1.Exploring on Quality Evaluation Methods of Clinical Case Reports in Traditional Chinese Medicine Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Feng ZHANG ; Bo ZHOU ; Haimin CHEN ; Yong ZHU ; Changcheng HOU ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Guoshuang ZHU ; Shukun GONG ; Jianwen HE ; Yang YE ; Yuqiu AN ; Chunquan SUN ; Qingjie YUAN ; Buman LI ; Xingzhong FENG ; Kegang CAO ; Hongcai SHANG ; Jihua GUO ; Xiaoxiao ZHANG ; Zhining TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):271-276
As the core vehicle for preserving and transmitting traditional Chinese medicine(TCM) academic thought and clinical experience, the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine, this study conducted a comprehensive analysis of critical challenges, including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic, encompassing three dimensions of authenticity and standardization, characteristics and advantages, application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment, while aligning with modern scientific research standards, achieving a balance between individualized TCM experience and standardized evaluation. Concurrently, this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases, contributing significantly to the inheritance of TCM knowledge, evidence-based practice, and the reform of talent evaluation mechanisms.
2.Staged Efficacy of Qijia Rougan Prescription Combined with Entecavir for Chronic Hepatitis B-related Hepatic Fibrosis with Qi Deficiency and Collateral Stasis Syndrome Based on "Zhu Ke Jiao" Theory
Baixue LI ; Xin WANG ; Jibin LIU ; Li WEN ; Cen JIANG ; Wenjun WU ; Dong WANG ; Shuwan LIU ; Huabao LIU ; Yongli ZHENG ; Liang HUANG ; Yue SU ; Song ZHANG ; Yanan SHANG ; Hang ZHOU ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):180-188
ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory, Qijia Rougan prescription, combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted, and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis (CHB-HF) who met the diagnosis and inclusion criteria were randomly assigned to an observation group (Qijia Rougan prescription + entecavir) and a control group (entecavir). The treatment duration was 24 weeks. Liver stiffness measurement (LSM), fibrosis-4 index (FIB-4), portal vein diameter, hepatitis B serology, biochemical indicators, hepatic fibrosis markers in serum [hyaluronic acid (HA), laminin (LN), procollagen Ⅲ peptide (PⅢP), and type Ⅳ collagen (Ⅳ-C)], and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis, with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment, the observation group showed a significant reduction in LSM and FIB-4 (P<0.01), as well as notable improvements in LN, Ⅳ-C, and various TCM syndrome scores (P<0.05, P<0.01). When compared to the control group after treatment, the observation group demonstrated significant improvements in LSM, FIB-4, and various TCM syndrome score indicators (P<0.05, P<0.01), indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment, the observation group had better improvement in regression of stages F2 and F3 (P<0.05). When compared to the control group after treatment, the observation group exhibited superior improvement in regression of stage F3 (P<0.05). No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone, the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3, which is a potential “interception” point of the “Zhu Ke Jiao” theory.
3.Development and feasibility study of a self-stabilizing home-based functional interactive training device
Xiaojuan FENG ; Fubiao HUANG ; Dongyue LI ; Mingyi ZHOU ; Yuxuan NIU ; Ismaili McGee PIRETI ; Xixian WANG ; Zile WANG
Chinese Journal of Rehabilitation Theory and Practice 2026;32(9):1068-1077
ObjectiveTo design a "roly-poly" style interactive home-based hand function training device based on the principle of self-stabilization and recovery in light of the characteristics of post-stroke hand dysfunction and the current scarcity of home-based hand function training devices; and explore the feasibility and clinical value of this device in hand function rehabilitation training for stroke patients. MethodsThis study adopted a phased research design consisting of two stages: device development and clinical validation. At the first stage, focusing on the principle of the tumbler's automatic return to center, combined with the clinical needs of hand function rehabilitation training for stroke patients, the development of a home-based interactive hand function training device was completed, and the application and authorization of a utility model patent were obtained. At the second stage, 30 stroke patients with post-stroke hand dysfunction hospitalized at Beijing Bo'ai Hospital from May to October, 2025 were randomly divided into control group (n = 15) and experimental group (n = 15). Both groups received conventional rehabilitation therapy, the control group added routine hand function training every evening, and the experimental group added hand function training using the device developed in this study every evening, for four weeks. The grip strength, lateral pinch strength, finger pad pinch strength, three-finger pinch strength and wrist joint range of motion (dorsal-flexion, palm-flexion, radial deviation and ulnar deviation) were measured before and after intervention. The upper limb and hand motor function was assessed with Fugl-Meyer Assessment (FMA), and the modified Barthel Index (MBI) was used to evaluate activities of daily living (ADL). ResultsA self-stabilizing hemispherical hand functional rehabilitation device was developed and granted a utility model patent. After intervention, the grip strength, lateral pinch strength, finger pad pinch strength, three-finger pinch strength, wrist joint range of motion, and FMA and MBI scores significantly improved in both groups (|t| > 5.683, P < 0.05); except for the score of MBI (P > 0.05), all the other indicators were better in the experimental group than in the control group (t > 2.633, P < 0.05). ConclusionThe self-stabilizing, closed-loop home-based functional hand interaction training device designed in this study effectively improves hand grip, pinching function and wrist joint range of motion of stroke patients, significantly enhancing upper limb and hand motor function, and demonstrates feasibility for home-based hand rehabilitation training. However, the device does not provide notable additional improvements in patients' ADL, necessitating further optimization to enhance its clinical application value.
