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:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To investigate the independent risk factors of comprehensive complication index(CCI)≥26.2 after radical resection of colon cancer,and use these factors to establish and verify a dynamic web-based nomogram model.Methods The clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected,and divided into main cohort(November 2020 to October 2021,n=438)and validation cohort(November 2021 to April 2022,n=196).CCI scores of all patients were obtained based on CCI calculator(http://www.assessurgery.com).Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI≥26.2,and a nomogram model was constructed.Receiver operator characteristic curve(ROC),C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model,and the decision curve analysis was conducted to assess the clinical benefits of the model.Internal validation of the model is performed in the validation cohort.Results A total of 438 patients were identified in present study,of which 63 cases(14.4%)had CCI≥26.2.Multivariate logistic regression analysis revealed that age≥60 years(OR=2.662,95%CI 1.341-5.285,P=0.005),low third lumbar spine skeletal muscle mass index(L3MI;OR=4.572,95%CI 2.435-8.583,P<0.001),NRS2002≥3(OR=4.281,95%CI 2.304-7.952,P<0.001),and preoperative bowel obstruction(OR=3.785,95%CI 1.971-7.268,P<0.001)were significant independent risk factors for postoperative CCI≥26.2.Based on these results,a static and web-based dynamic nomogram was established(https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/).The C-index and area under the curve(AUC)of the nomogram were 0.742 and 0.787,respectively.The calibration curve indicated a good consistency between the predicted probability and the actual probability.In the validation cohort,the nomogram also presented good discrimination(C-index=0.722,AUC=0.795)and predictive consistency.The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model.Conclusion This easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI≥26.2 after radical resection of colon cancer,which helps optimize the preoperative evaluation system,formulate precise individualized treatment strategies,and enhance recovery after surgery.

Objective:To study the expression of the Homeobox C6(HOXC6)gene in the homeobox family in PCa,its effect on the biological behavior of PCa cells and its action mechanism.Methods:Based on the studies of HOXC6 retrieved from the data-base of Gene Expression Profiling Interactive Analysis(GEPIA),we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients.We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot,stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prosta-tic epithelial RWPE-1 cells using the siRNA plasmid,and determined the effects of HOXC6 on the proliferation,migration and inva-siveness of PCa cells by CCK8,plate cloning and scratch healing and Transwell invasion assays.Using the GEPIA database,we ana-lyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1(SFRP1)gene with HOXC6,and detected the expressions of HOXC6,SFRP1,Wnt and β-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot.Results:The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue(P<0.01),and in the PCa cells than in the normal prostatic epithelial cells(P<0.01).Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression(P=0.011).The relative expression of the HOXC6 protein,absorbance value,number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls(P<0.05).Ac-cording to the GEPIA database,highly expressed SFRP1 was associated with a good prognosis of PCa,and the protein expressions of Wnt and β-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line(P<0.05).The expressions of the Wnt and β-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group com-pared with those in the siRNA negative control and PCa PC-3 groups(P<0.05).Conclusion:HOXC6 is highly expressed in PCa tissues and related to the proliferation,migration and invasiveness of PCa cells.HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/β-catenin signaling pathway,and may be a potential target for clinical treatment of PCa.

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ²=18.396,P<0.01;66.7% vs 16.7%,χ²=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ²=6.597,P<0.05;37.0% vs 7.4%,χ²=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were β-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ²=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.
Male ; Animals ; Cattle ; Female ; Child ; Humans ; Milk Hypersensitivity/diagnosis* ; Cross-Sectional Studies ; Food Hypersensitivity ; Allergens ; Immunoglobulin E

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ²=18.396,P<0.01;66.7% vs 16.7%,χ²=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ²=6.597,P<0.05;37.0% vs 7.4%,χ²=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were β-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ²=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.
Male ; Animals ; Cattle ; Female ; Child ; Humans ; Milk Hypersensitivity/diagnosis* ; Cross-Sectional Studies ; Food Hypersensitivity ; Allergens ; Immunoglobulin E

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Humans ; Infant ; Infant, Newborn ; Infant, Extremely Low Birth Weight ; Mesenchymal Stem Cell Transplantation ; Umbilical Cord/cytology* ; Skin/injuries*

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.