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*
;
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Humans
;
Mice
;
Network Pharmacology
;
Male
;
Female
;
Adult
;
Receptors, Glucocorticoid/metabolism*
;
Disease Models, Animal
;
Single-Blind Method
;
Middle Aged
;
Young Adult
4.Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition)
Jianling FAN ; Tiejun WANG ; Pengfei YANG ; Keke DING ; Xiaoning HAO ; Sunfang JIANG ; Ankang LÜ ; Jianping LU ; Sheng RONG ; Weibin SHI ; Shengwei SUN ; Yan TAN ; Qilei TU ; Zhiping WANG ; Bing WANG ; Jianyun WANG ; Weijian WANG ; Yan WANG ; Qun XU ; Chenli ZHANG ; Fan ZHANG ; Ping ZHANG ; Yansong ZHENG ; Jieru ZHOU ; Dan CHEN ; Jiaoyang ZHENG
Chinese Journal of Clinical Medicine 2025;32(6):1097-1111
Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.
5.Research progress of the role of intestinal microbiota-mediated bile acids in inflammatory bowel disease
Xixi XIA ; Keke DING ; Huiheng ZHANG ; Xufei PENG ; Yimin SUN ; Yajun TANG ; Xiaofang TANG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(7):839-846
It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease(IBD),causing a huge burden on healthcare systems and society.In the occurrence,progression,and treatment of IBD,the intestinal microbiota and its key metabolic product,bile acids,play a crucial role.The intestinal microbiota not only participates in the biotransformation of bile acids,enriching the diversity of bile acids,but also regulates their synthesis and transport through the farnesoid X receptor(FXR).Meanwhile,bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity,exerting direct toxicity,participating in indirect antimicrobial pathways,and influencing microbial metabolic capabilities.Furthermore,under normal physiological conditions,intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier.They also promote the balance of the immune system by modulating the functions of various immune cells including helper T(Th)cells 17,regulatory T(Treg)cells,CD8+T cells and natural killer T(NKT)cells,thereby slowing down the development of IBD.This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD,and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids,such as bile acid receptor modulators,probiotics,prebiotics,fecal microbiota transplantation(FMT),and phage therapy.
6.Research status of different doses of anti-vascular endothelial growth factor drugs in retinopathy of prematurity
Chinese Journal of Experimental Ophthalmology 2024;42(7):669-674
With the further study of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP), a variety of anti-VEGF drugs with 1/2 adult dose have been used at home and abroad to treat ROP, and initially achieved remarkable curative effect.However, further studies have shown that anti-VEGF drugs can enter the systemic circulation through the vitreous cavity, which temporarily reduces serum VEGF levels in children.As a result, it may have potential systemic side effects for premature infants during the period of rapid growth and development.At present, experts at home and abroad have begun to pay attention to the risk of systemic side effects of ROP treated with 1/2 adult dose, and have conducted a variety of low-dose anti-VEGF drugs in the treatment of ROP.However, most of the studies are retrospective studies with small samples, and there is a lack of multicenter prospective studies with large samples.Therefore, all doses of anti-VEGF drugs in the treatment of ROP need to be further investigated.This article reviews the efficacy and problems of different doses of anti-VEGF drugs in the treatment of ROP to provide a reference for the treatment of ROP.
