ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.
Humans ; Animals ; Neuroglia/metabolism* ; Signal Transduction/physiology* ; YAP-Signaling Proteins ; Nerve Regeneration/physiology* ; Nervous System Diseases/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Objective To analyze the possible mechanism and drug treatment plan of diffuse alveolar hemorrhage induced by human granulocyte colony-stimulating factor injection, point out medication risks and provide reference for medical treatment and pharmaceutical care of such patients. Methods The abnormal lung conditions of a patient treated with human granulocyte colony-stimulating factor injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of adverse drug reactions, optimization of medical treatment and pharmaceutical care. Results Diffuse alveolar hemorrhage was likely an adverse drug reaction caused by human granulocyte colony-stimulating factor injection. The physician discontinued the medication immediately and provided treatment such as oxygen inhalation, high-dose hormone shock, plasma exchange, etc. The patient’s oxygen saturation was improved, alveolar bleeding was decreased, and the condition was improved. Conclusion Clinical pharmacists participate in patients’ medication treatment, carry out pharmaceutical guardianship, and assist physicians in adjusting treatment plans, which could contribute to the effectiveness and safety of patient treatment.

Objective To explore the effect of enhancer of Zeste homolog 2(EZH2)on hepatocellular car-cinoma HepG2 cell proliferation by inhibiting Wnt/β-catenin signaling pathway.Methods The expression lev-els of mRNA and protein of EZH2 in hepatocellular carcinoma HepG2,SMMC-7721,BEL-7402 cells and nor-mal hepatocytes were detected by real time fluorescence quantitative reverse transcription polymerase chain reaction and Western blot.Transfected siRNA EZH2 and siRNA control in hepatocellular carcinoma HepG2 cells.siRNA EZH2 in HepG2 cells and siRNA control were transfected,MTT was used to measure the HepG2 cells' ability to proliferate.Western blot technique was used to identify the expression levels of proteins.By transfecting siRNA EZH2 in HepG2 cells and administering an activator of the Wnt/β-catenin signaling path-way,MTT assay was used to determine the proliferation ability of cells.Results The EZH2 mRNA and EZH2 protein levels in hepatocellular carcinoma HepG2,SMMC-7721 and BEL-7402 cells were higher than those in normal hepatocytes(P＜0.05),and the mRNA and protein levels of EZH2 in HepG2 cells were high-er than those in SMMC-7721 and BEL-7402 cells(P＜0.05).siRNA EZH2 could significantly inhibit the mR-NA and protein levels of EZH2 in hepatocellular carcinoma HepG2 cells.After EZH2 expression inhibition,the cell viability of HepG2 cells was lower at 24,48,72 h(P＜0.05),Wnt 1 and β-catenin protein levels were lower(P＜0.05).Conclusion EZH2 is overexpressed in hepatocellular carcinoma HepG2 cells,and knock-down of EZH2 significantly inhibits the proliferative ability of HepG2 cells and decreases the levels of proteins related to the Wnt/β-catenin signaling pathway.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Recurrent ulcerative colitis is a difficult point in clinical treatment.Its TCM property is deficiency in nature and excess in superficiality.Deficiency of spleen yang for a long time will affect the kidney;if Taiyang and Shaoyin meridians are attacked for a long time,Jueyin will be involved.San yin diseases will occur,and yang qi will be severely injured;dampness and heat,turbid poison,cold coagulation,food stagnation and other pathogenic factors invade and attack from outside to inside,lie down in the intestinal collaterals,remove heat by stasis,fumigate the lipid membrane and form internal ulcers.Deficiency of healthy qi,weakness and sores are the origin of the disease,stagnation of intestinal collaterals is the superficiality of the disease,and"stasis"as the main pathological factor carries out the disease from beginning to end.According to the idea of supporting sores and removing blood stasis,the self-made Xiaoyong Yukui Decoction can support sores to generate new ones,remove blood stasis and eliminate stagnation,and help regulate cold and heat,so as to strengthen the health and reduce toxin,remove blood stasis and unblock collaterals,so that the pathogenic factors can be removed and health can be restored,and the internal ulcer can heal,achieving good clinical efficacy in treating recurrent ulcerative colitis.

