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AIM:To investigate the therapeutic effect of mitochondrial fission inhibitor-1(Mdivi-1)on experi-mental autoimmune encephalomyelitis(EAE)in mice,and to explore its mechanism.METHODS:The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55(MOG35-55)were randomly divided into DMSO model group and Mdivi-1 intervention group.All mice were sacrificed on the 28th day after the first immunization.The demyelination was analyzed by Luxol fast blue staining.The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining,TUNEL staining and the in vitro experiment with MO3.13 oligodendrocytes treated with staurosporine.The mitochondrial depolarization was detected by JC-1 staining,the cell injury was checked by LDH leakage,and the viability of MO3.13 oligodendrocytes was determined by MTT assay.RESULTS:Compared with DMSO model group,the demyelinating injury was alleviated and the proportion of apoptotic CC1+ oligodendrocytes in Mdivi-1 group was decreased.The cleaved caspase-3,caspase-9,cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated.The in vitro MO3.13 cell experiments suggested that Mdivi-1 inhibited MO3.13 cell mitochondrial depolarization,attenuated the cell damage and increased the cell viability.CONCLUSION:Mdivi-1 pro-tects against the myelin injury in EAE mice,which may be related to the suppression of oligodendrocyte apoptosis.
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BackgroundThe incidence of mental disorders is steadily increasing. However, antipsychotic medications, commonly used in treatment, can lead to drug-induced amenorrhea in female patients. This side effect significantly reduces medication adherence and increases the risk of disease recurrence. Therefore, addressing drug-induced amenorrhea in female patients has become an urgent problem requiring effective solutions. ObjectiveTo explore the efficacy and safety of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea, so as to provide guidance for the treatment of this condition using traditional Chinese medicine compound. MethodsOn September 4, 2022, a computerized search was conducted on across multiple databases, including China National Knowledge Infrastructure, VIP Database, Wanfang Database, China Biomedical Literature Database, PubMed, Cochrane Library and Embase, and randomized controlled trials (RCT) of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea were collected. The quality of the included literature was assessed using Cochrane 5.3 bias risk assessment tool. Meta-analysis was performed to assess the total effective rate, cure rate, incidence of adverse reactions and recurrence rate using RevMan 5.3. ResultsUltimately, 22 RCT involving 1 879 patients were included. Meta-analysis results showed that the total effective rate (RR=1.29, 95% CI: 1.16~1.44) and cure rate (RR=1.62, 95% CI: 1.45~1.80) of traditional Chinese medicine compound or its combination with western medicine in treating antipsychotic-induced amenorrhea were significantly higher compared to western medicine alone. Moreover, the incidence of adverse reactions (RR=0.56, 95% CI: 0.41~0.76) and recurrence rate (RR=0.16, 95% CI: 0.06~0.42) were significantly lower than those of western medicine alone. ConclusionTraditional Chinese medicine compound may offer benefits in ameliorating antipsychotic-induced amenorrhea and its safety is better than simple western medicine treatment.
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Objective@#To establish the norm of the Physical Activity afterschool Questionnaire for Preschooler(P-PAQ) in urban areas of China, so as to provide a basis for graded guidance from the family perspective and to improve children s physical activity levels.@*Methods@#From October 2020 to January 2021, 6 267 children aged 3-6 years old were recruited from 40 kindergartens in eight cities across six major administrative regions by stratified cluster sampling, and the P-PAQ initially developed by the researchers of this study were completed by the primary caregivers. The questionnaire was administered to collect data relating to the amount of physical activity undertaken by the preschoolers, and the norm was determined by quartiles. Data relating to parental concepts of sports and parental behavior were assessed by calculating mean scores in order to establish the norm.@*Results@#Among preschoolers in urban areas, the M(P 25 ,P 75 ) of total physical activity time (min/day), moderate-to-vigorous physical activity time (min/day), outdoor time (min/day) and screen time (min/day) on school days outside kindergarten and on weekends were 84 (54,120), 22 (8,40), 12 (0,24) and 18 (6,30), and 170 (115,240), 60 (30,95), 90 (35,120) and 30 (20,60), respectively. When the score of parents sports concept and behavior (total score of 40) were≥34, 29-<34, 24-<29, <24, it was defined as four levels about above medium, medium, lower medium and lower, respectively. And for two dimensions,when the score of parental sports concept were ≥19, 17-<19, 15-<17, <15,and the score of parental behaviors were ≥16, 12-<16, 8-<12, <8, it was defined as four levels about upper medium, medium, lower medium and lower, respectively.@*Conclusion@#The norm of extracurricular activities among preschool children in Chinese cities has good representativeness and appropriate threshold values, which could provide a valuable reference for early assessment, as well as guidance in relation to out-of-school physical activity behaviors among children aged 3-6 years old.
