJECTIVE To investigate the effect of a new variety of Sambucus williamsii Hance Yandan on the healing in rats with fractures. METHODS SD rats were randomly allocated to sham surgery group， model group， Zhonghua dieda pill group （0.54 g/kg）， wild S. williamsii group （5.4 g/kg， using raw drug dosage）， and high-， medium-， and low-dose groups of Yandan （10.8， 5.4， 2.7 g/kg， using raw drug dosage）， with 12 rats in each group. Except for the sham surgery group， the remaining groups were prepared with a femoral fracture model. Starting from the second day after surgery， each group was intubated with the corresponding drugs and distilled water once daily for 8 consecutive weeks. At 2， 4， and 8 weeks after administration， the levels of calcium， phosphorus， alkaline phosphatase （ALP）， and osteocalcin （OCN） in rat serum were detected. Micro-CT scanning was used to evaluate the morphology and bone microstructural parameters of the fractured femur [bone mineral density （BMD）， bone volume/tissue volume （BV/TV）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， trabecular thickness （Tb.Th）]， and hematoxylin-eosin staining was adopted to observe the morphological changes at the bone fracture site. RESULTS Compared with the model group， the levels of calcium in rat serum were significantly decreased （except at 4 weeks after administration）， and the levels of phosphorus， ALP， and OCN were significantly increased （P＜0.05） at 2， 4， and 8 weeks after administration in the high- dose group of Yandan； bone callus formation， connection of fracture ends， gradual blurring or disappearance of the fracture line， and opening of the marrow cavity were observed in the bone repair process， and a large amount of granulation tissue， fibroblasts， chondrocytes， new trabeculae， and new bone plates were visible at the fracture site of bone tissue； after 8 weeks of administration， BMD， BV/TV， Tb.N， and Tb.Th were significantly increased， and Tb.Sp was significantly decreased （P＜0.05）. Most of the above indicators in the wild S. williamsii Hance group showed no significant changes. CONCLUSIONS Yandan has the effect of promoting fracture healing in rats， and its effect is superior to that of wild S. williamsii.

Objective:To analyze the significance of systemic immune inflammatory index (SII) combined with neutrophil lymphocyte ratio (NLR) in the treatment of advanced gastric cancer with PD-1/PD-L1 inhibitors.Methods:The clinical data of 90 patients with stage Ⅳ gastric adenocarcinoma who received immunotherapy from January 2020 to January 2023 were retrospectively analyzed, including 70 males and 20 females, aged from 36 to 80 years, with an average age of (53.76±15.58) years. The clinicopathological features and follow-up data were collected. SPSS 26.0 software was used to conduct statistical analysis. The critical values of NLR, SII, PLR and MLR were calculated, and the overall survival (OS) and progression free survival (PFS) of patients with different levels of markers were analyzed. The independent predictive factors of PFS and OS were determined, and the predictive value of risk factors for PFS and OS in patients with gastric cancer was evaluated.Results:The median follow-up time of all patients was 27.3 months, and the median PFS and OS were 10.0 months and 17.7 months, respectively. The area under the curve (AUC) of NLR and SII for predicting PFS and OS were>0.7, the critical values NLR were 4.75 and 3.85, and SII were 1154.67 and 887.90, respectively. PFS and OS in patients with high NLR, high MLR, high PLR and high SII were lower than those in patients with low levels. ECoG PS≥ 1, high NLR and high SII were independent influencing factors of disease progression or death. The AUC of the combination of NLR, ECoG PS and SII was 0.761, which was higher than that of any single factor. The fewer the number of risk factors, the longer the PFS and OS.Conclusions:NLR and SII are effective predictors of PFS and OS in patients with advanced gastric cancer receiving immunotherapy. Pre treatment detection of NLR and SII can provide reliable guidance for immunotherapy of advanced gastric cancer.

Intelligent control systems can effectively assist in the construction and management of laboratory animal facilities, improving operational efficiency, ensuring the reliability of animal experimental results, and significantly saving human resources. The intelligent control system for laboratory animal facilities at Shenzhen Institute for Drug Control was completed in April 2021. It includes an intelligent management platform and an information management system for animal laboratories. The intelligent management platform regulates room environment parameters such as temperature, humidity, and pressure through building equipment management system, controlling devices such as the Venturi valve, electric air valve, electric water valve, and steam humidification valve. At the same time, various environmental parameters are monitored online through the environmental monitoring system. The laboratory’s intelligence is further enhanced by systems such as automatic lighting control, full HD video monitoring, automatic access control and door system, independent ventilation and feeding, automatic cleaning, automatic exhaust gas treatment, centralized gas supply, and real-time instrument parameter monitoring. The information management system for animal laboratories integrates inspection, instrument and equipment, personnel, documents, standard substances, reagents, inspection standards, books, records, scientific research management, relevant applications, quality management, and query statistics. For animal experimentation, a management module has been developed to achieve a comprehensive digitization of animal management. Furthermore, real-time collection and recording of data such as balance calibration, sample quality, and animal weight are facilitated through electronic experimental recording. In summary, the Animal Laboratory of Shenzhen Institute for Drug Control has extensively utilized intelligent systems to achieve real-time online control and monitoring, improve efficiency, ensure high-quality facility operation, and meet standard requirements. Smooth execution of all inspection and research activities has been achieved over the past three years. This paper provides insights into the construction, management, and operation of laboratory animal facilities at Shenzhen Institute for Drug Control, offering guidance for the implementation of intelligent control in similar facilities across China.

AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.

Objective:To assess the association of cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). Methods:From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+ 49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group ( n=166) and poor prognosis group ( n=86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. Results:No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups ( P>0.05). The frequencies of GG genotype and G allele for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group ( P<0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups ( P>0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group ( P<0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P<0.001). Conclusion:The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.