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.

Reninoma is a rare renal secretory tumor，prevalent in the young population. This disease is mostly surgically resected，and the use of microwave ablation to treat reninoma in children is scarce. A case of reninoma in a child was reported in this paper. The patient presented with refractory hypertension，hypokalemia，hyperreninemia and hyperaldosteronemia. Enhanced CT and contrast-enhanced ultrasound showed mass in the lower pole of the right kidney，which was considered as reninoma and microwave ablation was performed. The renin concentration decreased to 68.42 pg/ml at 4 hours after surgery. After 1 year of postoperative follow-up，there was no recurrence of hypertension and hypokalemia，and no signs of tumor recurrence were seen on repeated ultrasound examinations.

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.

Owing to the insidious onset and limited awareness of early screening,many patients with esophageal squamous cell carcinoma(ESCC)are diagnosed at an advanced stage.Immunochemotherapy is the current standard first-line treatment for advanced ESCC;however,survival outcomes remain suboptimal.Radiotherapy,with its precise local control and potential immunomodulatory effects,is anticipated to act synergistically with immunochemotherapy,offering a novel direction for overcoming survival limitations.This review systematically sum-marizes the progress in the use of radiotherapy as a first-line treatment for advanced ESCC and discusses the synergistic mechanisms,clinical applications,and challenges associated with its combination with immunochemotherapy.

Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36％,and the accuracy of skin biopsy was 100％.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.

An 87-year-old female patient went to a hospital in Nanshan District on July 18, 2023 because of "vomiting and diarrhea for 2 days". She lived in a nursing home, where 43 similar cases were found within 8 days, including 31 elderly people and 12 caregivers. On July 23, 2023, 13 anal swab samples of the elderly patients were collected, to further find the source of infection, 89 anal swab samples of related nursing assistants and 9 environmental swab samples were collected at the same time. The pathogen was identified by reverse transcription polymerase chain reaction, a total of 22 out of 102 anal swab specimens were positive for Norovirus GⅡ, and the positive rate was 12/13 in the elderly people and 11.23% (10/89) in the caregivers, and one norovirus GⅡ positive sample among 9 environmental smear samples. The polymerase region and partial gene sequences of the capsid VP1 region were amplified and sequenced for the Norovirus-positive specimens, among which 20 strains were successfully sequenced and showed GⅡ.4[P16] under the Norovirus online typing tool. The sequences of 11 elderly people were highly homologous to those of 9 caregivers, with a homology of 95% in the polymerase region and 99% in the capsid VP1 region, which had sequence homology of 99% compared with the Genbank reference sequences of OP009779 (2022 Chengdu strain), OQ930719 (2023 Nanjing strain), and OL336359 (2021 Beijing strain).

Objective To investigate the lipid-lowering efficacy and safety of Xuezhikang combined with PCSK9 inhibitor in patients with coronary heart disease.Methods A total of 102 patients with coronary heart disease hospitalized in Jiangxi Provincial People's Hospital from June 2023 to November 2024 were enrolled in this study and randomly divided into a control group(50 cases)and an experimental group(52 cases).The control group received basic medication for secondary prevention of coronary heart disease,while the experi-mental group received Xuezhikang combined with PCSK9 inhibitor in addition to the basic medication.After 6 months of treatment,blood lipid indicators,liver function indicators,kidney function indicators,incidence of major adverse cardiovascular events(MACE),and incidence of adverse drug reactions were observed.Results After treatment,LDL-C,TC,AST,and ALT levels decreased in both groups compared with before treatment.The experimental group showed significantly lower levels of these indicators than the control group,with statistically significant differences(P<0.05).Both groups had one case of adverse drug reaction each,showing no statistically significant difference(P>0.05).The MACE incidence was higher in the control group than in the experimental group(18.0%vs.3.8%,P<0.05).The lipid goal achievement rate was low-er in the control group than in the experimental group(44.0%vs.73.1%,P<0.05).Conclusion The com-bination of Xuezhikang and PCSK9 inhibitors demonstrates definite clinical efficacy in coronary heart disease patients,reduces MACE risk,and improves lipid goal achievement rates.

Objective To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.

Objectives To explore the association of peripheral blood PIWI-interacting RNA,piR-hsa-2700592,with all-cause mortality and stroke outcomes in patients with atrial fibrillation(AF),and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.Methods A total of 127 patients with non-valvular AF were enrolled,and the relative expression level of plasma piR-hsa-2700592 was detected.Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients.Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke(or death)score to establish 2 new prediction models,the improvement of the predictive performance was compared and analyzed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),net reclassification index(NRI),and comprehensive discriminant improvement index(IDI)were used to evaluate the predictive performance,and decision curve analysis(DCA)was employed to assess the clinical benefit.Results Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke(HR:2.203,95%CI:1.120～4.332;P=0.022).In the stroke outcome,combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70(95%CI:0.55～0.85,P＜0.001)and 0.84(95%CI:0.73～0.96,P=0.02),respectively.But,no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients(HR:1.997;95%CI:0.884～4.509;P=0.096).Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models,with an NRI and IDI value of 44.20%(95%CI:3.40～59.90,P＜0.001)and 8.20%(95%CI:0.60～15.40,P＜0.001),respectively for the new CHA2DS2-VASc score model,and an NRI and IDI value of 44.20%(95%CI:9.80～58.90,P＜0.001)and 10.40%(95%CI:0.70～21.40,P＜0.001),respectively for the new ABC stroke score model.The DCA curve showed that both new prediction models obtained better net clinical benefits.Conclusion High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients,and the indicator has a good predictive value for prognosis of the patients.piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.