Traditional Chinese medicine （TCM） therapy has unique clinical advantages in the treatment of atrial fibrillation， mainly reflected in five aspects， improving quality of life， enabling early diagnosis and treatment， promoting cardiac rehabilitation， making up for the limitations of Western medicine， and improving the success rate of catheter ablation. However， there is insufficient evidence in current clinical research. Based on the current status of TCM research in the treatment of atrial fibrillation， it is suggested that future studies should focus on standardized research on syndrome differentiation and classification. This can be achieved through clinical epidemiological surveys， expert consensus， and other methods to establish a unified syndrome differentiation and classification standard for atrial fibrillation. Clinical efficacy evaluation indicators should be standardized， and core outcome measures for clinical research on TCM treatment of atrial fibrillation should be developed through systematic reviews， patient interviews， and other methods. Additionally， clinical research design， implementation， and data management should be improved. By leveraging modern information technologies such as artificial intelligence， the scientific and standardized nature of TCM intervention research on atrial fibrillation can be enhanced， ultimately improving the quality of research.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To analyze the mutation characteristics of rpoB gene in rifampicin-resistant Brucella strains. Methods:DNA of 4 rifampicin-resistant Brucella strains (JSY-26, G-9, WSY-13 and AW-3) isolated from Xinjiang Uygur Autonomous Region was selected, rifampicin rpoB gene was amplified by PCR and its nucleotide sequence was sequenced. The rpoB gene sequences of rifampicin-resistant Brucella standard strain (RB51) and sensitive strain (ALT-8) were used as reference, the mutation sites and types of the rpoB gene inside and outside the rifampicin resistance determination region (RRDR) of the 4 rifampicin-resistant Brucella strains were analyzed by Mega 7.0 software. Results:Through sequence alignment, both JSY-26 and WSY-13 strains underwent a single base point mutation at the RRDR 1 576 bp of the rpoB gene, with the base changing from guanine (G) to adenine (A). The G-9 strain underwent a single base point mutation at the RRDR 1 606 bp of the rpoB gene, with the base changing from cytosine (C) to A. The AW-3 strain showed 5 mutations of 3 types outside rpoB gene RRDR at 2 536, 2 537, 2 626, 2 636 and 2 654 bp, namely 3 insertion mutations [thymine (T) insertion once and C insertion twice], 1 deletion mutation (C deletion), and 1 single base point mutation (from G to C mutation).Conclusion:The RRDR mutations in the rpoB gene of the rifampicin-resistant Brucella strains are mainly characterized by single base point mutations, while multiple insertion and deletion mutations occur outside the RRDR.

Objective : To investigate the trends in incidence of malignant tumors in Yongkang City, Zhejiang Province from 2013 to 2019, so as to provide insights into formulation of the malignant tumor control strategy. Methods: Data pertaining to the incidence of malignant tumors from 2013 to 2019 were captured from the Zhejiang Chronic Disease Monitoring Information System. Based on the International Classification of Diseases 10th Revision (ICD-10) and data from the national population census, the constituent ratio, crude incidence and Chinese population-standardized incidence of malignant tumors were estimated, and the trends in incidence of malignant tumors were investigated using annual percent change (APC). Results: The annual mean crude incidence and Chinese population-standardized incidence of malignant tumors were 356.75/105 and 226.97/105, which both appeared an overall tendency towards a rise (APC=5.887% and 4.815%, both P<0.05). The crude incidence of malignant tumors appeared a tendency towards a rise among both men (APC=3.860%, P<0.05) and women (APC=8.534%, P<0.05) from 2013 to 2019, and the Chinese population-standardized incidence of malignant tumors appeared a tendency towards a rise among women (APC=8.392%, P<0.05). The largest increase in the crude incidence of malignant tumors was seen among women at ages of 15 to 44 years (APC=11.599%, P<0.05). In addition, the Chinese population-standardized incidence of lung cancer, colorectal cancer and thyroid cancer all showed a tendency towards a rise among men (all P<0.05), and the Chinese population-standardized incidence of lung cancer and thyroid cancer both appeared a tendency towards a rise among women (both P<0.05). Conclusions The incidence of malignant tumors showed a tendency towards a rise in Yongkang City from 2013 to 2019, and the elderly and young females are high-risk populations for malignant tumors. Lung cancer, thyroid cancer and colorectal cancer are cancers that should be given a high priority.

