Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To analyze the clinical data of patients with neurosyphilis(NS)and explore factors influencing their activity of daily living(ADL).Methods The clinical data of 90 patients with NS was retrospectively analyzed,and the ADL scores at admission were assessed by using the Barthel index(BI).The patients were divided into no-dependency,mild-dependency,and moderate-to-severe-dependency groups.The influencing factors of ADL were explored through comparative analysis and multiple linear regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of clinical indicators for poor ADL recovery(BI score≤60)at discharge in patients.Results Among the 90 NS patients,the average age was 54.17±12.45 years,with 70 males(77.78%).The most common clinical manifestation was abnormal mental behavior(44.44%),followed by limb sensory or motor disorders(25.56%)and dysarthria(16.67%).Based on the BI scores,41 patients(45.6%)were independent,31 patients(34.4%)had mild dependence,and 18 patients(20.0%)had moderate to severe dependence.The comparison results of the three groups showed that the neutrophil-to-lymphocyte ratio(NLR)was gradually increased[2.80(1.97,4.73)vs.3.80(2.28,4.89)vs.5.37(3.76,7.20)]which was higher in the moderate-to-severe-dependency group than in the independent and the mildly-dependent group(P<0.05);cerebrospinal fluid protein concentration[427(341,644)mg/L vs.553(425,830)mg/L vs.933(641,1706.5)mg/L]was gradually increased and there were significant differences in pairwise comparisons(P<0.05).Multiple linear regression analysis showed that NLR(β=-0.242,P=0.018)and cerebrospinal fluid protein concentration(β=-0.461,P<0.001)were negatively correlated with ADL at admission.The area under curve(AUC)for cerebrospinal fluid protein concentration in predicting poor ADL recovery at discharge was 0.806(95%CI:0.708-0.883,P<0.001),with an optimal cutoff value of 620 mg/L,sensitivity of 86.7%,and specificity of 69.4%.Conclusion The main clinical manifestations of NS patients are psychiatric/behavioral abnormalities.Elevated NLR and cerebrospinal fluid protein concentration may be associated with the decreased ADL.Early active intervention of inflammatory response and cerebrospinal fluid protein abnormalities may provide a new way to improve the prognosis of patients.

Objective:To compare the efficacy and safety of cold-endoscopic mucosal resection (C-EMR) and hot-endoscopic mucosal resection (H-EMR) for the treatment of colorectal polyps sized 10-20mm.Methods:Patients who underwent colonoscopy at the Gastrointestinal Endoscopy Center of the Eighth Affiliated Hospital, Sun Yat-sen University from January 2022 to January 2023 were selected as the research subjects. Patients meeting the inclusion criteria with at least one 10-20 mm, Paris type Ⅰs, type Ⅱa polyp were selected. They were divided into C-EMR group (no high-frequency current treatment) and H-EMR group (high-frequency electrical polyp removal) based on the random number table method. The main outcome measures were the complete resection rate of polyps, the incidence of postoperative complications (bleeding, perforation and infection), and the recurrence rate of polyps in the two groups. Secondary outcomes were the procedure time and cost-effectiveness.Results:A total of 209 eligible polyps were found in 209 patients, 105 in the C-EMR group (105 patients) and 104 in the H-EMR group (104 patients). There was no significant difference in the complete removal rate of polyps [91.4% (96/105) VS 95.2% (99/104), χ2=1.184, P=0.276], the recurrence rate of polyps [2.9% (3/105) VS 1.9% (2/104), χ2=0.195, P=0.683] or the incidence of complications [5.7% (6/105) VS 1.9% (2/104), χ2=2.040, P=0.280] between the C-EMR group and the H-EMR group. Compared with H-EMR group, the operation time of C-EMR group was shorter (5.26±2.41 min VS 9.34±5.63 min, t=-8.478, P<0.001), and the number of titanium clips used was fewer (2.55±0.94 VS 3.94±1.14, t=-9.623, P<0.001), and the differences between the two groups were statistically significant. The cost of polypectomy was lower in the C-EMR group than that in the H-EMR group (2 720±452 yuan VS 3 031±293 yuan), but the difference was not stastistically significant（ t=-5.896， P=0.651）. Conclusion:C-EMR demonstrates non-inferior efficacy and safety in treating 10-20 mm colorectal polyps compared with H-EMR. Widespread adoption of C-EMR may lead to reduced healthcare costs and expenditures.

OBJECTIVE To summarize the key points for design of case-control study,analyze the data and summa-rize the specifications so as to raise the quality of related clinical research on hospital-acquired infections.METHODS The types for design of the case-control study were systematically summarized based on the character-istics of hospital-acquired infection data with strong timeliness and various confounding factors.The design,data clearance and statistical analysis method were studied by analysis of typical cases,the common types for design of the case-control study and the key points of design were listed,and the specifications for report of the result of case-control study based on the clinical problems about hospital-acquired infections were summed up.RESULTS By starting from the key points for the design of the case-control study,the design framework of the study that con-tained three core elements was established based on the characteristics of related research on hospital-acquired in-fections,the three core elements were as follows:clarifying the temporal logic of exposure,developing strategies for the control of confounding factors,selecting appropriate statistical models.Meanwhile,the reporting specifica-tions were formulated to achieve the methodological transparency.CONCLUSION Clarifying the key points for de-sign of the case-control study and the specifications for report of results can improve the quality of clinical research on case-control design for hospital-acquired infection cases and boost the scientificity and feasibility.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective:To investigate the distribution of iodine and other chemical elements in soil, grain and vegetables in different water iodine areas of Xi'an City, and to provide theoretical basis for prevention and treatment of iodine related diseases and water improvement measures.Methods:From September to November 2021, a stratified cluster sampling method was used to select three survey villages in Xi'an, namely Yehu Village, Xingbei Village, and Quanzhong Village, where the iodine level of residents' drinking water < 10, 10 - 100, and > 100 μg/L. Drinking water samples were collected from seven survey sites based on the source of domestic drinking water to determine the iodine level of the water. At the same time, soil samples of cultivated land, residents' grains (wheat, corn), and vegetables were collected from survey villages to determine the content of 14 elements including calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, selenium, iodine, and fluoride.Results:The iodine level in the water of 7 survey sites in three survey villages was 5.80, 6.40, 25.51, 42.20, 53.90, 111.65, and 177.63 μg/L, respectively. A total of 70 samples of soil, 65 samples of wheat, 76 samples of corn, and 141 samples of vegetables were collected. Among them, the levels of various elements in vegetables and grains were lower than those in the soil. Only calcium and fluoride were higher in vegetables than in grains, while iron, chromium, copper, zinc, selenium, and iodine were lower in vegetables than in grains. According to the range of water iodine level, there were statistically significant differences in the content of calcium, iron, chromium, nickel, copper, zinc, mercury, iodine, and fluoride in soils from different water iodine regions ( Fcalcium, iron, chromium, nickel = 42.04, 13.55, 12.22, 11.20, Hcopper, zinc, mercury, iodine, fluoride = 14.27, 9.19, 14.72, 25.14, 16.50, P < 0.05). The comparison of magnesium, zinc, cadmium, arsenic, and selenium content in wheat showed statistically significant differences ( Fadmium, selenium = 6.34, 3.31, Hmagnesium, zinc, arsenic = 6.12, 11.55, 6.23, P < 0.05). The comparison of calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, iodine, and fluoride content in corn showed statistically significant differences ( Fmagnesium, chromium, nickel, copper, zinc, iodine = 18.89, 13.76, 17.86, 24.17, 28.46, 15.96, Hcalcium, iron, cadmium, lead, arsenic, mercury, fluoride = 11.57, 40.53, 26.50, 33.05, 33.73, 36.01, 29.21, P < 0.05). The comparison of calcium, iron, magnesium, chromium, zinc, cadmium, lead, arsenic, mercury, and selenium content in vegetables showed statistically significant differences ( H = 23.93, 8.12, 10.03, 7.01, 16.09, 18.36, 23.07, 6.51, 27.67, 7.86, P < 0.05). Conclusions:There are significant differences in the distribution of 14 elements in soil, grain, and vegetables in different water iodine regions. In addition to drinking water, precise guidance should also be provided based on the iodine content in soil, grain, and vegetables in different water iodine areas.

Objective:To explore the relationship between the osteosarcopenia and depressive symptom in the elderly in community,and the moderating effect of physical activity in the interrelationship.Methods:Using strati-fied random sampling,1 051 elderly people from 20 communities in Shihezi were selected for the study,and sur-veyed using the Strength,Assistance with walking,Rise from a chair,Climb stairs,Falls and Calf circumference(SARC-Cal F),grip strength measurements,previous fragility fracture,or osteoporosis risk one-minute test,and the Osteoporosis Self-Screening Tool for Asians(OSTA)to screen for osteoporosis,the short version of the Geriatric Depression Scale(GDS-15)and the Physical Activity Scale for the Elderly(PASE)were used to assess depressive symptoms and physical activity.Results:Osteosarcopenia were positively correlated with GDS-15 scores(r=0.54,P＜0.01),PASE scores were negatively correlated with both osteosarcopenia and GDS-15 scores(r=-0.45,-0.55,Ps＜0.01).Physical activity negatively moderated the association between osteosarcopenia anddepressive symptom in community elderly people(β=-0.01,P＜0.05).Conclusion:Osteosarcopenia associated with de-pressive symptoms,and physical activity moderates the association between osteosarcopenia and depressive symp-tom in community elderly people.

