OBJECTIVE: To explore the effect and mechanism of acupuncture at "Weizhong" (BL40) on microcirculation of paravertebral skeletal muscle in rats with chronic blunt injury of lumbar muscle based on the insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. METHODS: Forty-eight SPF-grade SD rats were randomized into a blank group (8 rats) and a modeling group (40 rats). Chronic blunt injury model was established by weight impact method in the modeling group. Forty rats were successfully modeled, and were randomly divided into a model group, an acupuncture at Weizhong group (Weizhong group), an acupuncture at non-acupoint group (non-acupoint group), an inhibitor group, and an inhibitor+acupuncture at Weizhong group (inhibitor+Weizhong group), 8 rats in each group. In the Weizhong group and the inhibitor+Weizhong group, acupuncture was applied at bilateral "Weizhong" (BL40). In the non-acupoint group, acupuncture was applied at non-acupoints, i.e. points 0.5 cm inward from bilateral "Weizhong" (BL40). The acupuncture intervention was delivered 20 min each time, once a day for continuous 2 weeks. In the inhibitor group and the inhibitor+Weizhong group, intraperitoneal injection of IGF-1 receptor (IGF-1R) inhibitor was given once a day, at a dosage of 2 mg/100 g, for continuous 2 weeks. Before modeling and on the 1st, 7th and 14th days of intervention, the body mass was measured. Before and after modeling, and after intervention, the limb grip strength and paw withdrawal threshold (PWT) were measured. After intervention, the morphology of psoas muscle was observed by HE staining; the ultrastructure of psoas muscle capillaries was observed by electron microscopy; the levels of serum vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were detected by ELISA; and the protein and mRNA expression of IGF-1, IGF-1R, PI3K, AKT of psoas muscle was detected by Western blot and real-time PCR. RESULTS: Compared with the blank group, in the model group, the body mass on the 7th and 14th days of intervention, the limb grip strength, and the PWT of left and right hind feet were decreased (P<0.001, P<0.01); the skeletal muscle cells showed enlarged intercellular space, loosely arranged and irregularly shaped, the capillaries in the psoas muscle tissues were edematous, and the lumen of the blood vessels was obviously atrophied; the levels of serum VEGF and eNOS were decreased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were decreased (P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was decreased (P<0.001, P<0.05). Compared with the model group, in the Weizhong group, the body weight was increased on the 7th and 14th days of intervention (P<0.001), the limb grip strength and the PWT of the left and right hind feet were increased (P<0.001, P<0.01); the arrangement of the skeletal muscle cells was relatively tight and the intercellular space was reduced, the blood vessels tended to be regular and the structure of the basement membrane was continuous, while the lumens of blood vessels were collapsed locally; the levels of serum VEGF and eNOS were increased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were increased (P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was increased (P<0.001, P<0.01). Compared with the model group, in the inhibitor group, the body mass was decreased on the 7th and 14th days of intervention (P<0.05, P<0.01); the limb grip strength and the PWT of the left hind foot were decreased (P<0.01, P<0.001); the intercellular space of skeletal muscle cells was larger, the nuclei of the cells and erythrocytes were scattered in the intercellular space, the damage of the capillaries in the muscular tissues was serious, the collagen fibers were sparsely distributed and disorganized; the levels of serum VEGF and eNOS were decreased (P<0.001, P<0.01); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (P<0.01, P<0.05, P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (P<0.01, P<0.001, P<0.05). Compared with the Weizhong group, in the non-acupoint group and the inhibitor+Weizhong group, the body mass was decreased on the 7th and 14th days of intervention (P<0.001, P<0.01), the limb grip strength was decreased (P<0.001); the morphology of muscle cell was relatively poor, with generally irregular, there was mild collapse and atrophy in the vascular lumen, and mild edema in the endothelial cells; the levels of serum VEGF and eNOS were decreased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (P<0.01, P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (P<0.001, P<0.01, P<0.05). Compared with the Weizhong group, the PWT of the left hind foot was decreased in the non-acupoint group (P<0.001), and PWT of the left and right hind feet was decreased in the inhibitor+Weizhong group (P<0.001). CONCLUSION Acupuncture at "Weizhong" (BL40) promotes lumbar muscle repair in chronic low back pain, its mechanism may be related to the activation of the IGF-1/PI3K/AKT pathway, thereby improving the microcirculation.
Animals ; Insulin-Like Growth Factor I/genetics* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Male ; Humans ; Muscle, Skeletal/metabolism* ; Signal Transduction ; Phosphatidylinositol 3-Kinases/genetics* ; Wounds, Nonpenetrating/metabolism* ; Acupuncture Points

