1.Mechanisms of Renshentang in Treating AS via Regulation of Endothelial Cell Inflammation Based on TRPV1
Ce CHU ; Yulu YUAN ; Zhen YANG ; Xuguang TAO ; Xiangyun CHEN ; Zhanzhan HE ; Yuxin ZHANG ; Yongqi XU ; Wanping CHEN ; Peizhang ZHAO ; Wenlai WANG ; Hongxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):46-53
ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis (AS) in mice, focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 (TRPV1). MethodsAn AS model was established in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet. The mice were randomly divided into a simvastatin group (0.02 g·kg-1·d-1) and low-, medium-, and high-dose Renshentang groups (1.77, 3.54, 7.08 g·kg-1·d-1), with 12 mice in each group. ApoE-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group (n=9). After continuous administration for 12 weeks, mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin (HE) staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as the expression of TRPV1, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-Akt) in the aortic root. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect endothelial nitric oxide synthase (eNOS) mRNA expression in the aorta, and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group, the model group showed a significant increase in aortic plaque formation (P<0.01) and significantly elevated levels of TNF-α and IL-1β in the aortic root (P<0.01). The expression levels of TRPV1, p-PI3K, and p-Akt were decreased (P<0.05, P<0.01), and eNOS mRNA expression was reduced (P<0.05, P<0.01). Compared with the model group, all Renshentang groups significantly reduced aortic plaque formation (P<0.01), significantly decreased TNF-α and IL-1β levels (P<0.01), and markedly increased the expression levels of TRPV1, p-PI3K, p-Akt, and eNOS mRNA (P<0.05, P<0.01). ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway, which may be one of the molecular mechanisms underlying its therapeutic effect against AS.
2.MRI findings of spinal cord atrophy after spinal cord injury in children and their injury level
Yingxin ZHANG ; Genlin LIU ; Di CHEN ; Hongxia ZHANG ; Yifan TIAN ; Yiji WANG ; Yang JING ; Ruidong CHENG ; Shaomin ZHANG ; Jiafeng YAO ; Bo SUN ; Xiaomeng SUN
Chinese Journal of Rehabilitation Theory and Practice 2026;32(4):387-392
ObjectiveTo delineate imaging findings using an imaging platform and investigate the correlation between MRI characteristics of spinal cord atrophy and clinical diagnosis in children with spinal cord injury (SCI). MethodsImaging data of 150 children with SCI admitted to Beijing Bo'ai Hospital, China Rehabilitation Research Center, from January, 2002 to March, 2024 were collected and imported into the imaging platform. The anteroposterior and transverse diameters of the middle part of the spinal cord at the cross-section with the most severe atrophy were measured, and the relevant indicators of the previous normal spinal cord segment were measured as controls; the radiomic features were extracted. Clinical data of the children including gender, age, cause of injury, sensory level, motor level, spinal cord injury level, injury severity and disease course were collected. ResultsSpinal cord atrophy was identified in 81 cases (54%), among which 78 cases (96%) were American Spinal Injury Association Impairment Scale (AIS) grade A and 3 cases (4%) were AIS grade C. The upper boundary of the spinal cord atrophy site strongly correlated with the injury level, motor level and sensory level (r > 0.8, P < 0.001). ConclusionMore than half of children with SCI may develop secondary spinal cord atrophy, the vast majority of whom suffer from complete spinal cord injury; the upper boundary of spinal cord atrophy is correlated with the injury level.
3.Expert consensus on the application of artificial intelligence in lung cancer screening, diagnosis, and treatment (2026 edition)
Wenzhao ZHONG ; Haibo WANG ; Yi HU ; Hao ZHANG ; Jigang DAI ; Junqiang FAN ; Guibin QIAO ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Zihao CHEN ; Hongxia TIAN ; Lunxu LIU ; Hecheng LI ; Xiaolong YAN ; Zongyang YU ; Zhenbin QIU ; Yihua SUN ; Jing HU ; Yuhang SHI ; Zhifei GUO ; Peng ZHANG ; Kezhong CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):848-856
With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.
4.Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.
Dongfang YOU ; Dianjianyi SUN ; Ziyu ZHAO ; Mingyu SONG ; Lulu PAN ; Yaqian WU ; Yingdan TANG ; Mengyi LU ; Fang SHAO ; Sipeng SHEN ; Jianling BAI ; Honggang YI ; Ruyang ZHANG ; Yongyue WEI ; Hongxia MA ; Hongyang XU ; Canqing YU ; Jun LV ; Pei PEI ; Ling YANG ; Yiping CHEN ; Zhengming CHEN ; Hongbing SHEN ; Feng CHEN ; Yang ZHAO ; Liming LI
Chinese Medical Journal 2025;138(14):1696-1704
BACKGROUND:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
METHODS:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
RESULTS:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037).