Objective To design a Five-Elements Music Software based on Traditional Chinese Medicine's(TCM)theory of five elements music therapy and music emotion classification.The software is intended to provide appropriate music selections tailored to the negative emotional states of cancer patients and evaluate its effectiveness in psychological rehabilitation.Methods ①Music screening and classification:Qualitative analysis was used by six experts in TCM,psychology,nursing,and musicology to screen five elements music and classify corresponding emotional categories.②Software design and development:Based on screening and classification of music materials,design and develop a"Five Elements Music Software Based on Emotion Classification".③Software application evaluation:Recruit 50 cancer patients from the"Beijing Anti Cancer Paradise"as participants to have a trial listening experience with music software,and fill out a satisfaction questionnaire to evaluate its application effect.Results This study established a music database containing 150 pieces of five-elements musical tunes and completed the classification of emotional categories.Among the included subjects,80%of the recruited objects were satisfied with the experience of the five elements music software,of which the application experience of female patients was significantly better than that of male patients,and breast cancer patients were better than other cancer patients,with a statistically significant difference(P<0.05).The five elements music Software in clinic showed comparing with other two groups after four weeks,there was a significant difference for HAMD when comparing five elements music software group and the other two groups(P<0.05).Conclusion The five-element music software designed based on emotion classification effectively meets the psychological rehabilitation needs of cancer patients.It provides appropriate music selections and convenient listening method to regulate cancer-related negative emotions,extending psychological rehabilitation from the hospital to the home.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To study the association between subtypes of hypertension and risk for all-cause mortality and cardio-cerebrovascular mortalities in the elderly in communities of Beijing.Methods:The data were collected from the Beijing Healthy Aging Cohort Study. The elderly in 5 urban areas (former Xicheng, former Xuanwu, Fangshan, Haidian and Tongzhou) and 4 rural areas (Yanqing, Miyun, Huairou and Daxing) in Beijing were selected as the study subjects by multi-stage stratified cluster random sampling. The baseline survey was conducted from July 2009 to September 2015. The follow-up was conducted until March 31, 2021, and a total of 6 326 participants were enrolled. Cox proportional hazard regression model was used to analyze the association of SBP, DBP, normal blood pressure, high normal blood pressure, simple systolic hypertension, simple diastolic hypertension and systolic diastolic hypertension with all-cause mortality and cardio-cerebrovascular mortality.Results:By March 31, 2021, the median follow-up time was 6.30 years, the all-cause mortality density was 201.67/10 000 person-years, and the cardio-cerebrovascular mortality density was 90.20/10 000 person-years. Multivariate Cox proportional hazard regression model analysis showed that the risk for all-cause mortality increased by 5.6% ( HR=1.056, 95% CI: 1.020-1.092), and the risk for cardio-cerebrovasculvar mortality increased by 12.5% ( HR=1.125, 95% CI: 1.071-1.182) for every 10 mmHg increase in SBP. The risk for all-cause mortality increased by 8.6% ( HR=1.086, 95% CI: 1.023-1.152), and the risk for cardio-cerebrovascular mortality increased by 19.9% ( HR=1.199, 95% CI: 1.101-1.306) for every 10 mmHg increase in DBP. Compared with the normal blood pressure group, the risk for all-cause mortality increased by 64.8% ( HR=1.648, 95% CI: 1.049-2.591) and the risk for cardio- cerebrovascular mortality increased by 112.8% ( HR=2.128, 95% CI: 1.069-4.233) in the simple diastolic hypertension group. The risk for all-cause mortality increased by 34.4% ( HR=1.344, 95% CI: 1.023-1.467) and the risk for cardio-cerebrovascular mortality increased by 111.3% ( HR=2.113, 95% CI: 1.384-3.225) in the systolic-diastolic hypertension group. Conclusions:In the elderly in communities of Beijing, beside systolic-diastolic hypertension. It is necessary to pay close attention to the simple diastolic hypertension, which has lower prevalence, and give targeted prevention and treatment.