Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

Objective To develop a composite nutritional preparation that can effectively improve exercise performance under calorie restriction(CR)condition.Methods A total of 24 male C57BL/6J mice(weighing 23～26 g,8 weeks old)were randomly divided into control group(CON),CR,CR+basal nutrient group(CRN1),and CR+compound nutrient group(CRN2).All groups underwent moderate-intensity running training 5 d per week,for totally 3 weeks.The grip strength of the forelimbs were measured weekly,and in 3 weeks after training,exhaustion and post-exhaustion distance tests were conducted to evaluate exercise performance.Blood biochemical indicators,levels of skeletal muscle and liver redox biomarkers,and histopathological conditions were measured and observed.Results After 21 d of intervention,the CR group and CRN1 group had the post-exhaustion running distance prolonged by 278%and 289%,respectively,reduced blood glucose level,and decreased muscle mass,subcutaneous fat and epididymal fat mass when compared with the CON group(P<0.05).Compared with the CON group,the CRN1 and CRN2 groups demonstrated significantly higher gastrocnemius glycogen content.The CRN2 group obtained even longer post-exhaustion distance(increased by 52%and 36%respectively,compared with the CON group and CRN1 group,P<0.05),enhanced grip strength of the forelimbs(raised by 9%,17%and 15%,respectively than the CON,CR and CRN1 groups,P<0.05),elevated brown fat mass(compared to the CON group and CRN1 group,P<0.05),increased blood glucose level(compared to the CRN1 group,P<0.05),decreased blood low-density lipoprotein cholesterol level(compared to the CON and CR groups,P<0.05),and increased glutathione peroxidase content in the gastrocnemius muscle(compared to the CON group,P<0.05).Conclusion Supplementing with compound nutritional supplements in mice under CR can promote exercise performance,including improving fatigue recovery after exhaustive exercise and enhancing forelimb grip strength.

OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

OBJECTIVES: To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells. METHODS: The differentially expressed RNAs in ESCC were identified using the GSE149612 dataset from the GEO database. PCR was used to detect LINC00261 expression levels in clinical ESCC and normal esophageal tissue samples and in multiple ESCC cell lines and normal esophageal epithelial cells (HEEC). In ESCC cells, the effects of overexpression of LINC00261 on cell proliferation, invasion, metastasis and apoptosis were analyzed using CCK-8 assay, clone formation assay, Transwell assay and flow cytometry. The potential targets of LINC00261 were predicted using bioinformatics tools including ENCORI and verified using dual-luciferase reporter assay and Western blotting. The effects of LINC00261 overexpression on ESCC were confirmed in a nude mouse model bearing ESCC xenograft. RESULTS: Analysis of the GSE149612 dataset revealed significantly lower LINC00261 expression in ESCC tissues and cell lines. In cultured ESCC cells, LINC00261 overexpression markedly suppressed cell proliferation, invasion, and metastasis and promoted cell apoptosis. Dual-luciferase reporter assays confirmed that LINC00261 targets the miR-23a-3p/ZNF292 axis. In the tumor-bearing mouse model, LINC00261 overexpression significantly inhibited ESCC xenograft proliferation and metastasis. CONCLUSIONS LINC00261 suppresses ESCC progression by targeting the miR-23a-3p/ZNF292 axis, suggesting a potential therapeutic strategy for ESCC treatment.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Esophageal Neoplasms/genetics* ; Animals ; Esophageal Squamous Cell Carcinoma ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Cell Line, Tumor ; Neoplasm Invasiveness ; Mice ; Carcinoma, Squamous Cell/genetics* ; Apoptosis ; Gene Expression Regulation, Neoplastic ; Neoplasm Metastasis

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective To investigate the current status and analyze the factors affecting the osteoporosis knowledge among orthopedic nurses,and to provide references for improving osteoporosis knowledge among orthopedic nurses.Methods We investigated 5 681 orthopedic nurses from 621 hospitals in 31 provinces(autonomous regions/municipalities)using a convenient sampling method from September 2023 to November 2023.We collected information using a general information questionnaire and osteoporosis knowledge assessment tool.We used univariate and multivariate logistic regression to identify risk factors.Results A total of 5 204 orthopedic nurses were included.The total mean score of osteoporosis knowledge assessment tool of nurses was[13.00(12.00,14.00)],and 23.48％nurses had a low level of osteoporosis awareness.Logistic regression analysis showed that the age,title and position of the nurses,location of the hospital,the level of the hospital,whether to conduct the fracture liaison service/to set up the refracture prevention team,whether to use calcium tablets/vitamin D,whether to carry out anti-osteoporosis drug therapy,and whether to conduct topical lectures on osteoporosis or secondary fractures,were the factors that affected orthopedic nurses'knowledge of osteoporosis(P＜0.05).Conclusion The osteoporosis knowledge of orthopedic nurses needs to be improved.Nursing managers should carry out personalized interventions from both hospital and nurse levels to improve the osteoporosis knowledge of orthopedic nurses in our country.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.