ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

Objective To explore the characteristics of gastric emptying in the whole process of drinking water for colonoscopy in the elderly,and to develop an elderly-friendly drinking water program,thereby improving the comfort and the quality of bowel preparation.Methods From April to September 2024,gastric ultrasound was used to monitor gastric emptying indicators in the whole process of drinking water for colonoscopy in the elderly,summa-rizing its physiological features.On this basis,in October 2024,through literature review and expert argumentation,a bowel preparation drinking water program that meets the characteristics of gastric emptying in the elderly was de-veloped.A convenience sample of 90 elderly patients scheduled for colonoscopy at 2 tertiary hospitals in Beijing was enrolled from November 2024 to January 2025.A non-concurrent controlled trial was conducted:an experimen-tal group from December 2024 to January 2025 received the new elderly-friendly drinking water program,while a control group in November 2024 followed the conventional program.Outcomes included drinking comfort assessed via Visual Analogue Scale(VAS),adverse events,total fluid intake volume and bowel preparation quality via Boston Bowel Preparation Scale(BBPS).Results The experimental group demonstrated superior VAS score(P＜0.05),bowel preparation quality(P＜0.05),total fluid intake(P＜0.05),and higher compliance with optimal stool consistency(P＜0.05),compared to the control group.The experimental group also exhibited a lower incidence of adverse events(P＜0.05).No significant difference was observed in total bowel preparation duration between 2 groups(P＞0.05).Conclusion The bowel preparation drinking water program based on the characteristics of gastric emptying in the elderly improved solution intake tolerance and bowel preparation quality,with practical implications for clinical implementation.

Objective To systematically evaluate and integrate qualitative studies on perception of exercise behaviors in community-dwelling older adults with frailty,and to provide references for clinical development of targeted exercise intervention strategies.Methods A systematic search of PubMed,Medline,Embase,PsycINFO,the Cochrane Library,SinoMed,Wanfang Database,CNKI,and VIP Database for qualitative studies on perception of exercise behaviors in older adults with frailty in the community was conducted from the inception of the databases to June 2024.Literature quality was evaluated using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016 edition),and Meta-synthesis was performed using the theme synthesis method.Results A total of 10 papers were included,grouped into 10 categories and integrated into the 3 domains of the capability,opportunity,and motivation-behavior model(COM-B model),i.e.Preparation for exercise behavior is influenced by capability factors(physical reserve,knowledge reserve,psychological preparation);stage-specific motivational evolution promotes the internalization of exercise behavior(guiding,focusing,stimulating,and maintaining);external conditions provide opportunities for exercise behavior(individual interaction,community environment,and social support).Conclusion Perceptions of exercise behavior among community-dwelling older adults with frailty or are complex and influenced by a variety of factors.Future exercise intervention strategies should consider modifiable factors,enhance knowledge education,stimulate intrinsic motivation,and solidify external conditions,while also accommodating individual differences and preferences,so as to promote exercise participation and health enhancement in this group.

To retrospectively analyze the clinical data of 465 newly diagnosed patients with multiple myeloma (NDMM) admitted to the First Affiliated Hospital of Nanjing Medical University from December 2016 to December 2024, and compare the prognostic value of high-risk cytogenetic abnormalities (HRCAs) in NDMM patients under mSMART 3.0 and mSMART 4.0 risk stratification systems. The results showed that in both stratification systems, the prognosis of high-risk patients was worse than that of standard-risk patients. Moreover, a higher number of HRCAs was associated with a worse prognosis. The mSMART 4.0 system, which considers the coexistence of various cytogenetic abnormalities, provides a more precise definition of HRCA than mSMART 3.0. It demonstrates a superior ability to differentiate between different categories of cytogenetic risk.