ObjectiveTo observe the effect of Sanhuang Tangshenkang on the Wnt/β-catenin signaling pathway in the bone tissue of diabetic rats. MethodA high-sugar and high-fat diet was administered for 4 weeks， along with intraperitoneal injection of freshly prepared 2% streptozotocin （pH 4.5） at 30 mg·kg^-1 body weight to induce a diabetes model in rats. The rats with diabetes were randomly divided into model group， low- and high-dose Sanhuang Tangshenkang groups （12.8， 38.4 g·kg^-1）， and Gushukang group （1.8 g·kg^-1） according to the blood glucose level. Rats of the same age were fed on a regular diet and assigned to the control group. After 12 weeks of respective treatments with drugs or physiological saline， the fasting blood glucose （FBG） levels of the rats were measured using an automated biochemical analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS）， bone-specific alkaline phosphatase （BALP）， and tartrate-resistant acid phosphatase （TRAP） levels. Micro-computed tomography （Micro-CT） was used to scan the femurs of rats to observe bone tissue microstructure and measure bone mineral density （BMD）. Hematoxylin-eosin （HE） staining and safranin O/fast green staining were performed to observe pathological changes in the femoral bone tissue. Immunohistochemistry （IHC） and Western blot were used to detect the expression of Wnt3a， low-density lipoprotein receptor-related protein 5 （LRP-5）， and β-catenin proteins. ResultCompared with the control group， the model group showed a significant increase in FBG， FINS， and TRAP levels （P<0.01）， a significant decrease in BALP level （P<0.01）， a significant decrease in BMD （P<0.01）， and disorganized， elongated， and sparse bone trabecular structures with fractures and increased lipid droplets. Additionally， the expression of Wnt3a， LRP-5， and β-catenin proteins decreased （P<0.05， P<0.01）. Compared with the model group， the low- and high-dose Sanhuang Tangshenkang groups showed a reduction in FBG and an increase in BALP （P<0.05）. The low-dose Sanhuang Tangshenkang group also exhibited a decrease in FINS （P<0.05）. All treatment groups showed a significant decrease in TRAP （P<0.01）， varying degrees of improvement in BMD （P<0.05， P<0.01））， increased and denser bone trabeculae with more regular arrangements and reduced lipid droplets， and improved bone microstructure morphology. The average optical density values of Wnt3a， LRP-5， and β-catenin proteins were significantly increased in all drug-treated groups （P<0.05， P<0.01）， and the expression of Wnt3a， LRP-5， and β-catenin proteins was elevated （P<0.05， P<0.01）. ConclusionSanhuang Tangshenkang may regulate the imbalance of the Wnt/β-catenin signaling pathway by increasing the expression of Wnt3a， LRP-5， and β-catenin proteins in bone tissue， which may promote bone formation， reduce bone resorption， and lower blood glucose levels， thereby achieving the effect of preventing and treating diabetic osteoporosis.

Objective:To investigate the epidemic status and molecular characteristics of Borrelia burgdorferi in ticks in Xinjiang Uygur Autonomous Region (referred to as Xinjiang). Methods:From April to June 2020, 312 samples of Ixodes were collected in 6 areas of Yili, Alashankou, Hutubi, Qinghe, Fuhai and Wujiaqu, Xinjiang. Nested PCR and fluorescence quantitative PCR were used to detect Borrelia burgdorferi in ticks. The positive samples by both methods were genotyped and identified by nested PCR products. Results:The positive rates of nested PCR and fluorescence quantitative PCR were 8.97% (28/312) and 11.86% (37/312), respectively. Among them, the fluorescence quantitative PCR positive rate of Qinghe was the highest of 35.29% (12/34), and the positive rate of Fuhai was the lowest of 2.00% (1/50). The positive samples by both methods was 26. Genotyping results showed that 12 samples were highly homologous to Borrelia garinii, 10 copies to Borrelia burgdorferi sensu stricto, and 4 copies to Borrelia afzelii. Conclusions:The positive rate of Borrelia burgdorferi in ticks in Xinjiang is higher, which has confirmed that there are 3 pathogenic Borrelia burgdorferi genotypes in Xinjiang. The dominant genotype is Borrelia garinii, followed by Borrelia burgdorgferi sensu stricto genotype and Borrelia afzelii genotype.

