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.

A case of multiple intracranial venous sinus thrombosis caused by a calreticulin(CALR)gene mutation in essential thrombocythemia is reported including the diagnosis,treatment process and outcome.The patient was a 39-year-old female presenting with headache,slurred speech and limb weakness.Physical examination revealed unclear speech,dysarthria and decreased muscle strength in the left limb.On the basis of anticoagulation therapy,mechanical thrombectomy,intrasinus contact thrombolysis,decompressive craniectomy and cytoreductive therapy targeting the cause were performed.After treatment,the venous sinuses were completely recanalized and the prognosis was good.There are no relevant literature reports on intracranial venous sinus thrombosis caused by CALR gene mutation in essential thrombocythemia.The diagnosis and treatment strategy of this case provide a reference for the identification and treatment of similar cases in clinical practice.

[Purpose]To analyze the trends of disease burden for lung cancer worldwide and in China from 1990 to 2021.[Methods]Data of the disease burden of lung cancer and population demographics in 1990 and 2021 stratified by sex and age groups for global,five SDI quintiles re-gions,and eight countries including China,Japan,Republic of Korea,United Kingdom,France,United States,Canada,and Australia were extracted from the Global Burden of Disease Study 2021(GBD 2021)database.The age-standardized mortality rate(ASMR)and age-standard-ized disability-adjusted life year rate(ASDR)of lung cancer attributable to 7 level-3 risk factors in China for 1990 and 2021 were also extracted.Counterfactual analysis was used to decompose changes in lung cancer deaths and DALY from 1990 to 2021 into four contributing factors:popu-lation size,population structure,age-standardized incidence or prevalence,and lung cancer case fatality or disease severity.The percentage changes in lung cancer deaths and DALY attributed to these four factors were calculated respectively.[Results]In 2021,there were 934 704 new cases and 814 364 deaths of lung cancer in China.From 1990 to 2021,the incidence,preva-lence,mortality,and DALY rates of lung cancer in China increased faster than those worldwide and in high-middle SDI regions,which was similar to Japan and Republic of Korea.In contrast,the mortality rates of lung cancer decreased in United States and United Kingdom;and the DALY rates of lung cancer decreased in United States,United Kingdom,Canada and Australia.From 1990 to 2021,the age-related lung cancer deaths and DALY in China increased by 193.91％and 146.20％,respectively.The primary contributor to the increase in lung cancer deaths was population aging(102.82％)among men and rising age-standardized incidence(119.00％)among women,while the primary contributor to the increase in DALY was rising age-standardized prevalence for both men(153.12％)and women(218.77％).In 2021,the top three risk factors contributing to lung cancer ASMR and ASDR in China were smoking,particulate matter pollution and occupational carcinogen exposure.Compared with 1990,the ASMR of lung cancer and its proportion at-tributable to particulate matter pollution and low dietary fruits were decreased,while the propor-tions in ASDR of lung cancer attributable to smoking and secondhand smoke increased.[Conclu-sion]Lung cancer is a major public health challenge in China.Compared with worldwide,high-middle SDI regions and certain developed countries,China has experienced faster growth in the incidence,prevalence,mortality and DALY of lung cancer,especially among women.To reduce disease burden,sustained efforts on lung cancer prevention and control are urgently required in China.

[Purpose]To analyze the epidemiological characteristics of esophageal cancer world-wide and in China.[Methods]Data were extracted from the GLOBOCAN 2022 database.The in-cidence and mortality of esophageal cancer worldwide and in China were analyzed,stratified by sex,age group,and human development index(HDI).Spearman correlation analysis was conducted to evaluate the association between the HDI and the mortality-to-incidence ratio(MIR)of esophageal cancer.[Results]In 2022,there were an estimated 511 054 new cases and 445 391 deaths from esophageal cancer globally,with age-standardized incidence and mortality rates(ASIR and ASMR)of 5.0/105 and 4.3/105,respectively.In China,there were an estimated 224 012 new cases and 187 467 deaths accounting for 43.8％and 42.1％of global totals,respectively.Both the new cases and deaths of esophageal cancer in China ranked the first worldwide.The ASIR and ASMR in China were 8.3/105 and 6.7/105,both were as twice as the global average.The ASIR and ASMR for males were higher than those for females.The incidence and mortality of esophageal cancer increased with age,and more than 50％of global cases and deaths in individuals aged over 70 years old occurred in China.Additionally,a significantly negative correlation was ob-served between HDI and MIR of esophageal cancer(ρ=-0.67,P＜0.001),and MIR in China(0.81)was comparable to that of countries or regions with a very high HDI.[Conclusion]The burden of esophageal cancer remains significant worldwide and in China,particularly among males and the elderly.The MIR of esophageal cancer in China is still relatively high.The primary and secondary prevention measures should be strengthened to reduce the incidence and mortality of esophageal cancer.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

