Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

ObjectiveTo analyze the long-term trend of incidence and mortality of type 2 diabetic kidney disease （DKD） in China from 1990 to 2021. MethodsThe Joinpoint regression model was used to analyze the average annual percentage change （AAPC） of standardized incidence rate and standardized mortality rate， and the age-period-cohort （APC） model was constructed to analyze the longitudinal age change， period and cohort effect risk ratio （RR）. ResultsFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in males and females showed an overall upward trend， with AAPC of 0.08% and 0.36%， respectively. The age-standardized mortality rate of the total population and female showed a downward trend， with AAPC of -0.61% and -1.03%， respectively. However， there was no significant difference in males. APC model showed that the age effect existed： the peak age was 75-79 years old， the mortality rate of females increased， and the mortality rate of males decreased after 80-84 years old. For the effect of time period， the risk of type 2 DKD incidence in females in 2017—2021 was 1.05 times that in 2002—2006， and the risk of death in males and females in 2017—2021 was 0.84 and 0.71 times that in 2002—2006， respectively. For cohort effects， the highest risk of disease was seen in men and women born in 1967—1971， and the highest risk of death was seen in men born in 1952—1956 and women born in 1912—1916. ConclusionFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in China shows an upward trend， and the standardized mortality rate shows a downward trend. It is necessary to strengthen the health behavior publicity and education of type 2 DKD， and actively carry out early screening to reduce the disease burden.

Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00％.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39％to 100.00％.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.

Objective To explore the latent profiles of kinesiophobia among patients with peritoneal dialysis and analyze the influencing factors of different categories.Methods A convenience sampling method was used to select peritoneal dialysis patients treated in the outpatient and ward of nephrology department in 7 tertiary A hospitals in Jiangsu Province from December 2023 to March 2024.General data questionnaire,Tampa Kinesiophobia-11 Scale,Exercise Self-efficacy Scale,Exercise Social Support Scale and Self-Rating Anxiety Scale were used for investigation.Results A total of 291 cases were included,and 3 potential categories of kinesiophobia were finally identified,namely low kinesiophobia-active exercise group(20.96％),high kinesiophobia-exercise avoidance group(24.06％),and moderate kinesiophobia-general exercise group(54.98％).Exercise self-efficacy,exercise social support,anxiety,monthly per capita household income,marital status and daily number of dialysis dose were influencing factors of kinesiophobia in peritoneal dialysis patients(P＜0.05).Conclusion There are significant category characteristics of kinesiophobia in patients with peritoneal dialysis.Medical staff should judge the category and influencing factors of kinesiophobia in time,and take targeted interventions to reduce the level of kinesiophobia in patients.

Objective To observe the clinical and imaging manifestations of disseminated nontuberculosis mycobacteria(NTM)disease involved multiple skeletons of non-HIV-infected patients.Methods Totally 11 cases of non-HIV-infected patients with disseminated NTM involved multiple skeletons(NTM group)and 30 patients of bone tuberculosis with multisite skeletal involvement(TB group)were retrospectively analyzed.Clinical and imaging manifestations were analyzed and compared between groups.Results Nine cases(9/11,81.82％)in NTM group were found with systemic underlying disease,including 5 cases of chronic anemia,4 cases of rheumatic immune diseases and 1 case of gout.NTM group had longer disease duration,lower incidence of fever and soft tissue masses,lower hemoglobin and higher erythrocyte sedimentation rate than TB group(all P＜0.05).NTM group exhibited higher incidences of pulmonary patchy/linear shadows,"skip-like"manifestations in spine and patchy/nodular high-density shadows in the affected bones,but lower incidences of pulmonary hematogenous/bronchial dissemination foci,polymorphic lung lesions and bone destruction with sequestrum/surrounding soft tissue abscesses than TB group(all P＜0.05).The thoracic vertebrae,shoulder joints and pelvis were most commonly affected in NTM group,while the thoracic and lumbar vertebrae were most commonly affected in TB group.Significant difference of skeletal involvement site was found between groups(P=0.035).After drug treatment,the conditions of 9 cases(9/11,81.82％)in NTM group improved,with better outcomes in bone destruction and surrounding soft tissue swelling,and bone hardening was more obvious than before.Conclusion Disseminated NTM disease involved multiple skeletons in non-HIV-infected patients was prone to secondarily develop in those with chronic anemia and rheumatologic immune diseases,characterized by prolonged disease duration and mild pulmonary manifestations,often revealed multiple skeletons destruction in thoracic spine,shoulder joints and pelvis,distributed in a"skip-like"pattern,with or without bone sclerosis and adjacent soft tissue swelling.

Metal-organic frameworks(MOFs)are a class of organic-inorganic hybrid materials formed by the self-assembly of metal ions or metal clusters with organic ligands through coordination,and possess high specific surface area,tunable pore size and diverse structures.In recent years,MOFs and their composites have shown great application potential in the field of drug detection,especially in selective recognition,enhancing detection sensitivity and on-site rapid detection.This paper summarized the structural characteristics,synthesis methods and detection principles of MOFs and their composites,and reviewed the latest research progresses in detection of various drugs such as opioids,amphetamines,cannabinoids,cathinones,cocaine,ketamine,fentanyls and psychotropic drugs.The advantages and challenges of MOFs materials in the pretreatment of complex biological samples,sensor construction and on-site rapid detection were discussed,and the prospects for future development were analyzed,with the aim of providing theoretical support and technical references for promoting the applications of MOFs in anti-drug practice.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective: To explore the correlation among picky eating levels in preschool children, parental self-efficacy and parenting stress. Methods: A convenience sampling method was employed to conduct an electronic questionnaire survey among 459 children aged 3-6 years and their parents from five kindergartens in Urumqi in November 2023. The survey included a general information questionnaire, the Children s Eating Behavior Questionnaire (CEBQ), the Parenting Sense of Competence Scale (PSOC), and the Parenting Stress Index-Short Form (PSI-SF). The Mann-Whitney U-test was used for twogroup comparisons, and the Kruskal-Wallis H-test was applied for multi-group comparisons. Spearman correlation analysis was conducted to examine the relationships between children s picky eating levels and parenting selfefficacy as well as parenting stress. Results: The picky eating score of preschool children was 10.00 (4.00), and the parenting self-efficacy score was 58.00 (12.00), both indicating a moderate level. The parenting stress score was 75.00 (16.00), reflecting a moderately low level. Spearman correlation analysis showed that children s picky eating levels were negatively correlated with the total score of parenting self-efficacy ( r =-0.28) and positively correlated with the total score of parenting stress( r =0.25)( P <0.01). Conclusions Picky eating levels of preschool children are closely associated with parenting self-efficacy and parenting stress. Picky eating behaviors in children can be reduced by implementing various effective measures to enhance parenting self-efficacy and alleviate parenting stress.