1.Mechanism of Traditional Chinese Medicine Against Gouty Arthritis via Regulating Nrf2 Signaling Pathway: A Review
Siyi CHEN ; Shumin HUANG ; Yushan ZHAO ; Jiajin LIN ; Qian SHI ; Yefeng CHEN ; Yize ZHANG ; Zhongwen ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):323-330
Gouty arthritis (GA) is an inflammatory disorder caused by monosodium urate (MSU) crystal deposition, accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines, resulting in joint tissue damage and intense pain. Nuclear factor E2-related factor 2 (Nrf2), a key transcription factor regulating the antioxidant defence system, exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 (Keap1) and activates downstream antioxidant response element (ARE)-mediated pathways. It can upregulate the expression of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), superoxide dismutase (SOD), and glutathione transferase (GST) to preserve redox homeostasis. Moreover, Nrf2 can suppress activation of NOD-like receptor protein 3 (NLRP3) inflammasomes, reduce pro-inflammatory cytokine production and release, modulate nuclear factor-κB (NF-κB) transcriptional activity, regulate gut microbiota balance, enhance mitophagy, and inhibit apoptosis, so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine (TCM) for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE, Nrf2/HO-1(NQO1), and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage, attenuate inflammatory responses, promote autophagy, and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.
2.Clinical and contrast-enhanced ultrasonographic characteristics of peripheral lung masses in patients infected with human immunodeficiency virus
Lei ZHAO ; Jingjing HUANG ; Xin MA ; Xia SHI ; Dou WU ; Zhi ZHANG ; Fengxiang SONG ; Jianjian LIU
Chinese Journal of Clinical Medicine 2025;32(2):276-282
Objective To evaluate the clinical characteristics of human immunodeficiency virus (HIV) infected patients with peripheral lung masses (PLMs), and to assess the diagnostic utility of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant PLMs. Methods A retrospective analysis was performed on the clinical data of 69 patients with PLM treated in Shanghai Public Health Clinical Center from January 2020 to December 2023. All patients underwent percutaneous biopsy, and were categorized into benign group (n=36) and malignant group (n=33). 25 patients were HIV-positive and 44 patients were HIV-negative. The clinical features and CEUS parameters in patients were compared across these groups. Results Patients with malignant masses were significantly older than those with benign masses (P<0.05). In the malignant group, HIV-negative patients exhibited significantly larger tumor diameters compared to HIV-positive patients (P<0.05); in the HIV-positive patients, no significant difference in tumor size was observed between benign and malignant masses. 19 patients underwent CEUS. 10 malignant masses, irrespective of HIV status (10 positive and 9 negative), commonly presented with indistinct margins, delayed enhancement, heterogeneous perfusion, and delayed peak enhancement on CEUS. 9 benign masses showed earlier peak enhancement compared to 10 malignant masses (P<0.05); no significant differences were observed in the initiation and washout time of enhancement between benign and malignant masses. In HIV-positive patients, 5 benign masses frequently demonstrated discrepancies between CEUS findings and pathological results. Conclusions The clinical and CEUS characteristics were different between benign and malignant PLMs. However, CEUS shows limited accuracy in distinguishing benign and malignant PLMs, underscoring the need for pathological confirmation.
3.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
4.Applications and advancements of instrumental variable approach in causal inference in environmental epidemiology
Hui SHI ; Guzhengyue ZHENG ; Xing ZHAO ; Shourui HUANG ; Baozhuo AI ; Jialong WU ; Hualiang LIN
Journal of Environmental and Occupational Medicine 2024;41(2):219-225
In environmental epidemiological research, extensive non-random environmental exposures and complex confounding biases pose significant challenges when attempting causal inference. In recent years, the introduction of causal inference methods into observational studies has provided a broader range of statistical tools for causal inference research in environmental epidemiology. The instrumental variable (IV) approach, as a causal inference technique for effectively controlling unmeasured confounding factors, has gradually found application in the field of environmental epidemiological research. This article reviewed the basic principles of IV and summarized the current research progress and limitations of applying IV for causal inference in environmental epidemiology. IV application in the field of environmental epidemiology is still in the initial stage. Rational use of IV and effective integration with other causal inference methods will become the focus of the development of causal inference in environmental epidemiology. The aim of this paper is to provide a methodological reference and basis for future studies involving causal inference to target population health effects of environmental exposures in China.
5.Influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation
Lingzhi SHI ; Heng HUANG ; Mingzhao LIU ; Hang YANG ; Bo WU ; Jin ZHAO ; Haoji YAN ; Yujie ZUO ; Xinyue ZHANG ; Linxi LIU ; Dong TIAN ; Jingyu CHEN
Organ Transplantation 2024;15(2):236-243
Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.
6.Pathological Mechanism of Diabetes Based on NF-κB Signaling Pathway and Traditional Chinese Medicine Intervention: A Review
Menglu WANG ; Lu SHI ; Changhao HE ; Yongcheng AN ; Yinglan LYU ; Chen WANG ; Huimin LI ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Ziyi SHAN ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):246-255
As people's living standards improve, the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B (NF-κB) in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors, so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer, and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine (TCM) treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad, it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation, oxidative stress, and energy metabolism, and it is involved in mediating inflammation, pancreatic β cell apoptosis, insulin signal transduction, and other physiological functions. Therefore, blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present, Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections, but the adverse reactions are obvious. TCM has been characterized by multi-target, extensive action, and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation, regulating qi and eliminating phlegm, clearing heat and detoxifying, and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper, the association between NF-κB signaling pathway and diabetes was summarized, and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed, so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.
7.Effect of Intestinal Microecology on Diabetic Kidney Disease Based on Yin-Yang Theory
Chao MO ; Guodong HUANG ; Wei SHI ; Jie ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):178-186
Diabetic kidney disease (DKD) is the main cause of end-stage renal disease. Its high prevalence, mortality rate, and medical cost bring a heavy economic burden to society and families, and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body, which is involved in important life activities such as material and energy metabolism, immune system regulation, and signal transduction, thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken, intestinal microbiota imbalance, intestinal mucosal barrier damage, immune dysfunction, and reduction of metabolite short-chain fatty acids (SCFAs) will occur, which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine (TCM), the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang, or Yin deficiency affecting Yang, or Yang deficiency affecting Yin, or waning and waxing of Yin and Yang. For different pathogenesis changes, "Yin disease treated through Yang", "treating Yin for Yang", or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota, inhibit immune inflammation, protect intestinal mucosal barrier, and increase SCFAs through TCM, thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory, this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.
8.Expert consensus on the workflow of digital aesthetic design in prosthodontics
Zhonghao LIU ; Feng LIU ; Jiang CHEN ; Cui HUANG ; Xianglong HAN ; Wenjie HU ; Chun XU ; Weicai LIU ; Lina NIU ; Chufan MA ; Yijiao ZHAO ; Ke ZHAO ; Ming ZHENG ; Yaming CHEN ; Qingfeng HUANG ; Yi MAN ; Mingming XU ; Xuliang DENG ; Ti ZHOU ; Xiaorui SHI
Journal of Practical Stomatology 2024;40(2):156-163
In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.
9.Bioequivalence study of gliclazide sustained-release tablets in Chinese healthy subjects
Zhou-Ping DUAN ; Xiao-Wei ZHAO ; Jin-Hua WEN ; Shi-Bo HUANG ; Pu LI ; Duan-Wen CAO
The Chinese Journal of Clinical Pharmacology 2024;40(15):2241-2245
Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90%confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80%and 125%.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.
10.Protective effect of ulinastatin on hepatic ischemia-reperfusion injury based on ferroptosis
Shi CHEN ; Yang ZHAO ; Yao ZHOU ; Dongling YU ; Jiao HUANG ; Yuyan LAN
Organ Transplantation 2024;15(5):780-788
Objective To evaluate the protective effect and underlying mechanism of ulinastatin on hepatic ischemia-reperfusion injury.Methods Twenty-four male SD rats were divided into three groups:sham operation group(Sham group),hepatic ischemia-reperfusion injury group(HIRI group)and hepatic ischemia-reperfusion injury+ulinastatin pretreatment group(HIRI+UTI group),with 8 rats in each group.The HIRI rat models were established by occluding hepatic portal vein and hepatic artery for 1 h.In the HIRI+UTI group,the rats were intraperitoneally injected with ulinastatin at 30 min before model establishment,and an equivalent amount of normal saline was given in the Sham and HIRI groups.The rats were sacrificed at 6 h after model establishment.Serum samples were collected to detect alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Pathological changes of liver tissues were observed by hematoxylin-eosin(HE)staining.Ultrastructural changes of mitochondria in liver tissues were observed by transmission electron microscopy.The expression of glutathione peroxidase 4(GPX4)was determined by immunofluorescent staining.The contents of malondialdehyde(MDA),glutathione(GSH),Fe,reactive oxygen species(ROS)and GPX4 were detected.The expression levels of GPX4 and acyl-CoA synthetase long-chain family 4(ACSL4)messenger RNA(mRNA)and proteins in liver tissue were measured.Results Compared with the Sham group,serum ALT and AST levels were up-regulated,pathological changes such as congestion,hepatocyte necrosis and abnormal hepatic lobule structure were observed,pathological score was increased,the mitochondria shrank,the membrane density was increased,the mitochondrial crest was damaged or even absent,the contents of ROS,MDA and Fe were elevated,the GSH content was decreased,the fluorescent intensity of GPX4 was weakened,the relative expression levels of ACSL4 mRNA and protein were up-regulated,and the relative expression levels of GPX4 mRNA and protein were down-regulated in the HIRI group(all P<0.05).Compared with the HIRI group,serum ALT and AST levels were down-regulated,liver tissue injury was alleviated,pathological score was decreased,mitochondrial shrinkage and crest breakage were mitigated,the contents of ROS,MDA and Fe were down-regulated,the GSH content was up-regulated,the fluorescent intensity of GPX4 was enhanced,the relative expression levels of ACSL4 mRNA and protein were down-regulated,and the relative expression levels of GPX4 mRNA and protein were up-regulated in the HIRI+UTI group(all P<0.05).Conclusions Ulinastatin may alleviate hepatic ischemia-reperfusion injury in rats probably through inhibiting ferroptosis.

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