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 effect of acupuncture on fatigue improvement and gut microbiota in mice with cancer-related fatigue(CRF),and explore its possible mechanism of action.Methods The mice model of CRF of breast cancer after chemotherapy was established by tumor bearing and chemotherapy.After acupuncture intervention,fatigue was evaluated by general condition,forced swimming and open field experiment.Then 16S rDNA sequencing was used to analyze the structural abundance of gut microbiota in mice.Results Acupuncture could significantly improve the fatigue degree and general condition of the mice model of CRF of breast cancer after chemotherapy.At the same time,acupuncture could adjust the abundance of gut microbiota structure,up-regulate the abundance levels of Lactobacillus,Bacteroides,firmicutes,actinobacteria,and down-regulate the abundance levels of Proteobacteria and Staphylococcus.There were also differences in the abundance of flora structure among the groups,but the abundance of beneficial bacteria was relatively high in the acupuncture group,and the abundance of pathogenic bacteria was relatively high in the other two groups.Conclusion Acupuncture may play a role in the treatment of CRF by regulating the abundance of gut microbiota structure,increasing intestinal beneficial bacteria,inhibiting pathogenic bacteria,improving body immunity,and alleviating adverse reactions caused by chemotherapy for breast cancer.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ²=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.
Infant ; Male ; Female ; Humans ; Child ; Infant, Newborn ; Child, Preschool ; Retrospective Studies ; Cough ; Coinfection ; Premature Birth ; Respiratory Sounds ; Metapneumovirus ; Pneumonia, Viral/epidemiology* ; Respiratory Syncytial Virus, Human ; Community-Acquired Infections/epidemiology* ; Risk Factors ; Dyspnea ; Malnutrition

The aim of this paper was to study the effect of Wubi Shanyao Pills on sexual dysfunction in rats with kidney-Yang deficiency and to investigate its possible mechanism. Adenine(100 mg·kg~(-1)) was administered to male SD rats for 8 weeks to establish kidney-Yang deficiency model, and at the same time, Wubi Shanyao Pills(2, 1, 0.5 g·kg~(-1)) were administered to rats for 8 weeks. The syndrome manifestation of kidney-Yang deficiency was observed in rats and the scores of symptoms were evaluated. Sexual behavior indexes(incubation period and times of capture, straddle and ejaculation) were measured by mating experiment. The levels of serum testosterone(T), estradiol(E_2), follicle stimulating hormone(FSH), luteinizing hormone(LH), and gonadotropin releasing hormone(GnRH) were measured by radioimmunoassay. The wet weights of testis and seminal vesicle were measured. The content of fructose in seminal plasma was detected by UV spectrophotometry. The pathological changes of testis and epididymis were observed by HE staining. The expression levels of transforming growth factor(TGF-β1) and cytochrome P450 aromatase(CYP19) in testis were detected by immunohistochemistry and Western blot. The results showed that Wubi Shanyao Pills could significantly reduce the score of kidney-Yang deficiency syndrome, improve the symptoms of kidney-Yang deficiency syndrome, shorten capture, straddle and ejaculation latency, increase capture and straddle times, increase serum T, LH, FSH, E_2 and GnRH levels, increase the wet weight of testis and seminal vesicle and fructose content in seminal plasma, improve the pathological structure of testis and epididymis, and inhibit the expression of TGF-β1 and increase CYP19 in testis of the model rats. Therefore, Wubi Shanyao Pills can significantly improve sexual dysfunction in rats with kidney-Yang deficiency, and its mechanism may be related to regulating the low function of hypothalamus pituitary gonad(HPG) axis and improving the disorder of sex hormone secretion. In addition, it may be also related to inhibiting the expression of testicular TGF-β1, increasing the expression of CYP19 protein, and then regulating the amount of T converted to E_2.
Adenine ; Animals ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Luteinizing Hormone ; Male ; Rats ; Rats, Sprague-Dawley ; Testis ; Testosterone ; Yang Deficiency

Background::High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach.Methods::For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays.Results::Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 μmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 μmol/L, Z = －5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 μmol/L, Z = －8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 μmol/L, Z = －1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ 2 = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 μmol/L, χ 2 = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min －1·1.73 m －2, χ 2 = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ 2 = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ 2 = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ 2 = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 ( P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine ( β = 0.76, P = 0.02), systolic blood pressure ( β = 0.26, P = 0.02), diastolic blood pressure ( β = 0.20, P = 0.01), and pathologic T lesion ( β = 0.01, P = 0.01) in IgAN. Conclusions::By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.