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Objective:To investigate the efficacy and safety of sivelestat sodium in patients with sepsis.Methods:The clinical data of 141 adult patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to January 1, 2022 were retrospectively analyzed. The patients were divided into the sivelestat sodium group ( n = 70) and the control group ( n = 71) according to whether they received sivelestat sodium or not. The efficacy indexes included oxygenation index, procalcitonin (PCT), C-reactive protein (CRP), white blood count (WBC), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) before and after 7 days of treatment, as well as ventilator supporting time, the length of ICU stay, the length of hospital stay and ICU mortality. The safety indicators included platelet count (PLT) and liver and kidney function. Results:There were no significant differences in age, gender, underlying diseases, infection site, basic drugs, etiology, oxygenation index, biochemical indexes, SOFA and APACHE Ⅱ scores between the two groups. Compared with the control group, the oxygenation index in 7 days was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 233.5 (181.0, 278.0) vs. 202.0 (153.0, 243.0), P < 0.01], the levels of PCT, CRP, alanine aminotransferase (ALT) and APACHE Ⅱ score were significantly decreased in the sivelestat sodium group [PCT (μg/L): 0.87 (0.41, 1.61) vs. 1.53 (0.56, 5.33), CRP (mg/L): 64.12 (19.61, 150.86) vs. 107.20 (50.30, 173.00), ALT (U/L): 25.0 (15.0, 43.0) vs. 31.0 (20.0, 65.0), APACHE Ⅱ: 14 (11, 18) vs. 16 (13, 21), all P < 0.05]. However, there were no significant differences in SOFA, WBC, serum creatinine (SCr), PLT, total bilirubin (TBil), aspartate aminotransferase (AST) in 7 days between the sivelestat sodium group and the control group [SOFA: 6.5 (5.0, 10.0) vs. 7.0 (5.0, 10.0), WBC (×10 9/L): 10.5 (8.2, 14.7) vs. 10.5 (7.2, 15.2), SCr (μmol/L): 76.0 (50.0, 124.1) vs. 84.0 (59.0, 129.0), PLT (×10 9/L): 127.5 (59.8, 212.3) vs. 121.0 (55.0, 211.0), TBil (μmol/L): 16.8 (10.0, 32.1) vs. 16.6 (8.4, 26.9), AST (U/L): 31.5 (22.0, 62.3) vs. 37.0 (24.0, 63.0), all P > 0.05]. The ventilator supporting time and the length of ICU stay in the sivelestat sodium group were significantly shorter than those in control group [ventilator supporting time (hours): 147.50 (86.83, 220.00) vs. 182.00 (100.00, 360.00), the length of ICU stay (days): 12.5 (9.0, 18.3) vs. 16.0 (11.0, 23.0), both P < 0.05]. However, there were no significant differences in the length of hospital stay and ICU mortality between the sivelestat sodium group and the control group [the length of hospital stay (days): 20.0 (11.0, 27.3) vs. 13.0 (11.0, 21.0), ICU mortality: 17.1% (12/70) vs. 14.1% (10/71), both P > 0.05]. Conclusions:Sivelestat sodium is safe and effective in patients with sepsis. It can improve the oxygenation index and APACHE Ⅱ score, reduce the levels of PCT and CRP, shorten ventilator supporting time and the length of ICU stay. No adverse reactions such as liver and kidney function injury and platelet abnormality are observed.