Objective:To investigate the effects of terlipressin (TP) combined with norepinephrine (NE) on liver function and prognosis of patients with septic shock.Methods:From June 2018 to December 2019, 96 patients with septic shock and liver function impairment admitted to the ICU of Tianjin First Central Hospital were selected for prospective study. The patients were divided into control group( n=48) and experiment group( n=48) by randomize number table derived by computer. Based on conventional treatment, NE was used in control group, and the low dose continuous infusion of TP combined with NE was used in experiment group. Serial measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum total bilirubin (TBIL), heart rate and mean arterial pressure (MAP), and blood lactic acid levels were made before the treatment and after the treatment at 24 and 48 hours. The mechanical ventilation time, intensive care unit (ICU) stay, and total length of hospital stay of the two groups were compared, and the 28-day mortality and serious adverse reactions of the two groups was also calculated. Results:The levels of ALT, AST, TBIL, heart rate and blood Lac of the two groups were significantly decreased after the treatment (all P<0.01), and the level of MAP was significantly increased (all P<0.01). Compared with the control group, the levels of 24-hour and 48-hour ALT, AST, TBIL, blood Lac of the experiment group were significantly decreased (all P<0.05), and the 48-hour level of MAP was significantly increased (all P<0.05), but there was no statistically significant difference between the two groups in the levels of 24-hour heart rate and 24-hour MAP (all P>0.05). Besides, there was no statistically significant difference between the two groups in the mechanical ventilation time, ICU stay, total length of hospital stay and the 28-day mortality (all P>0.05). And there were no serious adverse reactions such as avascular necrosis of the fingers and myocardial infraction in the two groups. Conclusions:In the treatment of septic shock, on the basic of adequate fluid resuscitation, continuous intravenous pumping of low-dose TP combined with NE can play a certain protective effect on the live, and the mechanisms of action may be mediated by stabilizing hemodynamics, reducing heart rate, reducing the level of blood Lac and improving liver perfusion, thereby protecting liver function in patients with septic shock.

[摘 要] 目的：探究微小RNA-504（miRNA-504）在胃癌（GC）组织中的表达水平及其对GC细胞生物学行为的调控机制。方法：收集2020年6月至2020年12月期间三亚中心医院外科收治的48例胃癌患者的肿瘤组织及癌旁组织标本，qPCR检测组织中miR-504、肿瘤蛋白53诱导型核蛋白1（tumor protein 53-induced nuclear protein 1，TP53INP1）mRNA的水平，WB法检测TP53INP1水平。体外培养人胃癌细胞BGC-823，分为对照组（正常培养的BGC-823细胞）、miR-504 mimic组、mimic-NC组、miR-504 inhibitor组、inhibitor-NC组、miR-504 inhibitor+si-NC组、miR-504 inhibitor+si-TP53INP1组，qPCR检测细胞中miR-504和TP53INP1 mRNA的表达，MTT法、流式细胞术、划痕实验和Transwell侵袭实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测各组细胞中增殖、迁移和侵袭相关蛋白（Cyclin D1、E-cadherin、MMP-2、MMP-9）以及TP53INP1的表达。双荧光素酶报告基因实验进一步验证miR-504与TP53INP1 mRNA的靶向关系。结果：与癌旁组织相比，胃癌组织中miR-504的表达显著升高（P<0.05），而TP53INP1 mRNA和蛋白表达水平显著降低（P<0.05或P<0.01），miR-504和TP53INP mRNA两者的表达呈负相关（P<0.01）。与对照组相比，miR-504 mimic组BGC-823细胞中miR-504的表达显著升高（P<0.05）、TP53INP1 mRNA和蛋白的表达显著降低（均P<0.05），且细胞增殖率、划痕愈合率、侵袭入Transwell小室下层的细胞数量，Cyclin D1、MMP-2、MMP-9蛋白表达均显著增加，细胞凋亡率和E-cadherin蛋白表达均显著降低（均P<0.05）。转染miR-504 inhibitor能显著下调BGC-823中miR-504的表达、上调TP53INP1 mRNA和蛋白的表达，抑制细胞的增殖、迁移与侵袭能力而促进细胞凋亡（均P<0.05）；而下调TP53INP1的表达可明显减弱miR-504下调对BGC-823细胞增殖、迁移与侵袭的抑制作用（P<0.01）。miR-504高表达能明显抑制野生型TP53INP1质粒的荧光素酶活性（P<0.05）。结论：miR-504在胃癌组织中呈高表达，下调miR-504可抑制胃癌BGC-823细胞的恶性生物学行为而促进其凋亡，其作用机制可能与靶向调控TP53INP1的表达有关。

