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ABSTRACT Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.
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Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.
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ObjectiveTo investigate whether the whole intestinal microbiota transplantation in Alzheimer's disease （AD） model mice has more significant effects on ileum intestinal microenvironment in normal mice under the guidance of the theory of traditional Chinese medicine that "interior-exterior relationship exists between the heart and small intestine". MethodsThe whole intestinal microbiota of fourteen 6-month-old specific pathogen free male APP/PS1 double-transgenic AD model mice was transplanted into the gut of six normal C57BL/6J mice of the same age and background treated with mixed antibiotics for 14 days. Then， after 14 days of normal rearing， the mice were sacrificed. Next， the pathological changes in the ileum and colon were observed， and the composition and diversity of the ileal and colonic microbiota was analyzed by sequencing. ResultsAfter the whole intestinal microbiota of AD mice was transplanted into normal mice， pathological analysis showed that only the ileum tissue had mucosal damage and crypt gland epithelial cell degeneration， necrosis， and shedding. Moreover， the microbiota analysis found that only the number of genera （P<0.01）， Chao1 index （P<0.01） and Simpson index of ileal microbiota in normal mice decreased （P<0.01）， and the composition of intestinal microbiota was quite similar to that of AD model mice. ConclusionUnder the effect of whole gut microbiota transplantation in AD mice， the diversity and composition of ileal microbiota change more than that of colonic microbiota in normal mice， and at the same time， it results in pathological damage to the ileal mucosa， indicating that the ileal microenvironment may be more closely related to the occurrence and development of AD， which is highly consistent with the traditional Chinese medicine theory of "interior-exterior relationship between heart and small intestine".
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This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.
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Animals , Rats , Rats, Sprague-Dawley , NF-kappa B , NF-KappaB Inhibitor alpha , NLR Family, Pyrin Domain-Containing 3 Protein , Galactose , Interleukin-6 , Neuroinflammatory Diseases , Toll-Like Receptor 4 , Tumor Necrosis Factor-alphaالملخص
Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342-centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference (P=0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients (P<0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues (t=1.56, P=0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 (t-values of -12.17, -23.26 and -388.57, respectively; all P<0.001). Knockdown of LINC00342 by transfecting si-LINC00342-1 and si-LINC00342-2 inhibited HNSCC cell proliferation (t-values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation (t-values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration (t-values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities (t-values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 (t-values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P-values<0.05). The LINC00342-centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342-regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.
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Humans , Female , Male , Squamous Cell Carcinoma of Head and Neck/genetics , RNA, Long Noncoding/genetics , Clinical Relevance , Epithelial Cells , Head and Neck Neoplasms/geneticsالملخص
Objective:To observe the influence of NOD-like receptor thermal protein domain associated protein 6 (NLRP6) on hepatic ischemia-reperfusion injury (IRI), and elucidate the related mechanism.Methods:Thirty C57BL/6 mice with body weight of (18.80±1.99) g, were divided randomly into 5 groups, with 6 mice in each group: the mice that experienced only exploratory laparotomy were Sham group; that only underwent an operation to establish a hepatic IRI model were IRI group; that were treated with tail intravenous injection of clodronate (Clo) liposomes before the establishment of hepatic IRI model were Clo group; that received tail intravenous injection of clodronate liposomes and transfusion of bone marrow derived macrophages (BMDM) before the operation were Clo+ BMDM group; that received preoperative tail intravenous injection of clodronate liposomes and transfusion of BMDM with NLRP6 knockdown were Clo+ NLRP6-knockdown group. Real time quantitative polymerase chain reaction analysis (RT-PCR) and Western blot were performed to analyze