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Objective:To evaluate the autogenous arteriovenous fistula(AVF) insufficiency by ultrasound monitoring of brachial artery resistance index(RI).Methods:The brachial artery RI and blood flow volume(FV) data of 828 patients who underwent color-Doppler ultrasound detection after AVF in the General Hospital of Western Theater Command from January 2019 to June 2021 were retrospectively analyzed. The patients were grouped according to the adequacy of clinical dialysis, including 668 patients in the group with normal AVF function and 160 patients in the group with insufficient AVF function. The general information and ultrasonic measurement parameters were compared between the two groups. The correlation between brachial artery FV and RI was analyzed. The evaluation of brachial artery flow RI for AVF insufficiency was analyzed by ROC curve.Results:There were statistically significant differences between the two groups in brachial artery RI and FV(both P<0.001). The results of Pearson correlation analysis showed that brachial artery FV was negatively correlated to RI ( r=-0.657, P<0.001). The area under ROC curve for assessing AVF function by brachial artery RI was 0.970, with 95% CI was 0.955-0.986, the optimal cut-off value was 0.665, and the sensitivity and specificity were 0.888 and 0.955, respectively. Conclusions:Brachial artery RI in patients with AVF insufficiency is significantly higher than that in patients with normal AVF function. The optimal cutoff value of brachial artery RI can be used as an evaluation parameter for rapid screening of AVF function.
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ObjectiveTo analyze the epidemiological characteristics and the vaccination status of the cases in Jing’an District from 2017 to 2019, so as to provide reference basis for the strategy of prevention and control of varicella epidemic. MethodsDescriptive epidemiological methods were used to analyze the epidemiological characteristics of varicella in Jing’an District. The differences between the vaccinated group and the unvaccinated group were compared by statistical methods. ResultsA total of 2 508 cases of varicella were reported with an average annual incidence of 78.7/105 from 2017 to 2019. There was no significant difference in the incidence among the three years(χ2=5.535,P=0.063). There were 1 308 males and 1 200 females, and sex ratio was 1.1∶1. The highest incidence occurred in the age group from 5 to 9 years old (562 cases, 479.3/105). Two annual peaks occured in May and November. The incidence in the aged 18 and below decreased year by year. There was significant difference in the proportion among the three years(χ2=78.129, P<0.001). The median interval from vaccination to onset was 5 years among the vaccinated cases. There was significant difference in the cases who received two doses of vaccine in three years(χ2=90.902, P<0.001). ConclusionWe should strengthen the monitoring system and pay more attention to the epidemiological characteristics of varicella. The protective efficacy of two-doses vaccine needs to be systematically evaluated.
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Porcine epidemic diarrhea (PED) is a highly contagious disease that causes high mortality in suckling piglets. Although several licensed inactivated and live attenuated vaccines were widely used, the infection rate remains high due to unsatisfactory protective efficacy. In this study, mRNA vaccine candidates against PED were prepared, and their immunogenicity was evaluated in mice and pregnant sows. The mRNA PED vaccine based on heterodimer of viral receptor binding region (RBD) showed good immunogenicity. It elicited robust humoral and cellular immune responses in mice, and the neutralizing antibody titer reached 1:300 after a single vaccination. Furthermore, it induced neutralizing antibody level similar to that of the inactivated vaccine in pregnant sows. This study developed a new design of PED vaccine based on the mRNA-RBD strategy and demonstrated the potential for clinical application.
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Gravidez , Animais , Feminino , Camundongos , Suínos , Anticorpos Antivirais , Doenças dos Suínos/epidemiologia , Vacinas Virais/genética , Anticorpos Neutralizantes , Vacinas Atenuadas , Diarreia/veterináriaRESUMO
Objective To investigate the clinical efficacy and related adverse reactions of the combination of camrelizumab with anlotinib as the third-line therapy on advanced non-small cell lung cancer. Methods We retrospectively analyzed the clinical data of 84 patients with advanced non-small cell lung cancer after second-line treatment. According to different treatment methods, 44 patients who received camrelizumab combined with anlotinib were included in the observation group, and 40 patients who received anlotinib alone were included in the control group. The PFS, ORR, DCR and incidence of adverse reactions were analyzed and compared between the two groups. Results The median PFS of the observation group was longer than that of the control group (7.0 vs. 5.6 months, P=0.001). No statistically significant difference was observed in ORR, DCR, the incidence of adverse reactions or the incidence of adverse reactions above grade 3 between two groups (all P > 0.05). Conclusion The clinical efficacy of camrelizumab combined with anlotinib as third-line therapy on advanced non-small cell lung cancer is better than anlotinib alone, and the safety is good.
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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.
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Ratos , Masculino , Animais , Ratos Sprague-Dawley , Microbioma Gastrointestinal , RNA Ribossômico 16S , Sepse/metabolismo , InflamaçãoRESUMO
Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.
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With the explosive growth of " City-customized Medical Insurance" products, the voice of commercial health insurance needs medical insurance data support is increasing.The authors took " City-customized Medical Insurance" as the representative of commercial health insurance, analyzed the demands and motivations of stakeholders in medical insurance data sharing through the power-interest matrix model, and summarized the medical insurance data sharing path at the commercial insurance product design end and claim settlement end. It is suggested to strengthen the top-level design, build the implementation path of standardized sharing of medical insurance data and the operation mechanism of hospital data docking, to realize the value increment of all stakeholders.
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@#<b>Objective</b> To evaluate the clinical significance of transvaginal color Doppler ultrasound for the differential diagnosis of benign and malignant ovarian cysts. <b>Methods</b> Patients who were diagnosed with clinically suspected or palpable adnexal masses and underwent gray-scale ultrasonography, transvaginal color Doppler ultrasonography, and ultrasound-guided fine-needle aspiration cytology (FNAC) during the period from 2018 to 2021 were enrolled in this study. The pulsatility index (<i>PI</i>) and resistance index (<i>RI</i>) were estimated, and an ovarian cyst with the lowest <i>PI</i> value of < 1.0 or the lowest <i>RI</i> value of < 0.4 was considered as malignant. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of gray-scale ultrasound and transvaginal color Doppler ultrasound for the differential diagnosis of benign and malignant ovarian cysts were estimated with FNAC as the gold standard. <b>Results</b> A total of 180 patients with ovarian cysts were recruited, and FNAC revealed that 81 of them had malignant lesions and 99 of them had benign lesions. The transvaginal color Doppler ultrasonograms showed that 75 patients (92.59%) with malignant lesions had blood-flow signals in their cysts and 42 patients (42.24%) with benign lesions had blood-flow signals in their cysts, with a significant difference in the proportion between the two groups (<i>χ</i><sup>2</sup> = 49.29, <i>P</i> < 0.01). Among the 75 patients with blood-flow signals in malignant ovarian cysts, 75 had <i>PI</i> < 1.0 and 24 had <i>RI</i> < 0.4; among the 42 patients with blood-flow signals in benign ovarian cysts, 15 had <i>PI</i> < 1.0 and no one had <i>RI</i> < 0.4; there were significant differences in the proportions of <i>PI</i> < 1.0 and <i>RI</i> < 0.4 between the two groups (<i>χ</i><sup>2</sup> = 62.68, <i>P</i> < 0.01; <i>χ</i><sup>2</sup> = 16.91, <i>P</i> < 0.01). In addition, compared with the combination of gray-scale ultrasound and transvaginal color Doppler ultrasound, gray-scale ultrasound alone had significantly lower sensitivity (51.85% <i>vs</i> 81.48%; <i>χ</i><sup>2</sup> = 16.00, <i>P</i> < 0.01), specificity (75.76% <i>vs</i> 93.94%; <i>χ</i><sup>2</sup> = 12.73, <i>P</i> < 0.01), PPV (63.64% <i>vs</i> 91.67%; <i>χ</i><sup>2</sup> = 15.90, <i>P</i> < 0.01), and NPV (65.79% <i>vs</i> 86.11%; <i>χ</i><sup>2</sup> = 12.44, <i>P</i> < 0.01) for the differential diagnosis of benign and malignant ovarian cysts. <b>Conclusion</b> Gray-scale ultrasound is effective for diagnosing ovarian cysts; however, gray-scale ultrasound combined with transvaginal color Doppler ultrasound can improve the differential diagnosis of benign and malignant ovarian cysts.