CONCLUSIONS
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans
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Male
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Female
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Prospective Studies
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Middle Aged
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Aged
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Vascular Diseases/etiology*
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Risk Factors
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China/epidemiology*
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Adult
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Proportional Hazards Models
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Cerebrovascular Disorders/epidemiology*
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East Asian People
5.Characteristics and management of pediatric pemphigus vulgaris
LIANG Wenhui ; CHEN Yuting ; DAN Hongxia
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):587-596
Pemphigus vulgaris (PV) is the most common subtype of pemphigus. It predominantly affects adults, with pediatric cases being exceedingly rare. Despite advancements in clinical treatment, the mortality rate of pediatric PV (PPV) has historically been alarmingly high, ranging from 70% to 100% in the absence of proper diagnosis and treatment. Although recent improvements in therapeutic strategies have led to a gradual decline in mortality, early and appropriate intervention remains crucial, particularly for children with acute onset and rapid disease progression, to prevent severe complications. However, due to the rarity of PPV, no standardized diagnostic and treatment guidelines are currently available. This study retrospectively analyzed 104 PPV cases recorded in the PubMed and China National Knowledge Infrastructure (CNKI) databases between 1969 and 2024, with the aim of providing insights for the standardized diagnosis and management of PPV. PPV presents with flaccid blisters affecting both cutaneous and mucosal surfaces. Upon rupture, these blisters result in painful, sharply demarcated erythematous erosions, accounting for approximately 1.4%-3.7% of all reported PV cases. The age of onset ranges from 1.5 to 18 years, with an average of 12.4 years, and no significant gender differences have been observed. In pediatric patients, the oral mucosa is typically the earliest and most frequently affected site, with an involvement rate as high as 87.3%, and it most commonly affects the buccal mucosa (27.9%). Other mucosal sites are affected in 52.9% of cases, with genital (28.8%) and perianal (6.7%) involvement being more frequent than in adult patients. Skin lesions are present in 80.4% of pediatric cases, a significantly higher rate than 16.0%-68.4% observed in adults. If lesions are relatively localized, local glucocorticoid therapy can be attempted first, with 8.3% of children achieving complete remission through local treatment alone. Systemic glucocorticoid therapy is the preferred option for cases that respond poorly to local therapy. Among these cases, 75.3% of pediatric patients were treated with prednisone, with 85.1% starting at an oral dose of 0.5-1.5 mg/kg/day, while 14.9% received an initial dose of 2 mg/kg/day. Alternative treatments, such as immunosuppressants, biologics, or other adjuvant medications, may be considered for pediatric patients who exhibit an inadequate response to glucocorticoid therapy or experience severe adverse effects. The most commonly used agents include azathioprine (24.0%), dapsone (21.7%), and rituximab (12.5%). The follow-up period for pediatric patients ranged from 1 to 120 months, with an average duration of 38 months. Prognosis in pediatric patients was more favorable compared to adults, with 43.8% achieving complete remission (cessation of treatment), 37.5% achieving partial remission (low-dose maintenance therapy), 9.6% still undergoing treatment, and only 1.1% succumbing to pneumonia or sepsis. Compared to adults, prolonged corticosteroid use in children poses a greater risk to physiological and psychological well-being, making them more susceptible to adverse effects related to growth, metabolism, and ocular health. Severe adverse reactions occurred in 22.1% of pediatric patients receiving corticosteroids, with Cushingoid facies (73.9%) and weight gain (39.1%) being the most common. In addition, 30.4% experienced growth and skeletal abnormalities, including growth retardation (17.4%), osteoporosis (8.7%), and fractures (4.3%). While PPV shares certain etiological, clinical, and histopathological characteristics with adult PV (APV), early diagnosis and timely intervention remain critical for optimal outcomes. Multidisciplinary collaboration is often necessary to ensure comprehensive management, improve treatment adherence, and safeguard the physical and psychological health of pediatric patients.
