ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass，strength，and function，and its occurrence and development are related to multiple factors，involving several signaling pathways. Among them，the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，as a key pathway regulating cellular growth，survival，and metabolism，plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism，resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine （TCM），with its multi-pathway and multi-target characteristics，has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years，various monomers， extracts，and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis，reducing protein degradation，inhibiting cell apoptosis and inflammatory response，and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms， aiming to provide new insights for the treatment of sarcopenia with TCM.

At present, the treatment of sepsis depends largely on non-specific methods, highlighting an urgent need for novel therapeutic strategies. Stem cells have garnered significant attention in the treatment of various diseases due to their unique biological properties. Stem cells enhance sepsis survival through mechanisms such as reducing bacterial burden, modulating inflammation, and ameliorating organ dysfunction. Recent studies have shown that stem cells can increase the survival rate of sepsis patients through multiple pathways such as reducing the bacterial load of the host, regulating inflammatory homeostasis, and improving multi-organ dysfunction. Their derivatives, exosomes, can also alleviate the imbalanced immune response in sepsis patients. Recent advances in stem cell-based therapies for sepsis were summarized in this paper.

Progress in biomimetic membrane systems has enabled the extensive application of cell membranes in constructing nano-drug delivery systems. These biological membranes endowed the delivery systems with advantages, including superior biocompatibility, precision targeting capabilities, and long circulation. Platelet membranes, owing to their distinctive biological properties, have emerged as exceptional natural materials for nano-drug delivery systems and have continuously promoted the development of the delivery systems in the field of disease treatment. This review comprehensively summarizes the biological characteristics and molecular basis of platelet-associated membranes, various coated systems and methods, and systematically summarizes the research progress of platelet-related membrane delivery systems in the treatment of tumors, inflammatory diseases, cardiovascular and cerebrovascular diseases, and thrombotic diseases. It also analyzes the application challenges in the biomedical field and looks forward to the future development direction.

BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

BACKGROUND:Currently,spinal endoscopic technology has become the mainstream technology in minimally invasive spinal surgery.The specifications of the instruments for different operating systems are different,and the choice of specific surgical protocols needs to be combined with the actual situation of the patient and the choice of the clinical surgeon. OBJECTIVE:To compare the early efficacy of percutaneous endoscopic interlaminar discectomy for L5-S1 disc herniation under the iLESSYS Delta System and Endo-Surgi Plus System. METHODS:Totally 80 patients with L5-S1 disc herniation were treated with percutaneous endoscopic interlaminar discectomy.Patients were divided into two groups based on the endoscopic system used.Among them,37 cases received the iLESSYS Delta System(Delta group)and 43 cases received the Endo-Surgi Plus System(Plus group).Patient demographic characteristics,perioperative indicators,and complications were analyzed between the two groups.Clinical outcomes were quantified using back and leg visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores at 1 day,1,3,and 6 months after surgery.Patient satisfaction was assessed according to modified MacNab criteria at final follow-up. RESULTS AND CONCLUSION:(1)The operative time and number of arthroplasties in the Plus group were less than those in the Delta group,and the differences were statistically significant(P<0.05).(2)Compared with the preoperative period,the visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores of patients in both groups improved at all follow-up time points,and the difference was statistically significant(P<0.001).(3)There was no statistically significant difference in the comparison of pain visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores of patients in the two groups(P>0.05).(4)At 6-month follow-up after surgery,the MacNab standard excellent and good rates in the Delta group and Plus group were 81%and 79%,respectively,with no significant difference(P=0.823).(5)The incidence of complications was 3%in the Delta group and 2%in the Plus group,but there was no significant difference between the two groups(P=0.914).(6)It is concluded that both iLESSYS Delta and Endo-Surgi Plus surgical systems achieved satisfactory early clinical results in the treatment of lumbar disc herniation,with Endo-Surgi Plus surgical moulding being more efficient and safer.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.