ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

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.

In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.

In recent years, the application of artificial intelligence (AI) in the field of biology has witnessed remarkable advancements. Among these, the most notable achievements have emerged in the domain of protein structure prediction and design, with AlphaFold and related innovations earning the 2024 Nobel Prize in Chemistry. These breakthroughs have transformed our ability to understand protein folding and molecular interactions, marking a pivotal milestone in computational biology. Looking ahead, it is foreseeable that the accurate prediction of various physicochemical properties of proteins—beyond static structure—will become the next critical frontier in this rapidly evolving field. One of the most important protein properties is thermodynamic stability, which refers to a protein’s ability to maintain its native conformation under physiological or stress conditions. Accurate prediction of protein stability, especially upon single-point mutations, plays a vital role in numerous scientific and industrial domains. These include understanding the molecular basis of disease, rational drug design, development of therapeutic proteins, design of more robust industrial enzymes, and engineering of biosensors. Consequently, the ability to reliably forecast the stability changes caused by mutations has broad and transformative implications across biomedical and biotechnological applications. Historically, protein stability was assessed via experimental methods such as differential scanning calorimetry (DSC) and circular dichroism (CD), which, while precise, are time-consuming and resource-intensive. This prompted the development of computational approaches, including empirical energy functions and physics-based simulations. However, these traditional models often fall short in capturing the complex, high-dimensional nature of protein conformational landscapes and mutational effects. Recent advances in machine learning (ML) have significantly improved predictive performance in this area. Early ML models used handcrafted features derived from sequence and structure, whereas modern deep learning models leverage massive datasets and learn representations directly from data. Deep neural networks (DNNs), graph neural networks (GNNs), and attention-based architectures such as transformers have shown particular promise. GNNs, in particular, excel at modeling spatial and topological relationships in molecular structures, making them well-suited for protein modeling tasks. Furthermore, attention mechanisms enable models to dynamically weigh the contribution of specific residues or regions, capturing long-range interactions and allosteric effects. Nevertheless, several key challenges remain. These include the imbalance and scarcity of high-quality experimental datasets, particularly for rare or functionally significant mutations, which can lead to biased or overfitted models. Additionally, the inherently dynamic nature of proteins—their conformational flexibility and context-dependent behavior—is difficult to encode in static structural representations. Current models often rely on a single structure or average conformation, which may overlook important aspects of stability modulation. Efforts are ongoing to incorporate multi-conformational ensembles, molecular dynamics simulations, and physics-informed learning frameworks into predictive models. This paper presents a comprehensive review of the evolution of protein thermodynamic stability prediction techniques, with emphasis on the recent progress enabled by machine learning. It highlights representative datasets, modeling strategies, evaluation benchmarks, and the integration of structural and biochemical features. The aim is to provide researchers with a structured and up-to-date reference, guiding the development of more robust, generalizable, and interpretable models for predicting protein stability changes upon mutation. As the field moves forward, the synergy between data-driven AI methods and domain-specific biological knowledge will be key to unlocking deeper understanding and broader applications of protein engineering.

BACKGROUND:The mechanism,manifestation,prevention and treatment of ischemia-reperfusion injury have been reported in the past.However,there are few studies on the ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty.This article focuses on the pathogenesis,clinical impact,prevention and treatment of the ischemia-reperfusion injury of lower limb caused by total knee arthroplasty. OBJECTIVE:To summarize the related literature of lower limb ischemia-reperfusion injury caused by total knee arthroplasty,analyze the mechanism and significance,and give hints for further research on skeletal muscle ischemia-reperfusion injury. METHODS:The relevant articles on PubMed,CNKI,WanFang and VIP databases published from January 1,2000 to April 30,2022 were searched by computer with the Chinese and English search terms of"ischemia-reperfusion injury,total knee arthroplasty,tourniquet,mechanism,pathophysiology,skeletal muscle,treatment".After excluding repetitive research and some basic articles with low correlation,68 articles were finally selected for review. RESULTS AND CONCLUSION:(1)The pathogenesis of ischemia-reperfusion injury is related to oxygen free radicals,intracellular calcium overload,neutrophil activation,as well as high concentration of nitric oxide,no reflow phenomenon,apoptosis and other mechanisms.More detailed mechanism research can provide basis for future prevention and treatment.(2)Ischemia-reperfusion injury of lower limbs will cause local skeletal muscle injury,which may be caused by the trauma of the operation itself or the role of ischemia-reperfusion injury.More targeted research is needed to distinguish the relationship between the two.(3)Ischemia-reperfusion injury of lower limbs may even affect the distal organs,causing kidney and lung damage.It also affects local and systemic circulation.(4)To clarify the effect of ischemia-reperfusion injury can point out the direction for future prevention and treatment.The current prevention and treatment measures mainly include ischemic preconditioning,anesthetic,antioxidant and other drug prevention.(5)The detailed review of ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty can provide basis for future diagnosis and treatment decisions.