6.Expert Consensus on Clinical Application of Ruyi Zhenbaowan
Ming CHEN ; Jingling CHANG ; Shangquan WANG ; Gejia ZHONG ; Qiang DENG ; Hongxia CHEN ; Qien LI ; Yaming LIN ; Zujian XU ; Changkuan FU ; Yuer HU ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):173-183
Osteoarthritis (OA) and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan, a classic prescription in Tibetan medicine, have the functions of clearing heat, awakening the brain and opening orifices, relaxing tendons and promoting meridian circulation, and eliminating yellow water. Clinically, they are used to treat osteoarthritis, post-stroke sequelae, neuropathic pain, and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory, analgesic, and nerve-repairing effects. However, current research remains insufficient regarding the appropriate indications, timing, and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use, a panel of national experts, including clinical specialists, Tibetan medicine practitioners, pharmacologists, and methodologists, formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan, including therapeutic indications, dosage and administration, treatment duration, and medication safety. The consensus specifically addresses the clinical efficacy, appropriate timing of administration, dosage strategies, treatment cycles, and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke, reduce medication-related risks, and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine, with the standard number GS/CACM 369-2024.
7.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
8.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
9.Data Mining of Professor Zhang Farong's Core Prescription for Type 2 Diabetes Mellitus and Its Clinical Efficacy
Wei FANG ; Jie XU ; Huanping WANG ; Xiaoran ZHANG ; Hongxia ZHU ; Qiu CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):174-182
ObjectiveTo explore the medication patterns of Professor Zhang Farong in treating type 2 diabetes mellitus (T2DM) and the clinical efficacy of his core prescription. MethodsClinical case records of T2DM treated by Professor Zhang Farong were collected to establish a prescription database. Frequency statistics, visual analysis, and factor analysis were employed to investigate the characteristics and principle of the prescriptions, and a core prescription was derived. A randomized controlled trial was conducted, enrolling 60 T2DM patients with the dampness-heat syndrome. The patients were allocated into an observation group (core prescription + metformin) and a control group (metformin alone), with both groups undergoing a 12-week treatment course. Changes in TCM symptom scores, glucose metabolism indicators [fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2 hPG), and glycated hemoglobin (HbA1c)], pancreatic function indicators [fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 hCP), and area under the C-peptide curve (AUCcp)], and lipid profiles were measured before and after treatment. The adverse reactions were observed and recorded. ResultsA core prescription named modified Gegen Qinlian Decoction was formulated, comprising Puerariae Lobatae Radix, Coptidis Rhizoma, Scutellariae Radix, Astragali Radix, Lycii Cortex, Mori Cortex, Jineijin Endothelium Corneum Gigeriae Galli, Rehmanniae Radix Praeparata, Atractylodis Rhizoma, Polygonati Rhizoma, and Pogostemonis Herba. The clinical trial results showed that both groups had significantly decreased FPG, 2 hPG, and HbA1c (P0.05), and the observation group outperformed the control group in recovering the level of HbA1c (P0.05). After treatment, both groups had declined TCM symptoms scores (P0.05), and the declines in the observation group were larger than those in the control group (P0.05). After treatment, the TC and LDL-C levels declined in the observation group (P 0.05), while the lipid levels showed a decreasing trend with no statistically significant difference in the control group. After treatment, both groups showed increases in FCP and AUCcp (P0.05), and the 2 hCP in both groups presented a recovering trend with no statistically significant difference. There was no statistically significant difference in the incidence of adverse reactions between the two groups. ConclusionModified Gegen Qinlian Decoction embodies Professor Zhang Farong's academic philosophy of treating consumptive thirst by tonifying the spleen and kidney, replenishing Qi and Yin, clearing deficiency and heat, unblocking stasis in collaterals, and addressing both deficiency and stasis. The combination of the core prescription with metformin alleviates clinical symptoms in T2DM patients with the dampness-heat syndrome, demonstrating potential effects in restoring pancreatic islet function, regulating blood glucose, and improving lipid profiles. It serves as a therapeutic option for T2DM in the patients with the dampness-heat syndrome under syndrome differentiation, meriting broader clinical application.
10.Prevalence and influencing factors of work-related musculoskeletal disorders of coal miners in a coal mine group
Xiaolan ZHENG ; Liuquan JIANG ; Ying ZHAO ; Hongxia ZHAO ; Fan YANG ; Qiang LI ; Li LI ; Yingjun CHEN ; Qingsong CHEN ; Gaisheng LIU
Journal of Environmental and Occupational Medicine 2025;42(3):278-285
Background The positive rate of work-related musculoskeletal disorders (WMSDs) among coal mine workers remains high, which seriously affects the quality of life of the workers. Objective To estimate the prevalence of WMSDs among coal miners in Shanxi Province and analyze their influencing factors. Methods From May to December 2023,


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