Objective: To investigate the incidence trend of tuberculosis in Haidong City, Qinghai Province from 2006 to 2020, and the effects of age, period, and cohort on tuberculosis incidence, so as to provide the basis for enhancing the prevention and control for tuberculosis. Methods: Data of tuberculosis cases in Haidong City from 2006 to 2020 were collected from the Chinese Disease Prevention and Control Information System. Incidence rates were calculated and standardized using data from the Sixth National Population Census in 2010. The trends in incidence of tuberculosis were analyzed by annual percent change (APC). Effects of age, period and cohort on the incidence of tuberculosis were analyzed by an age-period-cohort model. Results: The crude incidence rates of tuberculosis in Haidong City from 2006 to 2020 ranged from 37.69/105 to 100.93/105, and the standardized incidence rates ranged from 42.85/105 to 115.24/105. The standardized incidence rates from 2006 to 2015 showed a decreasing trend (APC=-7.148%, P<0.05), while there was no significant trend observed from 2015 to 2020 (all P>0.05). The age-period-cohort model analysis showed that the highest incidence risk of tuberculosis in Haidong City from 2006 to 2020 was observed in the age group of 20-<25 years (RR=2.973, 95%CI: 2.353-3.756), followed by the age group of 80-<85 years (RR=2.785, 95%CI: 2.206-3.516). The incidence risk of tuberculosis was higher in the period from 2016 to 2020 (RR=1.253, 95%CI: 1.203-1.306) compared to the period from 2011 to 2015 (RR=0.796, 95%CI: 0.770-0.823). Tuberculosis incidence risk was the highest in the birth cohort from 1936 to 1940 (RR=3.050, 95%CI: 2.356-3.949), and then gradually decreased over time thereafter. Conclusions The incidence of tuberculosis in Haidong City showed a decreasing trend from 2006 to 2015, while there was no significant trend observed from 2015 to 2020. The incidence risk of tuberculosis was higher in the age groups of 20-<25 years and 80-<85 years, and the risk decreased for those born in more recent years.

Sepsis is currently the leading cause of death in the intensive care unit, and its survivors also experience long-term immunosuppression and high rates of recurrent infections. At present, the clinical treatment of sepsis is still based on antibiotics, intravenous rehydration, and vasopressors, and there is no targeted drug treatment. However, as the rate of antibiotic resistance continues to increase, immunotherapy is highly anticipated as a new treatment. Patients with sepsis are often accompanied by acute leukocyte immune dysfunction and immunosuppression, which may be an important risk factor for the increasing morbidity and mortality of patients. Targeted inhibition of specific cell surface inhibitory immune checkpoint receptors and ligands, such as programmed death receptor-1 (PD-1), programmed death-ligand 1 (PD-L1), and other targets, can improve the host’s resistance to infection. In this paper, the research progress of PD-1 and PD-L1 in the immune response to sepsis was summarized to provide a theoretical basis for their further application in the treatment of sepsis in the future.

Abstract: Objective To analyze the resistance and spatial distribution of Mycobacterium tuberculosis (MTB) to six commonly used anti-tuberculosis drugs in Qinghai Province from 2016 to 2019, so as to provide a reference for tuberculosis treatment and drug-resistant tuberculosis control. Methods A total of 1 182 identified strains of Mycobacterium tuberculosis in Qinghai Province from 2016 to 2019 were collected, and 6 anti-tuberculosis drugs were subjected to drug susceptibility tests and strain confirmed by the proportional method. By means of ArcMap10.7 and SaTScan10.1 software, map visualization, spatial autocorrelation analysis and spatial scanning of MTB drug resistance were performed to identify MTB drug resistance clusters in Qinghai Province. Results From 2016 to 2019, the total drug resistance (TDR) rate of 1 182 Mycobacterium tuberculosis strains in Qinghai Province was 23.77% (281/1 182), with a mono-resistance (MR) rate of 11.08% (131/1 182), a poly-resistance (PDR) rate of 3.89% (46/1 182), a multi-drug resistance (MDR) rate of 8.80% (104/1 182), and an extensive drug resistance (XDR) rate of 0.85% (10/1 182). The rates of MDR, XDR and TDR all showed a decreasing trend year by year (P<0.01). The drug resistance spectrum displayed 21 combinations. The TDR rate and MDR rate in the retreatment patients were higher than those of the initial treated patients, and the difference was statistically significant (χ2 TDR=22.784, χ2MDR=45.082, P<0.01). In terms of demographic characteristics, the TDR rate in males was higher than that in females, and the middle-aged group was higher than other age groups, and the differences were statistically significant (χ2=7.541, 10.825, P<0.05). The results of global spatial autocorrelation analysis showed that there was no statistical significance in the autocorrelation and obvious spatial clustering of MTB drug resistance in Qinghai Province from 2016 to 2019 (P>0.05), which indicated a random distribution. The results of spatiotemporal scanning showed that there was a kind of clustering area, but the clustering effect was not significant (P>0.05), indicating a random distribution. Conclusions The TDR of MTB in Qinghai Province from 2016 to 2019 showed a downward trend year by year. In comparison with the national average, the rate of multi-drug resistance and extensive drug resistance was still high, and most of the multi-drug resistance resulted from rifampicin and isoniazid. The drugresistant population mainly consisted of retreatment, males, and young and middle-aged pop