BACKGROUND:Dexmedetomidine has the effect of anti-ischemia-reperfusion injury,but the comprehensive and systematic review of its signaling pathway is less. OBJECTIVE:To focus on the review of dexmedetomidine's signaling pathway in the mechanisms of antioxidant stress,inhibition of inflammation,anti-apoptosis,autophagy,and so on. METHODS:The relevant articles on PubMed,CNKI,WanFang,and VIP databases were searched by computer with the key words"ischemia-reperfusion inquiry;dexmedetomidine;signal path;oxidative stress;inflammation;apoptosis"in Chinese and English.After excluding repetitive research and some basic articles with low correlation,57 articles were finally included for review. RESULTS AND CONCLUSION:(1)Dexmedetomidine plays an important role in organ protection through many mechanisms,such as anti-oxidative stress injury,anti-inflammation,anti-apoptosis and autophagy.This involves many pathways,including Nrf2 and its downstream protein antioxidant stress pathway,Toll-like receptor 4 family and nuclear factor-κB-related anti-inflammatory pathway,JAK2/STAT3-related anti-inflammatory pathway,and cholinergic anti-inflammatory pathway,and the cholinergic pathway is the upstream mechanism of many nuclear factor-κB signaling pathways.(2)PI3K/Akt pathway plays different roles according to its activated downstream signals,inhibiting the activation of NLRP3 inflammatory body,activating signal molecules endothelial nitric oxide synthase,mammalian target of rapamycin,and hypoxia-inducible factor 1α to play an anti-inflammatory role,and activate Bad or Bax residues to play an anti-apoptotic role,and PI3K/Akt activates glycogen synthetase kinase-3β.It can also play an anti-inflammatory and anti-apoptotic role.(3)Dexmedetomidine activates SIRT3 to mediate anti-apoptosis and inhibit endoplasmic reticulum stress to produce anti-apoptosis.(4)The detailed review of the anti-ischemia-reperfusion injury signaling pathway of dexmedetomidine can provide a basis for future mechanism research and diagnosis and treatment decisions.

BACKGROUND:Kidney deficiency is the main pathogenesis of osteoporosis.To study the relationship between the two major syndrome types of kidney deficiency,Kidney-Yang deficiency and Kidney-Yin deficiency,is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE:To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills,and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS:The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model.At 10 weeks after modeling,all the rats were randomly divided into a Kidney-Yang deficiency group(n=30)and a Kidney-Yin deficiency group(n=30).Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone,while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension,once a day,for 14 consecutive days.After successful modeling,20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention.After gavage,the microstructural parameters of the bone were measured using Micro-CT scanning.Three-point bending,finite element simulation,femoral head compression,and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION:Micro-CT revealed that the femoral bone density,bone volume fraction,bone surface density,trabecular number,and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group(P＜0.05);the femoral bone volume fraction,bone surface density,trabecular number,and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group(P＜0.05).The three-point bending experiment showed that the femur elastic modulus,maximum bending strength and bending fracture strength were decreased(P＜0.05)and toughness was increased(P＜0.05)in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group.Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group,but had no significant effect on the Kidney-Yin deficiency group.The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group,but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group.To conclude,Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency,but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.

BACKGROUND:Sepsis-induced systemic inflammation leads to rapid bone mass loss;however,there is a lack of effective treatments.Ulinastatin is an anti-inflammatory drug,but its protective effect and mechanism on bone under sepsis-induced systemic inflammation are still unclear. OBJECTIVE:To explore whether ulinastatin can relieve acute bone loss caused by lipopolysaccharide. METHODS:(1)Animal experiment.Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group):control group,model group and experimental group.The control group was injected intraperitoneally with normal saline,the model group was injected intraperitoneally with lipopolysaccharide,and the experimental group was injected intraperitoneally with lipopolysaccharide and ulinastatin.In the experimental group,ulinastatin was injected continuously for 3 days.After intraperitoneal injection of ulinastatin for 14 days,femoral tissues were taken for CT scanning and pathological observation.(2)Cell experiment.C57BL/6 mouse primary osteoblasts were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide with ulinastatin was added to the experimental group.Cell proliferation and osteogenic differentiation were detected.C57BL/6 mouse bone marrow mononuclear cells were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide and ulinastatin were added to the experimental group.Osteoclast differentiation was detected. RESULTS AND CONCLUSION:(1)Animal experiment.CT scanning and hematoxylin-eosin staining showed that bone mass in lipopolysaccharide-treated mice was reduced but increased after treatment with ulinastatin.Tartrate resistant acid phosphatase staining showed that the number of osteoclasts in bone tissue increased in the model group,but significantly decreased in the experimental group compared with the model group.(2)Cell experiment.Cell counting kit-8 assay showed that lipopolysaccharide treatment inhibited the proliferation of osteoblasts,and ulinastatin elevated the proliferation of osteoblasts after lipopolysaccharide treatment.Alkaline phosphatase staining,alizarin red staining and osteogenesis-related gene(alkaline phosphatase,Runx2,osteocalcin,osteoblastin,nuclear factor κB receptor-activating factor ligand,osteoprotegerin)detection showed that lipopolysaccharide treatment inhibited osteogenic differentiation of osteoblasts and elevated the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio;ulinastatin did not have any significant effect on the reduction of osteoblast function induced by lipopolysaccharide but decreased the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio.Tartrate resistant acid phosphatase staining and osteoclast-related gene(tartrate resistant acid phosphatase and matrix metalloproteinase 9)detection showed that lipopolysaccharide treatment could promote osteoclast differentiation of bone marrow monocytes,while ulinastatin could inhibit lipopolysaccharide-induced osteoclast differentiation of bone marrow monocytes.(3)Overall,ulinastatin can significantly inhibit lipopolysaccharide-induced bone loss,mainly through promoting osteoblast proliferation and directly or indirectly inhibiting osteoclast differentiation to alleviate bone loss and achieve osteoprotective effects.

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.