Objective:To investigate the expression and clinical value of integrin-associated protein 47 (CD47) and soluble programmed death receptor-ligand 1 (sPD-L1) in patients with primary immune thrombocytopenia (ITP).Methods:The method of retrospective study was adopted, 76 patients with ITP admitted to the Affiliated Hospital of Jining Medical University from July 2016 to July 2022 were regarded as the study group, and another 76 cases of physical examination were regarded as the control group. The levels of serum CD47, sPD-L1, interleukin-33(IL-33) and transforming growth factor beta (TGF-β) were determined by the enzyme-linked immunosorbent assay, the diagnostic value of CD47 and sPD-L1 for ITP was analyzed by the receiver operating characteristic (ROC) curve, Pearson test was applied to analyze the correlation between serum CD47 and sPD-L1 in ITP patients, multivariate Logistic regression analysis was applied to analyze the risk factors affecting ITP.Results:The levels of serum CD47, sPD-L1 and IL-33 in the study group were higher than those in the control group: (40.31 ± 6.59) μg/L vs. (32.16 ± 6.33) μg/L, (78.42 ± 10.22) ng/L vs. (64.49 ± 10.36) ng/L, (73.29 ± 14.26) ng/L vs. (26.54 ± 5.16) ng/L; the level of serum TGF-β in the study group was lower than that in the control group: (1 752.66 ± 310.73) ng/L vs. (2 625.88 ± 389.58) ng/L, there were statistical differences ( P<0.05). The result of the Pearson test showed that there was a positive correlation between serum CD47 and sPD-L1 in ITP patients ( r = 0.572, P<0.05). The result of the ROC curve showed that the area under the curve predicted by the combination of serum CD47 and sPD-L1 was 0.948 (95% CI 0.916 - 0.979), which was better than that predicted by CD47 and sPD-L1 alone ( P<0.05). The result of multivariate Logistic regression analysis showed that CD47, sPD-L1, and IL-33 were the risk factors affecting ITP ( P<0.05), and TGF-β was the protective factor affecting ITP ( P<0.05). Conclusions:The serum levels of CD47 and sPD-L1 in patients with ITP are elevated, and the combined detection of the two indicators has a good diagnostic value for ITP.

Objective To develop a rehabilitation nursing model for knee osteoarthritis(KOA)of external treatment in traditional Chinese medicine(TCM).Methods Between February and June 2023,a preliminary KOA rehabilitation nursing model was developed through literature search and semi-structured interview method.Two rounds of Delphi consultations were conducted with the selected experts,to establish a rehabilitation nursing model for KOA of TCM external treatment.Results A total of 24 experts from different regions participated in the consultation.The final rehabilitation nursing model of TCM external treatment for KOA included 3 primary indicators,16 secondary indicators and 91 tertiary indicators.The response rates from the two rounds of expert consultation were 96.00%and 100.00%,respectively,and the rates of expert opinion proposal were 58.33%and 8.33%,respectively.The expert authority coefficient were 0.906 and 0.923.The two rounds of expert consultation were 0.137 and 0.236 in Kendall's coefficient of concordance(W),with statistically significant differences(both P<0.001).The importance scores of each item in the second inquiry ranged from 3.75 to 4.88,and the coefficient of variation ranged from 0.07 to 0.30,and the full score ratio ranged from 20.83%to 87.50%.Conclusion The rehabilitation nursing model for KOA of TCM external treatment developed in this study is significant,scientific and feasible.It provides a guidance for medical professionals.

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.

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.

