1.Observation of the therapeutic effect of rituximab combined with traditional Chinese medicine syndrome differentiation on treating steroid-dependent nephrotic syndrome in children and the regularity of traditional Chinese medicine use
Xia ZHANG ; Xuejun LI ; Tingting XU ; Guang LI ; Yifan LI ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN ; Ying DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):80-90
Objective:
To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS).
Methods:
One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis.
Results:
Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis.
Conclusion
RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.
2.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
3.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
4.Meta-analysis of efficacy and safety of rituximab for children with refractory nephrotic syndrome based on the real world
Xiangge REN ; Xin YU ; Jiawei ZHANG ; Peidong ZHAO ; Wensheng ZHAI
China Pharmacy 2024;35(21):2668-2675
OBJECTIVE To evaluate the efficacy and safety of rituximab (RTX) in the treatment of children with refractory nephrotic syndrome (RNS) based on the real world by meta-analysis. METHODS A systematic search was conducted on CNKI, Wanfang, VIP, PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL databases to strictly screen the literature and evaluate their quality. A meta-analysis was performed on the extracted literature data using R 4.2.2 and RStudio software. RESULTS A total of 26 real-world studies were included in this study, involving 996 children with steroid-dependent nephrotic syndrome/frequente-relapse nephrotic syndrome (SDNS/FRNS) and 205 children with steroid-resistant nephrotic syndrome (SRNS). The results of the meta-analysis showed that the complete remission (CR) rate of RTX treatment for RNS was 46% (95%CI: 37%-56%), the partial remission (PR) rate was 22% (95%CI: 14%-31%), and the discontinuation rate was 35% (95%CI: 25%-44%). The results of subgroup analysis showed that the CR rate of RTX treatment in SDNS/FRNS children was 49% (95%CI: 37%-62%), PR rate was 25% (95%CI: 0-50%), discontinuation rate was 41% (95%CI: 29%-52%); the CR rate in SRNS children was 42% (95%CI: 27%-56%), PR rate was 22%(95%CI: 12%-32%), discontinuation rate was 21% (95%CI: 4%-38%). The recurrence rate in children with SDNS/FRNS was 39% (95%CI: 21%-57%) within 1 year or less, 18% (95%CI: 18%-98%) in 2 years and more. As for safety, the majority of adverse reactions were mild infusion reactions, with an incidence of 13% (95%CI: 8%-22%). Sensitivity analysis suggested that the results were robust. There was publication bias in mild infusion 20210908-BZ-CACM) reaction rate. CONCLUSIONS RTX is effective and safe in the treatment of RNS in children.
5.Characteristics of Syndrome Differentiation and Immune Imbalance in Children with Atopic Dermatitis
Panpan ZHAI ; Yanjie HUANG ; Xiaofeng MEI ; Jiajia LI ; Xiumin LI ; Xia ZHANG ; Wensheng ZHAI ; Xianqing REN ; Ying DING ; Chenhong XUE ; Ge QIAN ; Mingsan MIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(6):2168-2173
Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.
6.A randomized controlled trial on sodium hyaluronate gel in prevention of postoperative intestinal adhesion
Wensheng HUANG ; Jiancong HU ; Chuanqing WU ; Liang SHANG ; Chengle ZHUANG ; Ke AN ; Zhichao ZHAI ; Changmin DING ; Zhaoya GAO ; Qingkun GAO ; Pengfei NIU ; Yanzhao WANG ; Qingmin ZENG ; Yuming HONG ; Wanshui RONG ; Fuming LEI ; Zhongchen LIU ; Leping LI ; Kaixiong TAO ; Xiaojian WU ; Jin GU
Chinese Journal of General Surgery 2023;38(11):809-813
Objective:To evaluate the efficacy and safety of sodium hyaluronate gel in preventing adhesion after prophylactic enterostomy.Methods:One hundred and twenty four patients from 6 hospitals were enrolled in this prospective multi-center randomized controlled trial. Patients were randomized into the study group ( n=59) or the control group ( n=65).All patients underwent prophylactic enterostomy. Patients of study group received odium hyaluronate gel for adhesion-prevention,while those in control group did not receive any adhesion-prevention treatment. The incidence of moderate to severe adhesion around the incision in the stoma area were evalutated during stoma reduction surgery. Results:The incidence of moderate to severe adhesion around the incision in the stoma area was 6.3% in the study group, the difference was statistically significant ( P<0.05) compared to that of the control group (32.6%). Conclusion:Sodium hyaluronate gel can safely and effectively reduce the incidence of moderate and severe adhesions after abdominal surgery.
7.Effect of Yiqi Yangyin Huoxue Prescription on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway in Diabetic Kidney Disease Rats
Pingping JIA ; Chundong SONG ; Fengyang DUAN ; Ningli WANG ; Ying DING ; Yaoxian WANG ; Xianqing REN ; Wensheng ZHAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):75-81
ObjectiveTo explore the possible mechanism of Yiqi Yangyin Huoxue prescription in the prevention and treatment of kidney injury of diabetic kidney disease(DKD)rats based on NOD-like receptor protein 3(NLRP3)/cysteine protease-1(Caspase-1)/gasdermin D (GSDMD)pyroptosis pathway. MethodFifty male SD rats were randomly divided into normal group (n=8) and modeling group (n=42). The modeling group was given a one-time intraperitoneal injection of streptozotocin (STZ) after high-sugar and high-fat diet for 6 weeks to induce the establishment of a DKD rat model. After successful modeling, the rats were randomly divided into model group, valsartan group (8.33 mg·kg-1), and Yiqi Yangyin Huoxue prescription low-dose and high-dose group (11,22 g·kg-1). After continuous gavage for 6 weeks, the fasting blood glucose (FBG), total cholesterol (CHO), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein quantification (24 h-UTP) were detected in each group of rats. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of kidney tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels. The protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue of rats in each group were determined by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the conditions in normal group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in model group were increased (P<0.01), and the kidney tissue lesions were severe. Compared with the conditions in model group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in each intervention group were decreased (P<0.05, P<0.01), and the degree of kidney tissue lesions was improved, with Yiqi Yangyin Huoxue prescription high-dose group showing the optimal effect. ConclusionYiqi Yangyin Huoxue prescription could inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway, and thus relieve the inflammatory response of DKD rats and alleviate the pathological damage of the kidneys.
