Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Objective To observe changes of thickness and elasticity of skeletal muscles in patients with type 2 diabetes mellitus(T2DM)and relative impact factors.Methods Totally 62 T2DM patients(T2DM group)and 60 healthy adults(HC group)were prospectively recruited.Shear wave elastography(SWE)technology was used to measure the maximum Young's modulus(Emax)of the rectus abdominis and gastrocnemius muscles under relaxed and contracted states in both groups.The thickness and elasticity modulus of the skeletal muscles under the two states were compared between groups.Multiple linear regression analysis was performed to screen impact factors of the elasticity modulus of the rectus abdominis and gastrocnemius muscles.Results No significant difference of muscle thicknesses of rectus abdominis,nor of gastrocnemius muscle was found between groups under relaxed and contracted states(all P＞0.05).Under both relaxed and contracted states,the Emax of the rectus abdominis and gastrocnemius muscle in T2DM group were all lower than those in HC group(all P＜0.05).Multiple linear regression analysis showed that in T2DM group,the elasticity modulus of the rectus abdominis and gastrocnemius muscle under both relaxed and contracted states decreased linearly with disease duration,fasting blood glucose(FBG)and glycosylated hemoglobin(HbA1c)(all P＜0.05).Conclusion The elasticity modulus of skeletal muscle decreased in T2DM patients,and the reducing scales linearly related to disease duration,FBG and HbA1c.

OBJECTIVE: Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism. METHODS: C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated. RESULTS: It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H₂O₂ in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol. CONCLUSION Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.

Cough variant asthma(CVA)is a common respiratory disease in clinical practice.The only or main clinical manifestation of CVA is cough.It has similar pathological pathogenesis with asthma,but its pathological changes are sligher than asthma.The research of CVA drugs needs appropriate CVA animal models as the research basis.Based on the characteristics of CVA clinical diseases and syndromes of traditional Chinese and western medicine,combined with the clinical diagnostic criteria of traditional Chinese and western medicine,the CVA animal models are combed and analyzed,in order to provide references for the establishment,evaluation and application of CVA animal models.Chemical induction was used to prepare the commonly used animal models of cough variant asthma,including mice,rats and guinea pigs.The selection of sensitizing agent,adjuvant,activator and cough inducing agent was basically the same in the animal models of cough variant asthma,but there were significant differences in the selection of sensitizing method,sensitizing and stimulating dose,modeling cycle and detection index.Western medicine has clear diagnostic criteria for cough variant asthma,while traditional Chinese medicine can classify cough-variant asthma into different types according to different syndromes.At present,the commonly used animal models of cough variant asthma are highly consistent with the diagnostic criteria of western medicine,but not well consistent with the diagnostic criteria of traditional Chinese medicine,which is insufficient to reflect the symptoms of traditional Chinese medicine.The establishment of CVA animal model combining disease and syndrome,including medical syndromes into the model evaluation criteria,meets the requirements of TCM research on CVA animal model.In model evaluation,behavioral manifestations,HE staining of lung tissue,cell counts in BALF and lung function indicators should be considered in various aspects,and airway excitation test,alveolar lavage fluid eosinophil count,behavioral and other aspects should be distinguished from asthma.

OBJECTIVE To screen t he active component s of Euchresta japonica against nasopharyngeal carcinoma. METHODS Main chemical components of E. japonica were selected ，and their target proteins were predicted in Swiss Target Prediction database. The target proteins of nasopharyngeal cancer were obtained with GeneCards database. Protein-protein interaction（PPI）network was established after the target of chemical components of E. japonica was intersected with the target of nasopharyngeal carcinoma ；PPI network was analyzed by using Cytoscape 3.6.1 software，and the potential active components and key targets of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking technology was used to evaluate binding ability of active component-key target ；active components of E. japonica against nasopharyngeal carcinoma were screened. The anti-nasopharyngeal cancer effect of potential active components of E. japonica was verified by cell proliferation experiment. RESULTS Seven potential active components （tonkinensisol，quercetin，sophoranone，matrine，genistein，coumarin，maackiain） and 10 core targets （SRC，PIK3CA，MAPK1，MAPK3，AKT1，MAPK8，MAP2K1，PTK2，EGFR，JAK3）of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking results showed that above potential active components all possessed certain anti-nasopharyngeal cancer effect. Cell proliferation activity test showed that tonkinensisol ，sophoranone and maackiain had a very significant inhibitory activity on nasopharyngeal carcinoma cells CNE- 1. CONCLUSIONS Tonkinensisol， sophoranone and maackiain might be the main active components of E. japonica against nasopharyngeal carcinoma.

Objective:To report a case of tocilizumab successfully used in a child with febrile infection-associated epilepsy syndrome (FIRES), and to provide a new idea for the treatment of FIRES in children.Methods:The diagnosis and treatment of 1 case of FIRES admitted in Children′s Hospital Affiliated to Zhengzhou University on February 15, 2021 were described, and the prognosis and follow-up of the child were evaluated. At the same time, the literatures on tocilizumab in the treatment of children′s FIRES were reviewed.Results:A 5-year-old case of FIRES was reported. The child was extremely refractory to immunotherapy and anti-seizure medicines, anesthetics and ketogenic diet. So he was treated with tocilizumab (each time 4 mg/kg) at the 36th day and 43rd day, and epileptic seizures were controlled 10 days after the 2nd doses of tocilizumab. During a follow-up of 10 months, his epileptic seizures were controlled and the cognitive behavior and speech function were well recovered. At present, only 3 cases of FIRES in children have been reported all over the world. All the seizures were well controlled and no obvious adverse reactions were observed.Conclusions:FIRES is a rare refractory epilepsy syndrome, resistant to many kinds of anti-seizure medicines or even anesthetic agents, which is difficult to treat and has poor prognosis. Preliminary trials have shown that tocilizumab is effective and well tolerated in children with FIRES. It may be a potential therapeutic modality for children with FIRES.

This paper collects information on the species resources of medicinal plants in Laos through various methods such as literature collation and analysis, sample line survey, visits and surveys, and initially obtains the medicinal plant resources in Laos, the use of folk herbs, and traditional medicine knowledge archives. It is found that Laos is rich with wild medicinal plant resources. There are 2 165 species (including varieties) belonging to 1 014 genera of 214 families, including 57 species belonging to 40 genera of 29 families of ferns, 32 species belonging to 17 genera of 8 families of gymnosperms, and 2 076 species belonging to 957 genera of 177 families of angiosperms. And, there are 108 kinds of medicinal materials currently circulatingin the market. Herbal resources is widely used in Laos, and many fresh herbs in the market have the special effects of relieving cough and promoting salivation, eliminating dampness, dispelling summer heat, nourishing yin and cooling blood.The medicinal materials for alleviating rheumatism and strengthening waist and knees in the market are with good prospects for development and utilization, so the development and management should be strengthened. China and Laos can conduct in-depth research and strengthen experience exchanges on traditional medicine experience.

The postoperative nervous system and neurocognition-related complications have become an important issue of research focus with the gradual increase of the survival rate after liver transplantation. Compared to other solid organ transplantation, the incidence of nervous system complications after liver transplantation is higher and closely related to death. This paper mainly overviewed the nervous system complications, neurocognition-related complications after liver transplantation and the risk factors inducing these complications. It also discussed how to evaluate, monitor, and prevent these complications in order to provide reference for future studies.