1.Modified Xiehuangsan Regulates Microglial Polarization and TLR4/MyD88/NF-κB Pathway to Treat Tic Disorders in Rats
Mengjie ZHAO ; Qiong ZHAO ; Cuiling YANG ; Hongyun ZHOU ; Xiangjuan SUN ; Xinyi GUO ; Sajiyue HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):10-18
ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders (TD) based on microglial polarization and the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor (NF)-κB pathway. MethodsSeventy-two Sprague-Dawley (SD) rats were randomly assigned into six groups: control, model, tiapride (0.025 g·kg-1), and low-, medium-, and high-dose (12, 24, 48 g·kg-1, respectively) modified Xiehuangsan, with 12 rats in each group. Except the control group, the other groups received intraperitoneal injection of 3,3'-iminodipropionitrile (IDPN) for 7 consecutive days for the modeling of TD. After successful modeling, the control and model groups were given normal saline via gavage, and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention, rat behaviors were observed, and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-4, TLR4, MyD88, and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 (Iba1), Fc receptor family for immunoglobulin (Ig)G type Ⅲ (CD16), mannose receptor (CD206), TLR4, MyD88, and NF-κB p65 in the striatum. ResultsCompared with the control group, the model group showed increased stereotyped behaviors, locomotor activity, total movement distance, and movement speed, shortened resting time (P<0.01), and noticeable pathological changes in the striatum. Compared with the model group, the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior, locomotor activity, total movement distance, and movement speed, prolonged resting time (P<0.05, P<0.01), and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups, the high-dose group had the best intervention effect and the mildest pathological changes. Therefore, the high-dose group was selected for further research. Compared with the control group, the modeling of TD increased Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the mRNA levels of IL-1β and TNF-α (P<0.05, P<0.01), down-regulated the mRNA level of IL-4 (P<0.05), up-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.05, P<0.01), and up-regulated the protein level of NF-κB p65 (P<0.01). Compared with the model group, modified Xiehuangsan reduced Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the protein level of CD206 (P<0.05, P<0.01), down-regulated the mRNA levels of IL-1β and TNF-α (P<0.05), up-regulated the mRNA level of IL-4 (P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, and NF-κB p65 (P<0.05, P<0.01). ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.
2.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
3.Role of neutrophil in fungal keratitis
Junming YANG ; Yanting LUO ; Hong HE ; Xingwu ZHONG
International Eye Science 2025;25(2):230-234
Fungal keratitis represents a significant cause of blindness, with current therapeutic approaches yielding limited success. The disease's onset and progression are primarily driven by fungal virulence factors and the host's immune response. The innate immune system is the first to respond, with neutrophils playing a pivotal role in the antifungal defense. Although neutrophils are critical for pathogen clearance, their excessive or abnormal activation can lead to tissue damage, exacerbating the disease. Thus, elucidating the mechanisms underlying neutrophil activity in fungal keratitis is crucial for refining treatment strategies. This article aims to systematically review the principal antimicrobial mechanisms employed by neutrophils, including phagocytosis, degranulation, and the formation of neutrophil extracellular traps(NETs). Furthermore, it explores the crosstalk between neutrophils and macrophages, alongside their collective impact and underlying mechanisms in the context of fungal keratitis. Exploration of the mechanisms of fungal keratitis facilitates precise intervention and enhances the efficacy of treatment.
4.GAO Shuzhong's Experience in Treating Idiopathic Tinnitus with Combination of Acupuncture and Chinese Materia Medica
Pengfei WANG ; Yiyang SUN ; Xiaoyan LI ; Wenli YAN ; Ningning MENG ; Guirong YANG ; Yuxia MA
Journal of Traditional Chinese Medicine 2025;66(3):233-237
To summarize Professor GAO Shuzhong's clinical experience in treating idiopathic tinnitus with a combination of acupuncture and Chinese meteria medica. It is believed that idiopathic tinnitus is mostly caused by weak lungs and spleen, kidney essence deficiency, liver constraint transforming into fire, and binding constraint of heart qi. Treatment advocates the combination of acupuncture and Chinese meteria medica in clinical practice. Acupuncture treatment mainly focus on the method of opening the orifices by syndrome identification in combination with Ermen (TE 21), Tinggong (SI 19), Tinghui (GB 2), Shenmai (BL 62) to regulate qi and blood, and supporting with Baihui (GV 20), Yintang (EX-HN 3), Taichong (LR 3), and Yanglingquan (GB 34) to soothe the liver, resolve constraint, and calm the mind. Oral administration of Chinese medicinal prescription usually includes modified Yiqi Congming Decoction (益气聪明汤) and Tongqi Powder (通气散), and the external administration of Chinese medicinal prescription can apply self-prescribed Wenqing Powder (温清散) to navel moxibustion.