Objective:To investigate the correlation between remnant cholesterol/high-density lipoprotein cholesterol ratio (RC/HDL-C) and metabolic dysfunction-associated fatty liver disease (MAFLD) in health check-up population.Methods:It was a cross-sectional study. A total of 5 299 subjects who received physical examination in the Health Management Center of Renmin Hospital of Wuhan University from January to December in 2023 and met the admission criteria were selected as the research subjects. The subjects were examined by demography, anthropometry, laboratory tests and liver instantaneous elastography. The Chi-square test, t-test, one-way analysis of variance, Mann-Whitney U test and Kruskal-Wallis H test were used to compare the indexes between the subjects with and without MAFLD. The subjects were divided into 4 groups (Q1-Q4 groups) according to the RC/HDL-C ratio quartiles by quartile method, and the indexes in each group were compared. The receiver operating characteristic (ROC) curves were drawn using MedCalc software and compared to assess the diagnostic efficacy of the RC/HDL-C ratio for MAFLD. Results:With the increase of RC/HDL-C ratio, the detection rate of MAFLD (12.56% vs 43.48%), male proportion (55.68% vs 85.60%), total cholesterol (TC) [(4.63±0.82) vs (5.10±1.06) mmol/L], triglyceride (TG) [0.90(0.71, 1.15) vs 2.58(1.96, 3.50) mmol/L], alanine aminotransferase (ALT) [17.00(13.00, 24.00) vs 26.00(19.00, 38.00) U/L], aspartate aminotransferase (AST) [20.00(17.00, 24.00) vs 23.00(19.00, 29.00) U/L], and controlled attenuation parameter (CAP) [(239.32±40.52) vs (274.60±44.98) dB/m] increased gradually, while high-density lipoprotein cholesterol (HDL-C) [1.40(1.20, 1.64) vs 0.93(0.84, 1.04) μmol/L] decreased gradually (all P<0.05). ROC curves showed that the AUC value of RC/HDL-C ratio was significantly higher in identifying MAFLD when compared with TC, HDL-C, LDL-C, non-HDL-C and RC (AUC=0.676, P<0.05). Conclusions:The RC/HDL-C ratio is positively correlated with the risk of morbidity of MAFLD in health check-up population.

Objective To investigate the incidence and adverse prognosis of late onset sepsis(LOS)in neonates in neonatal intensive care unit(NICU).Methods A retrospective study was conducted to collect and analyze the peri-natal condition,underlying diseases,invasive procedures,and adverse prognosis of neonates in NICU of a regional maternal and child healthcare hospital from 2019 to 2023.According to whether LOS occurred during hospitaliza-tion,neonates were divided into LOS group and non-LOS group.The LOS group was divided into 5 subgroups based on whether invasive procedures were performed:LOS plus umbilical vein catheter(UVC)group,LOS plus peripherally inserted central catheter(PICC)group,LOS plus sequential catheter group,LOS plus tracheal intuba-tion group,and LOS plus lumbar puncture group,the relationship between LOS and adverse prognosis was ana-lyzed.Results Among 2 945 neonates in NICU,354(12.02％)developed LOS.Comparison between LOS groups and non-LOS group were as follows:in term of perinatal condition of neonates,there were statistically significant difference in weight,gestational age,and whether they were twins between the two groups(all P＜0.001);in term of underlying diseases,there were statistically significant differences in the number of cases of maternal gestational hypertension,neonatal asphyxia,neonatal congenital heart disease,neonatal ventricular dilation,neonatal pneumo-nia,neonatal hyperthyrotropinemia,and neonatal anemia,as well as five invasive procedures between the two groups(all P＜0.05).Compared with the non-LOS group,the incidences of retinopathy of prematurity(ROP),neonatal necrotizing enterocolitis(NNEC),bronchopulmonary dysplasia(BPD),and neonatal respiratory distress syndrome(NRDS)in LOS group were all higher(all P＜0.001).Regression analysis showed that compared with the non-LOS groups,the risk of ROP increased in the LOS group and its subgroups,with the LOS plus sequential catheter group having a 2.27-fold higher risk of ROP than non-LOS group;the risk of NNEC increased in the LOS group and its subgroups,with the LOS plus UVC group having an 8.29-fold higher risk of NNEC than the non-LOS group.Except for the LOS plus UVC group,the risk of BPD increased in the LOS group and other subgroups,with the LOS plus PICC group and LOS plus sequential catheter group having 4.68-and 4.64-fold higher risk of BPD than the non-LOS group,respectively;the risk of NRDS in the LOS plus PICC group was 6.84-fold higher than the non-LOS group(all P＜0.05).The top three pathogens causing LOS were coagulase negative Staphylococcus,Klebsiella pneumoniae,and Escherichia coli.Conclusion LOS can significantly increase the risks of ROP,NNEC,BPD,and NRDS.LOS plus invasive procedures can further increase the risk of adverse prognosis.