7.Preliminary serum pharmacological exploration of method to preparate Ganlong capsule-containing serum
Keke ZHANG ; Hao BAI ; Jinyu LÜ ; Yue JIN ; Rui LUO
Chinese Journal of Pathophysiology 2024;40(5):956-960
AIM:To investigate the optimal time of blood collection and the best concentration of Ganlong capsule(GLC)-containing serum for steatohepatitis.METHODS:Sixty C57BL/6J mice were gavaged with GLC at a dose of 90 mg/kg body weight,twice a day for 7 days.Control mice were administered the same volume of 0.9%saline.After 0.5,1,2 and 4 h from the last gavage,blood was collected to prepare GLC-containing serum.The LC-MS/MS was used to detect the inosine content of blank and drug-containing serum at different blood collection times to determine the optimal time.Subsequently,NCTC1469 cells stimulated with palmitic acid(PA)were treated with different concentrations of the GLC-containing serum.Nile Red staining was used to detect lipid droplet formation,and RT-qPCR was employed to as-sess the expression of intracellular fatty acid synthesis(Fabp1,Scd1)and fatty acid β-oxidation gene(Pparα).RE-SULTS:(1)LC-MS/MS detection revealed that the inosine concentration peaked 2 h after the last administration.(2)Nile red staining demonstrated that the GLC-containing serum exerted a dose-dependent decreasing trend of lipid droplets in hepatocytes induced by PA.(3)GLC-containing serum significantly downregulated the mRNA expression levels of lipo-genesis-genes(Fabp1 and Scd1)with a dose-dependent decreasing trend in the PA-induced NCTC1469 cells.The mRNA expression of genes associated with fatty acid β-oxidation(Pparα)were upregulated with a dose-dependent increasing trend.CONCLUSION:The 10%GLC-containing serum collected 2 hours after the last administration in mice has the best therapeutic effect for steatohepatitis.
8.Effects of Aβ42 oligomers on expression of synaptic and extrasynaptic glutamate receptors
Qiuxuan CHEN ; Yani HE ; Yuxiang LIU ; Yi FENG ; Keke ZHANG ; Wei WEI
Chinese Journal of Pathophysiology 2024;40(6):1025-1032
AIM:To explore the expression and distribution of synaptic and extrasynaptic glutamate receptors under the action of amyloid β-protein 42 oligomers(Aβ42Os)in Alzheimer disease.METHODS:In vitro,primary neu-rons from neonatal mice were treated with different concentrations of Aβ42Os.In vivo,Aβ42Os were stereotaxically injected into the lateral ventricle of C57BL/6 mice.Western blot was used to detect the protein levels of metabotropic gultamate re-ceptor 5(mGluR5)and N-methyl-D-aspartate receptor(NMDAR)subunits(NR2A,NR2B and NR1)in mouse primary neurons and mice.Immunofluorescence staining was performed to observe the distribution of mGluR5 and NMDAR.Addi-tionally,Western blot was employed to examine the expression of mGluR5 downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway-related proteins,calcium signaling pathway-related proteins and synapse-related proteins in mouse hippocampal tissues.RESULTS:(1)High concentrations of Aβ42Os increased mGluR5 expression in mouse primary neurons,but reduced the expression of NR2A,NR2B and NR1(P<0.01).Treatment of pri-mary neurons with high concentration of Aβ42Os resulted in aggregation of mGluR5 on the membrane surface,and re-duced the expression of NR2A,NR2B and NR1 on the membrane surface.(2)High concentration of Aβ42Os increased the expression of synaptic mGluR5 in mouse hippocampal tissues(P<0.01),but reduced the expression of synaptic NR2A(P<0.05)and NR2B(P<0.01)and increased the expression of extrasynaptic NR2B(P<0.01).High concentration of Aβ42Os inhibited the expression of PI3K and the phosphorylation of AKT and extracellular signal-regulated kinase(ERK),and overactivated calcium/calmodulin-dependent protein kinase IIα(CaMKIIα).High concentration of Aβ42 decreased the expression of postsynaptic density protein 95,spinophilin,synaptophysin and microtubule-associated protein 2(P<0.01).CONCLUSION:(1)High concentrations of Aβ42Os increase mGluR5 expression and decrease NR2A,NR2B and NR1 expression in synapse,along with an increase in extrasynaptic NR2B.(2)High concentrations of Aβ42Os inhibit the PI3K/AKT and ERK signaling pathways,overactivated the CaMKIIα pathway,and destroyed the synaptic structures.
9.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.
10.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.

Result Analysis
Print
Save
E-mail