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Objective:To explore the application effect of the problem-originated clinical medical curriculum (PCMC) and problem-based learning (PBL) on teaching interns in the department of emergency.Methods:A total of 71 interns received in the department of emergency from January 2018 to January 2020 were selected and divided into an observation group ( n=38) and a control group ( n=33) according to different teaching methods. Among them, the control group received traditional teaching, the observation group took PCMC combined with PBL teaching method. The comprehensive ability scores and teaching quality of the two groups of interns were observed, and their satisfaction with teaching and the patient's evaluation on them were recorded. SPSS was used for t test. Results:There was no significant difference in the theoretical test scores, case analysis ability, and operational skills scores between the two groups before the teaching. After teaching, they were all improved, and the improvement effect of the observation group was significantly better than that of the control group [(92.30±4.37) vs. (83.75±3.98); (90.24±5.31) vs. (85.35±4.57); (91.33±5.28) vs. (86.49±4.42), all P<0.05]; the scores of basic job mastery, work attitude, adaptability and doctor-patient communication of the two groups were all improved, and the observation group was higher than the control group ( P<0.05); the satisfaction of the interns and the evaluation results of patients in the observation group were better than those of the control group ( P<0.05). Conclusion:PCMC combined with PBL used in the teaching of interns in the department of emergency can not only stimulate the interns' interest in learning, increase their theoretical knowledge, improve their learning ability and practical ability, but also improve the quality of teaching and improve their clinical resilience.
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Objective:To explore the relationship between the changes in the lipid profiles and the intensity of inflammatory response and disease severity in patients with sepsis, in order to find a biomarker that can quickly evaluate the condition and prognosis of sepsis.Methods:A retrospective analysis was performed on 449 patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from October 2019 to May 2021, and 355 patients without sepsis hospitalized in the same period served as the control. The general demographic data, blood lipid and other clinical indicators within 24 hours after admission were collected and compared between the two groups. Bivariate correlation study was used to analyze the relationship between blood lipid levels and inflammation indicators and severity of illness in patients with sepsis. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each blood lipid component on the 28-day mortality of patients with sepsis. According to the results of ROC curve analysis, the blood lipids were divided into two groups with different levels, and the Kaplan-Meier survival curve was used to compare the cumulative survival rates of the two groups without end-point event (the 28-day mortality was the end-point event).Results:Compared with non-septic patients, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in patients with sepsis [TC (mmol/L): 2.93±1.33 vs. 4.01±1.14, HDL-C (mmol/L): 0.78±0.47 vs. 1.16±0.40, LDL-C (mmol/L): 1.53±1.00 vs. 2.71±0.98, all P < 0.05]. In patients with sepsis, plasma cholesterol levels were correlated with the degree of inflammation and severity of the disease to varying degrees, but the HDL-C had the strongest correlation with interleukin-6 (IL-6; r = -0.551, P = 0.000), procalcitonin (PCT, r = -0.598, P = 0.000), sequential organ failure assessment (SOFA; r = -0.285, P = 0.000). The ROC curve analysis showed that among all blood lipid components, HDL-C had the highest predictive value for 28-day mortality of sepsis patients, and the area under the ROC curve (AUC) was 0.718, when the best cut-off value was 0.69 mmol/L, the sensitivity and specificity were 67.3% and 65.2% respectively, and the positive predictive value and negative predictive value were 60.6% and 71.5% respectively. According to Kaplan-Meier survival curve analysis, the mortality of sepsis patients with HDL-C ≤ 0.69 mmol/L was significantly higher than the patients with HDL-C > 0.69 mmol/L, and the difference was statistically significant ( P < 0.000 1). In addition, the 28-day mortality [59.73% (135/226) vs. 28.70% (64/223)], the incidence of multiple organ dysfunction [41.15% (93/226) vs. 31.84% (71/223)], the probability of requiring mechanical ventilation and vasoactive drugs [mechanical ventilation: 56.64% (128/226) vs. 46.18% (103/223); vasoactive drugs: 54.42% (123/226) vs. 38.57% (86/223)], the positive rate of microbial culture [45.58% (103/226) vs. 35.43% (79/223)], and the probability of drug-resistant bacteria [19.91% (45/226) vs. 10.31% (23/223)] in the low HDL-C group of sepsis patients were all higher than the high HDL-C group, the differences were statistically significant (all P < 0.05). Conclusions:Plasma cholesterol levels, especially the HDL-C levels, can well reflect the intensity of inflammation and the severity of the disease in patients with sepsis. And the HDL-C levels can be used as a good biomarker for predicting the short-term prognosis of sepsis.