the expressions of pyroptosis related proteins and factors. Simulate a hypoxia/reoxygenation (H/R) model in vitro, and set up experimental groups: lipopolysaccharide (LPS) + adenosine triphosphate (ATP), LPS+ ATP+ NLRP6-knockdown, H/R, and H/R+ NLRP6-knockdown. The changes of expressions of pyroptosis related proteins and factors were detected by RT-PCR and Western blot. Expression of NF-κB in vivo and in vitro was measured.Results:Compared with those in Sham group, protein expressions of NLRP6, NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 were remarkably increased in IRI group, but the levels of these proteins were dramatically decreased in Clo group with the exhaustion of macrophages in comparison with in IRI group, which were significantly different statistically (all P<0.05). The levels of these proteins were enhanced again in Clo+ BMDM group with the reconstruction of macrophages in contrast to those in Clo group, while the enhancements were more obvious in Clo+ NLRP6-knockdown group comparing to those in Clo+ BMDM group, with significant differences (all P<0.05). In vitro, pyroptosis rate for LPS+ ATP group was (16.39±1.06)%, which was lower than (27.34±2.79)% for LPS+ ATP+ NLRP6-knockdown group, with a statistical significance ( P<0.05). Meanwhile, pyroptosis rate for H/R group was (20.59±5.66)%, also much more reduced than (37.76±2.00)% for H/R+ NLRP6-knockdown group ( P<0.05). Expressions of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 and NF-κB p65 in LPS+ ATP+ NLRP6-knockdown group were more elevated than in LPS+ ATP group, and these indices were also more enhanced in H/R+ NLRP6-knockdown group than which in H/R group. Compared to the Sham group, expression of NF-κB p65 significantly increased in IRI group, which was reversed in Clo group, but enhanced again in Clo+ BMDM group and reached a peak in Clo+ NLRP6-knockdown group. Conclusions:Macrophage plays a critical role in immune response to hepatic IRI, wherein NLRP6 functions specifically. NLRP6 acts to suppress inflammation during hepatic IRI through regulating macrophage pyroptosis via inhibiting NF-κB.
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Objective@#To investigate the epidemiological characteristics of human brucellosis in Jiaxing City from 2010 to 2021, so as to provide insights into the development of the brucellosis control strategy.@*Methods@#The epidemiological and clinical data of brucellosis patients and epidemiological data of brucellosis outbreaks in Jiaxing City from 2010 to 2021 were collected from Chinese Disease Control and Prevention Information System, and the epidemiological features and outbreaks of brucellosis were analyzed descriptively.@*Results@#Totally 160 brucellosis patients were reported in Jiaxing City from 2010 to 2021, and the incidence of brucellosis appeared a tendency towards a rise (χ2trend=28.564, P=0.002), with annual mean incidence of 0.29/105. No deaths due to brucellosis occurred in Jiaxing City from 2010 to 2021. Brucellosis cases were reported each month, which were concentrated in the first and second quarters, and the greatest number was seen in May (27 cases, 16.88%). The brucellosis cases were predominantly reported in Tongxiang City (114 cases, 71.25%), and 75.00% were male (120 cases) and 70.63% were occupational populations (113 cases). The patients had a median (interquartile range) age of 57 (12) years at onset, and the median duration (interquartile range) from onset to definitive diagnosis was 18 (28) days. The clinical manifestations mainly included fever and weakness, and a total of 18 Brucella melitensis isolates and one B. bovis isolate were cultured.@*Conclusions@#The incidence of brucellosis was rising in Jiaxing City from 2010 to 2021. The brucellosis patients were predominantly reported in Tongxiang City in the first and second quarters, and young, middle-aged men and occupational populations were at a high risk of brucellosis.
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Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.
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Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.
الموضوعات
Humans , Female , Middle Aged , Aged , Male , Mitral Valve Insufficiency/etiology , Retrospective Studies , East Asian People , Heart Valve Prosthesis Implantation , Treatment Outcome , China , Heart Failure/etiology , Cardiac Catheterizationالملخص
Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.
الموضوعات
Humans , Female , Middle Aged , Aged , Male , Mitral Valve Insufficiency/etiology , Retrospective Studies , East Asian People , Heart Valve Prosthesis Implantation , Treatment Outcome , China , Heart Failure/etiology , Cardiac Catheterizationالملخص
This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.