BACKGROUND:In the occurrence and development of demyelinating diseases of the central nervous system,neuroinflammation caused by microglia is the main pathological feature,so inhibiting the inflammatory response is very important to alleviate demyelination.Hydroxysafflor yellow A can protect the blood-brain barrier,inhibit neuronal apoptosis,and improve neurological function.OBJECTIVE:To explore the mechanism of hydroxysafflor yellow A inhibiting bicyclohexanone oxalyl dihydrazone-induced demyelination in mice.METHODS:(1)In vivo:Thirty healthy male C57BL/6 mice were randomly divided into three groups:normal group,cuprizone group,and hydroxysafflor yellow A group.The mice in the cuprizone group and the hydroxysafflor yellow A group were fed with 0.2％cuprizone diet for 6 weeks to establish mouse models of demyelination.The mice in the normal group were fed with normal diet.At the end of the 4th week,the mice in the hydroxysafflor yellow A group were intraperitoneally injected with hydroxysafflor yellow A 20 mg/kg per day.The mice in the normal and cuprizone groups were intraperitoneally injected with normal saline for 2 weeks.The behavioral changes of mice were evaluated by open field test and elevated plus maze test.The loss of myelin sheath in corpus callosum was detected by black gold staining,myelin basic protein and degraded myelin basic protein immunofluorescence staining.The activation of microglia and the expression of inflammatory factors were detected by I ba-1 immunofluorescence staining and ELISA,respectively.The protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 in the brain of mice in each group were detected by western blot assay.(2)In vitro experiment:The inflammation model of BV2 microglia was established by lipopolysaccharide induction.BV2 cells were divided into normal group,lipopolysaccharide group(1 μg/mL),and lipopolysaccharide(1 μg/mL)+hydroxysafflor yellow A(25 μmol/L)group.The expression levels of tumor necrosis factor α and interleukin 6 in the supernatant were detected by ELISA.RESULTS AND CONCLUSION:(1)Compared with the normal group,the mice in the cuprizone group had severe anxiety,abnormal autonomic movement ability,and a large amount of myelin sheath loss in the corpus callosum.The average fluorescence intensity of myelin basic protein was significantly reduced,and the average fluorescence intensity of degraded myelin basic protein was significantly increased.The number of lba1+microglia increased,the contents of interleukin 1β,tumor necrosis factor α,and interleukin 6 in the brain increased,and the protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 increased significantly.The above symptoms and indexes of mice were reversed after hydroxysafflor yellow A treatment.(2)Hydroxysafflor yellow A significantly inhibited the expression of inflammatory factors such as tumor necrosis factor α,and interleukin 6 induced by lipopolysaccharide in BV2 microglia.(3)The above results demonstrate that hydroxysafflor yellow A can significantly improve cuprizone-induced demyelination in mice.The mechanism of action is related to the inhibition of microglial activation-mediated inflammatory response through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor κB p65 signaling pathway.

BACKGROUND:Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia.In basic studies,models of spleen-deficiency and hyperlipidemia are commonly found in rats,pigs,and other animals.This has limitations for medical research that can only use mouse models.It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia.OBJECTIVE:To establish a mouse model of spleen-deficiency hyperlipidemia.METHODS:Totally 24 C57BL/6J mice were randomly divided into normal group(n=12)and spleen-deficiency hyperlipemia group(n=12).Mice in normal group were fed basic diet.Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model.In the first 2 weeks,the mice were forced to swim to their endurance limit on a single day and were only fed cabbage,with free access to water.They were also gavaged with refined lard+high-fat feed on two-day intervals.After 2 weeks,the mice were fed a high-fat diet every day and the diet continued until 12 weeks.The mice were fed with a high-fat diet for 4 and 12 weeks,and their body weight,food intake,gripping strength,fecal water content,small intestinal charcoal propulsion rate,serum D-xylose and gastrin levels,spleen index and thymus index,blood lipid level,total body fat mass,body fat percentage,and liver lipid deposition were tested.RESULTS AND CONCLUSION:(1)Compared with the normal group,the body weight,fecal water content,total body fat mass,body fat percentage,triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased(P＜0.05);the daily food intake,gripping force,and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased(P＜0.05);the spleen index of the mice fed with high-fat diet for 4 weeks was increased(P＜0.05);the small intestinal carbon propulsion rate,gastrin level,spleen index,and thymus index of the mice fed with high-fat diet for 12 weeks were decreased(P＜0.05);the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased(P＜0.05).(2)The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group,and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group.(3)The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders,exhaustion,and high-fat feeding.

