1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
Sigma-1 receptor (σ 1R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K i < 4 nmol/L) and selective σ 1R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ 1R in relation to σ 2R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ 1R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.
3.Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods.
Xiao-Yan ZHENG ; Zi-Yi JIANG ; Yi-Ting LI ; Chao-Liang LI ; Hao ZHU ; Zheng YU ; Si-Yi YU ; Li-Li YANG ; Song-Yuan TANG ; Xing-Yu LÜ ; Fan-Rong LIANG ; Jie YANG
Journal of Integrative Medicine 2025;23(5):528-536
OBJECTIVE:
To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods.
METHODS:
In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator.
RESULTS:
The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups.
CONCLUSION
This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans
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Female
;
Propensity Score
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Embryo Transfer
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Adult
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Acupuncture Therapy
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Retrospective Studies
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Pregnancy
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Live Birth
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Birth Rate
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Cohort Studies
4.Identification and biomimetic synthesis of iphionanes and cyperanes from Artemisia hedinii and their anti-hepatic fibrosis activity.
Xiaofei LIU ; Xing WANG ; Chunping TANG ; Changqiang KE ; Bintao HU ; Sheng YAO ; Yang YE
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):871-880
Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry*
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Sesquiterpenes/chemical synthesis*
;
Molecular Structure
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Humans
;
Liver Cirrhosis/genetics*
;
Biomimetics
;
Plant Extracts/pharmacology*
5.HIV Pretreatment Drug Resistance and Transmission Clusters among Newly Diagnosed Patients in the China-Myanmar Border Region, 2020-2023.
Huan LIU ; Yue Cheng YANG ; Xing DUAN ; Yi Chen JIN ; Yan Fen CAO ; Yi FENG ; Chang CAI ; He He ZHAO ; Hou Lin TANG
Biomedical and Environmental Sciences 2025;38(7):840-847
OBJECTIVE:
This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China.
METHODS:
Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site.
RESULTS:
Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL.
CONCLUSION
The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans
;
HIV Infections/virology*
;
China/epidemiology*
;
Drug Resistance, Viral
;
Male
;
Adult
;
Female
;
Middle Aged
;
HIV-1/genetics*
;
Anti-HIV Agents/therapeutic use*
;
Myanmar/epidemiology*
;
Young Adult
;
Prevalence
;
Adolescent
;
Mutation
6.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.
7.Epidemic characteristics of HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province, 2000-2023
Renhai TANG ; Yuecheng YANG ; Runhua YE ; Lifen XIANG ; Yurong GONG ; Shijiang YANG ; Qunbo ZHOU ; Xing DUAN ; Song DUAN ; Duo SHAN
Chinese Journal of Epidemiology 2024;45(12):1633-1638
Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.
8.Consideration on"Patient-Centered"Drug Development for Rare Diseases
Ling TANG ; Xing AI ; Tian ZHAO ; Zhimin YANG
JOURNAL OF RARE DISEASES 2024;3(2):168-174
The unmet clinical needs of patients with rare diseases persist.Many rare diseases lack effec-tive treatments,and drug development for rare diseases faces greater challenges than that for common multiple diseases.In recent years,the concept of"patient-centered"drug development has been widely adopted.The Center for Drug Evaluation(CDE)of the National Medical Products Administration has successively issued a series of relevant guiding principles,such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials,to promote a"patient-centered"drug development model.The implementation of the"patient-centered"approach in rare disease drug research and development,with a focus on patient perspectives and ac-tive engagement,can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises,researchers,and regulatory agencies.This approach also en-hances the accuracy and efficiency of rare disease drug research and development.The CDE will continue to pri-oritize the integration of the"patient-centered"concept into rare disease drug research and development,effec-tively enhance the involvement of rare patients in the drug research and development process,and leverage the guiding role of patients'perspectives on drug research and development.
9.Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency
Chengcheng WANG ; Xing TANG ; Chunmei LI ; Zhongbo WANG ; Yanlin FU ; Min DAI ; Min YANG ; Congcong YU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):163-169
ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome (CFS) with Qi deficiency and its effects on TCM syndromes, fatigue symptoms, serum superoxide dismutase (SOD), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group (100 cases) and an observation group (100 cases). The control group was treated with vitamin B compounds, and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes, fatigue symptoms, levels of serum SOD, MDA, and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment, the total effective rate of the control group was 54.34% (50/92), while that of the observation group was 88.54% (85/96). The total effective rate of the observation group was higher than that of the control group (χ2=27.13,P<0.05). Compared with those in the two groups before treatment, scores of fatigue self-assessment scale (FSAS), physical fatigue and mental fatigue, and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased (P<0.05). After treatment, scores of FSAS, physical fatigue and mental fatigue, and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group (P<0.05). Compared with those in the two groups before treatment, TCM syndrome scores in the two groups after treatment were significantly decreased (P<0.05). After treatment, TCM syndrome scores in the observation group were significantly decreased compared with those in the control group (P<0.05). Compared with those in the two groups before treatment, MDA levels in the two groups were significantly decreased (P<0.05), ox-LDL levels in the observation group were significantly decreased (P<0.05), and SOD levels were significantly increased (P<0.05). After treatment, compared with those in the control group, the serum MDA and ox-LDL levels in the observation group were significantly decreased (P<0.05), and the serum SOD was significantly increased (P<0.05). No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency, which can effectively improve the fatigue symptoms of patients, increase the level of SOD, and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants, inhibiting the production of lipid peroxides, and improving the body's ability to resist oxidative stress.
10.Development and validation of a prediction model for severe community-acquired pneumonia in adults based on peripheral blood inflammatory indicators
Shuang CHEN ; Haike LEI ; Xinyi TANG ; Jiao WANG ; Ling LIU ; Weibo HU ; Yulin HUANG ; Jian'e HU ; Xiangju XING ; Zailin YANG
International Journal of Laboratory Medicine 2024;45(3):282-288
Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.


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