With the arrival of an aging population,the development of China's elderly care industry is facing numerous problems and challenges.The low-altitude economy is a typical representative of new quality productive forces and has received strong support from the national level.It is expected to improve the quality of life of the elderly,enrich the elderly care service market,and alleviate the pressure of elderly care.Developing the silver economy is a key strategic deployment for the country to actively respond to the aging population issue.It provides various application scenarios,industrial innovation directions,a large number of consumer groups and consumption demands for the low-altitude economy.This article summarizes the current development status of low-altitude economy and silver economy in China,analyzes the necessity of integrated development from the perspectives of market demand,technological progress,and policy support,and explores the development strategies in the fields of elderly care and medical emergency,tourism,and logistics.By exploring the implementation path planning for the integration of the two in real application scenarios,the development advantages and challenges were summarized.The integration of low-altitude economy and silver economy is of great significance for the high-quality development of the elderly care industry and the social economy.However,it still faces challenges such as policies,technology,and social recognition.

Objective To investigate the relationship between polymorphisms at the rs3093030 and rs5498 loci of the intercellular adhesion molecule-1(ICAM-1)gene in combination with high sensitive C-reactive protein(hs-CRP)and susceptibility to type 2 diabetes mellitus complicated with HTN(T2MH)susceptibility.Methods 200 newly diagnosed T2DM patients,175 T2MH patients and 200 healthy controls from Affiliated Hospital of Guilin Medical University between September 2021 and January 2022.Single nucleotide polymorphisms(SNP)-scan high-throughput technology was used to detect the genotyping of serum rs3093030 and rs5498 polymorphisms in the study subjects and to detect hs-CRP levels in peripheral plasma to analysed and explore the correlation between them and the development of T2MH.Results The peripheral blood hs-CRP expression level of patients in the T2MH group[2.65(1.18,6.50)mg/L]was significantly higher than that in the T2DM group[1.82(0.80,4.48)mg/L]and healthy controls[1.02(0.54,2.29)mg/L],and the differences were statistically significant(Z=-2.729,-7.132,all P<0.001).After population classification by genotype,it was found that compared with healthy controls,rs3093030 CC(Z=-3.912,-5.800),rs5498 AA(Z=-3.293,-4.944)and AG(Z=-3.275,-4.872)genotypes had significantly higher hs-CRP levels.The peripheral blood hs-CRP levels of patients with rs3093030 CT genotype in the T2MH group were significantly higher than that of healthy controls(Z=-3.987),and the differences was statistically significant(all P<0.001),respectively.Meanwhile,regression analysis showed that HS-CRP was a risk factor for both T2MH group and healthy control group(OR=1.181,95%CI=1.095～1.274,P<0.001).Conclusion There is a correlation between ICAM-1 gene rs3093030 and rs5498 polymorphisms combined with hs-CRP levels in peripheral blood and the pathogenesis of T2MH patients.

Objective To investigate the serological and molecular biological characteristics of 4 samples and family with ABO positive and negative stereotypes caused by ABO*AW and to study its inheritance mode.Methods The ABO blood group phenotype of the samples was identified by conventional blood group serology and absorption-elution test.The seven exons and their flanking introns of the ABO gene were amplified by PCR,and the amplified products were analyzed by direct sequencing and cloning sequencing.A pedigree investigation was carried out on the relatives of the proband.Results The blood group serology of the proband 1,2,3 were AweakB,with IgM-A1 antibody.The blood group serology of the proband 4 was AweakB.Sequencing.The genotypes of the four probands were as follows:ABO*AW.25/B.01,ABO*AW.26/B.01,ABO*AW.37/B.01,ABO*AW.37/B.01.Compared with the ABO*A1.01,ABO*AW25 exhibits c.467C>T,c.829G>A and c.1061del G mutation sites.ABO*AW.26 has c.467C>T,c.527G>A and c.1061del G mutation sites.ABO*AW.37 has a c.940A>G mutation site.The pedigree investigation showed that the blood group serological results of the 4th proband's father,mother,husband and son were Aweak,B,A and A,the ABO*AW.37 allele existed in the ABO gene of the 4th proband's father and son.Conclusion The point mutation on the ABO*A1.01 can generate the ABO*AW,resulting in weak expression of a antigen on erythrocytes,and it can descend stably.

