1.Analysis of factors influencing immune checkpoint inhibitor-related thyroid adverse reactions
Jiayu LI ; Qianqian ZHANG ; Meng HOU ; Siqi ZHANG ; Keke WANG
China Pharmacy 2025;36(3):341-345
OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor (ICI). METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event (irAE) group (subdivided into clinical hypothyroidism, clinical hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism subgroups) and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included, with 137 cases in the thyroid irAE group (accounting for 35.9%) and 245 cases in the non-thyroid irAE group (accounting for 64.1%). Multivariate Logistic regression analysis, following univariate screening, revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio (OR)=2.157, 95% confidence interval (CI) (1.144, 4.066), P<0.05], while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR=0.600, 95%CI (0.369, 0.975), P<0.05]. Among various thyroid irAE, nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR=4.678, 95%CI (1.149, 19.042), P<0.05]; ICI combined with radiotherapy [OR=2.622, 95%CI (1.227, 5.603), P<0.05] and lung adenocarcinoma [OR=2.013, 95%CI (1.078, 3.759), P<0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR=0.944, 95%CI (0.896, 0.995), P<0.05]; age [OR=0.963, 95%CI (0.932, 0.994), P<0.05] and ICI combined with chemotherapy [OR=0.332, 95%CI (0.137, 0.802), P<0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment, younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism, while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.
2.Key Information Research and Ancient and Modern Application Analysis of Classic Prescription Houpo Sanwutang
Wenli SHI ; Qing TANG ; Huimin CHEN ; Jialei CAO ; Bingqi WEI ; Lan LIU ; Keke LIU ; Yun ZHANG ; Yujie CHANG ; Yihan LI ; Jingwen LI ; Bingxiang MA ; Lvyuan LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):214-221
Houpo Sanwutang, included in the Catalogue of Ancient Classical Prescriptions (Second Batch), was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining, statistical analysis, and data processing, combined with modern articles, this study employed bibliometrics to investigate the historical origin, composition, decoction methods, clinical application, and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty, it is recommended that 110.4 g Magnolia Officinalis Cortex, 55.2 g Rhei Radix et Rhizoma, and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first, and 1 000 mL should be taken from the decocted liquid. Following this, Rhei Radix et Rhizoma should be added for further decoction, and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL, and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi, relieving stuffiness and fullness, removing food stagnation, and regulating bowels. It can be used in treating abdominal distending pain, guarding, constipation, and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.
3.Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.
Keke HUANG ; Qingkai LIU ; Ruoxi ZHANG ; Hua NIAN ; Ying LUO ; Yue LUO ; Xiaoya FEI ; Le KUAI ; Bin LI ; Yimei TAN ; Su LI ; Xin MA
Frontiers of Medicine 2025;19(1):134-148
To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy*
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Animals
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Drugs, Chinese Herbal/administration & dosage*
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Humans
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Mice
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Network Pharmacology
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Male
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Female
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Adult
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Receptors, Glucocorticoid/metabolism*
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Disease Models, Animal
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Single-Blind Method
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Middle Aged
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Young Adult
4.Changes of binocular surface indexes after unilateral endoscopic dacryocystorhinostomy
Xiaolin ZHANG ; Meng LI ; Keke ZHANG ; Yan GONG
International Eye Science 2024;24(3):479-483
AIM: To investigate the effect of unilateral endoscopic dacryocystorhinostomy on binocular surface indexes.METHODS: Totally 45 cases with monocular primary acquired nasolacrimal duct obstruction(PANDO)who successfully underwent endoscopic dacryocystorhinostomy between 1 December 2022 and 31 July 2023 were enrolled in the study. Ocular surface indexes, including the non-invasive tear break-up time(NIBUT), Sjögren's International Collaborative Clinical Alliance ocular staining score(SICCA OSS), Korb score of lid wiper and Schirmer test scores, were collected preoperatively and at 0.5, 1 and 3 mo post-operatively. Subsequently, various indexes were compared at each time point between the operated and healthy eyes pre- and post-operatively.RESULTS: There was no significant differences between operated and healthy eyes in NIBUT, SICCA OSS, Korb scores and Schirmer test(all P>0.05). Furthermore, the Korb scores of operated eye at 0.5, 1 and 3 mo post-operatively were significantly lower than the preoperative value(P=0.034, 0.044, 0.027). Moreover, the Schirmer test score of the operated eye at 1 mo post-operatively was significantly lower than the preoperative value(P=0.0461).CONCLUSION:After a successful endoscopic dacryocystorhinostomy, tear drainage is restored, however, ocular surface damage worsens. These changes typically peak at 1 mo post-operatively before gradually improving.