Objective To evaluate the effect of clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot by antibiotics management index and health economics index. Methods 40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department of Air Force Medical Center from April to September 2017 were selected as control group, and 40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department from April to September 2019 were selected as interventional group. No clinical pharmacists were involved in drug treatment of patients in the control group, while the clinical pharmacists in the interventional group participated in drug treatment, and implemented antimicrobial stewardship, medication reconciliation, pharmaceutical care and medication education. Antibiotics management indexes (use intensity of antibiotics, use rate of special class antibiotics) and health economics indexes (medicine expenses, hospitalization expenses) of the two groups were compared. Results The efficacy of the two groups was similar. The use intensity of antibiotics and use rate of special class antibiotics of the interventional group in which clinical pharmacists participated were significantly lower than the control group (P<0.01), so were the medicine expenses and hospitalization expenses (P<0.01). Conclusion Clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot could reduce antibiotics administration index and health economics index, promote rational medicine use and save medical expenses.

Humans ; Endovascular Aneurysm Repair ; Endovascular Procedures ; Blood Vessel Prosthesis Implantation ; Aortic Aneurysm, Abdominal/surgery* ; Treatment Outcome ; Postoperative Complications ; Risk Factors ; Aortic Rupture/surgery* ; Retrospective Studies

Objective:To explore the team construction and treatment strategy of the Diabetic Foot-Multidisciplinary Team.Methods:The clinical data of 19 patients with severe ischemic diabetic foot treated by our Diabetic Foot-Multidisciplinary Team Center from Apr 2021 to Mar 2022 were collected, and the overall amputation rate, above-ankle major amputation rate, minor amputation rate and mortality, Diabetic Foot-Multidisciplinary Team consultation discipline participation rate and treatment participation degree were retrospectively analyzed.Results:Nineteen patients (15 males and 4 females) were enrolled, aged 26 to 94 (68.6±14.2). All were with severe ischemic diabetic foot ulcer:Rutherford grade 5 or up and dysfunction in 2 or more organs. Complications included arteriosclerosis obliterans of the lower extremities in 18 cases, heart diseases in 18, hypertension in 15, and renal insufficiencies in 10. The overall amputation rate was 36.8%, major amputation rate in 21.1%, minor amputation rate in 15.8%, and mortality rate was 15.8%. A total of 16 disciplines participated in Diabetic Foot-Multidisciplinary Team; the main participating disciplines were vascular surgery (19 times), endocrinology (12 times), and cardiology (11 times). The main treatment disciplines were vascular surgery (14 times), plastic surgery (3 times), and cardiology (2 times).Conclusion:For the diagnosis and treatment of diabetic foot, it is necessary to set up a multidisciplinary team as early as possible to control the causes of diabetic foot ulcer, prevent the recurrence of diabetic foot ulcer, reduce the mortality and amputation rate, and improve the quality of life of patients.

Objective:To investigate the clinical characteristics of patients with combined oxidative phosphorylation deficiency type 4 (COXPD4) related to TUFM gene variation, in order to improve clinicians′ understanding of the disease. Methods:A case of COXPD4 with cystic leukodystrophy admitted to the Children′s Hospital of Zhengzhou University in June 2021 was taken as the study subject, and her clinical characteristics and genetic testing results were retrospectively analyzed. The "combined oxidative phosphorylation deficiency type 4" " TUFM gene" "cystic leukodystrophy" "combined oxidative phosphorylation deficiency 4" "COXPD 4" " TUFM" and "cystic leukodystrophy" were used as keywords, and the documents on COXPD4 related to TUFM gene mutations were reviewed from Wanfang Data Knowledge Service Platform, CNKI, PubMed Document Database, and National Center for Biotechnology Information (NCBI) until August 2021. The COXPD4 patients that have been reported internationally were analyzed for clinical features and variant types. Results:The patient was a 2-month-old girl with clinical manifestations of delayed development and progressive aggravation, elevated lactic acid in serum and cerebrospinal fluid, and diffuse white matter dysplasia with multiple cystic lesions in cerebral magnetic resonance imaging (MRI). Whole exome sequencing showed TUFM gene complex heterozygous variants c.684_684+4delGGTGA and c.1105C>T, which had not been reported in the past. A total of 5 cases of COXPD4 were reported in 4 English literatures. Together with 1 case in this study, there were 4 cases with detailed clinical history data, including 1 male and 3 females. The clinical manifestations were severe early-onset lactic acidosis and developmental lag, and 3 cases were accompanied by progressive infantile encephalopathy. Among them, 3 cases underwent head MRI examination, all of which showed diffuse white matter signal with multiple cystic lesions, 2 cases with basal ganglia involvement and multiple cerebellar gyri deformity. Genetic test indicated different types of TUFM gene variation. Conclusions:COXPD4 is a rare hereditary mitochondrial disease. For cases with COXPD4 clinical and imaging features, TUFM gene mutations can be screened first.