Objective: The study aims to explore the epidemiological characteristics of tuberculosis among students in Qinghai Province, to provide scientific basis for the prevention and control of students tuberculosis. Methods: Data on tuberculosis among students from 2016 to 2019 in Qinghai province were collected and epidemiological characteristics were analyzed, the spatial distribution map were drawn by using ArcMap 10.8. Results: During 2016-2019, there were 2 691 reported cases of tuberculosis among students in Qinghai Province the reporting rate were 46.10/10 5, 68.50/10 5, 73.49/10 5, 85.96/10 5, increased year by year( χ 2=116.45, P <0.01). With a high incidence from March to September each year. The tuberculosis patients were mainly aged 18 years and above, with more reported female cases than male cases and more Tibetan cases. Most of students tuberculosis cases were reported in southern Qinghai, especially in Yushu and Guoluo areas, and sharp increase was observed in Xining during 2018 to 2019. Conclusion Students tuberculosis in Qinghai is still serious. Schools should strengthen education on tuberculosis prevention, especially those in southern Qinghai and Xining.

Objective:To investigate the vitamin D level of pulmonary tuberculosis patients in Qinghai Province, and to explore the correlation between vitamin D level and pulmonary tuberculosis.Methods:From May to September 2020, 208 bacterial confirmed pulmonary tuberculosis patients who were admitted to The 4th People′s Hospital of Qinghai Province were enrolled as the pulmonary tuberculosis group, and 129 healthy people who underwent physical examination during the same period were enrolled as the healthy control group. Independent sample t test and chi-square test were used for statistical analysis. Results:The deficiency rate of vitamin D was 11.06%(23/208) in the pulmonary tuberculosis group, which was higher than that (3.10%(4/129)) in the healthy control group, and the difference was statistically significant ( χ2=6.840, P=0.009). The vitamin D level was (56.84±20.03) μg/L in the pulmonary tuberculosis group, which was lower than that ((67.39±17.07) μg/L) in the healthy control group, and the difference was statistically significant ( t=5.154, P<0.01). The vitamin D levels were not different between the newly treated ((56.66±20.02) μg/L)) and retreated pulmonary tuberculosis patients ((59.11±20.81) μg/L) ( t=0.468, P=0.650). The vitamin D level of simple pulmonary tuberculosis patients ((57.82±20.01) μg/L) was higher than that of pulmonary tuberculosis patients combined with other diseases ((48.08±18.46) μg/L), and the difference was statistically significant ( t=2.132, P=0.034). Conclusion:Pulmonary tuberculosis is associated with decreased vitamin D levels, and patients with pulmonary tuberculosis are more likely to suffer from decreased or deficient vitamin D, which suggests clinicians considering the vitamin D status when treating pulmonary tuberculosis patients.

Sorafenib is a multi-tyrosine kinase inhibitor targeting a variety of tyrosine kinase receptors involved in angiogenesis, tumor growth and tumor metastasis. It is currently widely used in renal cell carcinoma and hepatocellular carcinoma's treatment. Sorafenib prolongs overall survival of many patients with malignant tumors. However, the adverse drug reactions, especially serious cardiovascular adverse reactions, still reduce its clinical benefits. Therefore, it is important to prevent or reduce adverse cardiovascular reactions caused by sorafenib. This article reviews the adverse cardiovascular reactions and its possible mechanisms caused by sorafenib.