الموضوعات
Humans , Child , Drugs, Chinese Herbal/therapeutic use , Nonprescription Drugs/therapeutic use , Technology Assessment, Biomedical , Tiapride Hydrochloride/therapeutic use , Tics/drug therapy , Tic Disorders/drug therapy , Medicine, Chinese Traditionalالملخص
OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
الموضوعات
Child , Humans , Infant , Child, Preschool , Adolescent , Antineoplastic Agents, Phytogenic/adverse effects , Cohort Studies , Peripheral Nervous System Diseases/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Vincristine/adverse effectsالملخص
Objective:To investigate the expression of long non-coding RNA 00665 (LINC00665) in hepatocellular carcinoma (HCC) and its regulatory effect on angiogenesis of hepatocellular carcinoma cells and its potential molecular mechanism.Methods:HCC tissues and corresponding paracancerous tissues of 100 patients with HCC in the First Affiliated Hospital of Nanjing Medical University from May 2016 to April 2017 were collected, and the survival prognosis was compared. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00665 in HCC tissues and cells. The effect of LINC00665 overexpressed Hep-3B cells on the angiogenesis of human umbilical vein endothelial cells (HUVEC) was examined by tube formation assay and chick chorioallantoic membrane assay. Bioinformatics database predicted the downstream microRNA (miRNA) and target genes of LINC00665, and the relationship between LINC00665, miR-126-5p and vascular endothelial growth factor A (VEGFA) was verified by RT-qPCR, Western blot and dual-luciferase reporter gene assay.Results:The expression level of LINC00665 in HCC (6.5±2.8) was significantly higher than that in paracancer tissues (4.8±3.1), the difference was statistically significant ( t=4.12, P<0.001). According to the median LINC00665 expression level of 100 patients with HCC, the cumulative survival rate of LINC00665 high expression group ( n=50) was lower than that of LINC00665 low expression group ( n=50), and the difference was statistically significant (χ 2=3.79, P=0.008). After co-culture with LINC00665 group (Hep-3B cells overexpressing LINC00665), the length of HUVEC cell tubule formation was (596.0±22.3) μm, and the number of HUVEC cell tubules was (36.3±4.5), which were both higher than NC group with the tubule formation length (127.0±13.5) μm and the number (9.3±1.5) of HUVEC cells co-cultured with Hep-3B cells of control group, and the differences were statistically significant ( t=31.15, 9.82, P<0.001, P=0.001). The chick chorioallantoic membrane assay results were similar to tube formation assay. Western blot detected that the relative expression of VEGFA in LINC00665 group was higher than that in NC group, the difference was statistically significant ( t=7.15, P<0.001). StarBase and DIANA database were used to predict and screen LINC00665 downstream miR-126-5p. StarBase database was used to predict the binding sites of LINC00665/miR-126-5p/VEGFA axis. In dual-luciferase reporter gene assay, the fluorescence intensity of LINC00665 and VEGFA vector co-transfected with miR-126-5p mimics decreased. Conclusion:LINC00665 is highly expressed in HCC and is associated with poor prognosis in patients with HCC. LINC00665 promotes angiogenesis of HCC by regulating the miR-126-5p/VEGFA axis.
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Objective:To investigate the molecular epidemiological characteristics of HIV-1 infection among men who have sex with men (MSM) in Jiaxing city, and provide methods and ideas for the prevention and control of HIV-1 infection.Methods:This study retrospectively collected the blood samples from all newly reported cases of HIV-1 infection among MSM without antiviral treatment from 2020 to 2022. HIV-1 pol genes in the blood samples were amplified and sequenced. MEGA v6.0 software was used to analyze nucleic acid sequences. A phylogenetic tree was constructed to analyze HIV-1 subtypes. The calibrated population resistance program (CPR) was used to detect drug-resistant mutations. After calculating the genetic distance between gene sequences, molecular transmission networks were constructed using Cytoscape v3.6.0 software. Results:A total of nine genetic subtypes were identified, with CRF07_BC (43.3%) and CRF01_AE (36.9%) accounting for the most. The recombinant forms that were not clustered with the reference subtype accounted for 5.0%. Drug-resistant mutations were identified in 21 cases (7.0%), and the mutation rates among strains of CRF07_BC and CRF01_AE subtypes were 8.2% and 7.8%, respectively. The detection rates of drug-resistant mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors were 1.7%, 0.7% and 4.7%, respectively. The optimal genetic distance threshold of the molecular network was 0.018. At this genetic distance, the molecular network access rate was 43.3%, and 38 molecular clusters (ranging from 2 to 26 nodes per cluster) were included. Cases with ≥6 homosexual partners and a degree value of ≥4 were more likely to access the active molecular cluster. The population of high-risk transmission cases with TNS>0.75 were mainly nonlocal residents and commercial service providers. The recombinant forms showed high similarity in sequences with the strains from other provinces.Conclusions:The distribution of HIV-1 subtypes in MSM in Jiaxing city was complex. Given the increasing detection rate of recombinant forms, the high transmission rate of drug-resistant mutations, and the active molecular clusters and high-risk transmission clusters mainly detected in nonlocal residents and commercial service providers, strengthened surveillance and intervention are needed.