4.PRMT1-mediated asymmetric dimethylation of arginine residue 602 in DDX1 promotes cholangiocarcinoma progression
Wenzheng LIU ; Yangwei LIAO ; Yiyang KUAI ; Xin GAO ; Xingmin YAN ; Jingjing LI ; Junsheng CHEN ; Jukun SU ; Jingcong ZHOU ; Yizhu KONG ; Siqin HUANG ; Zhiwei ZHANG ; Feng PENG ; Bing WANG ; Yongjun CHEN
Clinical and Molecular Hepatology 2026;32(2):843-865
Background/Aims:
Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA.
Methods:
Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development.
Results:
DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression.
Conclusions
Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.
5.Analysis of 7 cases of childhood blastic plasmacytoid dendritic cell neoplasm
Ziqing FENG ; Chunju ZHOU ; Ningning ZHANG ; Ling JIN ; Jing YANG ; Shuang HUANG ; Meng ZHANG ; Nan LI ; Yanlong DUAN
Chinese Journal of Pediatrics 2025;63(11):1207-1211
Objective:To evaluate the clinical characteristics, pathology, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in children.Methods:Clinical data (including gender, age of disease onset, affected sites, treatment, timing of allogeneic hematopoietic stem cell transplantation (allo-HSCT), etc.) of 7 children with BPDCN who were admitted to Beijing Children′s Hospital, Capital Medical University from December 2018 to December 2023 were analyzed retrospectively. Clinical outcomes were also assessed, with patients followed up until December 2024.Results:Among 7 patients, there were 3 males and 4 females. Age at disease onset ranged from 3.2 to 12.9 years. Initial presentations included subcutaneous nodules in 5 cases, rash in 1 case, and ankle pain in 1 case. Extra-cutaneous involvement was seen in the bone marrow, lymph nodes, and central nervous system. Six patients received induction chemotherapy using a modified lymphoblastic lymphoma regimen, 1 patient received the high-risk protocol for pediatric lymphoblastic lymphoma/leukemia and salvage therapy regimens. Allo-HSCT was performed soon after chemotherapy remission. The time to bridge allo-HSCT was 3.5 to 6.5 months. The follow-up time was 1.6 to 6.0 years. Six patients were in disease-free survival, while 1 patient survived with disease after recurrence following transplantation.Conclusions:BPDCN is rare in children and presents diverse clinical manifestations, with skin involvement being the predominant feature. Early allo-HSCT following complete remission with chemotherapy can improve prognosis.
6.Clinical application research of 5G-based robot-assisted remote urological surgery
Yunhan HUANG ; Haidi LYU ; Fenghai ZHOU ; Bin FENG ; Xiaofeng ZHANG ; Baihong GUO
Chinese Journal of Urology 2025;46(1):49-54
Objective:To evaluate the feasibility and safety of performing multi-procedure remote urological surgeries by integrating 5G communication technology with domestically manufactured robotic surgical systems.Methods:Patients requiring urological laparoscopic surgery for benign lesions or tumors were prospectively enrolled at Gansu Provincial Hospital from May 2023 to June 2024. Inclusion criteria included age ≥18 years, body mass index (BMI) between 18 and 30 kg/m 2, and American Society of Anesthesiologists (ASA) classification Ⅰ-Ⅲ. Tumor-related surgical indicators were as follows: renal tumors staged ≤T 2, solitary tumors, or maximum diameter ≤10 cm; intermediate- to low-risk prostate cancer (clinical stage ≤T 2b), with preoperative prostate-specific antigen (PSA) ≤20 ng/ml or Gleason score ≤7; adrenal tumors with a diameter ≤7 cm or ≥3 cm for non-functional adenomas; and bladder tumors staged ≤T 2. Exclusion criteria included participation in other investigational drug or device clinical trials within the past 1 month, pregnancy or breastfeeding, and patients requiring emergency surgery. Patients with severe cardiovascular or circulatory diseases contraindicating surgery, and individuals with epilepsy, psychiatric disorders, or cognitive impairments were also excluded. Additionally, patients with active bleeding, coagulation disorders, or platelet counts <80×10 9/L were excluded. A 5G communication link was established between the main campus and the new branch of Gansu Provincial Hospital, approximately 70 km apart. Remote surgeries were performed using the domestically manufactured robotic surgical system (Toumai MT-1000). Perioperative key indicators, intraoperative network conditions, and robotic system performance were systematically recorded. Results:This study involved 14 patients, comprising 3 cases of renal cysts, 3 cases of renal tumors, 3 cases of nonfunctional kidneys, 2 cases of adrenal tumors, 1 case of bladder tumor, 1 case of prostate cancer, and 1 case of ureteral-bladder