In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To evaluate the prognostic value of C-reactive protein (CRP), performance status (PS), lactate dehydrogenase (LDH), albumin (ALB) and derived neutrophil-to-lymphocyte ratio (dNLR) composite index (C-PLAN) as a prognostic indicator in advanced esophageal cancer patients treated with immune checkpoint inhibitor (ICI). Methods Hematologic indexes of 147 patients with advanced esophageal cancer treated by ICI in the Affiliated Hospital of Yangzhou University were collected before the first immunotherapy. CRP, PS, LDH, ALB and dNLR were scored and added to obtain C-PLAN index. Chi-square test was used to analyze the correlation between C-PLAN index and clinicopathological features; Kaplan-Meier survival curve was used to analyze the effects of C-PLAN index on overall survival (OS) and progression-free survival (PFS). Univariate and multifactor Cox proportional regression models were used to analyze whether C-PLAN index could be used as an independent factor affecting prognosis. Results A total of 147 patients with advanced esophageal cancer were divided into low-risk group (scored < 2, n=46) and high-risk group (scored ≥2, n=101) according to C-PLAN index. C-PLAN index was not correlated with age, sex, PS score, smoking, clinical stage, body mass index, pathological type, treatment strategy and operation (P>0.05). PFS and OS in the low-risk group were significantly better than those in the high-risk group (P < 0.001). In univariate Cox regression analysis, C-PLAN index was the influencing factor of PFS (P < 0.001) and OS (P=0.002). In multivariate Cox analysis, C-PLAN index was an independent prognostic factor of PFS (P=0.001) and OS (P=0.006). Conclusion C-PLAN index can be used as a reliable clinical index to predict the prognosis of patients with advanced esophageal cancer treated by ICI.

OBJECTIVES: To estimate postmortem interval (PMI) by analyzing the protein changes in skeletal muscle tissues with the protein chip technology combined with multivariate analysis methods. METHODS: Rats were sacrificed for cervical dislocation and placed at 16 ℃. Water-soluble proteins in skeletal muscles were extracted at 10 time points (0 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d and 9 d) after death. Protein expression profile data with relative molecular mass of 14 000-230 000 were obtained. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) were used for data analysis. Fisher discriminant model and back propagation (BP) neural network model were constructed to classify and preliminarily estimate the PMI. In addition, the protein expression profiles data of human skeletal muscles at different time points after death were collected, and the relationship between them and PMI was analyzed by heat map and cluster analysis. RESULTS: The protein peak of rat skeletal muscle changed with PMI. The result of PCA combined with OPLS discriminant analysis showed statistical significance in groups with different time points (P<0.05) except 6 d, 7 d and 8 d after death. By Fisher discriminant analysis, the accuracy of internal cross-validation was 71.4% and the accuracy of external validation was 66.7%. The BP neural network model classification and preliminary estimation results showed the accuracy of internal cross-validation was 98.2%, and the accuracy of external validation was 95.8%. There was a significant difference in protein expression between 4 d and 25 h after death by the cluster analysis of the human skeletal muscle samples. CONCLUSIONS The protein chip technology can quickly, accurately and repeatedly obtain water-soluble protein expression profiles in rats' and human skeletal muscles with the relative molecular mass of 14 000-230 000 at different time points postmortem. The establishment of multiple PMI estimation models based on multivariate analysis can provide a new idea and method for PMI estimation.
Animals ; Humans ; Rats ; Multivariate Analysis ; Postmortem Changes ; Protein Array Analysis ; Technology

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.
B-Cell Maturation Antigen ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen ; Remission Induction

Conclusion:The clinical assessment and classification of scapular dyskinesis had been summarized. Scapular dyskinesis is mainly secondary to rotator cuff injury, subacromial impingement syndrome, glenohumeral instability, injury of acromioclavicular joint, throwing shoulder and adhesive capsulitis, etc. Scapular exercise may be a supplement to routine rehabilitation management. Objective:To review the pathogeny, clinical assessment and classification, and rehabilitation management of scapular dyskinesis. Results and Methods:The literatures in recent ten years were reviewed and summarized.

Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 （coagulation factor V gene Leiden）, rs6025 （prothrombin gene G20210A）, rs1042579 （thrombomodulin protein gene c.1418C>T） and rs1801131 （methylenetetrahydroflate reductase gene） and lower extremity deep venous thrombosis （LEDVT）. Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction （KASP）, then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT.
Blood Coagulation/genetics* ; Humans ; Lower Extremity ; Polymorphism, Genetic ; Risk Factors ; Venous Thrombosis/genetics*

Objective To explore the method of distinguishing the degree of hypoxic-ischemic brain damage ( HIBD) in living mice in early stage, so as to lay a foundation for the follow-up study of the molecular mechanism of different degrees of HIBD. Methods The modified Rice-Vannucci method was used to duplicate the HIBD model of C57BL/6 J mice. On the 1 day and 3 days after the model, the scalp of mice were cut and the brain tissue were observed to distinguish between mild and severe lesions in living mice, and then 2,3, 5-triphenyltetrazolium chloride (TTC) staining, laser speckle cerebral blood flow imaging, HE staining, Fluoro-Jade B ( FJB ) staining and body weight difference before and after operation were used to verify the reliability of observation in living mice. Results Through the gross observation of brain tissue in living mice, HIBD could be divided into mild injury (HI-M) group and severe injury (HI-S) group. On day 1 and day 3 after HIBD, a significant decrease in cerebral blood flow, obvious gray infarction and a large number of necrotic neurons were observed in the HI-S group, and the body weight was significantly lower than that before operation. In the HI-M group, the cerebral blood flow of the injured side decreased only on the 3rd day after HIBD, and the loose arrangement of neurons in the cortex and hippocampus of the injured side was observed morphologically. The body weight was lower than that before operation. Conclusion Gross observation of brain tissue by cutting the scalp is a reliable method to distinguish mild and severe brain injury in the early stage of HIBD in living mice.

With the development of the new generation of 16S rRNA sequencing technology and metagenomics, the relationship between the microbiota and bronchial asthma (asthma for short) has been increasingly recognized, and has become a research hotspot in the pathogenesis of asthma. It is estimated that more than 10,000 different microbial species inhabit the human body, affecting nutrition, metabolism and immune function of body. The imbalance of microbial flora leads to the disturbance of the internal environment in the body, which causes diseases such as asthma. Asthma is determined by both genetic and environmental effects, and the microbiota plays an important role in the pathogenesis, phenotype and disease severity of asthma. This paper reviews the role of different microbiota in the development of asthma.

Objective To obtain the protein expression profile of rat liver tissue after death by the 2100 bioanalyzer combined with protein chip, and infer the relationship between protein expression profile and postmortem interval. Methods Rats were killed by abdominal anesthesia and placed at 16 ℃. Water-soluble proteins in liver tissues were extracted at 14 time points after death. The expression profile data of proteins with relative molecular weight of 14 000-230 000 were obtained using protein chip, and principal component analysis （PCA）, partial least squares-discriminant analysis （PLS-DA） and Fisher discriminant were used to analyze the data. Results According to the changes of protein expression profile, the postmortem interval was divided into group A （0 d）, group B （1-9 d）, group C （12-30 d） according to the result of PLS-DA. The prediction accuracy of the training set and test set of the model were all 100.0%, and the internal cross-validation of the training set was 100.0% according to Fisher discriminant. The Fisher discriminant model at each time point of group B and C was established to narrow the time window of postmortem interval estimation. The prediction accuracy of the training set and test set were all 100.0%, and the internal cross-validation accuracy of the training set was 100.0% in group B. The prediction accuracy of the training set and test set were respectively 95.2% and 78.6% in group C, and the internal cross-validation of the training set was 88.1%. Conclusion Protein chip detection technology can quickly and easily obtain the expression profile of water-soluble proteins of rat liver tissue with a relative molecular weight of 14 000-230 000 at different time points after death. PLS-DA and Fisher discriminant models are established to classify and predict the postmortem interval, in order to provide new ideas and methods for postmortem interval estimation.
Animals ; Autopsy ; Discriminant Analysis ; Least-Squares Analysis ; Postmortem Changes ; Protein Array Analysis ; Rats ; Technology