This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

OBJECTIVE: To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. METHODS: The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. RESULTS: A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. CONCLUSION Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.
Humans ; Child ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/diagnosis* ; Risk Factors ; C-Reactive Protein ; Acute Disease

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
COVID-19/epidemiology* ; Contact Tracing ; Humans ; Incidence ; Nucleic Acids ; Prospective Studies ; SARS-CoV-2

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

BACKGROUND: Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients. METHODS: Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances. RESULTS: Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score. CONCLUSION Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.
Humans ; Parkinson Disease/complications* ; Polysomnography ; REM Sleep Behavior Disorder ; Sleep ; Sleep Wake Disorders/etiology*

【Objective】 To study the mutation characteristics of Tyrosine hydroxyls（TH） gene in a pedigree with dopa-responsive dystonia（DRD）. 【Methods】 Extraction of genomic DNA from peripheral blood of a proband and his parents and two sisters using high- throughput sequencing （NGS） method were detected on 256 known pathogenicity genes associated with dystonia and dyskinesia.【Results】Mutations on tyrosine hydroxylase（TH）gene in the exon 14 and exon 9 were detected in the proband and his eldest sister in this pedigree. They had a complex heterozygosity of c.1481C > T（p.Thr494Met）and c.943G >A（p.Gly315Ser），and one heterozygous mutation was carried by parents respectively. The mutation was not detected in his second sister and 50 people with normal phenotype controls. 【Conclusion】 The mutations of TH gene c. 1481C > T（p.Thr494Met）and c. 943G > A（p.Gly315Ser）led to the gene abnormality in DRD family，and a new mutation of TH gene was found，which expanded the relationship between DRD genotype and clinical phenotype. It is vital that early accurate diagnosis and treatment of DRD is the key to improve prognosis.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Multiple Myeloma/therapy* ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVE: To investigate the effect of perioperative dexamethasone on nausea, vomiting and pain after unilateral total knee arthroplasty and to evaluate its safety. METHODS: From February 2014 to June 2016, 100 patients with unilateral advanced osteoarthritis treated by total knee arthroplasty were divided into two groups: 50 patients in dexamethasone group including 27 males and 23 females, aged (72.30±7.02) years, were given intravenous drip of dexamethasone 10 mg before operation; 50 patients in saline group, including 26 males and 24 females, aged (71.30±6.08) years, were given the same amount of saline at the corresponding time. The VAS scores of pain at rest and at 45 degrees of knee flexion were recorded at 2, 4, 6, 8, 12, 24, 36 and 48 h after operation. Vomiting, antiemetic drugs and opioids were recorded at 0 to 24 h and 24 to 48 h after operation. The side effects and complications were recorded. RESULTS: All the 100 patients were followed up for an average of 14.5 months. VAS score of pain at rest in dexamethasone group was lower than that in saline group at 8, 24 and 48 h after operation (<0.05); VAS score of dexamethasone group at 45 degrees after knee flexion was lower than that of saline group at 8 and 48 h after operation(<0.05); VAS score of dexamethasone group at rest and 45 degrees after knee flexion was lower than that of saline group(<0.05). The dosage of opioids and total opioids in dexamethasone group was lower than that in saline group at 0 to 24 h, 24 to 48 h after operation (<0.05). The proportion of nausea and vomiting occurred at 0 to 24 h and 24 to 48 h after operation, and the proportion of antiemetic required at 0 to 24 h after operation had statistical significance between two groups(<0.05). The total antiemetic dosage of dexamethasone group was less than that of saline group(<0.05). As of the last follow-up, no complications such as infection, gastrointestinal ulcer and bleeding occurred in the two groups. CONCLUSIONS Preoperative systemic application of dexamethasone can effectively reduce pain and nausea and vomiting after TKA without increasing postoperative complications.
Aged ; Arthroplasty, Replacement, Knee ; Dexamethasone ; Female ; Humans ; Male ; Nausea ; Pain, Postoperative ; Vomiting