Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective: To summarize the clinical characteristics of inflammasomopathies, enhance the recognition of those diseases, and help to establish the early diagnosis. Methods: The clinical manifestations including fever, rash, systems involvement as well as laboratory results and genotypic characteristics of 35 children with inflammasomopathies diagnosed by the Department of Pediatrics, Peking Union Medical College Hospital, from January 1, 2008 to December 31, 2020 were analyzed retrospectively. Results: A total of 35 cases of inflammasomopathies were diagnosed, and 20 of them were boys while 15 were girls. Inflammasomopathies patients have early onset, the age of onset as well as diagnostic age were 1 (0,7) and 7 (3,12), respectively. Among those patients, 10 had familial mediterranean fever, 3 had mevalonate kinase deficiency, 15 cases had NLRP3 gene associated autoinflammatory disease, 4 cases had NLRP12-associated autoinflammatory disease, 2 cases had familial cold autoinflammatory syndrome 3, and 1 case had familial cold autoinflammatory syndrome 4. A total of 34 cases (97%) showed recurrent fever, 27 cases (77%) had skin rashes, while 11 cases (31%), 10 cases (29%), and 8 cases (23%) were presented with lymphadenopathy, hepatosplenomegaly and growth retardation, respectively. In terms of systemic involvement, there were 18 cases (51%), 12 cases (34%), 8 cases (23%), and 5 cases (14%) with skeletal, neurological, auditory, and renal involvement, respectively. Central nervous system involvement was seen only in NLRP3 gene associtated autoinflammatory diseases (12 cases), sensorineural deafness was seen in NLRP3 gene associtated autoinflammatory diseases (6 cases) and NLRP12 gene associated autoinflammatory diseases (2 cases), and abdominal pain was observed in familial Mediterranean fever (5 cases), mevalonate kinase deficiency (1 case) and NLRP12 gene related autoinflammatory diseases (1 case). In the acute inflammatory phase, the acute phase reactants (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) of 35 cases (100%) were significantly increased. There were 21 cases received ferritin examination, and only 4 cases (19%) showed an increase of it. In terms of autoantibodies, among all 35 patients, 4 cases (11%) were positive for antinuclear antibodies (ANA). Conclusions: Fever, skin rash, and skeletal manifestations are the most common clinical features, accompanied with increased CRP and ESR, and negative results of autoantibodies such as ANA. The clinical manifestations of those diseases are complex and diverse, and it is prone to delayed diagnosis and treatment.
Child ; Familial Mediterranean Fever ; Female ; Fever/etiology* ; Genotype ; Hereditary Autoinflammatory Diseases ; Humans ; Male ; Retrospective Studies

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.
Animals ; Bile ; Humans ; Hydrophobic and Hydrophilic Interactions ; Indigo Carmine ; Indigofera ; Plant Extracts ; Rats

OBJECTIVE: To observe the changes of symptoms, Chinese medicine (CM) syndrome, and lung inflammation absorption during convalescence in patients with coronavirus disease 2019 (COVID-19) who had not totally recovered after hospital discharge and whether CM could promote the improvement process. METHODS: This study was designed as a prospective cohort and nested case-control study. A total of 96 eligible patients with COVID-19 in convalescence were enrolled from Beijing Youan Hospital and Beijing Huimin Hospital and followed up from the hospital discharged day. Patients were divided into the CM (64 cases) and the control groups (32 cases) based on the treatment with or without CM and followed up at 14, 28, 56, and 84 days after discharge. In the CM group, patients received the 28-day CM treatment according to two types of CM syndrome. Improvements in clinical symptoms, CM syndrome, and absorption of lung inflammation were observed. RESULTS: All the 96 patients completed the 84-day follow-up from January 21 to March 28, 2020. By the 84th day of follow-up, respiratory symptoms were less than 5%. There was no significant difference in the improvement rates of symptoms, including fatigue, sputum, cough, dry throat, thirst, and upset, between the two groups (P>0.05). Totally 82 patients (85.42%) showed complete lung inflammation absorption at the 84-day follow-up. On day 14, the CM group had a significantly higher absorption rate than the control group (P<0.05) and the relative risk of absorption for CM vs. control group was 3.029 (95% confidence interval: 1.026-8.940). The proportions of CM syndrome types changed with time prolonging: the proportion of the pathogen residue syndrome gradually decreased, and the proportion of both qi and yin deficiency syndrome gradually increased. CONCLUSIONS Patients with COVID-19 in convalescence had symptoms and lung inflammation after hospital discharge and recovered with time prolonging. CM could improve lung inflammation for early recovery. The types of CM syndrome can be transformed with time prolonging. (Registration No. ChiCTR2000029430).
Adult ; Aged ; COVID-19/drug therapy* ; Case-Control Studies ; Convalescence ; Female ; Follow-Up Studies ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Patient Discharge ; Pneumonia/drug therapy* ; Prospective Studies ; SARS-CoV-2

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

AIM: To study the anti-inflammatory mechanism of emodin in rats with Aspergillus fumigatus keratitis.