Objective:To investigate the expression and clinical value of integrin-associated protein 47 (CD47) and soluble programmed death receptor-ligand 1 (sPD-L1) in patients with primary immune thrombocytopenia (ITP).Methods:The method of retrospective study was adopted, 76 patients with ITP admitted to the Affiliated Hospital of Jining Medical University from July 2016 to July 2022 were regarded as the study group, and another 76 cases of physical examination were regarded as the control group. The levels of serum CD47, sPD-L1, interleukin-33(IL-33) and transforming growth factor beta (TGF-β) were determined by the enzyme-linked immunosorbent assay, the diagnostic value of CD47 and sPD-L1 for ITP was analyzed by the receiver operating characteristic (ROC) curve, Pearson test was applied to analyze the correlation between serum CD47 and sPD-L1 in ITP patients, multivariate Logistic regression analysis was applied to analyze the risk factors affecting ITP.Results:The levels of serum CD47, sPD-L1 and IL-33 in the study group were higher than those in the control group: (40.31 ± 6.59) μg/L vs. (32.16 ± 6.33) μg/L, (78.42 ± 10.22) ng/L vs. (64.49 ± 10.36) ng/L, (73.29 ± 14.26) ng/L vs. (26.54 ± 5.16) ng/L; the level of serum TGF-β in the study group was lower than that in the control group: (1 752.66 ± 310.73) ng/L vs. (2 625.88 ± 389.58) ng/L, there were statistical differences ( P<0.05). The result of the Pearson test showed that there was a positive correlation between serum CD47 and sPD-L1 in ITP patients ( r = 0.572, P<0.05). The result of the ROC curve showed that the area under the curve predicted by the combination of serum CD47 and sPD-L1 was 0.948 (95% CI 0.916 - 0.979), which was better than that predicted by CD47 and sPD-L1 alone ( P<0.05). The result of multivariate Logistic regression analysis showed that CD47, sPD-L1, and IL-33 were the risk factors affecting ITP ( P<0.05), and TGF-β was the protective factor affecting ITP ( P<0.05). Conclusions:The serum levels of CD47 and sPD-L1 in patients with ITP are elevated, and the combined detection of the two indicators has a good diagnostic value for ITP.

Objective To develop a rehabilitation nursing model for knee osteoarthritis(KOA)of external treatment in traditional Chinese medicine(TCM).Methods Between February and June 2023,a preliminary KOA rehabilitation nursing model was developed through literature search and semi-structured interview method.Two rounds of Delphi consultations were conducted with the selected experts,to establish a rehabilitation nursing model for KOA of TCM external treatment.Results A total of 24 experts from different regions participated in the consultation.The final rehabilitation nursing model of TCM external treatment for KOA included 3 primary indicators,16 secondary indicators and 91 tertiary indicators.The response rates from the two rounds of expert consultation were 96.00%and 100.00%,respectively,and the rates of expert opinion proposal were 58.33%and 8.33%,respectively.The expert authority coefficient were 0.906 and 0.923.The two rounds of expert consultation were 0.137 and 0.236 in Kendall's coefficient of concordance(W),with statistically significant differences(both P<0.001).The importance scores of each item in the second inquiry ranged from 3.75 to 4.88,and the coefficient of variation ranged from 0.07 to 0.30,and the full score ratio ranged from 20.83%to 87.50%.Conclusion The rehabilitation nursing model for KOA of TCM external treatment developed in this study is significant,scientific and feasible.It provides a guidance for medical professionals.