Objective:To analyze the clinical characteristics, risk factors for critical illness and death of severe adenovirus pneumonia in children, so as to provide clinical evidences for early diagnosis and reliable treatment.Methods:A total of 75 pediatric cases with severe adenovirus pneumonia admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to October 2019 were studied. The clinical features, laboratory and imaging data, therapeutic approaches, efficacy of the treatments and prognosis were investigated retrospectively. Patients were divided into severe group and critical group. Chi square test and Mann-Whitney U rank sum test were used to analyze the data of the two groups. The risk factors for critical illness and death were analyzed by univariate and multivariate Logistic regression. Results:Among the 75 children, there were 52 males and 23 females, aged from 3 months to 8 years, including 30 of severe cases and 45 of critical case. The positive rate of adenovirus antigen in nasopharyngeal swab was 21% (15/72), and the positive rate of serum adenovirus IgM antibody was only 13% (10/75). However, the positive rate of adenovirus nucleic acid in nasopharyngeal swab was 75% (21/28). What is more, the positive rates of metagenomics next generation sequencing (mNGS) in plasma and bronchoalveolar lavage fluid were 92% (33/36) and 96% (54/56), respectively, of which 95% (63/66) were confirmed as adenovirus type 7. Relatively high dose of ribavirin and integrated therapeutic approaches (respiratory support, glucocorticoids, immunoglobulin and organ supportive therapies) were used. The recovery rate was 77% (58/75), the improvement rate was 8% (6/75) and the mortality rate was 15% (11/75). The proportion of children with the duration of fever longer than 3 days after ribavirin treatment in the critical group was significantly higher than that in the severe group(51% (18/35) vs. 8% (2/26), χ 2=12.949, P<0.05). The risk factors for critical illness were younger than 4 years, longer duration of fever before and after admission to PICU, oxygenation index<300 mmHg (1 mm Hg=0.133 kPa), ferritin>1 000 μg/L, lactate dehydrogenase (LDH)>1 500 U/L, 5 lung lobes involvement, pleural effusion and (or) air leakage (all P<0.05). Among them, 5 lung lobes involvement was the independent risk factor for critical illness (adjusted OR=49.641, 95% CI 4.186-588.618, P=0.002). Risk factors for death included longer duration of fever after being admitted to PICU, oxygenation index<100 mmHg, ferritin>2 000 μg/L, interleukin (IL)-6>100 ng/L, LDH>1 500 U/L, pleural effusion and (or) air leakage (all P<0.05). Among them, IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children (adjusted OR=16.094, 95% CI2.059-25.787, P=0.008). Conclusions:The mortality rate of severe pediatric adenovirus pneumonia caused by adenovirus type 7 is high. High positive rates of adenovirus nucleic acid in nasopharyngeal swabs and mNGS in plasma or bronchoalveolar lavage fluid contribute to early diagnosis, and mNGS can also be used for serotyping. Younger children under 4 years of age, persistent fever, extensive pulmonary lesions and significantly increased inflammatory cytokines such as IL-6 are warning indicators for critical illness and poor prognosis. Relatively high dose of ribavirin combined with integrated therapeutic approaches are beneficial for prognosis.

BACKGROUND: Airway stents has been widely used in airway stenosis and fistula, yet clinical date of airway stents in reestablishment a complex airway is insufficient. The aim of this study is to evaluate the efficacy and safety to combine the silicon stent and the metal stent in reestablishment a complex malignant airway. METHODS: Patients with non-operable complex malignant airway stenosis and fistula were recruited in this study. Silicon Y stent combined with covered metal stent (Hybrid stent) were inserted to reestablishment the airway. Clinical outcomes and complications were observed over six months. RESULTS: A total of 23 silicon Y stents and 25 covered metal stents were inserted in 23 patients. Nineteen of 23 (19/23, 82.6%) patients felt a immediately relieving of current symptoms. The mean duration of stents placement in patients was (153.43±9.14) days. The modified British Medical Research Council, Karnofsky Performance Status and Performance Status scale were improved significantly after stenting. A total of 12 patients living with stent at 6 months. Others dead of tumor progression. There were no death or immediate complications related to hybrid stenting implication. CONCLUSIONS Hybrid stenting proved to be useful and was well-tolerated in the management of complex malignant airway stenosis and fistula.