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Objective To investigate the expression of TP53, PDGF and EGFR in primary astrocytomas, and analyze their correlation with clinicopathological features and prognosis. Methods We analyzed retrospectively the clinicopathological data of 90 patients with primary astrocytoma. The expressions of TP53, PDGF and EGFR in primary astrocytoma tissue samples were detected by immunohistochemistry. The survival of patients was followed up and Cox regression analysis was used to determine the prognostic factors. Results TP53 was expressed in the nucleus, PDGF and EGFR were expressed in the cytoplasm and cell membrane. The positive expression rates of TP53, PDGF and EGFR were 58.89%, 51.11% and 48.89%, significantly higher than those in normal brain tissues (all P < 0.05); the positive expression rate of TP53 in patients with tumor size ≥3 cm was higher than that in patients with tumor size < 3 cm. The positive expression rates of TP53, PDGF and EGFR in patients with WHO stages Ⅲ-Ⅳ were higher than those in patients with WHO stageⅠ-Ⅱ(all P < 0.05); the survival time of patients with positive expression of TP53, PDGF and EGFR were shorter than those of negative expression (all P < 0.05). Cox regression analysis found that WHO staging, TP53, PDGF and EGFR were all factors influencing the prognosis of primary astrocytomas patients. Conclusion TP53, PDGF and EGFR are highly expressed in primary astrocytomas and closely related to tumor progression. They are factors that affect the prognosis of patients.
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By means of analysis of related national policies on medical alliances, and investigation of their current development in China, the authors summarized the conceptual category of existing medical alliances. Typical cases were selected for comparative analysis in terms of urban medical groups, medical communities, specialized alliances and telemedicine collaboration networks. In view of such setbacks found as lack of health services, ambiguity of power and duties of stakeholders, and low penetration rate of composite medical insurance payment, as well as lack of effective incentives and poor online diagnosis and treatment mechanism, the authors recommended on development of medical alliances in respect of framework improvement and mechanism optimization among others.
