1.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
2.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
3.Serological and Molecular Biological Detection of RhD Variants.
Dao-Ju REN ; Chun-Yue CHEN ; Xiao-Wei LI ; Jun XIAO ; Xiao-Juan ZHANG ; Cui-Ying LI
Journal of Experimental Hematology 2025;33(2):498-503
OBJECTIVE:
To analyze the RHD genotyping and sequencing results of RhD serology negative samples in the clinic, and to further explore the laboratory methods for RhD detection, in order to provide a basis for clinical precision blood transfusion.
METHODS:
A total of 27 200 whole blood samples were screened for RhD blood group antigen using microcolumn gel card method.Serologic RhD-negative confirmation tests were performed on blood samples that were negative for RhD on initial screening using three different clonal strains of IgG anti-D reagents. The 10 exons of the RHD gene on chromosome 1 were also analyzed by PCR-SSP to determine RHD genotyping.When the PCR-SSP method did not yield definitive results, the RHD gene of the sample was analyzed by the third-generation sequencing.
RESULTS:
The results of the initial screening test by the microcolumn gel card method showed that 136 of the 27 200 samples were RhD-negative, of which 86 underwent RhD-negative confirmation testing and RHD genotyping, 88.37% (76/86 cases) of the RhD-negative confirmation test results were negative for the three anti-D reagents, and the results of RHD genotyping showed that 67.44% (58/86 cases) of the cases had a complete deletion of 10 exons, and the remaining 28 cases were RHD*711delC (1 case), RHD*D-CE(1-9)-D (1 case), RHD*D-CE(2-9-)D (2 cases), RHD*D-CE(3-9)-D (4 cases), RHD*DEL1 (c.1227G >A) mutation (16 cases), RHD*weak partial 15(845G >A) mutation (3 cases), and a mutation of c.165C >T base was found in 1 sample by three-generation sequencing.
CONCLUSION
RHD genotype testing of samples that are serologically negative for RhD antigen shows that some of the samples have RHD gene variants, not all of which are total deletions of RHD, suggesting that there are some limitations of the serologic method for RhD detection. Due to the polymorphism of the RHD gene structure, different RhD variants present different serologic features, which need to be further detected in combination with molecular biology testing, especially for the identification of Asian-type DELs, which is important for clinical precision blood transfusion.
Humans
;
Rh-Hr Blood-Group System/genetics*
;
Genotype
;
Polymerase Chain Reaction
;
Exons
;
Blood Grouping and Crossmatching
4.Evolution-guided design of mini-protein for high-contrast in vivo imaging.
Nongyu HUANG ; Yang CAO ; Guangjun XIONG ; Suwen CHEN ; Juan CHENG ; Yifan ZHOU ; Chengxin ZHANG ; Xiaoqiong WEI ; Wenling WU ; Yawen HU ; Pei ZHOU ; Guolin LI ; Fulei ZHAO ; Fanlian ZENG ; Xiaoyan WANG ; Jiadong YU ; Chengcheng YUE ; Xinai CUI ; Kaijun CUI ; Huawei CAI ; Yuquan WEI ; Yang ZHANG ; Jiong LI
Acta Pharmaceutica Sinica B 2025;15(10):5327-5345
Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with 99mTc, 68Ga, and 18F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.
5.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.
6.Application of 3D-printed auxiliary guides in adolescent scoliosis surgery.
Dong HOU ; Jian-Tao WEN ; Chen ZHANG ; Jin HUANG ; Chang-Quan DAI ; Kai LI ; Han LENG ; Jing ZHANG ; Shao-Bo YANG ; Xiao-Juan CUI ; Juan WANG ; Xiao-Yun YUAN
China Journal of Orthopaedics and Traumatology 2025;38(11):1119-1125
OBJECTIVE:
To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents.
METHODS:
A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire.
RESULTS:
A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05).
CONCLUSION
In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans
;
Male
;
Scoliosis/surgery*
;
Female
;
Adolescent
;
Printing, Three-Dimensional
;
Retrospective Studies
;
Pedicle Screws
;
Child
7.Textual Research and Discrimination of Gypsum fibrosum and Its Similar Substances
Jianxiong WEI ; Hongjiao CUI ; Lun ZHANG ; Fansen JIN ; Mingyang YUAN ; Guohua ZHENG ; Juan LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2585-2597
Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.
8.Accessory cavitated uterine malformation:one case report and literature review
Bai-juan DING ; Li-wei ZHANG ; Yan-qiu WEI ; Xiu-juan CUI
Fudan University Journal of Medical Sciences 2025;52(5):747-751
Accessory cavitated uterine malformation(ACUM)is a rare unique congenital Müllerian duct malformation.Its main clinical manifestations are abdominal pain shortly after menarche and progressive aggravation,also may present as chronic periodic lower abdominal pain or abnormal uterine bleeding.Because it occurs rarely,it is easy to cause misdiagnosis or delay diagnosis.This paper reports the clinical manifestations,diagnosis and treatment of a young patient with ACUM,and reviews the literature to deepen the understanding of this rare genital tract malformation.
9.Effects of Conbercept on different optical coherence tomography biomarkers in patients with retinal vein occlusion-related macular edema
Haiyue YU ; Juan TENG ; Zeying DONG ; Lili ZHANG ; Huixian CUI ; Chang LIU ; Guang ZHU ; Xin LI
International Eye Science 2025;25(10):1656-1661
AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.
10.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.

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