Objective To explore the effect of sex on the incidence of immune-related cutaneous adverse event (ircAE) during immunotherapy for gastric cancer, and to further analyze the correlation between sex, ircAE and prognosis. Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received immune checkpoint inhibitors at the Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, from February 1, 2022, to December 31, 2024. Clinicopathological characteristics, occurrence of ircAE, and survival data were collected. The incidence of ircAE was compared between male and female patients. Kaplan-Meier method was used to plot survival curves, and univariate Cox regression analysis was performed to assess prognostic factors. Results A total of 116 patients with advanced gastric cancer were enrolled, including 76 males (65.5%) and 40 females (34.5%). The overall incidence of ircAE was 23.28%, with a higher incidence in male patients than in female patients (28.95% vs 12.50%, P＝0.046). Kaplan-Meier survival analysis on 86 patients with complete follow-up data indicated that patients with ircAE had longer overall survival (OS) than those without ircAE (P＝0.045). Univariate Cox regression analysis showed that male (HR＝0.43, 95%CI 0.22–0.83, P＝0.012) was associated with prolonged OS. Conclusions In gastric cancer immunotherapy, male patients are more likely to develop ircAE and have longer OS than female patients, and the occurrence of ircAE may be related to prolonged OS.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.