5.Mechanism of Modified Si Junzitang and Shashen Maidong Tang in Improving Sensitivity of Cisplatin in EGFR-TKI Resistant Lung Adenocarcinoma Cells Based on Aerobic Glycolysis
Yanping WEN ; Yi JIANG ; Liping SHEN ; Haiwei XIAO ; Xiaofeng YANG ; Surui YUAN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):39-46
ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang [Yiqi Yangyin Jiedu prescription (YQYYJD)] in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD (0, 2, 3, 4, 5, 6, 7, 8 g·L-1) and cisplatin (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 mg·L-1) on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 (CCK-8) assay after 24 hours of intervention. The half-maximal inhibitory concentration (IC50) for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group (complete medium), YQYYJD group (5 g·L-1), cisplatin group (12 mg·L-1), and combined group (YQYYJD 5 g·L-1 + cisplatin 12 mg·L-1). After 24 hours of intervention, cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay, and cell migration was evaluated by scratch and Transwell assays. Glucose consumption, lactate production, and adenosine triphosphate (ATP) levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins, including hexokinase 2 (HK2), phosphofructokinase P (PFKP), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4), were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC50 of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L-1 and 12.91 mg·L-1, respectively. In terms of cell proliferation, compared with the blank group, the cell survival rate and the number of colonies formed in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in cell survival rate and colony formation (P<0.01). In terms of cell migration, compared with the blank group, the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane (P<0.01). In terms of glycolysis, compared with the blank group, glucose consumption, lactate production, and ATP levels in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in glucose consumption, lactate production, and ATP levels (P<0.05). Compared with the blank group, the protein expression levels of HK2, PFKP, PKM2, and LDHA in the YQYYJD, cisplatin, and combined groups were significantly decreased (P<0.01). The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups (P<0.01). No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes, including HK2, PFKP, PKM2, and LDHA, thereby inhibiting glycolysis.
6.Gandouling Regulates PI3K/Akt/mTOR Autophagy Signaling Pathway via LncRNA H19 for Treatment of Wilson Disease Liver Fibrosis
Xin YIN ; Han WANG ; Daiping HUA ; Lanting SUN ; Yunyun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):131-138
ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling (GDL) exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups: the normal group, the model group, the GDL low-, medium-, and high-dose groups (0.24, 0.48, 0.96 g·kg-1), and the penicillamine group (90 mg·kg-1), with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of hyaluronic acid (HA), laminin (LN), procollagen type-Ⅲ peptide (PC-Ⅲ), and collagen type-Ⅳ (C-Ⅳ). Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 (LncRNA H19), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Western blot analysis was performed to assess the expression levels of PI3K, Akt, mTOR, and their phosphorylated forms, as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3-Ⅱ/LC3-Ⅰ) in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group, the model group exhibited inflammatory cell infiltration in hepatocytes, unclear nuclear boundaries with cell cleavage and necrosis, and collagen fiber deposition around confluent areas. The levels of HA, LN, PC-Ⅲ, and C-Ⅳ were significantly elevated (P<0.01). Transmission electron microscopy revealed an increased number of autophagic vesicles, with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased (P<0.01), and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were reduced (P<0.01), while LncRNA H19 expression was increased (P<0.01), and mRNA expression levels of PI3K, Akt, and mTOR were decreased (P<0.01). After treatment with GDL, the degree of liver fibrosis was significantly improved, with decreased levels of HA, LN, PC-Ⅲ, and C-Ⅳ. The number of autophagic vesicles was significantly reduced, and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower (P<0.01). The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were elevated (P<0.01), while the expression level of LncRNA H19 was reduced (P<0.01). Furthermore, the mRNA expression levels of PI3K, Akt, and mTOR increased (P<0.05, P<0.01). ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.
7.Quantitative analysis on microvasculature in the optic disc area of patients with unilateral branch retinal vein occlusion
Jia SUN ; Jian LIU ; Peng YAN ; Nan LU ; Zhiming SHAN ; Dongni YANG
International Eye Science 2025;25(1):152-156
AIM: To observe the changes of retinal nerve fiber layer(RNFL)thickness and radial peripheral capillary(RPC)density in patients with unilateral branch retinal vein occlusion(BRVO), and further analyze the correlation between RPC density and RNFL thickness.METHODS: Observational study. Totally 37 patients with unilateral BRVO diagnosed at the ophthalmology department of First Hospital of Qinhuangdao from October 2020 to January 2022 were selected, the 37 affected eyes were the unilateral BRVO group, and 37 fellow healthy eyes were the contralateral unaffected group, and 35 healthy individuals(35 right eyes were selected)without ocular diseases during the same period were selected as the normal control group. The best corrected visual acuity, intraocular pressure, anterior segment, fundus and optical coherence tomography angiography(OCTA)were examined in both eyes of all BRVO patients and healthy individuals. The central macular thickness(CMT), the RNFL thickness, and the optic disc-AV crossing distance(DAVD)were measured by built-in software of the OCTA equipment. The optimized U-net algorithm was used to eliminate the large blood vessels, and then the RPC density was calculated. The CMT, RNFL thickness and RPC density were compared among the three groups. And the correlations of the RPC density with the CMT, RNFL thickness, and the DAVD were investigated.RESULTS: Compared with the contralateral unaffected group and the normal control group, the CMT and the RNFL thickness were significantly thickened in the unilateral BRVO group(all P<0.05); there were no statistical differences in the CMT and the RNFL thickness between the contralateral unaffected group and the normal control group(all P>0.05). The RPC density in the unilateral BRVO group increased compared with the contralateral unaffected group and decreased compared with the normal control group, but there was no statistically difference(all P>0.05). However, the RPC density in the contralateral unaffected group decreased compared with the normal control group(P<0.05). The RPC density in the unilateral BRVO group was not correlated with the CMT(P=0.960), but positively correlated with the RNFL thickness(r=0.401, P=0.014)and negatively correlated with the DAVD(r=-0.339, P=0.040).CONCLUSION: The RNFL thickened significantly and the RPC density did not change significantly in the optic disc area of BRVO patients. The RPC density is positively correlated with the RNFL thickness, indicating that the RNFL thickness can be used as a monitoring indicator to analyze and study the damage degree of the RPC density.
