1.Mechanism of Huangqi Guizhi Wuwutang in Treatment of Sarcopenia Associated with Rheumatoid Arthritis by Improving Skeletal Muscle Homeostasis Through Regulation of Autophagy
Yakun WAN ; Yuan LIU ; Yuan QU ; Jingyu GUO ; Ting LIU ; Zhihui BAI ; Di ZHANG ; Ping JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):12-23
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.
2.YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases.
Lin LIN ; Yinfeng YUAN ; Zhihui HUANG ; Yongjie WANG
Neuroscience Bulletin 2025;41(3):501-519
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
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Animals
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Neuroglia/metabolism*
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Signal Transduction/physiology*
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YAP-Signaling Proteins
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Nerve Regeneration/physiology*
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Nervous System Diseases/metabolism*
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Adaptor Proteins, Signal Transducing/metabolism*
3.Participation of clinical pharmacists in patient of diffuse alveolar hemorrhage induced by human granulocyte colony-stimulating factor
Zhihui YANG ; Huadan CAI ; Fangchu XU ; Yuan LIU ; Hailong YUAN
Journal of Pharmaceutical Practice and Service 2025;43(11):567-571
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.
4.Associations between parental adherence to healthy lifestyles and cognitive performance in offspring: A prospective cohort study in China
Rongxia LV ; Yuhui HUANG ; Siyi HUANG ; Shiyi WU ; Siwen WANG ; Guangyu HU ; Yanan MA ; Peige SONG ; E. Jorge CHAVARRO ; S.V. SUBRAMANIAN ; Chunling LU ; Zhihui LI ; Changzheng YUAN
Chinese Medical Journal 2024;137(6):683-693
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.
5.Experience of Xiaoyong Yukui Decoction in the Treatment of Recurrent Ulcerative Colitis
Xiaoyu HE ; Zhihui WANG ; Qichao LYU ; Xingdong NIU ; Yuan GAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(7):166-170
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.
6.Genome characteristics of influenza B virus in Suzhou city, 2021-2022
Zefeng DONG ; Ruimin YANG ; Yang LIU ; Di WANG ; Zhihui XU ; Xuan YUAN ; Qiang SHEN ; Yuanyuan PANG ; Yu XIA
Chinese Journal of Experimental and Clinical Virology 2023;37(2):178-183
Objective:To understand the genome and genetic evolution characteristics of influenza B virus (FluB) in Suzhou city from July 2021 to January 2022.Methods:Real-time fluorescence reverse transcription polymerase chain reaction (Real-Time RT-PCR) was used for the typing of influenza virus (Flu). The detected FluB strains were sequenced by Miseq high-throughput sequencing platform through whole genome capture and library construction. The FluB hemagglutinin (HA), neuraminidase (NA) and matrix protein (MP) gene phylogenetic trees were constructed by Neighbor-Joining method (NJ) with MEGA X software. The Potential N-glycosylation sites of HA and NA proteins were predicted by NetNGlyc 1.0 server software.Results:FluB was detected in 280 of the 1 500 throat swab samples, and the FluB genome sequence was completed in 53 strains. The nucleic acid identity of 8 gene fragments (PB1, PB2, PA, HA, NP, NA, MP, NS) in the FluB strains was 99.3%-100%, 98.1%-100%, 98.8%-100%, 98.0%-100%, 99.2%-100%, 98.4%-100%, 98.2%-100% and 99.0%-100%, respectively. Except for the 4 samples in July 2021, which belonged to the V1A.3 clade of FluB, the rest of the samples belonged to the V1A.3a.2 clade. Every amino acid sequence of HA protein of Flu B collected after October 2021 showed 9-11 substitutions compared with the reference strain (B/Washington/02/2019), which sharing 9 mutation sites (H122Q, A127T, R133G, P144L, N150K, G184E, N197D, K203R and R279K). No drug-resistant mutations associated with NA inhibitors such as oseltamivir were found. Respectively, 11 and 4 potential glycosylation sites were identified in HA and NA proteins of the FluB strains.Conclusions:From July 2021 to January 2022, V1A.3a2 was the dominant FluB strains in Suzhou city, and the amino acid sequences of HA and NA proteins showed multiple site mutations.