5.Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis
Jialin YANG ; Bingjie CAI ; Yuhao DAI ; Shuting LI ; Keke ZHANG ; Yanhua GAO ; Qiman ZHANG ; Ying ZHANG ; Jianying SHEN ; Shaojing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):91-100
ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula (YQ) in treating ischemic stroke (IS) from the perspective of the microbial-gut-brain axis (MGBA). MethodRats were randomly divided into five groups, with six in each group, including sham surgery group, model group, and low, medium, and high dose YQ groups (1, 5, and 25 mg·kg-1). Except for the sham surgery group, all other groups were established with a middle cerebral artery occlusion (MCAO) model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring, and the protective effect of YQ on IS was evaluated. Then, the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology, and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-17A (IL-17A), and interleukin-10 (IL-10) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue, and hematoxylin-eosin staining (HE) was used to observe pathological changes in the cerebral cortex and colon, so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats (P<0.01) and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them, significantly changed microorganisms include Morgentia, Escherichia Shigella, Adlercreutzia, and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group, the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A (P<0.01) and a decrease in the content of anti-inflammatory factor IL-10 (P<0.01). Compared with the model group, the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased (P<0.05), and that of anti-inflammatory factor IL-10 increased (P<0.01). The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats (P<0.05), while the expression levels of both increased in the treatment group (P<0.05). ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier, and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia, inhibit systemic inflammatory response, and improve the disruption of the gut-blood brain barrier, preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.
6.Observation on the efficacy of ruiyun procedure for hemorrhoids combined with conformal suture in the treatment of severe prolapsed hemorrhoids
Yu ZHANG ; Hongping GAO ; Jiao ZHENG ; Hang SUN ; Keke MA
China Modern Doctor 2024;62(4):11-14
Objective To observe the efficacy of ruiyun procedure for hemorrhoids(RPH)combined with conformal suture in the treatment of severe prolapsed hemorrhoids.Methods Seventy-eight patients with severe prolapsed hemorrhoids admitted to the First People's Hospital of Xuzhou from June 2021 to August 2022 were selected and divided into observation group and control group according to random number table method,with 39 cases in each group.Patients in observation group were treated with RPH combined with conformal suture,and patients in control group were treated with external peeling and internal ligation.Operation duration,intraoperative blood loss,postoperative complications,wound healing time,anal function and overall satisfaction were compared between two groups.Results The intraoperative blood loss in observation group was significantly less than that in control group,hospital stay was significantly shorter than that in control group(P<0.05).Postoperative pain,bleeding,anal edema and the formation of anal skin pad in observation group were significantly better than those in control group(P<0.05).At 12 weeks after surgery,Wexner anal incontinence scores in both groups were significantly lower than before surgery(P<0.05),and the Wexner anal incontinence score in observation group was significantly lower than that in control group(P<0.05).The cure rate of observation group was significantly higher than that of control group(92.31%vs.74.36%,χ2=55.46,P=0.03),and the overall satisfaction with treatment was significantly higher than that of control group(χ2=58.57,P=0.02).Conclusion RPH combined with conformal suture is effective in treatment of severe prolapsed hemorrhoids,which can reduce the pain of patients,shorten the length of hospital stay,reduce complications,and improve the comfort and satisfaction of patients.