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Adhering to Chinese culture and philosophy, the development of traditional Chinese medicine(TCM) should be cooperative and open. TCM should learn from the achievements of ancient and modern scientific and technological civilization in human history and promote cultural exchange. TCM advocates unity, harmony, and interaction, and keeps going in a new information and digital era with Big Science and Extensive Health. The disciplinary development of TCM should embrace inheritance and innovation, and explore the scientific research and transformation of clinical experience. The dual attributes of science and humanity of TCM should be followed. In terms of education, "reading classics, acquiring clinical experience, and consulting experienced tutors" cannot be ignored. Underpinned by Xiang-thinking, TCM development should highlight the originality and learn from the failures of excessive westernization in the past with an inclusive attitude to forge through disciplines to the leading position.
الموضوعات
Humans , Medicine, Chinese Traditionalالملخص
@#Objective To assess the occupational health risk of noise in a plastic products enterprise and determine the key risk Methods - points. The workplace of a plastic products enterprise and its 388 noise exposed workers were selected as the ， research subjects using a convenient sampling method. The noise intensity in the workplace of the enterprise was measured and - GBZ/T 229.4-2012 the individual noise exposure level and pure tone hearing test were carried out in the noise exposed workers. Classification of Occupational Hazards at Workplaces--Part 4： Occupational Exposure to Noise（ GBZ/T hereinafter referred to as 229.4-2012） - was used to evaluate the hazardous degree of noise in different posts. The risk of high frequency hearing loss （ ） - （ ） - ， ， HFHL and occupational noise induced deafness ONID in noise exposed workers in different posts at 45.0 50.0 55.0 and WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard（ 60.0 years of age were predicted using hereinafter WS/T 754-2016）Results referred to as . The noise in the workplace of this plastic product enterprise was found to exceed the - occupational exposure limits with the rate of 46.6%. The maximum level of normalization of equivalent continuous A weighted - （ ） sound pressure level to a nominal 40 h working week of exposure to noise in workers of six posts was 84.0 93.0 dB A . - ， ， ， According to GBZ/T 229.4 2012 the noise hazards of the posts including extrusion premixing unloading and utility - ， maintenance were mild or moderate except for the film and packaging posts. According to WS/T 754 2016 the risks of HFHL in ， ， the film and packaging operators at age ≥50.0 years old were at acceptable risk and the risks of HFHL in operators of extrusion ， ， premixing unloading and utility maintenance at age ≥45.0 years old were at moderate risk or high risk. The risks of ONID for ， the film packaging and utility maintenance operators at age ≥55.0 years old were at acceptable risk or moderate risk. The risksof ONID for extrusion premixing and unloading operators at age ≥50.0 years old were at high risk. Extrusion operators with （ ） exposure to toluene below the occupational exposure limit had a higher risk of HFHL high risk than unloading operators （ ） Conclusion moderate risk at age 45.0 years with the same noise intensity. The noise exposure intensity is high in the ， workplace of the plastic product enterprise. The workers in posts of extrusion premixing and unloading are at high risk levels of HFHL and ONID.
