OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.

Objective:To evaluate our self-designed guide device for Kirschner-wire placement in the surgery for paediatric fractures of supracondylar humerus.Methods:A retrospective study was conducted of the 117 children who had been treated for fractures of supracondylar humerus at Department of Orthopedics, The First People's Hospital of Huaian Affiliated to Nanjing Medical University from March 2019 to January 2023. There were 64 boys and 53 girls with an age of (5.8±1.5) years. By the Gartland classification, there were 67 fractures of type Ⅱ and 50 fractures of type Ⅲ. The time from injury to operation averaged (48.5±10.8) hours. The children were divided into 2 groups according to how their Kirschner-wires were placed. In the control group of 58 cases, external percutaneous Kirschner-wire placement was assisted using a syringe needle; in study group of 59 cases, external percutaneous Kirschner-wire placement was assisted using our self-designed guide device for Kirschner-wire placement. The operation time, rate of one-time placement of disposable K-wire, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time, Flynn score of elbow joint function at the final follow-up, and postoperative complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The 117 pediatric patients were followed up for (15.3±3.2) months after operation. The operation time [(30.6±4.5) min] and intraoperative fluoroscopy frequency [(15.6±2.1) times] in the study group were significantly less than those in the control group [(40.6±7.3) min and (23.7±4.9) times], while the rate of one-time placement of disposable K-wire in the study group was significantly higher than that in the control group [84.2%(149/177) versus 32.2%(56/174)] ( P<0.05). There were no significant differences in Baumann angle, carrying angle, fracture healing time, or Flynn score of elbow joint function at the final follow-up between the 2 groups ( P>0.05). The incidence of complications in the study group (6.8%, 4/59) was significantly lower than that in the control group (20.7%, 12/58) ( P<0.05). Conclusions:Our self-designed guide device for Kirschner-wire placement is simple and convenient to use. In the surgery for paediatric fractures of supracondylar humerus, it can improve the rate of one-time placement of disposable K-wire, reduce intraoperative fluoroscopy, and decrease the incidence of complications.

Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90％confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00％and 125.00％,and the 95％upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00％and 125.00％.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.

Objective:To explore the changes in acoustic features of 9-10-year-old primary school students with depressive symptoms, and based on these features and the random forest (RF) algorithm, construct a model for identifying depressive symptoms in primary school students, so as to provide an intelligent psychological health screening tool for schools and education departments.Methods:This was a case-control study.A total of 1 186 primary school students aged 9-10 from three primary schools in three regions of Jiangsu Province were selected as research subjects for psychological health screening from October 26, 2022 to February 13, 2023.Their demographic data, Depression-Anxiety-Stress Scale (DASS-21) scores, Insomnia Severity Index scores, and voice recordings were collected.Based on the DASS-21 scores, the participants were divided into a control group ( n=1 086) and a depression group ( n=100).Voice recordings were made using the neutral text " The North Wind and the Sun". openSMILE was used to extract 523 acoustic features from the pre-processed voice recordings.Group differences were assessed using independent-samples t-tests or chi-square tests.Pearson correlation analysis was conducted to examine the relationship between acoustic features and depression scores.Depressive symptoms were set as the dependent variable, and the correlated acoustic features were set as the independent variable to construct a classification model using the RF algorithm.The model performance was assessed using the receiver operating characteristic (ROC) curve, the area under the curve (AUC), precision, accuracy, recall, and F1 score. Results:Compared with the control group, the depression group showed significant differences in 105 acoustic features (44 spectral features, 49 source features, and 12 prosodic features) (all P<0.05).Correlation analysis showed that 12 acoustic features (7 spectral features, 4 source features, and 1 prosodic feature) were significantly correlated with the depression score (all P<0.05).Among the RF algorithm-based classification models, the spectral features demonstrated superior performance compared to source features and prosodic features (AUC=0.793), and the performance of the model based on the combination of these features was the best (AUC=0.818). Conclusions:Acoustic features may be an objective indicator to identify the depression of 9-10-year-old primary school students, and the classification model established based on acoustic features can identify the depressed primary school students.

Objective To explore a method for assessing the irregular small opacities profusion associated with occupational pneumoconiosis in chest computed tomography (CT). Methods A total of 20 occupational pneumoconiosis patients whose primary manifestation was irregular small opacities on chest digital radiography (DR) were collected as the research subjects using a retrospective study method. Comparative analysis was performed between chest DR and five mm coronal multi-planar reconstruction (MPR) of chest CT images to identify the causes of irregular small opacities. An evaluation method for the profusion of associated images of irregular small opacities in chest CT was established using technique for order preference by similarity to ideal solution-analytic hierarchy process (TOPSIS-AHP), and the results were compared against GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis. Results The abnormal image distribution on the five mm coronal chest CT MPR images of the 20 patients was as follows: three cases of high-density small circular opacities, seven cases of low-density circular small opacities, six cases of diffuse low-density ground-glass opacities (GGO), four cases of reticular opacities, three cases of plate-like GGO, three cases of honeycomb opacities, and four cases of increasing lung texture. The CT values of abnormal images, from high to low were: honeycomb opacities > plate-like GGO > low-density circular small opacities > diffuse low-density GGO (all P<0.05). The consistency test results indicated that the evaluation method for the profusion of associated images of irregular small opacities in chest CT showed high level of agreement with the profusion determination criteria outlined in GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis (Kappa=0.78). Conclusion Irregular small opacities observed on chest DR are formed by the superposition of multiple images of abnormal pulmonary fibrosis in patients with occupational pneumoconiosis. TOPSIS-AHP can be used to establish an evaluation method of the profusion of associated image of irregular small opacity in chest CT.

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.
Animals ; Humans ; Bufonidae ; Powders ; Bufanolides/pharmacology* ; Quality Control ; Chromatography, High Pressure Liquid ; Pain/drug therapy*

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in Transwell^TM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. Transwell^TM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.
Humans ; Arthritis, Rheumatoid/genetics* ; Interleukin-23 ; Macrophages ; RNA, Messenger ; RNA, Small Interfering/genetics* ; Smad7 Protein/genetics* ; Transforming Growth Factor beta1/genetics* ; Smad3 Protein/genetics* ; Gene Silencing