Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Cardiovascular diseases and psychological disorders represent two major threats to human physical and mental health. Research on electrocardiogram (ECG) signals offers valuable opportunities to address these issues. However, existing methods are constrained by limitations in understanding ECG features and transferring knowledge across tasks. To address these challenges, this study developed a multi-resolution feature encoding network based on residual networks, which effectively extracted local morphological features and global rhythm features of ECG signals, thereby enhancing feature representation. Furthermore, a model compression-based continual learning method was proposed, enabling the structured transfer of knowledge from simpler tasks to more complex ones, resulting in improved performance in downstream tasks. The multi-resolution learning model demonstrated superior or comparable performance to state-of-the-art algorithms across five datasets, including tasks such as ECG QRS complex detection, arrhythmia classification, and emotion classification. The continual learning method achieved significant improvements over conventional training approaches in cross-domain, cross-task, and incremental data scenarios. These results highlight the potential of the proposed method for effective cross-task knowledge transfer in ECG analysis and offer a new perspective for multi-task learning using ECG signals.
Humans ; Electrocardiography/methods* ; Mental Health ; Algorithms ; Signal Processing, Computer-Assisted ; Machine Learning ; Arrhythmias, Cardiac/diagnosis* ; Cardiovascular Diseases ; Neural Networks, Computer ; Mental Disorders

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

Objective:To explore the diagnostic value of transcranial magnetic stimulation (TMS), transsacral magnetic root stimulation combined with sacral reflexes, external anal sphincter electromyography and pudendal nerve somatosensory evoked potentials in the assessment of neurogenic lower urinary tract dysfunction (NLUTD).Methods:Twenty-one NLUTD patients (1 with a supra-pontine lesion, 5 with a spinal cord injury, 5 with a cauda equina injury, and 10 with pelvic floor disorders) were enrolled. Needle electromyography (EMG) was used to record TMS-induced and transsacral magnetic stimulation-induced motor evoked potentials (tc-MEPs and ts-MEPs, respectively) related to the external anal sphincter (EAS). The dorsal nerve of the penis or clitoris was stimulated electrically to record the latency of the sacral reflex related to the EAS. Central motor conduction time (CMCT) and the tc/ts-MEP latency ratio were calculated to distinguish central from peripheral lesions.Results:In the one patient with a supra-pontine lesion, although the tc-MEP and ts-MEP latencies were within normal limits, the CMCT was prolonged (28.2ms) and the tc/ts-MEP ratio was large (7.4). Among the five patients with a spinal cord injury, one exhibited prolonged tc-MEP latency (50.6ms) and CMCT (47.8ms), along with a large tc/ts-MEP ratio (18.1). In the five patients with cauda equina injury and the ten with NLUTD secondary to pelvic floor disorders, CMCT was within the normal range [averaging (22.9±4.9ms) and (24.2±3.5ms), respectively], but the ts-MEP latency was prolonged [(7.1±2.1ms) and (8.6±3.7ms), respectively], and the tc/ts-MEP ratio was small [(4.4±0.9) and (4.3±1.5), respectively]. The tc/ts-MEP ratio demonstrated the best rate of abnormality detection (93.8%), with an area under the curve of 0.99, indicating good sensitivity.Conclusions:The tc/ts-MEP ratio can be useful for distinguishing central and peripheral lesions. A markedly increased tc/ts-MEP ratio may suggest central nervous system injury, whereas a decreased ratio may indicate peripheral nervous system injury.

Hemiplegic migraine （HM） is a specific subtype of migraine with aura and is difficult to diagnose due to its low incidence rate and diverse clinical symptoms. This article reports a case of HM with hemiplegia as the initial presentation. This patient had a long course of disease and critical conditions and was comorbid with intractable epileptic seizures. A literature review is performed to improve the understanding of this disease among clinicians.
Stroke

Colorectal cancer is one of the most common malignant tumors, which is a great threat to human life and health. The change of bile acid homeostasis can activate their corresponding receptors to regulate the immune functions, which is closely related to the occurrence of colorectal cancer. In addition, some bile acids can directly induce colorectal cancer and play an important role in the development of colorectal cancer. In this paper, the metabolic process of bile acids in vivo and the immunomodulatory role of bile acid receptors were reviewed, and the evidence of associations between bile acids and colorectal cancer were summarized, which showed the rebalancing the bile acid levels might play a role in the prevention or treatment of colorectal cancer.

