Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

ObjectiveTo delineate imaging findings using an imaging platform and investigate the correlation between MRI characteristics of spinal cord atrophy and clinical diagnosis in children with spinal cord injury (SCI). MethodsImaging data of 150 children with SCI admitted to Beijing Bo'ai Hospital, China Rehabilitation Research Center, from January, 2002 to March, 2024 were collected and imported into the imaging platform. The anteroposterior and transverse diameters of the middle part of the spinal cord at the cross-section with the most severe atrophy were measured, and the relevant indicators of the previous normal spinal cord segment were measured as controls; the radiomic features were extracted. Clinical data of the children including gender, age, cause of injury, sensory level, motor level, spinal cord injury level, injury severity and disease course were collected. ResultsSpinal cord atrophy was identified in 81 cases (54%), among which 78 cases (96%) were American Spinal Injury Association Impairment Scale (AIS) grade A and 3 cases (4%) were AIS grade C. The upper boundary of the spinal cord atrophy site strongly correlated with the injury level, motor level and sensory level (r > 0.8, P < 0.001). ConclusionMore than half of children with SCI may develop secondary spinal cord atrophy, the vast majority of whom suffer from complete spinal cord injury; the upper boundary of spinal cord atrophy is correlated with the injury level.

AIM:To assess the influence of preoperative lacrimal passage probing and dilation on the therapeutic effectiveness of nasolacrimal silicone intubation in cases of incomplete primary acquired nasolacrimal duct obstruction(PANDO).METHODS: A retrospective case-control clinical study was conducted. The study included patients with incomplete PANDO who underwent nasolacrimal silicone intubation at the hospital between October 2022 and October 2024. Participants were categorized into two groups based on their receipt of nasolacrimal duct probing and dilation prior to intubation. Group A consisted of patients who had undergone one or more sessions of nasolacrimal duct probing and dilation before nasolacrimal silicone intubation, while Group B included patients who did not receive nasolacrimal duct probing and dilation before intubation. All patients had their nasolacrimal silicone tubes removed 3 mo postoperatively and were monitored for 6 mo following tube removal to evaluate surgical success rates.RESULTS: A total of 136 patients(152 eyes)completed the six-month follow-up period. The overall surgical success rate for both groups was 72.4%(110/152 eyes).Group A included 22 males and 36 females, mean age 58.09±11.07 y, and achieved a success rate of 82.8%(53/64 eyes), while Group B included 27 males and 51 females, mean age 59.35±8.84 y and attained a success rate of 64.8%(57/88 eyes). The difference in surgical success rates between the two groups was statistically significant(P=0.014). Furthermore, Group A achieved a complete success rate of 67.2%(43/64 eyes), compared to 47.7%(42/88 eyes)in Group B, with this difference also reaching statistical significance(P=0.017). No serious postoperative complications were observed in either group.CONCLUSION: Nasolacrimal silicone intubation is a safe and effective intervention for incomplete PANDO, with preoperative nasolacrimal duct probing and dilation potentially enhancing therapeutic outcomes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the associated factors and cumulative effects of cardiometabolic multimorbidity (CMM) among residents in southern Xinjiang.Methods:A stratified random cluster sampling method was used to conduct questionnaire surveys, physical examinations and laboratory tests among the personnel of the 51st Brigade, 3rd Division, Xinjiang, in 2016. The multivariate logistic regression, multivariate linear regression, restricted cubic spline, and network analysis methods were used to study the association of lifestyle (smoking, alcohol consumption and physical activity), socioeconomic (occupation, education and marital status) and clinical factors (waist circumference, body mass index and family history) with CMM.Results:A total of 12 773 study subjects were included. The prevalence of cardiovascular metabolic diseases among residents in southern Xinjiang was 52.49%. Specifically, the prevalence rates of dyslipidemia, hypertension, coronary heart disease, diabetes, and stroke were 31.14%, 29.95%, 6.78%, 6.26%, and 2.47%, respectively, and the prevalence of CMM was 19.06%. Multivariate logistic regression analysis revealed that the associations between clinical and socioeconomic factors and CMM significantly increased with higher scores. Specifically, the OR rose from 1.75 (clinical factors) and 1.07 (socioeconomic factors) on a score of 1 to 4.41 and 1.93 on a score of 3, respectively. The association between lifestyle factors and CMM was only observed at higher scores ( OR=1.26, 95% CI:1.07~1.62). The trend test using the scores of each group as continuous variables in the model showed that the risk of disease increased with the accumulation of clinical, socioeconomic and lifestyle factors (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear relationship between the total number of associated factors and CMM ( Poverall<0.05 and Pnon-linear<0.05). Network analysis identified hypertension (strength=0.42) as the “core node” among the five diseases. When analyzing the three types of influencing factors, hypertension (strength=0.68), dyslipidemia (strength=0.47), coronary heart disease (strength=0.37), and clinical factors (strength=0.53) emerged as “core nodes”. In the network of nine associated factors, abnormal waist circumference and BMI (strength=0.90 and 0.84) were identified as “key factors”, while hypertension (strength=0.68) and dyslipidemia (strength=0.52) were identified as “key diseases”. Conclusion:The prevalence of CMM among residents in southern Xinjiang is high, and there is a cumulative effect of multiple factors. Hypertension and dyslipidemia are key diseases in the multimorbidity network, while abnormal BMI and waist circumference are key associated factors.

Objective:To understand the usage situation of e-cigarettes among residents aged 18-65 in Beijing, explore the relationship between e-cigarette use and cigarette smoking as well as smoking cessation behaviors, and provide scientific support for the developing and improving policies and measures related to e-cigarettes.Methods:Using 19 684 residents data from the Beijing Non-communication Chronic Disease and Risk Factors Surveillance in 2022, complex sampling weighted methods were used to estimate proportions, and complex sampling logistic regression analysis was applied to explore the relationship between e-cigarette use, cigarette smoking, and smoking cessation.Results:Among all study participants, the proportion of those who had ever used e-cigarettes was 3.36%, with the current e-cigarette use at 1.26%. The proportion of current e-cigarette users (1.87%) and the former e-cigarette users (3.47%) were higher ( χ2=64.70, P<0.001) among males compared to females (0.60% and 0.64% respectively). The top three reasons for using e-cigarettes were wanting to quit smoking, perceiving e-cigarettes as less harmful, and enjoying the flavors of e-cigarettes. 83.54% of e-cigarette users started with cigarettes. The results of the complex sampling multivariable logistic regression analysis showed that current smoking ( OR=61.35, 95% CI: 36.98-101.76) and former smoking ( OR=31.20, 95% CI: 15.52-62.71) were positively associated with e-cigarette, while current e-cigarette use ( OR=0.13, 95% CI: 0.04-0.39) was negatively associated with quitting cigarette smoking. Conclusions:The proportion of e-cigarette use in Beijing was relatively low. E-cigarette use was associated with cigarette use and was not conducive to smoking cessation. Therefore, stronger regulatory measures and health education campaigns regarding the risks of e-cigarettes should be implemented.

Objective To investigate the characteristics and differences between two type 2 diabetic model mice,db/db and KK-Ay,as models of diabetic nephropathy(DN),and to verify them with irbesartan treatment.Methods A total of 102 db/db and 102 KK-Ay mice(12 weeks old)were screened based on the albumin-to-creatinine ratio(ACR)and 24-hour urinary total protein(UCFP),with 78 mice of each strain selected and divided into 6 groups.The db/db+irbesartan group and KK-Ay+irbesartan group were administered irbesartan(40 mg/kg),the db/db group and KK-Ay group received an equal volume of drinking water for experimental animals,and the db/db+test article A groups and KK-Ay+test article A groups were given different doses of test article A(only the result of mortality data in the test articles groups were presented in the study,while other result were not shown).Wild-type C57BL/6J(WTa/WTb group)served as the normal control and were given experimental animal drinking water.Daily clinical observations were made,body mass was measured weekly,and ACR and UCFP were monitored periodically.At the end of administration,the mice were dissected,and the brain,liver,lungs and kidneys were collected,and the organ coefficients(organ mass× 1000/body mass)were calculated.Blood was collected to measure serum total protein(TP),albumin(Alb),blood urea nitrogen(BUN),glucose(GLU),triglycerides(TG),and cholesterol(CHO).Kidney tissues were stained with HE,MASSON,and PAS to observe histopathological changes.Results Among the 78 KK-Ay mice,5 died over 8 weeks,while among the 78 db/db mice,21 died over 6 weeks.ACR increased with age in both the db/db and KK-Ay groups but decreased in the db/db+irbesartan and KK-Ay+irbesartan groups,though without statistical significance(P＞0.05).UCFP increased with age in the KK-Ay group but significantly decreased after irbesartan treatment(P＜0.05).Compared with the WT groups,the kidney coefficients in the db/db and KK-Ay groups showed no significant changes(P＞0.05),while the brain liver coefficients decreased significantly(P＜0.01)and the liver coefficients increased significantly(P＜0.01),but they did not change after irbesartan treatment(P＞0.05).Compared with the WT groups,GLU and TG levels were significantly increased in the db/db and KK-Ay groups(P＜0.01).Compared with the KK-Ay group,GLU and TG levels were significantly reduced in the KK-Ay+irbesartan group(P＜0.01).In the db/db and KK-Ay groups,kidney tissues showed thickening of the glomerular mesangial matrix and mesangial cell proliferation,which were alleviated after irbesartan treatment.Conclusions Both 12-week-old db/db and KK-Ay mice can serve as models for DN research.Compared with db/db mice,KK-Ay mice exhibited smaller individual differences in ACR,fewer animal deaths after urine collection,and significant improvements in GLU,TG and UCFP after irbesartan treatment.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