8.Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy
Fengyang DUAN ; Chundong SONG ; Dan SONG ; Ying DING ; Xianqing REN ; Xia ZHANG ; Wensheng ZHAI ; Ting GUO ; Yaoxian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):16-23
ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets (TWPT) in the prevention and treatment of kidney injury in diabetic nephropathy (DN) through the nuclear factor of activated T-cells 2(NFAT2)/cyclooxygenase-2(COX-2) pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group (n=8) and an experimental group (n=34) after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin (STZ) following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated, the remaining 24 model rats were randomly divided into model group, valsartan (8.33 mg·kg-1·d-1) group, and TWPT (5 mg·kg-1·d-1) group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks, body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta, and then the rats were sacrificed for sampling. Biochemical indicators, such as serum blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), blood lipid, blood glucose, and 24-hour urine total protein (24 h UTP), were determined. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay (ELISA) was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)were adopted to detect NFAT2, COX-2 protein and mRNA expression in kidney tissues, respectively. ResultCompared with the normal group, the model group showed elevated 24 h UTP, BUN, SCr, CHO, TG, and FBG, increased serum NFAT2 and COX-2 production and expression (P<0.01), and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). In addition, the pathology of the kidney showed enlarged glomeruli, mild proliferation of mesangial cells, and widened mesangial stroma. Compared with the model group, the TWPT group showed decreased 24 h UTP, BUN, SCr, CHO, TG, and FBG (P<0.05,P<0.01), basically normal glomerular morphology, decreased expression of serum NFAT2 and COX-2 (P<0.01), and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). ConclusionTWPT can alleviate 24 h UTP in DN model rats, protect renal function, and improve renal pathology, and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
9.Research progress on application of artificial intelligence in the field of kidney transplantation
Xiangge REN ; Wensheng ZHAI ; Bing LI
Organ Transplantation 2023;14(4):505-
In recent years, artificial intelligence has been persistently developed and increasingly applied in the medical field, including risk prediction, diagnosis and treatment of various diseases, which enhances the diagnosis and management levels of diseases and shows a promising application prospect in the medical field. Artificial intelligence has been rapidly advanced in the field of kidney transplantation. Researchers have attempted to apply it in multiple scenarios, such as preoperative evaluation and prediction of postoperative complications of kidney transplantation, prompting that artificial intelligence has tremendous application prospect in the field of kidney transplantation. In this article, the application of artificial intelligence in donor-recipient matching, evaluation of renal allograft function, prediction of clinical outcomes, diagnosis of postoperative complications, monitoring and management of immunosuppressants were reviewed, research progress on the application of artificial intelligence in the field of kidney transplantation was summarized, and the limitations of artificial intelligence were discussed, aiming to provide reference for promoting the practical application and popularization of artificial intelligence in the field of kidney transplantation.
10.Meta-analysis of efficacy and safety of belimumab in the treatment of childhood-onset systemic lupus erythematosus
Xin YU ; Wensheng ZHAI ; Mengmeng ZHANG ; Xiangge REN
China Pharmacy 2023;34(16):2003-2007
OBJECTIVE To evaluate the efficacy and safety of belimumab in the treatment childhood-onset systemic lupus erythematosus (cSLE), and to provide evidence-based references for clinical medication. METHODS Randomized controlled trials (RCTs) about belimumab or belimumab combined with hormone or belimumab combined with hormone and traditional drugs (test group) compared with placebo or hormone or traditional drugs or traditional drugs combined with hormone (control group) were collected by computer searching CNKI, Wanfang data, VIP, SinoMed, PubMed, Embase, Web of Science and the Cochrane Library; the search deadline was from the establishment of the databases to April 9th, 2023. After screening the literature and extracting the data, the quality of the included literature was evaluated by using the bias risk assessment tool recommended by Cochrane system evaluation manual 5.1.0; meta-analysis and sensitivity analysis were conducted by using RevMan 5.4 software. RESULTS A total of 510 children were included in 7 RCTs. Results of the meta-analysis showed that the clinically effective rate of test group was significantly better than the control group [OR=6.16, 95%CI (2.23, 17.00), P=0.000 4]. There were no statistically significant differences in SLE disease activity index (SLEDAI) [MD=-1.73, 95%CI (-3.50, 0.05), P=0.06], the incidence of adverse drug reactions [OR=0.72, 95%CI (0.43, 1.19), P=0.02], complement C3 levels [MD=0.12, 95%CI (-0.06, 0.30), P=0.18], complement C4 levels [MD=0.08,95%CI (-0.07,0.24), P=0.30] or the response rate of SLE responder index 4 [OR=1.52, 95%CI (0.94,2.44), P=0.09] between 2 groups. The results of sensitivity analysis showed that when SLEDAI, the complement C3 levels and complement C4 levels were used as indicators, the results obtained in this study were robust. CONCLUSIONS The efficacy of belimumab in the treatment of cSLE is good, and its safety is comparable to the basic treatment.


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