ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

Objective To systematically retrieve and integrate the best evidence of enteral and parenteral nutrition support in adult patients with severe bums.Methods 2 nursing master students who had studied evidence-based nursing systematically searched the clinical decisions,recommended practices,guidelines,expert consensuses,systematic reviews,evidence summaries and other evidences on enteral and parenteral nutrition support for adult patients with severe bums in domestic and foreign guideline networks,relevant institutional websites and databases.The retrieval time was from the establishment of the databases to April 2023.2 researchers who had obtained master's degrees and undergone systematic evidence-based training in Fudan University used the appraisal of guidelines for research and evaluation n and JBI critical appraisal tools to evaluate the methodological quality,and extracted and summarized the evidence according to the theme.Results A total of 28 articles were included,including l clinical decision,9 guidelines,3 expert consensuses,9 systematic reviews,and 6 evidence summaries.A total of 20 pieces of evidence were summarized from 6 aspects:nutritional risk screening and assessment,energy requirement calculation,timing and route of nutritional support,nutrient intake,nutritional support monitoring and effect evaluation.Conclusion The best evidence of enteral and parenteral nutrition support for adult patients with severe burns summarized in this study is more comprehensive and scientific.It is suggested that in clinical application,targeted screening should be carried out according to the promotion and hindering factors of evidence,so as to scientifically carry out nutritional support for adult patients with severe burns.

Objective To identify the pathogenic mutations in a family with piebaldism.Methods Clinical infor-mation and peripheral blood were collected from the patient with piebaldism and their parents.Whole exome se-quencing was performed to identify the potential pathogenic mutations.QPCR was used to determine the deletion of the target gene,while gap-PCR and Sanger sequencing was used to determine the size and the specific deletion site.Results The proband had a heterozygous deletion mutation of approximately 1.74 Mb located at chromosome 4,in-cluding a full length of the pathogenic gene KIT for mottled disease and it was the smallest micro deletion causing isolated piebaldism due to the loss of the KIT.Conclusions The heterozygous deletion including the KIT is a poten-tial cause of the piebaldism phenotype found in this family.

Objective:To investigate whether dual-energy computed tomography(DECT) measurement of monosodium urate(MSU) crystal loading can predict the risk of gout flares.Methods:A single-center, prospective, observational study included 229 gout patients initially diagnosed at the Gout Clinic of Qingdao University from August 2021 to February 2022. The patients underwent MSU assessment of the bilateral feet using DECT. Following enrolment, all patients commenced uric acid-lowering therapy(ULT) and were followed up at 3 and 6 months. Patients who experienced at least one flare within 6 months were compared with those who did not, and the odds ratio( OR) for the risk of gout flares was calculated. Results:Patients who experienced gout flare had a significantly longer disease duration[(6.69±5.42) vs(4.14±4.86) years, P<0.01], a higher number of flares in the past year(4.80±1.73 vs 2.02±1. 23, P<0.01), a higher proportion of fatty livers(11.0% vs 1.4%, P<0.05), and a greater volume of MSU crystals in the feet[(3.52±9.74) vs(0.29±0.98)cm 3,P<0.05] compared to patients without gout flare. The results of the multifactorial logistic regression analysis indicated that the number of flares in the past year( OR=1.295, 95% CI 1.032-1.613, P<0.05) and feet MSU crystal volume( OR=3.245, 95% CI 1.164-9.064, P<0.05) were independent risk factors for gout flares. The receiver operating characteristic(ROC) curve indicated the integration of the MSU prediction model into the clinical prediction model resulted in a comprehensive prediction model with an area under curve(AUC) value of 0.780(95% CI 0.710-0.840), sensitivity of 0.83, and specificity of 0.62. Internal validation of the comprehensive prediction model using the Bootstrap method yielded a C-index of 0.770(95% CI 0.701-0.833) for predicting flares. The calibration curve of the model demonstrated a good fit between the predicted probability of flares and the actual probability, indicating high calibration accuracy. Conclusion:The volume of MSU crystals in the feet is an independent risk factor for flares following ULT. A larger volume of MSU crystals in the foot increases the likelihood of a flare. This study provides a basis for early prediction of flare and a reference for early preventive treatment.

Objective: : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods: : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results: : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

The presence of replication-competent HBV DNA in the liver and/or serum of HBsAg-negative individuals is a sufficient and necessary condition for the diagnosis of occult hepatitis B virus infection (OBI). In recent years, Chinese scholars have proposed what is considered a more "rigorous" definition, i.e., on this basis, HBV window period (WP) infection is excluded, which corresponds to a serum HBV DNA level of below the lower limit of detection or a low positive value (< 200 IU/mL). As the definition of WP for HBV infection remains unclear and its duration is highly variable, "HBV DNA < 200 IU/mL" is not the only criterion in OBI patients. Therefore, it is believed that there is still a lack of sufficient basis and operability for the definition of OBI based on "the exclusion of HBV WP infection" and "HBV DNA < 200 IU/mL" as "rigorous" conditions for the diagnosis of OBI.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objective:To explore the pathway of influencing factors of self-management in elderly patients with type 2 diabetes mellitus (T2DM) based on health belief theory.Methods:It was a cross-sectional study. A total of 210 elderly patients with T2DM admitted to Shanghai 10th People′s Hospital from January 2021 to March 2022 were selected as research subjects.The surveys of general data questionnaire, social support rating scale, the diabetes self-management scale, the health literacy survey scale for patients with chronic diseases, and the self-efficacy scale for patients with diabetes were conducted in all the subjects. The t test and Spearman correlation analysis were used to test the correlation among variables. Results:Social support, health literacy and self-efficacy were positively correlated with self-management scores in these patients ( r=0.380, 0.392, 0.274, all P<0.001). Univariate analysis showed that there were statistically significant differences in self-management among patients with different age, education level, physical exercise, medical payment method, family history and sleep quality (all P<0.05). Path analysis showed that the mediating effect of social support in the relationship between health literacy and self-efficacy was significant (95% CI: 0.014-0.117), social support, self-efficacy and health literacy directly affected self-management( β=0.25, 0.27, 0.35, all P<0.01). Self-efficacy and health literacy also positively affected self-management through multiple mediators of social support ( β=0.16, 0.27, both P<0.01). Conclusion:Social support, self-efficacy and health literacy mediate in the self-management of elderly patients with T2DM complicated with chronic complications and interact with each other.

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; MicroRNAs/metabolism* ; Glioma/genetics* ; Genes, Tumor Suppressor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47G>A, p.W16*) in LAMA3, a known recurrent variant (c.74C>T, p.P25L) in KRT5, 2 novel (c.2531T>A, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187C>T, p.R2063W; c.7097G>A, p.G2366D; c.8569G>T, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.
Humans ; Asian People/genetics* ; China ; Collagen Type VII/genetics* ; Epidermolysis Bullosa/genetics* ; Epidermolysis Bullosa Dystrophica/genetics* ; Keratin-5/genetics* ; Mutation ; Pedigree ; Laminin/genetics*