Objective To analyze the current status and influencing factors of occupational stress, job burnout and sleep quality among workers in the secondary industry in Jinshan District, Shanghai City. Methods A total of 1 418 workers from six key industries in Jinshan District, Shanghai City were selected as the study subjects by the stratified cluster sampling method. The Occupational Stress Core Scale, Maslash Burnout Inventory General Survey and Pittsburgh Sleep Quality Index were used to investigate occupational stress, job burnout and sleep quality of the workers. Results The detection rates of occupational stress, job burnout and sleep disturbance among the study subjects were 33.6%, 65.4% and 23.3%, respectively. Multivariate logistic regression analysis showed that the workers with a monthly income <5 000 yuan had a higher risk of occupational stress than those with a monthly income ≥5 000 yuan (P<0.01). The workers with ≥5.0 years of service had a higher risk than those with <1.0 year (P<0.05). Lack of physical exercise, employment in medium- and large-sized enterprises, and shift work were risk factors of occupational stress in the workers (all P<0.01). The workers aged 18-<30 years had a higher risk of job burnout than those aged 45-<60 years (P<0.05). The workers monthly income <5 000 yuan was associated with a higher risk of job burnout than those with ≥9 000 yuan (P<0.05). The workers with 1.0-<10.0 years or ≥15.0 years of service had higher job burnout risks than those with <1.0 year (all P<0.05). Being unmarried, lack of physical exercise, and employment in medium- and large-sized enterprises were risk factor of job burnout in the workers (all P<0.05). The workers with an educational level of high school or above had a higher risk of sleep disturbance than those with junior school or below (P<0.05). The workers who work >56 hours per week had a higher risk than those working ≤40 hours per week (P<0.01). Conclusion There is a high detection rate of occupational stress, job burnout, and sleep disturbance in the secondary industry workers in Jinshan District, Shanghai City. Special attention should be given to workers with low income, lack of physical exercise, employment in medium- and large-sized enterprises, shift work, long service duration, and long weekly working hours to protect their physical and mental health.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the effect of dexmedetomidine(Dex)on bone loss in tail-suspended rats and primarily explore its regulatory mechanism on bone metabolism.Methods A total of 30 male rats were randomly divided into a control group,a model group,and a Dex group,with 10 animals in each group.Rat model of osteoporosis was established by hind limb suspension for 4 weeks.Dex at a dose of 10 μg/kg was given intraperitoneally,once every other day from the day of tail suspension.And equal amount of normal saline was given to the control and model group.Bone histological staining was used to observe the trabecular bone area fraction.Biomechanical three-point bending test was employed to measure the maximum load,stiffness,and fracture energy.Dual calcein/alizarin red fluorescence labeling and tartrate resistant acid phosphatase(TRAP)staining were applied respectively to detect the mineral apposition rate and bone formation rate as well as the number of osteoclasts on bone surfaces.Secondly,after primary osteoblasts were isolated from the tibiae of tail-suspended rats and then treated with 1 nmol/L Dex,the proportion of alkaline phosphatase(ALP)-positive osteoblasts and the activity of the enzyme were detected by ALP staining and activity test.qRT-PCR was applied to measure the expression of osteogenic activity-related factors,including osteocalcin(Ocn),Runt related transcription factor 2(Runx2),Osterix protein(Osx),and type 1 collagen(Col1).Results The animal experiments revealed that Dex treatment significantly increased the tibial trabecular bone area fraction,inhibited the decrease in bone mechanical strength,and enhanced the mineralization deposition rate and new bone formation rate of trabecular bone in the tail-suspended rats(all P＜0.001).The in vitro experiments showed that Dex treatment obviously improved ALP activity and the number of ALP-positive osteoblasts in primary osteoblasts isolated from tail-suspended rats(P＜0.01),and up-regulated the expression levels of osteogenic differentiation-related genes,such as Ocn,Runx2,Osx and Col1(P＜0.01).Conclusion Dex exerts anti-bone loss effect in tail-suspended rats,which may be associated with its stimulation on osteoblast-mediated bone formation.