It is proposed that the pathogenesis of rheumatoid arthritis （RA） is centered on deficiency， dampness， and blood stasis， which interact with and evolve into one another during the onset and progression of the disease. The development of RA is closely associated with insufficiency of healthy qi and the interbinding of dampness and blood stasis. Accordingly， treatment emphasizes an integrated approach that combines tonifying deficiency， eliminating dampness， and resolving blood stasis， and is implemented in three main stages. In the initial stage， therapy focuses on supporting healthy qi， dispelling dampness， and relieving impediment， with modified Huangqi Guizhi Wuwu Decoction （黄芪桂枝五物汤） combined with Yiyiren Decoction （薏苡仁汤）. In the active stage， treatment aims to eliminate dampness， resolve blood stasis， and unblock the collaterals， using modified Wutou Decoction （乌头汤） or Guizhi Shaoyao Zhimu Decoction （桂枝芍药知母汤）. In the remission stage， therapy emphasizes strengthening the spleen and reple-nishing qi to prevent recurrence， with modified Shenling Baizhu Powder （参苓白术散） combined with Guipi Decoction （归脾汤）.

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.

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

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.

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

OBJECTIVE To provide a reference for improving postoperative pain management outcomes,accelerating patient recovery,and ensuring the safe use of opioids.METHODS A prospective cohort study was conducted,in which patients undergoing elective hip or knee replacement in the Department of Orthopedics at Baoding No.1 Central Hospital(hereinafter referred to as"our hospital")from November 2021 to November 2023 were randomly divided into control group and observation group using a random number table,with 178 cases in each group.Patients in the control group received postoperative pain management implemented by medical staff according to the clinical pathway for perioperative pain treatment.Patients in the observation group,under the enhanced recovery after surgery model,received postoperative pain management through a multidisciplinary collaborative team including clinical pharmacists.The occurrence and resolution of opioid-related drug-related problems(DRPs)were compared between the two groups,and the DRPs were classified and analyzed using the Pharmaceutical Care Network Europe Classification System(V9.1).Postoperative pain scores,sleep quality scores,length of hospital stay,and incidence of adverse reactions were compared between the two groups.RESULTS A total of 162 opioid-related DRPs were identified in 2 groups,with 58 in the observation group(identified 52 patients)and 104 in the control group(identified 91 patients),showing a statistically significant difference(P＜0.05).The primary issue involved in the DRPs for both groups was therapeutic effectiveness.Clinical pharmacists in the observation group conducted 88 interventions for the identified 58 opioid-related DRPs,achieving an overall intervention success rate of 84.5%.The pain scores and sleep quality scores from postoperative day 1 to 7,the length of hospitalization for hip replacement,the average hospitalization duration,and the total incidence of opioid-related adverse reactions were all significantly lower or shorter in the observation group compared to the control group(P＜0.05).Furthermore,the main time effect,time-group interaction effect for pain scores and sleep quality scores were statistically significant in both groups(P＜0.05),indicating that the control group exhibited greater reductions in these scores and observation group exhibited more rapid improvements.CONCLUSIONS The full involvement of clinical pharmacists in postoperative pain management and opioid medication administration in the orthopedics department enables timely identification and intervention of DRPs,enhance postoperative analgesia efficacy,decrease adverse drug reactions,shorten hospital stays,and accelerate patient recovery.

Attention deficit hyperactivity disorder （ADHD）， also known as hyperactivity disorder in children， is a behavioral disorder commonly found in children， particularly preschool-aged children. This disorder can lead to cognitive impairment， learning difficulties， conduct disorders， and other mental health issues， severely impacting the quality of life for affected children. Moreover， the global prevalence of ADHD continues to rise. Establishing an animal model that closely aligns with clinical symptoms and the pathogenesis of the disease is crucial for advancing research on the prevention and treatment of ADHD. In recent years， research on animal models of ADHD has rapidly developed. Researchers have developed nearly 20 animal models from genetic and environmental perspectives. However， most of these models are still in the exploratory stage， and there is insufficient research to thoroughly investigate their pathogenesis， core characteristics， and drug effects. The spontaneously hypertensive rat （SHR） is currently the most commonly used animal model for ADHD because of its excellent face validity and developmental stage that better corresponds to childhood. In addition， dopamine transporter （DAT） knockout mice， LPHN3 knockout rats， and neonatal rat hypoxia models have also shown good face validity. Some researchers have injected SHRs with daily doses of levothyroxine sodium， which not only induces typical ADHD symptoms in the rats but also exhibits signs of Yin deficiency and Yang hyperactivity， which successfully simulates the Yin deficiency and Yang hyperactivity syndrome type of ADHD， providing a new approach for constructing and evaluating ADHD animal models that combine both traditional Chinese and western medicine. This article reviewed ADHD animal models reported in China and abroad over the past decade， summarized rodent models of ADHD into three major categories： genetic models， chemically induced models， and environmentally induced models， and analyzed each category to provide a reference for selecting and exploring appropriate models for experimental ADHD research.

Attention deficit hyperactivity disorder(ADHD),also known as childhood hyperactivity disorder,is a very common clinical disorder in children,which seriously affects their physical and mental health.Animal models conforming to the clinical diseases of Chinese and Western medicine are the basis for in-depth research on the pathogenesis and prevention and treatment of ADHD.Taking"Attention Deficit Hyperactivity Disorder"as the theme,this paper summarizes the modeling methods and model features of ADHD animal models in CNKI,Wanfang,Wipu,and pubmed databases in the past 20 years,evaluates their strengths and weaknesses,and analyzes the extent to which the models are in agreement with the clinical diseases of Chinese and Western medicine.The results show that there are many existing animal models of ADHD,which can be mainly divided into three kinds:spontaneous model,induced model and gene model,among which the SHR rat model has become a popular and ideal animal model because of its good surface validity,moderate price and other advantages.Currently,animal models of ADHD are dominated by disease models of Western medicine,and models that meet the characteristics of Chinese medicine clinical conditions are rare,with insufficient reflection of Chinese medicine evidence.Therefore,it is suggested that the subsequent construction of animal models of ADHD should consider adding the relevant pathogenic factors and indexes of different certificates of Chinese medicine,such as the animal's tongue,mental state,water intake and heart rate,etc.,with the aim of constructing an animal model that is more close to the clinic.

Attention deficit hyperactivity disorder(ADHD),also known as childhood hyperactivity disorder,is a very common clinical disorder in children,which seriously affects their physical and mental health.Animal models conforming to the clinical diseases of Chinese and Western medicine are the basis for in-depth research on the pathogenesis and prevention and treatment of ADHD.Taking"Attention Deficit Hyperactivity Disorder"as the theme,this paper summarizes the modeling methods and model features of ADHD animal models in CNKI,Wanfang,Wipu,and pubmed databases in the past 20 years,evaluates their strengths and weaknesses,and analyzes the extent to which the models are in agreement with the clinical diseases of Chinese and Western medicine.The results show that there are many existing animal models of ADHD,which can be mainly divided into three kinds:spontaneous model,induced model and gene model,among which the SHR rat model has become a popular and ideal animal model because of its good surface validity,moderate price and other advantages.Currently,animal models of ADHD are dominated by disease models of Western medicine,and models that meet the characteristics of Chinese medicine clinical conditions are rare,with insufficient reflection of Chinese medicine evidence.Therefore,it is suggested that the subsequent construction of animal models of ADHD should consider adding the relevant pathogenic factors and indexes of different certificates of Chinese medicine,such as the animal's tongue,mental state,water intake and heart rate,etc.,with the aim of constructing an animal model that is more close to the clinic.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation