OBJECTIVE To explore the effects of dexmedetomidine （DEX） increasing serpin peptidase inhibitor clade E member 1 （SERPINE1） protein on the malignant biological behavior of thyroid carcinoma （THCA） cells. METHODS THCA cells （KTC-1， TPC-1） were treated with 1， 10 and 100 nmol/L DEX， and their viabilities， clone formation rates， migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected， and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group （0 nmol/L DEX）， DEX at 1， 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells （except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h）， concentration-dependently elevated the rates of clone formation， migration rates （except for 2 types of THCA cells in 1 nmol/L DEX group）， and the number of invasion （P＜0.05）. A total of 287 differently expressed genes （75 up- tongxueyan180@163.com regulated and 212 down-regulated） were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B， Wnt， and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA， and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients （P＜0.05）. Compared with the control group， mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1， 10 and 100 nmol/L DEX groups， while the secretion of this protein in conditioned medium was also significantly increased， all of which showed concentration-dependence （P＜0.05）. After knocking down SERPINE1， the promoting effects of DEX on the proliferation， colony formation， migration and invasion abilities of two types of THCA cells were significantly inhibited （P＜0.05）. CONCLUSIONS DEX can promote the proliferation， migration and invasion of THCA cell， and the above effects may be associated with the expression of increased secretory SERPINE1 protein.

Objective To analyze the clinical characteristics of stiff left atrial syndrome (SLAS) after Mei mini maze procedure for atrial fibrillation (AF), and to explore its risk factors and treatments. Methods We retrospectively analyzed the clinical data of the patients who underwent Mei mini maze procedure in Xinhua Hospital between 2010 and 2020. According to whether SLAS occurred in the early postoperative period, patients were divided into a SLAS group and a non-SLAS group. The basic data, perioperative echocardiogram and laboratory test indexes of the two groups were compared. Results A total of 1 056 patients were collected. There were 672 (63.6%) males with an average age of 63.6±9.3 years, including 489 patients with persistent AF and 567 patients with paroxysmal AF. Fourteen (14/1 056, 1.3%) patients developed SLAS, with an average occurrence time of 2.1±1.1 days after the surgery. The average follow-up time of the whole group was 21.4±7.8 months. Two patients in the SLAS group developed SLAS again after discharge, and the occurrence time was 3 weeks and 4 weeks after the operation, respectively; while no SLAS occurred after discharge in the non-SLAS group. Diabetes and small preoperative left atrial diameter were risk factors for SLAS after surgery. Patients with SLAS had a good prognosis after adequate diuretic therapy. Conclusion The incidence of SLAS after Mei mini maze procedure for AF is low, and it mostly occurs in the early postoperative period. After adequate diuretic treatment, the prognosis is good.

Objective To investigate the molecular typing,virulence,and drug resistance features of bacterial strains in a simultane-ous outbreak of paratyphoid fever A and B,and then provide evidence for the prevention and treatment of the simultaneous transmission of different types of paratyphoid fever.Methods The clinical data of 31 patients confirmed as paratyphoid fever in the Hospital of Xin-jiang Production and Construction Corps from September 2018 to November 2018 were retrospectively analyzed.The isolated strains were performed serotyping and drug sensitivity tests.The molecular typing and the detection of virulence and drug resistance genes were carried out by multiplex PCR,pulsed-field gel electrophoresis(PFGE),and multilocus sequence typing(MLST).Results A total of 32 strains of Salmonella paratyphi were isolated from 31 patients,with 19 strains classified as type A and 13 as type B.The intermedi-ate rates of all strains against ciprofloxacin were 100%.The molecular typing and serotyping results of 11 representative strains were consistent.The PFGE fingerprints of Salmonella paratyphi A and B were also consistent.The MLST of Salmonella paratyphi A was ST85,and that of Salmonella paratyphi B was ST86.All strains carried virulence island SPI1-SPI5 representative genes such as invA,sitC,sseL,sifA,mgtC,siiE,and sopB,and regulatory gene phoP.Salmonella paratyphi A also carried cytolethal distending toxin(CDT)genes with trimeric structure such as cdtB,pltA,and pltB.The virulence plasmid genes such as pefA,prot6E,and spvB were all negative.Conclusion The simultaneous transmission of Salmonella paratyphi A and B has the characteristics of high pathogenicity and poor sensitivity to ciprofloxacin,which should be highly concerned by clinical and laboratory personnel.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective To explore the molecular mechanism of prolonged atrial repolarization in rats with reperfusion atrial arrhythmia.Methods Sixteen Langendorff isolated heart perfusion models made by male SD rats were randomly divided into control group(group C,n = 8)and hypothermic ischemia-reperfusion group(group IR,n = 8).According to the occurrence of atrial arrhythmia after reperfusion,group IR was further subdivided into reperfusion non-atrial arrhythmia subgroup(group N-RAA)and reperfusion atrial arrhythmia subgroup(group R-AA).Group C was perfused with 37℃K-H solution for 120 min.In group IR,the isolated heart was perfused with 37℃K-H solution for 30 min and stopped,and the isolated heart was perfused with 4℃Thomas solution(20 mL/kg)for 60 mins.When the heart stopped for 30 mins,the isolated heart was perfused with a half dose of 4℃Thomas solution(10℃).During cardioplegia,the isolated heart was protected by low temperature Thomas solution(4℃),and then reperfused for 30 mins with 37℃K-H solution.The monophasic action potential(MAP)of the right atrium was recorded at balanced perfusion for 30 mins(T0),balanced perfusion for 105 mins in group C/reperfusion for 15 mins in group IR(T1)and balanced perfusion for 120 mins in group C/reperfusion for 30 min in group IR(T2);The duration of 50%and 90%repolarization of monophasic action potential(MAPD50 and MAPD90)was measured.After electrophysiological monitoring,the expression of Kir2.1 and CaMKⅡ in right atrium was detected by Western blot.Results Compared with T0,MAPD50 and MAPD90 at T1 and T2 were significantly prolonged in group R-AA(P<0.05),and MAPD90 at T1 and T2 in group R-NAA and group R-AA were significantly longer than those in group C(P<0.05).Compared with group R-NAA,MAPD50 and MAPD90 in group R-AA were significantly prolonged at T1 and T2(P<0.05).The results of Western blot showed that the expression of Kir2.1 in group R-NAA and group R-AA was significantly lower than that in group C(P<0.05),and that in group R-AA was significantly lower than that in group R-NAA(P<0.05).The expression of CaMKⅡ in group R-NAA and group R-AA was significantly higher than that in group C(P<0.05),and the expression of CaMKⅡ in group R-AA was significantly higher than that in group R-NAA.Conclusion The prolonged duration of atrial repolarization in rats with hypothermic ischemia-reperfusion atrial arrhythmia may be related to the down-regulation of Kir2.1 expression and the up-regulation of CaMKⅡ expression.

ObjectiveTo explore the effect of low frequency or high frequency repetitive transcranial magnetic stimulation (rTMS) on right Broca's homologue in stroke patients with nonfluent aphasia. MethodsFrom January, 2019 to August, 2022, 80 inpatients in Beijing Bo'ai Hospital were randomly divided into control group (n = 20), sham stimulation group (n = 20), low-frequency (1 Hz) rTMS (LF-rTMS) group (n = 20) and high-frequency (10 Hz) rTMS (HF-rTMS) group (n = 20). All the patients received routine language therapy. LF-rTMS group and HF-rTMS group received ten days of rTMS (1 Hz or 10 Hz), and the sham group received ten days of sham rTMS. The Western Aphasia Battery (WAB) was used to evaluate the language function before, after treatment, and two months after treatment. ResultsBefore treatment, there was no significant difference in the scores of WAB among four groups (P > 0.05). All the scores improved in the four groups immediately after treatment and two months after treatment (P < 0.05). Compared with immediately after treatment, all the scores of WAB improved in LF-rTMS group (P < 0.05), and the scores of recall, name and aphasia quotient (AQ) improved in HF-rTMS group (P < 0.05) two months after treatment. Immediately after treatment, the scores of content and fluency, auditory comprehension and AQ were higher in LF-rTMS group than in HF-rTMS group (P < 0.05). Two months after treatment, the scores of content and fluency were higher in LF-rTMS group than in HF-rTMS group (P < 0.05). ConclusionBoth 1 Hz and 10 Hz rTMS could improve the language function of stroke patients with nonfluent aphasia, especially 1 Hz.