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

Objectives:To finely divide the aortic sinus into sections and accurately localize the coronary ostium through CARTO three-dimensional mapping,and to assess the clinical effects of treating aortic sinus cusps premature ventricular contraction(ASC-PVC)and the ablation risk in the corresponding area with zero X-ray radiofrequency ablation. Methods:A total of 66 patients who underwent radiofrequency ablation for ASC-PVC from January 2020 to January 2023 were included in this analysis,patients were divided into experimental group(n=34)and conventional group(n=32).In the conventional group,the CARTO 3 system was used to create an aortic sinus model through the conventional method.The earliest stimulating target was identified by using electrical stimulation mapping(ESM).Radiofrequency ablation treatment was performed after the distance between the target and the coronary ostium was precisely measured by coronary angiography through the hollow tube of the ablation catheter or coronary angiography tube.In the experimental group,the CARTO 3 system was used to build a model of the aortic sinus and the coronary ostium and aortic sinus were divided into sections.The earliest stimulating target was identified by ESM.After localizing coronary ostium through the impedance changing pattern on the ablation catheter tips,catheter ablation was performed with zero X-ray.The data regarding the impedance of the ablation catheter in the aortic sinus were collected.The total operative time,the operative time in the aortic sinus,contrast dosage,X-ray exposure time,immediate and short-term success rates of the operation and complication rates were compared between the two groups.Besides,the distribution of successfully ablated targets and their relationship with the risk of ablation were analyzed in both groups. Results:There was no significant statistical difference in the immediate and short-term success rates between the two groups(93.8%vs.94.1%;90.6%vs.88.2%,both P>0.05).The experimental group did not receive contrast agents during the operation,and the total operation time and intra-aortic sinus operation time in the experimental group were significantly shorter than those in the conventional group([58.76±4.94]min vs.[66.91±5.94]min,P<0.001;[43.12±4.49]min vs.[50.31±5.18]min,P<0.001).During the process of moving the ablation catheter from the intra-aortic sinus to the coronary artery opening and into the coronary artery,the impedance suddenly increased,which was significantly different from the impedance in other parts of the intra-aortic sinus(all P<0.001). Conclusions:Radiofrequency ablation of ASC-PVC with zero X-ray can simplify the procedures and shorten the operative time.The steep increase in impedance at the tip of the ablation catheter can be used as a basis for localizing the coronary ostium.Dividing the aortic sinus into sections allows a detailed assessment of the risk for ablation treatment at the targets.

Objective : To investigate the mediating effect of negative emotions on visual impairment and resilience among middle-aged and elderly populations, so as to provide insights into improving psychological health among middle-aged and elderly populations. Methods: Demographic information, visual impairment, negative emotions and resilience in the residents at ages of 45 years and older were collected through the database of the Yushu Physical and Mental Health Survey carried out by Institute of Psychology of Chinese Academy of Sciences. Structural equation model was used to analyze the effects of visual impairment and resilience and the mediating role of negative emotions. Results: Totally 2 997 middle-aged and elderly populations were enrolled, with the median age of 50.00 (interquartile range, 47.00) years. There were 1 320 males (44.04%) and 1 677 females (55.96%), 1 627 illiterate persons (54.29%), and 2 780 married persons (92.76%). The scores of visual impairment, negative emotions and resilience were (6.79±2.59), (6.35±3.05) and (33.38±10.41) points, respectively. The results of structural equation model analysis showed that after adjusting for age, gender, educational level and marital status, visual impairment had a direct negative positive effect on resilience, with a direct effect value of -0.157 (95%CI: -0.177 to -0.137), and visual impairment could also negatively affect residence through negative emotions, with a mediating effect value of -0.112 (95%CI: -0.126 to -0.104), and the mediating effect contributed 41.64% to the total effect. Conclusion visual impairment could reduce residence directly or indirectly through the mediating effect of negative emotions among middle-aged and elderly populations.