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ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease （AD） under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 （Aβ1-42）. The rats were then randomly divided into the blank group， sham-operated group， model group， low-， medium-， and high-dose （5.6， 11.2，22.4 g·kg-1·d-1） Qishengwan groups， and donepezil （0.46 mg·kg-1·d-1） group. After medication for 28 successive days， the spatial memory ability of rats was observed in water maze test， and the levels of Aβ1-42， nuclear transcription factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in the hippocampus were analyzed by enzyme-linked immunosorbent assay （ELISA）. Additionally， the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group， the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings （P<0.05， P<0.01） and elevated Aβ1-42 content in the hippocampus （P<0.01） and central inflammatory factors NF-κB， TNF-α， and IL-6 （P<0.05， P<0.01）. Compared with the model group， Qishengwan at each dose significantly alleviated the impaired spatial memory function （P<0.05， P<0.01）， improved the deposition of Aβ1-42 in the hippocampus of rats （P<0.05， P<0.01）， and reduced the expression of central nervous system inflammatory factors （P<0.05， P<0.01）， thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased （P<0.01）， while that of Escherichia-Shigella was reduced （P<0.05， P<0.01）. Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats， which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae， the attenuation of the central neuroinflammatory response， and the reduction of central Aβ1-42 deposition.
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The present study explored the effect and mechanism of repeatedly steamed and sundried Rehmanniae Radix Praeparata(RRP) in delaying brain aging in ovariectomized mice. After ovariectomy, the mice were randomly divided into a model group, an estradiol valerate group(0.3 mg·kg~(-1)), and low-(1.0 g·kg~(-1)), medium-(2.0 g·kg~(-1)), and high-dose(4.0 g·kg~(-1)) RRP groups, and a sham operation group was also set up, with 15 mice in each group. One week after the operation, intragastric administration was carried out for 15 consecutive weeks. The step-down test and Morris water maze test were used to detect the behavioral changes of mice. HE staining and Nissl staining were used to observe the morphological changes of mouse brain tissues. Immunohistochemistry was used to detect the expression of Aβ and ER_β in mouse brain tissues. The serum estrogen levels and cholinesterase and cholinesterase transferase levels in brain tissues of mice were detected by assay kits. The extracted hippocampal protein was detected by the Nano-ESI-LC-MS system, identified by the Protein Discovery, and analyzed quantitatively and qualitatively by the SIEVE. The PANTHER Classification System was used for GO analysis and KEGG pathway enrichment analysis of the differential proteins. Compared with the sham operation group, the model group showed decreased learning and memory ability, shortened step-down latency(P<0.05), prolonged escape latency(P<0.05), reduced platform crossings and residence time in the target quadrant, scattered nerve cells in the hippocampus with enlarged intercellular space, increased expression of Aβ-positive cells(P<0.05), declining expression of ER_β-positive cells and estrogen level(P<0.05), and weakened cholinergic function(P<0.05). Compared with the model group, the RRP groups showed improved learning and memory ability, prolonged step-down latency(P<0.05), increased estrogen level(P<0.05), neatly arranged nerve cells in the hippocampus with complete morphology, declining Aβ-positive cells, and elevated expression of ER_β-positive cells. A total of 146 differential proteins were screened out by proteomics, and KEGG pathway enrichment yielded 75 signaling pathways. The number of proteins involved in the dopaminergic synapse signaling pathway was the largest, with 13 proteins involved. In summary, RRP can delay brain aging presumedly by increasing the level of estrogen, mediating the dopaminergic synapse signaling pathway, and improving cholinergic function.