OBJECTIVE: To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. METHODS: A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. CONCLUSIONS Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Sepsis/metabolism* ; Inflammation

Objective:To evaluate the effect of rat cardiac fibroblasts (RCF) on the expression of connexin43 (Cx43) in H9c2 cells during hypothermic hypoxia/reoxygenation.Methods:H9c2 cells cultured in vitro were divided into 4 groups ( n=12 each) using the random number table method: control group (group C), hypothermic hypoxia/reoxygenation group (group HHR), RCF co-culture group (group Co) and RCF co-culture plus hypothermic hypoxia/reoxygenation group (group Co+ HHR). Group C was incubated at 37℃ in 5% CO 2 + 95% air for 5 h. Group HHR was incubated at 4 ℃ in 5% CO 2 + 95% N 2 for 1 h and then at 37 ℃ in 5% CO 2 + 95% air for 4 h. In group Co and group Co+ HHR, H9c2 cells 0.3×10 5 cells/well were inoculated in the lower chamber and RCF 0.6×10 5 cells/well in the the upper chamber of a transwell ? culture dish.Group Co was incubated at 37 ℃ in 5% CO 2 + 95% air for 5 h. Group Co+ HHR was incubated at 4℃ in 95% N 2 + 5% CO 2 for 1 h, and then incubated at 37 ℃ in 5% CO 2 + 95% air for 4 h. The mortality rate of H9c2 cells was measured by trypan blue staining, the expression of Cx43 and extracellular signal-regulated protein kinases 1/2 (ERK1/2) by immunofluorescence, and the expression of Cx43, phosphorylated Cx43, ERK1/2 and phosphorylated ERK1/2 by Western blot. Results:Compared with group C, the mortality rate of H9c2 cells was significantly increased, the expression and phosphorylation of Cx43 were decreased, and the expression and phosphorylation of ERK1/2 were increased in group HHR ( P<0.05), and no significant change was found in the mortality rate of H9c2 cells or expression and phosphorylation of Cx43 and ERK1/2 in group Co ( P>0.05). Compared with group Co, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Compared with group HHR, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Conclusions:RCFs can decrease the expression and activity of Cx43 in H9c2 cells during hypothermic hypoxia/reoxygenation, and the mechanism may be related to the down-regulation of ERK1/2 expression and inhibition of ERK1/2 activity.

Objective:To evaluate the effects of different densities of rat cardiac fibroblasts (RCF) subjected to hypothermic hypoxia-reoxygenation on cardiomyocyte injury and intercellular coupling.Methods:RCF was cultured in vitro and divided into 3 groups ( n=12 each) using a random number table method: RCF density 0.5×10 5 cells/ml group (T 0.5 group), RCF density 1.0×10 5 cells/ml group (T 1.0 group), and RCF density 2.0×10 5 cells/ml group (T 2.0 group). The three groups were placed in an anoxic device, into which 95% N 2 + 5% CO 2 was continuously blown at the speed of 5 L/min for 15 min, and then placed in a 4 ℃ refrigerator for 1 h for low temperature treatment.After completion of culture, cells were placed in a incubator containing 95% air + 5% CO 2 at 37 ℃ for 4 h of reoxygenation.After the end of culture, RCF in three groups were indirectly co-cultured with cardiomyocytes of the same density (1.0×10 5 cells/ml) in a Transwell chamber for 16 h, cardiomyocytes were seeded in the lower chamber of Transwell, and RCF were seeded in the upper chamber of Transwell.After the end of co-culture, cardiomyocytes were collected for determination of the cell viability (by CCK8 method), apoptosis rate (by flow cytometry), expression of connexin 43 (Cx43) mRNA (by real-time fluorescence quantitative polymerase chain reaction), and expression of Cx43 and phosphorylated Cx43 (p-Cx43) (by Western blot). Results:Compared with T 0.5 group, the cell viability, apoptosis rate and expression of Cx43, p-Cx43 and Cx43 mRNA were significantly decreased in T 1.0 and T 2.0 groups ( P<0.01). Compared with T 1.0 group, the cell viability, apoptosis rate and expression of Cx43 and p-Cx43 were significantly decreased ( P<0.01), and no significant change was found in expression of Cx43 mRNA in cardiomyocytes in T 2.0 group ( P>0.05). Conclusions:RCF subjected to hypothermic hypoxia-reoxygenation induces cardiomyocyte injury in a density-dependent manner in a certain range, and the mechanism may be related to down-regulation of the expression of Cx43 and reduction of the activity of Cx43.