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Objective:To investigate the related mechanism of miRNA-34a (miR-34a) reverses cisplatin resistance of osteosarcoma through targeted inhibition of high mobility group box 1 (HMGB1).Methods:The MG-63 cisplatin-resistant cell line (MG-63/DDP) was constructed by using dose escalation and intermittent action, and then the successfully constructed MG-63/DDP cells were treated with different concentrations of cisplatin (0, 1, 5, 10, 20, 30 μg/ml), and CCK-8 method was used to detect cell survival rate. The MG-63/DDP cells were transfected respectively and then randomly divided into two groups: the miR-34a overexpression vector group and the miR-34a empty expression vector (miR-34a-NC) group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of miR-34a. Transfected cells were treated with different concentrations of cisplatin (0, 1, 5, 10, 20, 30 μg/ml), and CCK-8 method was used to detect cell survival rate, flow cytometry was used to detect cell apoptosis. The dual luciferase reporter gene experiment was used to verify whether miR-34a regulated the expression of HMGB1, and Western blotting method was used to detect the HMGB1 protein expression level of the transfected cells. MG-63/DDP cells were transfected respectively and then randomly divided into two groups: HMGB1 gene silencing vector (si-HMGB1) group and its negative control vector (si-NC) group. Western blotting method was used to detect HMGB1 protein expression level and CCK-8 method was used to detect cell survival rate.Results:The MG-63/DDP cell line was successfully constructed. The survival rate of MG-63/DDP cells was higher than that of MG-63 cells when cells were treated with different concentrations of cisplatin (all P < 0.01), and half inhibitory concentration ( IC50) value of MG-63/DDP cells and MG-63 cells on cisplatin was 25.80 μg/ml and 0.47 μg/ml, respectively. qRT-PCR results showed that the relative expression level of miR-34a in MG-63/DDP cells was lower than that in MG-63 cells (0.46±0.04 vs. 1.02±0.05, t = 15.14, P < 0.01); compared with miR-34a-NC group, the relative expression of miR-34a in MG-63/DDP cells was increased in miR-34a overexpression vector group (1.67±0.09 vs. 1.00±0.02, t = -12.58, P < 0.01). Cell survival rate of miR-34a overexpression vector group and miR-34a-NC group was decreased with the increase in the concentration of cisplatin; cell survival rate of miR-34a overexpression vector group was lower than that of miR-34a-NC group when cells were treated with different concentrations of 5- 30 μg/ml cisplatin (all P < 0.01). The apoptotic rate of MG-63/DDP cells in miR-34a-NC group and miR-34a overexpression vector group was (25.1±1.7)% and (42.3±2.3)%, respectively when cells were treated with 20 μg/ml cisplatin; and in miR-34a overexpression vector group, MG-63/DDP cells had a higher rate of apoptosis ( P < 0.01). The dual luciferase reporter gene experiment results showed that compared with miR-34a-NC group, miR-34a overexpression vector group could inhibit the luciferase activity of PGL3- wild-type-HMGB1, and the difference was statistically significant ( t = 6.37, P < 0.01), while miR-34a overexpression vector group had no significant inhibitory effect on the luciferase activity of PGL3- mutant-HMGB1 ( t = 0.35, P = 0.74). The relative expression level of HMGB1 protein in miR-34a overexpression vector group was lower than that in miR-34a-NC group (0.43±0.02 vs. 1.00±0.14, t = 6.98, P < 0.01). Compared with si-NC group, the relative expression level and IC50 value of HMGB1 protein in si-HMGB1 group were reduced (all P < 0.05). Conclusion:Overexpression of miR-34a can enhance the chemosensitivity of osteosarcoma cells MG-63/DDP to cisplatin, and its mechanism may be related to the inhibition of HMGB1 expression.
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Objective:To investigate the current status of prevention and treatment of esophagogastric variceal bleeding (EVB) in cirrhotic portal hypertension patients in Ningxia region.Methods:The retrospective and descriptive study was conducted. The clinical data of 820 cirrhotic portal hypertension patients who were admitted to 21 medical centers in Niangxia region from January 2018 to December 2020 were collected, including 85 cases in Ningxia Hui Autonomous Region People′s Hospital, 73 cases in the Fifth People′s Hospital of Ningxia Hui Autonomous Region, 59 cases in the Wuzhong People′s Hospital, 52 cases in the Qingtongxia People′s Hospital, 50 cases in the Guyuan People′s Hospital, 47 cases in the Yuanzhou District People′s Hospital of Guyuan City, 47 cases in the Yinchuan Second People′s Hospital, 40 cases in the General Hospital of Ningxia Medical University, 40 cases in the Tongxin People′s Hospital, 35 cases in the Yinchuan First People′s Hospital, 34 cases in the Third People′s Hospital of Ningxia Hui Autonomous Region, 32 cases in the Zhongwei People′s Hospital, 30 cases in the Lingwu