METHODS: The model of Aspergillus fumigatus keratitis was established and divided into model group and emodin group, 8 in each group and 10 in the normal group. The emodin group was treated with rhubarb, and the model group and the normal group were treated with saline of equal volume. Corneal inflammation index and pathological characteristics were observed. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), intercellular adhesion molecule-1(ICAM-1), peroxisome proliferator-activated receptor(PPAR), MAPK and NF-κB protein were detected.

RESULTS: The corneal inflammation index, corneal inflammatory cell count, TNF-α, IL-6, ICAM-1, MAPK and NF-κB protein in emodin group were lower than those in model group, and the expression of PPAR protein was higher than that in model group(P<0.05).

CONCLUSION: Emodin can improve the levels of TNF-α, IL-6 and ICAM-1 inflammatory factors by regulating PPAR, MAPK and NF-κB proteins, and play an anti-inflammatory role in rats with Aspergillus fumigatus keratitis.

Neutrophils are one of the most abundant leukocytes present in the human blood circulation system, which could provide continuous immune surveillance. Recent studies have shown that neutrophils are closely related to angiogenesis. Neutrophils could release various cytokines, which regulate the angiogenic process by affecting the growth and migration of endothelial cells directly or indirectly. In the present review, the regulatory effects of neutrophils on angiogenic process and mechanisms are analyzed and summarized, which would provide clues for the treatment of related diseases using neutrophils as the targets in the future.

OBJECTIVE:To evaluate the efficacy and safety of cerebrolysin in adjuvant treatmenut of acute cerebral infarction systematically,and to provide evidence-based reference in clinic.METHODS:Retrieved from SCI,Cochrane Library,EMBase,PubMed,CJFD,VIP and Wanfang Database,RCTs about cerebrolysin combined with routine plan (trial group) vs.routine plan alone or combined with placebo (control group) in adjuvant treatment of acute cerebral infarction were collected.After data extraction and quality evaluation by using Cochrane systematic review manual 5.1.0,Meta-analysis was conducted by using Rev Man 5.2 statistical software.RESULTS:A total of 20 RCTs were included,involving 3 313 patients.Meta-analysis showed that NIHSS score [MD=-1.77,95％CI(-2.33,-1.21),P＜0.001],response rate [OR=2.85,95％CI(1.75,4.63),P＜0.001] and Barthel index (BI) score [MD =7.30,95 ％ CI (3.48,11.13),P＜ 0.001] in trial group were significantly higher than control group,with statistical significance.There was no statistical significance in disability rate [OR=0.46,95％ CI(0.20,1.03),P=0.06],mortality [OR=0.79,95％ CI (0.52,1.19),P=0.25],the incidence of ADR [OR=1.04,95％ CI (0.85,1.27),P=0.72] or the incidence of severe ADR [OR=0.01,95％CI(-0.02,0.04),P=0.51] between 2 groups.CONCLUSIONS:Cerebrolysin is good for adjanctive therapy of acute cerebral infarction,can significantly improve neurologic impairment and life quality and dosen't increase the incidence of ADR.

ObjectiveTo evaluate the integrated performance of age, serum PSA, and transrectal ultrasound images in the prediction of prostate cancer using a Tree-Augmented NaÏve (TAN) Bayesian network model.

METHODSWe collected such data as age, serum PSA, transrectal ultrasound findings, and pathological diagnoses from 941 male patients who underwent prostate biopsy from January 2008 to September 2011. Using a TAN Bayesian network model, we analyzed the data for predicting prostate cancer, and compared them with the gold standards of pathological diagnosis.

RESULTSThe accuracy, sensitivity, specificity, positive prediction rate, and negative prediction rate of the TAN Bayesian network model were 85.11%, 88.37%, 83.67%, 70.37%, and 94.25%, respectively.

CONCLUSIONSBased on age, serum PSA, and transrectal ultrasound images, the TAN Bayesian network model has a high value for the prediction of prostate cancer, and can help improve the clinical screening and diagnosis of the disease.

Bayes Theorem ; Biopsy ; Humans ; Male ; Predictive Value of Tests ; Prostate ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; Sensitivity and Specificity

OBJECTIVESTo evaluate the expression profile of myoD microRNA-29 (miR-29) family in L6 myoblast differentiated to myotube of L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.

METHODSThe expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis. The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search. The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay. Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence. Moreover, overexpression of myoD was achieved by a recombinant adenovirus system (Ad-myoD). L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.

RESULTSThe expression levels of myoD, miR-29a, miR-29b, and miR-29c were increased in L6 myoblast differentiated to myotube. The expression of myoD, miR-29b, and miR-29c was up-regulated in L6 myotube treated with glucose and insulin, but miR-29a depicted no significant change. Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster. Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.

CONCLUSIONMyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.

Animals ; Cell Differentiation ; drug effects ; physiology ; Cell Line ; Gene Expression Regulation ; drug effects ; physiology ; Glucose ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Mice ; MicroRNAs ; biosynthesis ; genetics ; Multigene Family ; physiology ; Muscle Fibers, Skeletal ; cytology ; metabolism ; MyoD Protein ; genetics ; metabolism ; Myoblasts ; cytology ; metabolism ; Sweetening Agents ; pharmacology