Objective To investigate the efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting.Methods Clinical data and results of 17 patients with occlusion after carotid artery stenting and treated with hybrid surgery from June 2016 to April 2023 at the Department of Neurosurgery Cerebral Blood Flow Reconstruction Center of Xuanwu Hospital,Capital Medical University were retrospectively analyzed.According to whether the recanalization was successful,17 patients were divided into the the successful recanalization group and the failed recanalization group.Successful recanalization was defined as achieving modified thrombolysis in cerebral infarction(mTICI)grade ≥2b and residual stenosis＜50％.Baseline data(age,sex,body mass index,smoking history,alcohol consumption history,hypertension history,diabetes history,hyperlipidemia history,coronary heart disease history),clinical data(National Institutes of Health Stroke Scale[NIHSS]score at admission,fasting blood glucose,low density lipoprotein,high density lipoprotein,total cholesterol,triglyceride,occlusion side and segment,combination with severe stenosis or occlusion of the contralateral carotid artery,opening of the anterior communicating artery,opening of the posterior communicating artery,compensation of the external and internal carotid artery,compensation of the pia artery,stump morphology,and time from imaging diagnosis of occlusion to recanalization)were documented and compared between groups.The recanalization of occlusive vessels and perioperative complications were recorded.Imaging and clinical follow-up were performed 3,6 months and≥1 year after surgery.Results Among the 17 patients,the ratio of successful recanalization was 13/17.One patient had re-occlusion after operation,which was re-opened after thrombolysis,but neck hematoma with dyspnea occurred,and recovered after emergency operation.There was no postoperative stroke or death.The incidence of perioperative complications was 1/17.Compared with the successful recanalization group,the levels of high density lipoprotein and total cholesterol in the failed recanalization group were higher,and the differences between the groups were statistically significant(high density lipoprotein[1.3±0.3]mmol/L vs.[0.9±0.3]mmol/L,t=-2.139;total cholesterol:[4.2±0.8]mmol/L vs.[3.1±0.7]mmol/L,t=-2.649;both P＜0.05);There were no significant differences in other baseline data and clinical data(all P＞0.05).Imaging follow-up was completed in 9 of the 13 patients in the successful recanalization group,and the follow-up time was 3.8-36.9 months,with a median follow-up time of 22.8(12.8,34.7)months.Among them,1 patient(1/9)developed restenosis of recanalization vessels at 33.0 months after surgery and underwent stent implantation again.Conclusions The preliminary analysis showed that the occlusion after carotid artery stenting had better recanalization success and lower perioperative complications.In patients with chronic occlusion after carotid stenting,the application of a hybrid surgery for opening may be attempted under multimodal imaging assessment.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy.Whether pregnancy-related or not,liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality.Thus,the European Association for the Study of the Liver invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations,based on the best available evidence,for the management of liver diseases in pregnancy for hepatologists,gastroenter-ologists,obstetric physicians,general physicians,training specialists and other healthcare professionals who provide care for this patient population.

With the rapid development of society and the improvement of Western medicine,the average life expectancy of the Chinese population has steadily increased. Since the beginning of the 21th century,China has officially entered an aging society and is currently in a phase of rapid growth in the elderly population. The effective management and improvement of the health levels of the elderly have become urgent issues that society needs to address. Traditional Chinese medicine (TCM),rooted in Chinese traditional culture,has developed a rich system of health preservation through thousands of years of historical practice,which has important guiding significance in actively coping with the aging of the population. This article discusses the historical evolution of the theory of health preservation in TCM,the interpretation of aging mechanisms by TCM,and the strategies for elderly health preservation from the perspective of TCM. By exploring TCM health preservation concepts,a theoretical framework for the health care of the elderly is constructed,so as to provide a scientific basis for their health management.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.