Objective:To investigate the clinical application effects of the pedicled anterior intercostal artery perforator flap in breast reconstruction after breast-conserving surgery for breast cancer.Methods:This study was a retrospective observational study. From January to December 2023, 16 female breast cancer patients who met the inclusion criteria were hospitalized in the Department of Breast Surgery of the Affiliated Hospital of Southwest Medical University, with the age of (48±8) years. The pedicled anterior intercostal artery perforator flap was used for breast reconstruction of patients after breast-conserving surgery. After complete resection of tumor tissue, a "crescent-shaped" incision was designed at the inframammary fold. The pedicled anterior intercostal artery perforator flap was harvested based on the tumor location and the defect area after tumor removal. The flap was de-epithelialized, coapted, and rotated anterogradely or retrogradely to fill the defect. The donor site wound was closed with layered sutures. The following parameters were recorded: breast tissue loss volume during surgery, surgical duration, retention duration of the drainage tube, positive proportion of tumors in the breast incision margin tissue, breast loss ratio, flap survival, and incidence ratio of complications after operation. Patients were followed up for local recurrence or distant metastasis of tumor. At the last follow-up, the Ueda score was used to evaluate cosmetic outcomes of reconstructed breasts after breast-conserving surgery, and the Breast-Q scale version 2.0 was applied to assess patients' satisfaction and quality of life with breast reconstruction after breast-conserving surgery.Results:The breast tissue loss volume during surgery in this group of patients was 20-128 (59±34) cm3, the surgical duration was 105-200 (143±27) min, the retention duration of the drainage tube was 3-7 (4.6±1.0) d, and the positive proportion of tumors in the breast incision margin tissue was 1/16, with breast loss ratio of 0. After the surgery, the patient's transplanted flaps all survived. One patient had postoperative fat liquefaction in the surgical area, and the incidence ratio of postoperative complications was 1/16. The patients were followed up for 3-12 (11±4) months, and no local breast cancer recurrence or distant metastasis occurred. At the last follow-up, the cosmetic score of breast reconstruction after breast-conserving surgery were excellent in 6 cases, good in 8 cases, and fair in 2 cases, with an excellent and good ratio of 14/16. At the last follow-up, the highest score in the evaluation of patients' satisfaction with breast reconstruction and quality of life after breast-conserving surgery was the satisfaction with the surgeons, with a score of 59-100 (91±13), followed respectively by physiological health of the chest with a score of 60-100 (77±14), psychological health with a score of 35-100 (74±20), breast satisfaction with a score of 55-100 (73±13), satisfaction with information acquisition with a score of 53-100 (70±14), and sexual health with a score of 34-100 (70±23).Conclusions:The pedicled anterior intercostal artery perforator flap is safe and reliable for breast reconstruction after breast-conserving surgery for breast cancer, and can achieve high cosmetic effects and patient satisfaction. This flap is simple in design, easy to operate and highly reproducible, and is worthy of clinical promotion and application.

Background and Aims:Oncoplastic breast-conserving surgery(OBCS)integrates oncologic and plastic surgical techniques and includes two primary approaches:volume displacement and volume replacement.The pedicled lateral thoracic artery perforator(LTAP)flap is a commonly used technique for volume replacement.Although recent studies in China have confirmed its safety in OBCS,its patient-reported outcomes have not been systematically evaluated,and comparative data with volume displacement techniques remain lacking.Therefore,this study was performed to compare the clinical outcomes and patient satisfaction of LTAP flap versus mammoplasty(volume displacement)in OBCS,to inform surgical decision-making.Methods:A retrospective case-control study was conducted,including 106 patients with unilateral stage 0-Ⅲ breast cancer who underwent OBCS at the Affiliated Hospital of Southwest Medical University from January 2023 to June 2024.Patients were divided into the LTAP flap group(27 cases)and the mammoplasty group(79 cases)based on the surgical technique.Intraoperative variables,cosmetic outcomes,postoperative complications,and Breast-Q scores before and after surgery were compared between the two groups.Results:There were no significant differences between the two groups in clinicopathological characteristics or preoperative Breast-Q scores(all P>0.05).The LTAP group had longer operative times,larger excised tissue volumes,and greater postoperative drainage volumes(all P<0.001).Postoperative cosmetic outcomes were significantly better in the LTAP group,with a higher rate of excellent-to-good cosmetic results(88.9%vs.57.3%)and higher Breast-Q scores in breast satisfaction,psychosocial well-being,and physical well-being(all P<0.05).There were no significant differences in complication rates or local recurrence between the two groups(all P>0.05).Conclusion:In OBCS,the LTAP flap demonstrates comparable safety to mammoplasty while achieving superior cosmetic outcomes and patient satisfaction.It is particularly suitable for patients with small breast volumes requiring large tissue excision and holds promise for broader clinical application.