7.Effect evaluation of the clinical pharmacists participating in the treatment of patients with diabetic foot
Zhihui YANG ; Lili ZHANG ; Yan ZHAO ; Jinghui HUANG ; Yuan LIU ; Hailong YUAN
Journal of Pharmaceutical Practice 2023;41(11):686-688
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.
8.Making Progress through Exploration——Summary and Reflection on the Implementation of the Plan for the Protection and Development of Traditional Chinese Medicine(2015-2020)
Jinying SU ; Min YUAN ; Lu CHEN ; Jinsheng ZHANG ; Zhihui LI ; Jianlin ZHA ; Gangqiang SU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(8):2648-2652
Chinese medicinal materials are the basis for the inheritance and development of traditional Chinese medicine,as well as strategic resources related to the national economy and people's livelihood.In 2015,12 departments,including the Ministry of Industry and Information Technology,and the State Administration of Traditional Chinese Medicine,jointly formulated the Plan for the Protection and Development of Traditional Chinese Medicine(2015-2020)(hereinafter referred to as the Plan),focusing on seven major construction tasks for the protection and development of traditional Chinese medicine.Through the summary and evaluation of the Plan,it can be seen that the overall development goals and 7 specific indicators have been achieved by 2020.It has been focused on solving the problems of the loss and depletion of some wild Chinese medicinal materials resources and the shortage of Chinese medicinal materials supply.Promoting to alleviate the problems,including the abuse of chemical fertilizers,pesticides,and growth regulators.The extensive production and management of Chinese medicinal materials,as well as the poor exchange of supply and demand information were effectively improved.On the whole,the development and protection of Chinese medicinal materials were promoted.Moreover,the dependence on wild Chinese medicinal materials was reduced through scientific development of Chinese medicinal materials production.And the sustainable development of the Chinese medicinal materials industry was coordinated with the protection of the ecological environment.However,there were still some problems and deficiencies,such as a lack of accurate information guidance,an incomplete price formation mechanism,and an incomplete whole-process traceability system of Chinese medicinal materials.It is suggested that during the 14th Five-Year Plan period,we should continuously strengthen the protection and sustainable development of traditional Chinese medicine resources,and build a new development pattern for traditional Chinese medicine industry based on the new development concept and requirement.
10.Late-onset cluster seizures caused by a truncation variation in SMC1A gene: a case report and literature review
Lifang SONG ; Daoqi MEI ; Yuan WANG ; Li WANG ; Wenjing BI ; Zhihui TANG ; Xuan ZHENG ; Shiyue MEI
Chinese Journal of Neurology 2023;56(11):1237-1243
Objective:To summarize the clinical phenotype and genotypic characteristics of children with truncation variation in SMC1A gene. Methods:The clinical data of a child with late-onset cluster seizures caused by truncation variation in SMC1A gene diagnosed in February 2021 in Children′s Hospital Affiliated to Zhengzhou University were collected. The relevant literature was reviewed to summarize the clinical characteristics. Results:The proband was a 5-year-old girl, presenting with first seizure at the age of 5 and cluster seizures. She had poor response to multiple antiepileptic drugs, and had normal neurodevelopment before seizures. Whole exome sequencing results revealed a spontaneous heterozygous nonsense variation c.55C>T in SMC1A gene, causing a nonsense variant in the amino acid sequence p.Gln19Ter(p.Gln19 *), which has not been reported. There were a total of 14 relevant literatures, and there were in total 32 cases with truncation variation in SMC1A gene including this case. All children were female and 30 children had early-onset intractable epilepsy, and first seizure median age was 5 months (range: 4 weeks to 40 months); 78.1% (25/32) of them had cluster seizures; 93.8% (30/32) had mental retardation; Cornelia de Lange syndrome clinical score in 68.8% (22/32) of them was≥4. The truncation variations in SMC1A gene of 31 children were de novo, and there were 16 children with frameshift variation (16/32), 12 children with nonsense variation [12/32; 3 children (9.4%, 3/32) with c.2923C>T], 4 children with splice variation (4/32). Conclusions:This study further expands the clinical phenotype and genotype of cases with truncation variation in SMC1A gene. Case presenting with female late-onset cluster seizures has not been reported in China, and genetic testing can be beneficial for early diagnosis of hereditary epilepsy and precision treatment.

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