People′s Hospital, 30 cases in the Wuzhong New District Hospital, 30 cases in the Yanchi People′s Hospital, 29 cases in the Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, 28 cases in the Shizuishan Second People′s Hospital, 25 cases in the Shizuishan First People′s Hospital, 21 cases in the Haiyuan People′s Hospital, 20 cases in the Pengyang People′s Hospital, 13 cases in the Longde People′s Hospital. There were 538 males and 282 females, aged (56±13)years. Observation indicators: (1) clinical charac-teristics of cirrhotic portal hypertension patients; (2) overall prevention and treatment of EVB in cirrhotic portal hypertension patients; (3) prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Clinical characteristics of cirrhotic portal hypertension patients: of 820 cirrhotic portal hypertension patients, 271 cases were in compensated stage and 549 cases were in decompensated stage. Of the 271 cases in compensated stage, there were 183 maels and 88 females, aged (53±12)years. There were 185 Han people, 85 Hui people and 1 case of other ethic group. The etiological data of liver cirrhosis showed 211 cases of viral hepatitis B, 4 cases of alcoholic liver disease, 8 cases of viral hepatitis C, and 48 cases of other etiology. There were 235 cases of Child-Pugh grade A and 36 cases lack of data. Of the 549 cases in decompensated stage, there were 355 males and 194 females, aged (57±14) years. There were 373 Han people, 174 Hui people and 2 cases of other ethic group. The etiological data of liver cirrhosis showed 392 cases of viral hepatitis B, 33 cases of alcoholic liver disease, 10 cases of viral hepatitis C, and 114 cases of other etiology. There were 80 cases of Child-Pugh grade A, 289 cases of grade B, 170 cases of grade C and 10 cases lack of data. (2) Overall prevention and treatment of EVB in cirrhotic portal hypertension patients: of 271 patients in compensated stage, 38 cases received non-selective β-blocker (NSBB) therapy, 16 cases received endoscopic treatment, 6 cases received interventional therapy. Of 549 patients in decompensated stage, 68 cases received NSBB therapy, 46 cases received endoscopic treatment, 28 cases received interventional therapy. (3) Prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals: of 271 patients in compensated stage, 181 cases came from tertiary hospitals, of which 28 cases received NSBB therapy, 15 cases received endoscopic treatment, 6 cases received interventional therapy. Ninety cases came from secondary hospitals, of which 10 cases received NSBB therapy, 1 cases received endoscopic treatment. There was no significant difference in NSBB for prevention of EVB between tertiary and secondary hospitals ( χ2=0.947, P>0.05), while there was a significant difference in endoscopic treatment for prevention of EVB between tertiary and secondary hospitals ( χ2=5.572, P<0.05). Of 549 patients in decompensated stage, 309 cases came from tertiary hospitals, of which 22 cases received NSBB therapy, 29 cases received endoscopic treatment, 22 cases received interventional therapy. Two hundreds and fourty cases came from secondary hospitals, of which 46 cases received NSBB therapy, 17 cases received endoscopic treatment, 6 cases received interven-tional therapy. There were significant differences in NSBB and interventional therapy for prevention of EVB between tertiary and secondary hospitals ( χ2=18.065, 5.956, P<0.05). Conclusions:The proportion of receiving EUB prevention in cirrhotic portal hypertension in Ningxia is relatively low. For patients with compensated liver cirrhosis, the proportion of NSBB therapy and endoscopic treatment in the secondary hospitals was lower than that in tertiary hospitals. For patients with decompensated liver cirrhosis, the proportion of interventional treatment in secondary hospitals is lower than that of tertiary hospitals, but the proportion of NSBB in secondary hospitals taking is higher than that of tertiary hospitals.
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@#Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.
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Objective:To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS).Methods:A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels.Results:A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHEⅡ score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk ( RR) = 1.444, 95% confidence interval (95% CI) was 1.090-1.914, P = 0.010], APACHEⅡ score ( RR = 2.249, 95% CI was 1.688-2.997, P = 0.000), SChE ( RR = 1.469, 95% CI was 1.057-2.043, P = 0.022), and Lac ( RR = 2.190, 95% CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHEⅡ score and Lac was greater than APACHEⅡ score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group ( n = 88), the 28-day mortality of patients in the low SChE group ( n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ 2 = 5.852, P = 0.016). Conclusions:Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.