To promote the effective implementation of China's Essential Public Health Services Program(EPHSP)and ensure the secure and efficient utilization of project funds,China officially initiated the performance evaluation of EPHSP in 2011.This performance evaluation has evolved through three distinct phases:initial exploration(2011-2014),steady advancement(2015-2018),and reform and enhancement(2019—present).The evaluation objectives have progressively expanded from an initial focus on fund security and service coverage to a broader emphasis on enhancing service quality,improving residents'health status and sense of benefit,and facilitating the refinement of policy frameworks and the implementation of primary responsibilities.Performance evaluation has emerged as a critical instrument for strengthening project governance and optimizing resource allocation,gradually establishing a performance-driven incentive mechanism that aligns rewards with both the quantity and quality of work.This approach has effectively contributed to the continuous improvement of service quality.To further advance the high-quality development of EPHSP,future efforts should optimize the performance evaluation system,prioritize the adoption of a full-cycle performance management approach and the integration of health outcome-based indicators.Additionally,it is essential to deepen the application of information technologies to enhance the precision and efficiency of evaluations,and to innovate mechanisms for utilizing evaluation results to reinforce accountability at the local level.These measures will collectively strengthen project performance management capabilities.

This study was aimed at preliminarily investigating the molecular biological functions of the PPE65 protein from Myco-bacterium tuberculosis,and providing foundational data for tuberculosis prevention and control.The basic biological properties of the PPE65 gene-encoded protein were predicted with bioinformatics tools.Sequence information for the Mycobacterium tuberculosis Rv3621c gene and PPE65 protein was retrieved from the NCBI database.The Rv3621c gene was amplified through PCR with the H37Rv genome as a template,then cloned into the pET22b(+)expression vector.The recombinant pET22b(+)-PPE65 plasmid was transformed into Escherichia coli BL21(DE3)competent cells for IPTG-induced expression.Solubility analysis,purification,and identification of the recombinant PPE65 protein were performed.BEAS-2B cells were treated with various concentrations of PPE65 protein for 24 h,and cell proliferation was assessed with CCK-8 assays.PPE65 was found to be composed of 413 amino acids and to have a molecular formula of C????H????N???O???S??,a relative molecular mass of 40 679.88,a theoretical isoelectric point of 4.60,an ali-phatic index of 81.94,and an average hydrophilicity value of 0.319,thus indicating a stable hydrophobic protein lacking signal pep-tides or transmembrane domains.Secondary structure analysis revealed 53.03%α-helix(Hh),2.66%β-sheet(Ee),and 44.31%ran-dom coil(Cc).Bioinformatics predictions identified 38 B-cell epitopes and 22 CTL/Th-cell epitopes.The full-length PPE65 gene(1 308 bp)was confirmed through double restriction enzyme digestion and sequencing,thereby validating the correct construction of the pET22b(+)-PPE65 recombinant plasmid.SDS-PAGE analysis demonstrated that the recombinant protein was found in inclusion bodies,and a single band at 43.7 kDa was observed after purification.Western blotting revealed specific binding to mouse-derived His monoclonal antibodies,thereby confirming successful expression of the PPE65 protein.BEAS-2B cells treated with a PPE65 protein concentration gradient(2.5-20 μg/mL)exhibited a dose-dependent increase in cell number.Compared with those in the PBS control group,TGF-β relative expression levels were significantly higher in all treatment groups(t2.5=4.893,P<0.001,t5.0=4.640,P<0.05,t10=7.535,P<0.05,t20=16.44,P<0.000 1).This study elucidated the structural characteristics of the PPE65 protein,successfully obtained the recombinant protein through prokaryotic expression and purification,and demonstrated its ability to promote BEAS-2B cell proliferation.The underlying mechanism might involve suppression of TGF-β/S mad signaling pathway activation.These findings provide a theoretical basis for understanding the role and regulatory mechanisms of PPE65 during M.tuberculosis infection.