الموضوعات
Animals , Female , Mice , Aging , Hippocampus/metabolism , Learning , Plant Extracts , Proteomics , Rehmanniaالملخص
Objective:To explore the correlation between the efficacy of <italic>Usnea diffracta</italic> in treating atherosclerosis （AS） and the altered microbial flora in rat ileum based on the interior-exterior relationship between heart and small intestine in traditional Chinese medicine （TCM）. Method:Forty-eight SD rats were randomized into a normal group （<italic>n</italic>=8） and a modeling group （<italic>n</italic>=40）. The AS model was established with high-fat diet combined with intraperitoneal injection of vitamin D<sub>3</sub>. The successfully modeled rats were further randomly divided into the model group， positive control （simvastatin， 4 mg·kg<sup>-1</sup>） group， and low- （0.7 g·kg<sup>-1</sup>）， medium- （1.4 g·kg<sup>-1</sup>）， and high-dose （2.8 g·kg<sup>-1</sup>） <italic>U. diffracta</italic> ethanol extract groups， with eight rats in each group. After four weeks of intervention， the blood， aorta， ileum， and ileum content of rats in each group were collected. The levels of serum lipopolysaccharide （LPS）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） and interleukin 6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）， and the pathological changes in rat thoracic aorta was detected by hematoxylin-eosin （HE） staining. Western blot was conducted to determine the protein expression levels of tight junction protein zonula occluden （ZO-1） and Occludin in rat ileum， and the high-throughput 16S rRNA sequencing technology was employed to detect changes in microbial diversity and abundance in rat ileum of each group. Result:Compared with the normal group， the model group exhibited obvious aortic plaque deposition， increased LPS， TNF-<italic>α</italic>， and IL-6 levels （<italic>P</italic><0.01）， but decreased ZO-1 and Occludin protein expression （<italic>P</italic><0.01）. The comparison with the model group revealed that <italic>U. diffracta</italic> significantly ameliorated the aortic plaque deposition of model rats， lowered serum LPS， TNF-<italic>α</italic>， and IL-6 levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， and up-regulated ZO-1 and Occludin protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01）. The abundance of Proteobacteria and Bacteroidetes in the model group changed significantly in contrast to that in the normal group， and the Bacteroidetes/Firmicutes（B/F） value declined （<italic>P</italic><0.05）. Alpha and Beta diversity analysis indicated higher total number of intestinal flora species in the model group， but lower richness and uneven distribution （<italic>P</italic><0.05， <italic>P</italic><0.01）， with a large number of pathogenic bacteria enriched. The ethanol extract of <italic>U. diffracta</italic> significantly increased the B/F value， corrected the structural disorder of microbial flora in ileum， reduced pathogenic bacteria， and increased the relative abundance of probiotics. Conclusion:<italic>U. diffracta</italic> exerts the therapeutic effect against AS possibly by improving the intestinal microbial communities， strengthening the intestinal mucosal barrier function， and reducing the serum LPS and inflammatory factors.
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Objective:To construct the molecular transmission network of human immunodeficiency virus type 1 (HIV-1) epidemic strains in northern Zhejiang Province (Jiaxing City and Huzhou City) and to explore the HIV-1 transmission characteristics in this region.Methods:A total of 371 newly diagnosed human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Jiaxing City and Huzhou City in 2017 were included as study subjects, and the blood samples were collected and the basic demographic and epidemiological information were obtained. RNA in plasma was extracted, and the pol region gene sequence was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (PCR) to construct phylogenetic tree for identifying subtypes. The pairwise genetic distances were calculated, and the optimal threshold of genetic distance was selected, and finally the molecular transmission network was constructed. Chi-square test was used for statistical analysis. Results:The pol region gene sequences of 336 samples were successfully obtained, and 11 subtypes were detected, mainly including circulating recombinant form (CRF)07_BC (40.8%, 137/336) and CRF01_AE (31.2%, 105/336). Based on the 1.0% genetic distance threshold, the molecular transmission network of HIV-1 was plotted. A total of 38 transmission clusters (cluster sizes ranging from two to 28) including 119 patients were found, with males predominantly (82.4%, 98/119) and most of the patients aged over 40 (include 40) years old (52.9%, 63/119), mainly infected with CRF07_BC subtype (57.1%, 68/119) and CRF01_AE (24.4%, 29/119). The clustering rate of CRF07_BC (49.6%, 68/137) was significantly higher than that of CRF01_AE (27.6%, 29/105), the difference was statistically significant ( χ2=5.27, P=0.022). Two large clusters C1 (28 cases) and C2 (11 cases) were identified, the majority of which were men who have sex with men (17 cases and seven cases, respectively). High-risk cases generally sought sexual partners in local or nearby cities through mobile phone dating software, of which the infected sequences mostly had high homology with other economic developed regions (Guangdong Province, Beijing City and Hangzhou City, etc.). Conclusions:The HIV-1 subtypes are diverse in Jiaxing City and Huzhou City, mainly CRF07_BC and CRF01_AE. The HIV-1 transmission networks are complex, among which high-risk cases may be the key factor leading to the HIV-1 epidemic in the region. Therefore, it is urgent to deepen the transmission network monitoring and formulate timely precise intervention and prevention strategies.