8.Treating diabetic kidney disease based on "using bitter herbs to nourish or purge" theory
Weimin JIANG ; Yaoxian WANG ; Shuwu WEI ; Jiale ZHANG ; Chenhui XIA ; Jie YANG ; Liqiao SUN ; Xinrong LI ; Weiwei SUN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):1-7
The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.
9.Discussion of sequential diagnosis and treatment model of diabetes mellitus of spatiotemporal syndrome differentiation from the perspective of qi, blood, and fluid
Jinhao HU ; Guiyan SUN ; Yufeng YANG ; Yan SHI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):8-13
The dysfunction of qi, blood, and fluid underlies the pathology of diabetes mellitus. The symptoms, signs, and physical and chemical indexes of diabetes mellitus patients reflect the duration, degree, primary and secondary pathological state of the abnormal metabolism of qi, blood, and fluid. It is necessary to construct a three-dimensional syndrome differentiation system of diabetes mellitus based on spatial and temporal dimensions. According to the four stages of depression, heat, deficiency, and damage, the location of the disease can be locked into qi, ying, and blood levels. The process reflects the pathological trend of the abnormal metabolism of qi, blood, and fluid: qi depression (prodromal stage: asymptomatic metabolic disorder/early stage of qi level) → qi heat (initial stage: index stage/late stage of qi level) → deficiency of both qi and yin (middle stage: symptom stage of three more and one less/stage of ying level) → damage of zang-fu viscera and meridians (late stage: complication stage/stage of blood level). According to the time process, the treatment principles are proposed as follows: during the early stage of qi level, treatment should focus on strengthening the spleen to regulate qi flow, to prevent the accumulation of glucose; during the late stage of qi level, treatment should focus on clearing heat and resolving turbidity, to remove the stagnated heat caused by glucose; during the stage of ying level, treatment should focus on benefiting qi and nourishing yin, to improve the symptoms about deficiency of both qi and yin; during the stage of blood level, treatment should focus on promoting blood circulation and removing blood stasis, to remove the complication. According to the etiology and pathogenesis of diabetes mellitus, the sequential treatment strategy is thus proposed, which is strengthening the spleen to regulate qi flow, clearing heat and resolving turbidity, benefiting qi and nourishing yin, and promoting blood circulation and removing blood stasis. The compound prescriptions such as Houpo Sanwu Decoction, Baihu Jia Renshen Decoction, Danggui Liuhuang Decoction, and Taohong Siwu Decoction are used with modification in the stage-based treatment.
10.Correlation between driver gene mutation and environmental exposure factors in patients with non-small cell lung cancer in Xi'an City
Yang HU ; Qianrong WANG ; Mengxue WANG ; Na CHENG ; Meijuan WU ; Xianna WU ; Juanhua SUN
Journal of Public Health and Preventive Medicine 2025;36(1):114-117
Objective To understand the driver gene mutation status in patients with non-small cell lung cancer (NSCLC) in Xi'an City, and to analyze the association with environmental exposure factors. Methods A total of 305 NSCLC patients admitted to the First Affiliated Hospital of the Air Force Medical University from January 2019 to December 2023 were included. The driver gene mutation status was observed, and the relationship with environmental exposure factors was analyzed. Results The driver gene mutation rate of 305 patients was 46.89%, with EGFR gene mutation accounting for the highest proportion, and 4 cases of gene co-mutations were detected. There was a difference in gender among patients with different single drive gene mutations (P<0.05), and the proportion of EGFR in women was significantly higher (P<0.05). Univariate analysis showed that there were statistical differences in family history, smoking history, long-term cooking history, and fried smoked food intake between patients with driver gene mutation and patients without driver gene mutation (P<0.05). Logistic regression analysis suggested that long-term cooking history (OR=2.392), and fried smoked food intake (OR=2.849) were the environmental exposure factors affecting EGFR gene mutation (P<0.05), and smoking history (OR=1.377) was an environmental exposure factor of KRAS gene mutation (P<0.05). Conclusion EGFR gene mutation accounts for the highest proportion of NSCLC patients in Xi'an City, and is mainly female. Long-term cooking history, and fried smoked food intake are related to EGFR gene mutation. There is a certain association between smoking history and KRAS gene mutation.


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