Objective:To analyze the disease burden of respiratory syncytial virus (RSV)- associated lower respiratory tract infection (LRTI) in Chinese children under one year of age from 1990 to 2021.Methods:Using the Global Burden of Disease (GBD) 2021 database ( https://vizhub.healthdata.org/gbd-results/), we calculated deaths, mortality, age-standardized mortality rates (ASMR), disability- adjusted life years (DALYs), DALY rates, and age-standardized DALY rates (ASDR) to assess the disease burden of RSV-associated LRTI in Chinese children under one year of age. Joinpoint regression modeling was employed to analyze temporal trends in disease burden in China from 1990 to 2021, with stratification by time, age, and sex. Comparisons were made with global and high socio-demographic index (SDI) regions. Results:In 2021, there were 324 deaths (95% UI: 179-539) from RSV-LRTI in Chinese infants under one year of age, with a mortality rate of 2.82 per 100 000 (95% UI: 1.55-4.69), ASMR of 0.10 per 100 000 (95% UI: 0.06-0.16), DALYs of 29 131.28 years (95% UI: 16 050.27-48 398.30), DALY rate of 253.56 per 100 000 (95% UI: 139.70-421.26), and ASDR of 6.70 per 100 000 (95% UI: 3.72-11.12). All metrics were lower than global levels but significantly higher than high-SDI regions. From 1990 to 2021, substantial reductions were observed in deaths, mortality rates, DALYs, and DALY rates of RSV-LRTI among children under one year of age in China, globally, and in high-SDI regions. China achieved ASMR and ASDR reductions of－95.91% (95% CI:－97.75% to－92.96%) and－96.70% (95% CI:－98.19% to－94.33%), comparable to high-SDI regions but exceeding global averages. Joinpoint analysis showed average annual percentage changes (AAPC) in ASMR of－9.80% (95% CI:－10.45% to－9.14%) for China,－5.38% (95% CI:－5.83% to－4.91%) globally, and－7.13% (95% CI:－9.07% to－5.14%) for high-SDI regions (all P<0.001). The AAPC for ASDR were－10.41% (95% CI:－11.01% to－9.79%),－5.40% (95% CI:－5.82% to－4.97%), and－7.09% (95% CI:－9.70% to－4.41%) for China, the global average, and high-SDI regions, respectively, with the most pronounced decline occurring between 2019 and 2021 (ASMR decreased by 53.33%, 45.81%, and 61.31%, while ASDR declined by 52.50%, 44.54%, and 58.88% in China, globally, and in high-SDI regions, respectively). In 2021, both China and high-SDI regions exhibited declining mortality and DALY rates for RSV-LRTI with increasing age among children under one year, while neonates younger than 28 days consistently demonstrated the highest burden metrics. The rate of decline was comparable between China and high-SDI regions, with both exceeding the global average. Furthermore, from 1990 to 2021, male infants under one year of age in China, globally, and in high-SDI regions consistently showed higher overall trends in deaths, mortality rates, DALY, and DALY rates for RSV-LRTI compared to female infants. Conclusions:Although China's RSV-LRTI disease burden in infants under one year remains lower than global levels but higher than high-SDI regions, the country achieved reduction rates comparable to high-SDI regions, exceeding global averages. RSV-LRTI continue to pose significant health threats to neonates and male infants, necessitating age-specific and sex-specific prevention strategies.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.