wall thickening with pelvic ureteral stones. The cohort included 7 male and 7 female patients, with an average age of (57.4±12.3) years, a BMI of (24.6±3.0) kg/m 2, and ASA classifications of grade Ⅱ in 9 cases and grade Ⅲ in 5 cases. All remote surgeries were successfully completed without the need for conversion to alternative surgical methods. Three renal cyst unroofing decompression procedures were performed, with an average console operation time of (32.0±6.6) minutes and intraoperative blood loss of (13.3±2.9) ml. Two partial nephrectomies were conducted, with console operation times of 140 and 160 minutes, intraoperative blood loss of 20 ml each, and warm ischemia times of 19 and 25 minutes, respectively. The preoperative estimated glomerular filtration rates (eGFR) for these cases were 115.2 and 107.3 ml/(min·1.73m 2), and postoperative eGFR were 102.0 and 95.5 ml/(min·1.73m 2), respectively. Four radical nephrectomies were completed, with an average console operation time of (50.2±13.7) minutes and intraoperative blood loss of (20.5±13.2) ml. Two adrenal tumor resections were performed, each with console operation times of 45 and 50 minutes and intraoperative blood loss of 10 ml. Additionally, one partial bladder resection was conducted, requiring a console operation time of 60 minutes and resulting in intraoperative blood loss of 10 ml. A single radical prostatectomy was carried out, with a console operation time of 180 minutes, intraoperative blood loss of 120 ml, and pre- and postoperative PSA levels of 11.7 ng/ml and 0.06 ng/ml, respectively. One ureteral-bladder reimplantation was also performed, with a console operation time of 240 minutes and intraoperative blood loss of 10 ml. The average total delay for the 14 remote surgeries ranged from 194 to 250 ms, while the average network transmission delay ranged from 13 to 55 ms. During the procedures, six instances of sudden large fluctuations in network transmission delay were observed, ranging from 333 to 654 ms. These fluctuations resolved automatically within approximately 10 seconds but resulted in temporary disruptions: 2 cases of master-slave console lock (reset process lasted around 5 seconds) and 1 case of switching to the local console for emergency hemostasis (lasting approximately 7 minutes). These interruptions did not significantly affect the surgical process. Postoperative complications in all patients were classified as Clavien-Dindo grade Ⅰ and were unrelated to the surgical procedures or equipment. No cancer was detected in the resection margins of malignant tumors. Follow-up evaluations at three months, including blood tests, liver and kidney function tests, and CT scans of the surgical sites, revealed no significant abnormalities or adverse events. Conclusions:5G communication technology, with an average total latency of less than 250 ms, enables domestic surgical robots to perform multi-procedural remote urological surgeries effectively. However, during procedures requiring extensive suturing for urological reconstruction or managing unplanned intraoperative bleeding, network latency fluctuations exceeding 333 ms can extend the operation time and may necessitate switching to local control for emergency hemostasis.
7.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
8.Analysis of the efficacy of total knee arthroplasty with partial varus retention in the treatment of moderate knee varus
Xing'an BAO ; Youquan CHEN ; Hao ZHOU ; Hui YANG ; Yi HUANG ; Weimin FAN ; Feng LIU
Chinese Journal of Orthopaedics 2025;45(6):327-334
Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.
9.Clinical efficacy and safety of a domestic calcipotriol/betamethasone dipropionate ointment in the treatment of stable plaque psoriasis: a multicenter, randomized, double-blind, controlled study
Lixin XIA ; Guang XIANG ; Qingchun DIAO ; Kun HUANG ; Shoumin ZHANG ; Shanshan LI ; Yumei LI ; Zhiqiang SONG ; Qing SUN ; Xiumin YANG ; Meng PAN ; Yuling SHI ; Shuping GUO ; Huiping WANG ; Tiechi LEI ; Xiaoyong ZHOU ; Songmei GENG ; Suchun HOU ; Juan SU ; Yong CUI ; Rixin CHEN ; Yanyan FENG ; Hongxia FENG ; Rushan XIA ; Zudong MENG ; Fang YIN ; Jingjing WANG ; Xinghua GAO
Chinese Journal of Dermatology 2025;58(11):1020-1026
Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.
10.Mechanism by which IRF1 affects hepatic ischemia-reperfusion injury by regulating the polarization of Kupffer cells
Jingbo YANG ; Hao HUANG ; Feng ZHANG ; Liying SUN ; Liuxin ZHOU ; Haiming ZHANG ; Shipeng LI ; Zhijun ZHU ; Yamin ZHANG
Chinese Journal of Hepatobiliary Surgery 2025;31(4):290-295
Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.

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