Objective: To investigate whether elevated levels of C-reactive protein (CRP) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence. Methods: From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow-up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer. Results: A total of 92 735 participants were enrolled in this study. During the follow-up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg/L and NE≤4×10⁹/L(Group A), CRP≤3 mg/L and NE>4×10⁹/L(Group B), CRP>3 mg/L and NE≤4×10⁹/L(Group C), CRP>3 mg/L and NE>4×10⁹/L(Group D). The cumulative incidence of lung cancer were 950/100 000, 1 030/100 000, 1 081/100 000 and 1 596/100 000 in these four groups, respectively (P<0.001). Multivariate Cox proportional risk model showed that participants from Group D had an significantly increased 72% risks of lung cancer when compared to Group A (95% CI: 1.40~2.12, P<0.001). Stratified analyses gender showed that males in Group D had higher risk of lung cancer when compared with participants in Group A (HR=1.73, 95% CI: 1.40~2.15, P<0.001). Conclusion Elevated levels of CRP and NE might increase the risk of lung cancer.

Objective To investigate whether elevated levels of C?reactive protein ( CRP ) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence. Methods From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow?up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer. Results A total of 92 735 participants were enrolled in this study. During the follow?up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg／L and NE≤4×109／L(Group A), CRP≤3 mg／L and NE＞4×109／L( Group B), CRP＞3 mg／L and NE≤4× 109／L(Group C), CRP＞3 mg／L and NE＞4×109／L(Group D). The cumulative incidence of lung cancer were 950／100 000, 1 030／100 000, 1 081／100 000 and 1 596／100 000 in these four groups, respectively (P＜0.001 ). Multivariate Cox proportional risk model showed that participants from Group D had an significantly increased 72% risks of lung cancer when compared to Group A ( 95% CI: 1.40～2.12, P＜0.001). Stratified analyses gender showed that males in Group D had higher risk of lung cancer when compared with participants in Group A (HR＝1.73, 95% CI: 1.40～2.15,P＜0.001).Conclusion Elevated levels of CRP and NE might increase the risk of lung cancer.

Objective: To investigate the prevalence and risk factors of diabetic peripheral neuropathy in type 2 diabetic patients under community management programs. Methods: A cross-sectional study was conducted on T2DM patients in eight communities in Wuhan and Changshu cities. Data would included questionnaire, body measurement, blood testing and clinical examination. The criterion of diabetic peripheral neuropathy was under the combination of symptoms with five physical examinations. Binary logistic regression model was used to analyze the influential factors. Results: The overall prevalence of peripheral neuropathy was 71.2% among the diabetic patients who were managed in primary care health services in the two cities. The binary logistic regression method identified older age (≥60 years, OR=2.39, 95%CI:1.95-2.94), longer diabetic duration (≥10 years, OR=1.25, 95%CI: 1.02-1.54), and worse postprandial glucose control (2 h postprandial plasma glucose >10.0 mmol/L: OR=1.65, 95%CI:1.33-2.04) (all P<0.05) as risk factors for the presence of diabetic peripheral neuropathy, while higher education level was protective factor (compared to patients with education levels of primary school or below, OR=0.52, 95%CI: 0.41-0.66; OR=0.59, 95%CI: 0.44-0.79; OR=0.64, 95%CI: 0.44-0.94 for those with education levels of junior high school, senior high school, and college, respectively). Conclusions High rates of diabetic peripheral neuropathy among T2DM patients suggested the urgent need for early screening and standardized management at the community levels. It is necessary to promote appropriate screening techniques and methods to identify the peripheral neuropathy, in the primary health service institutions.

Objective To investigate whether elevated levels of C?reactive protein ( CRP ) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence. Methods From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow?up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer. Results A total of 92 735 participants were enrolled in this study. During the follow?up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg／L and NE≤4×109／L(Group A), CRP≤3 mg／L and NE＞4×109／L( Group B), CRP＞3 mg／L and NE≤4× 109／L(Group C), CRP＞3 mg／L and NE＞4×109／L(Group D). The cumulative incidence of lung cancer were 950／100 000, 1 030／100 000, 1 081／100 000 and 1 596／100 000 in these four groups, respectively (P＜0.001 ). Multivariate Cox proportional risk model showed that participants from Group D had an significantly increased 72% risks of lung cancer when compared to Group A ( 95% CI: 1.40～2.12, P＜0.001). Stratified analyses gender showed that males in Group D had higher risk of lung cancer when compared with participants in Group A (HR＝1.73, 95% CI: 1.40～2.15,P＜0.001).Conclusion Elevated levels of CRP and NE might increase the risk of lung cancer.