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 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.

Objective To compare the midterm outcomes of the Bentall procedure versus isolated aortic valve replacement(AVR)in patients with bicuspid aortic valve(BAV)complicated with severe stenosis and ascending aortic dilation in order to assess the therapeutic value of these surgical approaches for this complex cardiac condition.Methods A retrospective cohort study was conducted on 96 eligible patients who underwent surgical treatment in our institute between January 2018 and December 2022.According to surgical approaches,they were divided into an AVR group(65 cases)and a Bentall group(31 cases).Demographic features,comorbidities,preoperative status,and echocardiographic parameters were collected in all patients.Propensity score matching(PSM)was applied in a 1:1 ratio to balance baseline characteristics.Perioperative indicators and follow-up data were compared and analyzed between matched cohorts after control of cofounding factors.Results After PSM,25 matched pairs were screened out and analyzed with comparable baseline data(all P>0.05).The Bentall group demonstrated significantly more superior intraoperative effective orifice area(EOA,2.69±0.47 vs 2.35±0.47 cm2,P=0.013)and EOA index(EOAI,1.69±0.30 vs 1.47±0.29 cm2/m2,P=0.010),and obviously longer cardiopulmonary bypass time[190.00(147.00,257.00)vs 101.00(88.50,124.50)min,P<0.01]and aortic cross-clamp time[141.00(120.00,166.00)vs 66.00(55.00,81.50)min,P<0.01]when compared with the AVR group.During a median follow-up of 28 months,the AVR group had notably larger aortic sinus diameter[32.00(30.00,34.00)vs 26.80(26.00,28.00)mm,P<0.01]and ascending aortic diameter[38.00(34.50,42.00)mm vs 26.00(26.00,28.00)mm,P<0.01],with ongoing dilation in the ascending aorta,while the Bentall group maintained stable dimensions.The Bentall group also showed statistically lower peak aortic valve pressure gradients[21.00(15.50,27.00)vs 25.00(19.50,31.00)mmHg,P=0.049].Conclusion Both Bentall procedure and AVR are effective in treatment of BAV complicated with severe stenosis and ascending aortic dilation.But,Bentall procedure offers advantages in hemodynamic optimization and aortic stability.

Forced oscillation technique (FOT) enables early diagnosis of chronic obstructive pulmonary disease (COPD) by quantifying the impedance of COPD patients during normal breathing and reflecting the airway obstruction and distribution of the patients. The flow sensors using in FOT for diagnosis of COPD mainly include differential pressure flow sensors, ultrasonic flow sensors, hot wire gas flow sensors, fiber-optic flow sensors and flow sensors based on friction nanoelectricity technology. In this review, the principles, characteristics, and current application status of these five types of flow sensors were summarized, and their future development prospects were prospected.

In recent years, a variety of innovative fast algorithm techniques have emerged in the field of transcranial magnetic stimulation (TMS) electric field solving, which show great potential to meet the requirements of real-time clinical applications. In this review, the crucial processes of TMS electric field modeling were summarized, focusing on two prominent fast algorithm techniques, namely the basis function method and the deep neural network (DNN)-based method. The advantages and limitations of these two techniques were analyzed in detail. Commonly used software tools for electric field modeling were discussed, and a prospective discussion of future developments was offered, aiming to provide a reference for the further development of TMS electric field modeling technology.

Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique that demonstrates great potential in treatment of neurological disorders due to its high spatial resolution and focused penetration ability, enabling millimetre-level precision modulation of specific brain regions with ultrasound to achieve neuromodulation of targeted areas. At present, numerous animal experiments and human studies have been carried out on the regulation of Alzheimer′s disease by TUS. In this review, the regulation effects of TUS on Alzheimer′s disease were introduced from the perspective of targeting different brain regions, including the hippocampus, frontal lobe and whole brain.

Alzheimer′s disease (AD) is a degenerative disorder of the central nervous system. In the early stages of AD, i.e. when cognitive impairment is mild or absent but biomarkers are present, patients show abnormal neuroelectric activity. Repetitive transcranial magnetic stimulation (rTMS) is an important method of non-invasively regulating neuroelectric activity in the brain. It does so by inducing microcurrents to change the membrane potential of nerve cells in the brain based on electromagnetic induction. In this review, the characteristics of neuroelectric activity of AD patients and AD model mice in the early stage of AD were mainly introduced, and the regulation of rTMS on the neuroelectric activity of early AD was discussed.

Emotion is defined as a physiological and psychological state that encompasses human thoughts, behaviors, and feelings. This phenomenon is also regarded as a spontaneous physiological and psychological response generated by the human body to external stimuli. Given the established correlation between electroencephalogram signal and cerebral activity, it is possible to extrapolate the emotional state of subjects by means of electroencephalogram signal analysis. In this review, emotion models, datasets, and popular machine learning and deep learning methods in recent years used in emotion recognition research were summarized. In addition, the research progress of emotion recognition based on electroencephalogram signal was reviewed, with the aim of assisting subsequent researchers in understanding developments in electroencephalogram signal domain and offering insights for addressing clinical challenges in emotion recognition.

The prevalence of neurological diseases is increasing, and conventional clinical treatments frequently exhibit suboptimal efficacy and substantial adverse effects. Transcranial magnetic stimulation (TMS) has garnered significant interest due to its non-invasiveness and favorable tolerability. In this review, the etiology of neurological disorders was described, including Alzheimer's disease, stroke, epilepsy, Parkinson's disease and neuropathic pain. The application methods and therapeutic effects of TMS in these diseases were reviewed as well. While TMS demonstrates considerable promise in the treatment of neurological disorders, further large-scale studies and additional research on its mechanisms and personalized treatment protocols are necessary.