Childhood household dysfunction(CHD)is a common adverse childhood experience,which brings the heavy physical and mental afflictions to children and adolescents.Trauma-focused cognitive behavioral therapy(TF-CBT)is an evidence-based psychotherapy that helps children and adolescents who have experienced childhood trauma with traumatic memories.It aims to enhance the coping abilities of CHD children and adolescents,thereby improving the negative effects caused by trauma and effectively reducing psychological burden.TF-CBT can effectively improve post-traumatic stress disorder,emotional and behavioral problems,and family function in children and adolescents with CHD.It is recommended to conduct high-quality original research in the future,develop targeted TF-CBT intervention plans based on potential predictive factors,adopt a combination of online and offline methods,and construct TF-CBT interventions suitable for the Chinese CHD population to meet the mental health service needs of CHD children and adolescents.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Traditional Chinese medicine （TCM）， as an invaluable scientific legacy and cultural patrimony of China， encapsulates the cumulative wisdom of millennia from the Chinese civilization. The deeply rooted medical theories and extensive empirical practices of TCM hold an indispensible central role within China's healthcare framework. Facing the challenges of modern medicine and health needs， it is particularly urgent to explore the mechanisms of Chinese medicines. Post-translational modification （PTM）， as a core mechanism to regulate the complex and diverse protein functions， is a bridge between environmental stimuli and physiological responses. Different PTMs can interact with each other to form a complex regulatory network， which is in line with the multi-component and multi-target action of Chinese medicines. In recent years， protein modification omics has emerged as a powerful means to probe into PTMs， and studies have employed protein modification omics to investigate the mechanisms of Chinese medicines. However， the research in this field is still in the initial stage. This article summarizes the basic theory of PTM and the basic research process of protein modification omics， reviews the application status of protein modification omics in the research on the mechanisms of Chinese medicines， and analyzes the existing research limitations. This study aims to explore an innovative research paradigm for analyzing the mechanisms of Chinese medicines from the perspective of PTM and provide a theoretical basis and practical guidance for understanding the mechanisms of Chinese medicines in the future.

Objective To understand the drug resistance surveillance situation of Mycobacterium tuberculosis in Hainan Province from 2018 to 2022, analyze the drug resistance status and trends of Mycobacterium tuberculosis in Hainan Province, and provide scientific basis for the formulation of tuberculosis prevention and treatment strategies. Methods A total of 2 481 sputum culture-positive isolates from pulmonary tuberculosis patients collected from 2018 to 2022 were subjected to strain identification and drug sensitivity testing. Strain identification was performed using the p-nitrobenzoic acid (PNB) inhibition test, and the sensitivity test for six anti-tuberculosis drugs, including Rifampicin (RFP), Isoniazid (INH), Streptomycin (SM), Ethambutol (EMB), Ofloxacin (OFX), and Kanamycin (KM), was conducted using the solid culture proportion method. The drug sensitivity results were statistically analyzed. Results Of the 2 481 isolates, 2 211 were identified as Mycobacterium tuberculosis complex (MTBC). The overall drug-resistance rate was 19.9% (441/2 211). The drug resistance rates for initial-treatment and retreatment patients were 15.7% (271/1 729) and 35.3% (170/482) respectively, with a statistically significant difference (χ2=90.65, P<0.01). The mono-resistance rate (MR) was 6.0% (132/2 211), with monoresistance rates of 5.6% (97/1 729) for initial-treatment patients and 7.3% (35/482) for retreatment patients, with no statistically significant difference (χ2=1.83, P>0.05). The overall poly-resistance rate (PR) was 4.1% (91/2 211), with polyresistance rates of 3.5% (61/1 729) for initial-treatment patients and 6.2% (30/482) for retreatment patients. The overall multidrug-resistance rate (MDR) was 8.0% (176/2 211), with multidrug resistance rates of 4.2% (72/1 729) for initial-treatment patients and 21.6% (104/482) for retreatment patients. According to the χ2 test, the retreatment group had significantly higher rates of polyresistance and multidrug resistance than the initial-treatment patient group, with statistically significant differences (χ2=6.94, P<0.01; χ2=155.98, P<0.01). The resistance rates to individual drugs in descending order were 11.6% (251/2 211) to INH, 11.4% (255/2 211) to RFP, 8.6% (191/2 211) to SM, 8.2% (181/2 211) to OFX, 4.0% (88/2 211) to EMB, and 1.6% (35/2 211) to KM. Conclusions The overall drug-resistance rate, poly-resistance rate, and multidrug resistance rate of Mycobacterium tuberculosis in retreatment patients in Hainan Province are higher than those in initial-treatment patients. Standardized treatment and management of TB patients are particularly important.