7.Research Progress of IL-13 Regulating Mucus Hypersecretion in Allergic Rhinitis and the Intervention of Traditional Chinese Medicine
ZHAO Yue ; WANG Zhiwang ; HUANG Keting ; LIANG Keke ; QUAN Ping ; ZHANG Yue
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1836-1843
Allergic rhinitis(AR) is an allergic inflammatory disease of the nasal mucosa in which the immune inflammatory response alters the local microenvironment of the nasal mucosa, causing mucus hypersecretion as one of the main pathological features of AR. Interleukin-13(IL-13) is the main inflammatory factor secreted by Th2 cells, it can be involved in AR mucus hypersecretion process by regulating Goblet cell proliferation and Mucin 5ac expression through various signaling pathways. Traditional Chinese medicine has obvious advantages in the treatment of AR and its mucus hypersecretion, while the IL-13-mediated signaling pathways are one of the important mechanisms in treating AR mucus hypersecretion. This article reviews the regulation of IL-13-mediated signaling pathways on AR mucus hypersecretion and the intervention effects of traditional Chinese medicine, which providing a theoretical basis for experimental research and new drug development in AR mucus hypersecretion.
8.Analysis of latent classes and predictive factors of health behavior among stroke patients
Lina GUO ; Yuanli GUO ; Mengyu ZHANG ; Caixia YANG ; Keke MA ; Gege ZHANG ; Miao WEI ; Yanjin LIU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(1):21-26
Objective:To explore the latent classes of health behavior and explore the predictive factors among stroke patients.Methods:A total of 1 250 participants were recruited using cluster random sampling in September 2022. The general information, the modified Rankin scale(mRS), stroke prevention knowledge questionnaire(SPKQ), health behavior scale for stroke patients (HBS-SP), and short form-health belief model scale (SF-HBMS) were administered in the cross-sectional survey. Mplus 8.3 software was used to conduct a latent class analysis (LCA) on the health behavior of stroke patients, and SPSS 27.0 software was used to carry out multinomial Logistic regression to analyze the predictive factors of different latent classes of health behavior of stroke patients.Results:The health behavior of stroke patients obtained three latent classes: low health behaviors-lack of health responsibility group (66.9%, n=794), moderate health behaviors-poor compliance group (11.9%, n=141), and good health behaviors-insufficient exercise group (21.2%, n=251). Compared with good health behaviors-insufficient exercise group, stroke patients with shorter duration education time ( B=-0.589, OR=0.555, P=0.036), hemorrhagic stroke ( B=0.082, OR=1.086, P<0.001), fewer comorbidities ( B=-0.022, OR=0.978, P=0.026), higher mRS score ( B=-0.046, OR=1.047, P=0.004), lower SPKQ score ( B=-0.055, OR=0.947, P=0.016), and lower SF-HBMS score ( B=-0.085, OR=0.919, P<0.001) were more likely to be included in moderate health behaviors-poor compliance group. However, stroke patients with shorter duration education time ( B=-0.026, OR=0.974, P=0.003), rural areas dwelling ( B=0.800, OR=2.225, P=0.004), fewer comorbidities ( B=-0.056, OR=0.945, P<0.001), lower SPKQ score ( B=-0.101, OR=0.904, P<0.001), and lower SF-HBMS score ( B=-0.071, OR=0.931, P<0.001) were more likely to be included in low health behaviors-lack of health responsibility group. Conclusion:The health behavior of stroke patients has three latent classes. A targeted intervention should be carried out according to the characteristics of different classes to improve their health behavior levels.
9.Mechanism study on the intervention of Jiawei Tongmai Huazheng Decoction on Wnt/β-catenin pathway promoting apoptosis of lesion cells in mice model of adenomyosis
Yang LIU ; Keke ZHANG ; Runhan WANG ; Wei SHI
International Journal of Traditional Chinese Medicine 2024;46(3):323-329
Objective:To study the effects of intervention of Jiawei Tongmai Huazhi Decoction in the Wnt/β-catenin pathway on apoptosis of lesion cells in mice with adenomyosis (AM); To discuss its mechanism of action.Methods:The AM mouse model was established using tamoxifen. The mice were divided into model group, Jiawei Tongmai Huazhi Decoction group, and progesterone group according to random number table method, with 7 mice in each group. Additionally, a blank group of 7 female mice was set up. Jiawei Tongmai Huazhi Decoction group received oral administration of Jiawei Tongmai Huazhi Decoction at a dosage of 36.51 g/kg/day, once daily. The progesterone group received oral administration of progesterone at a dose of 0.32 mg/kg twice a week. The blank group and model group received oral administration of the same volume of physiological saline once daily. After 2 months of intervention, the morphology of uterine tissues was observed by HE staining. The levels of carbohydrate antigen 125 (CA125) and prolactin (PRL) in the serum were measured by ELISA. The mRNA levels of Wnt3a and β-catenin in uterine tissues were determined by PCR. The protein expressions of Wnt3a, β-catenin, Bax, and Bcl-2 in uterine tissues were detected by Western blot.Results:Compared with the model group, the levels of serum CA125 and PRL were reduced in the Jiawei Tongmai Huazhi Decoction group ( P<0.05). The protein expressions of Wnt3a, β-catenin, and Bcl-2 were also reduced ( P<0.05), the protein expressions of Wnt3a, β-catenin, and Bcl-2 decreased ( P<0.05), while the protein expressions of Bax increased ( P<0.05). Conclusion:Jiawei Tongmai Huazhi Decoction alleviates the progression of lesions by reducing serum CA125 and PRL levels in AM model mice, and can down-regulate Bcl-2 expression and up-regulate Bax expression, promoting apoptosis of ectopic lesion cells in mice. Its mechanism of action may be related to the inhibition of Wnt/β-catenin pathway related expression proteins.
10.Textual Research of Pediatric Famous Classical Formula Daochisan Based on Ancient and Modern Literature
Lyuyuan LIANG ; Hejia WAN ; Jinyan ZHANG ; Keke LIU ; Jialei CAO ; Xianghan TAN ; Bingqi WEI ; Bingxiang MA ; Yajing HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):218-227
Daochisan is a pediatric famous classical formula in traditional Chinese medicine(TCM) specializing in clearing the heart, disinhibiting water and enriching Yin, which has been inherited and developed by medical experts of successive generations. The formula can be traced back to Xiaoer Yaozheng Zhijue written by QIAN Yi from Song dynasty, and most of the later-developed Daochisan(Daochitang) is based on this formula with additions and subtractions. So as to promote the literature excavation of this formula, this paper conducts a thorough textual research and analysis of the composition, processing, preparation methods, clinical applications of Daochisan based on a systematic collation of relevant ancient and modern literature in the method of bibliometrics. A total of 127 pieces of data involving 86 antient TCM books were collected. Statistical analysis showed that the drug origin of Daochisan is basically clear, we suggest that Rehmanniae Radix is the root tuber of Rehmannia glutinosa of Scrophulariaceae, Akebiae Caulis is the dry stem of Akebia quinata of Lardizabalaceae, Glycyrrhizae Radix et Rhizoma is the dry root and stem of Glycyrrhiza uralensis of legume, bamboo leaf is the dry leaves of Phyllostachys nigra var. henonis of gramineous plants. Four herbs are recommended to use its raw products. The key information of the dosage and decocting method is supposed to be "4.13 g each of raw Rehmanniae Radix, raw Glycyrrhizae Radix et Rhizoma, Akebiae Caulis, adding 300 mL of water, and then adding 4.13 g of bamboo leaf, decocting together to 150 mL, taking warmly after meal". Daochisan has the effect of clearing the heart and enriching Yin, disinhibiting water and relieving stranguria, and is widely used in treating symptoms such as heart vexed hotness, hydrodipsia and reddish complexion. Modern studies have showed that Daochisan are frequently used in treating oral ulcer, herpetic stomatitis, urinary tract infection, herpes zoster and other diseases. The above research results can provide scientific reference for the future development and research of Daochisan.


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