Objective: To investigate the effect of estrogen on expression of the cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) in myocardium of lipopolysaccharide (LPS)-induced mice model of sepsis. Methods: Totally 12 female and 12 male Balb/c mice of specific pathogen-free (SPF) level with 7 weeks were served as objectives. The female and male mice were randomly divided into model groups and control groups, respectively, with 6 mice in each group. The model of sepsis was reproduced by intraperitoneal injection of 10% LPS (5 mg/kg), and the mice in control groups were injected with the same volume of normal saline. The general condition of mice during experiment was observed at 24 hours after injection. All the mice were sacrificed and the heart was harvested after collecting the whole blood. The concentration of estrogen in serum was determined by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The myocardial tissue homogenate was prepared at the same time, and the total protein was extracted. The expression level of CRISPLD2 was determined by Western Blot. Pearson correlation analysis was used to analyze the bivariate correlation. Results: All of the experimental mice survived at 24 hours after injection. The mice in the model groups showed disorder and gray signs of body hair, with diarrhea and decreased appetite. No significant abnormality was observed in the control groups. There was no significant difference in the body weight or concentration of estrogen in serum between model and control group of both female and male mice [body weight (g): 24.6±1.8 vs. 24.5±1.3 in male mice, 18.0±0.8 vs. 17.5±1.1 in female mice; estrogen (ng/L): 11.93±2.59 vs. 12.17±3.87 in male mice, 28.20±5.75 vs. 29.82±6.10 in female mice, all P > 0.05]. There was no statistical difference in the expression of CRISPLD2 in myocardium between male control mice and female control mice (gray value: 1.02±0.19 vs. 1.00±0.11, P > 0.05). No significant difference in the expression of CRISPLD2 in myocardium was found between female sepsis mice and female control mice (gray value: 1.05±0.13 vs. 1.00±0.11, P > 0.05). The expression of CRISPLD2 in myocardium of male sepsis mice was significantly lower than that of male control mice (gray value: 0.29±0.08 vs. 1.02±0.19, P < 0.01), and it was significantly lower than that of female sepsis mice (P < 0.01). It was shown by correlation analysis that the expression level of CRISPLD2 in myocardium of sepsis mice was significantly correlated with serum estrogen concentration [R² = 0.736, 95% confidence interval (95%CI) = 0.560-0.960, P < 0.001]. Conclusions In female mice with sepsis, the expression of CRISPLD2 is comparable to that of female healthy mice. It is suggested that estrogen can maintain the expression of CRISPLD2 in LPS-induced septic mice at the normal level.

OBJECTIVE: To investigate the effect of estrogen on expression of the cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) in myocardium of lipopolysaccharide (LPS)-induced mice model of sepsis. METHODS: Totally 12 female and 12 male Balb/c mice of specific pathogen-free (SPF) level with 7 weeks were served as objectives. The female and male mice were randomly divided into model groups and control groups, respectively, with 6 mice in each group. The model of sepsis was reproduced by intraperitoneal injection of 10% LPS (5 mg/kg), and the mice in control groups were injected with the same volume of normal saline. The general condition of mice during experiment was observed at 24 hours after injection. All the mice were sacrificed and the heart was harvested after collecting the whole blood. The concentration of estrogen in serum was determined by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The myocardial tissue homogenate was prepared at the same time, and the total protein was extracted. The expression level of CRISPLD2 was determined by Western Blot. Pearson correlation analysis was used to analyze the bivariate correlation. RESULTS: All of the experimental mice survived at 24 hours after injection. The mice in the model groups showed disorder and gray signs of body hair, with diarrhea and decreased appetite. No significant abnormality was observed in the control groups. There was no significant difference in the body weight or concentration of estrogen in serum between model and control group of both female and male mice [body weight (g): 24.6±1.8 vs. 24.5±1.3 in male mice, 18.0±0.8 vs. 17.5±1.1 in female mice; estrogen (ng/L): 11.93±2.59 vs. 12.17±3.87 in male mice, 28.20±5.75 vs. 29.82±6.10 in female mice, all P > 0.05]. There was no statistical difference in the expression of CRISPLD2 in myocardium between male control mice and female control mice (gray value: 1.02±0.19 vs. 1.00±0.11, P > 0.05). No significant difference in the expression of CRISPLD2 in myocardium was found between female sepsis mice and female control mice (gray value: 1.05±0.13 vs. 1.00±0.11, P > 0.05). The expression of CRISPLD2 in myocardium of male sepsis mice was significantly lower than that of male control mice (gray value: 0.29±0.08 vs. 1.02±0.19, P < 0.01), and it was significantly lower than that of female sepsis mice (P < 0.01). It was shown by correlation analysis that the expression level of CRISPLD2 in myocardium of sepsis mice was significantly correlated with serum estrogen concentration [R² = 0.736, 95% confidence interval (95%CI) = 0.560-0.960, P < 0.001]. CONCLUSIONS In female mice with sepsis, the expression of CRISPLD2 is comparable to that of female healthy mice. It is suggested that estrogen can maintain the expression of CRISPLD2 in LPS-induced septic mice at the normal level.
Animals ; Cysteine ; Estrogens ; Female ; Lipopolysaccharides ; Male ; Mice ; Myocardium ; Sepsis

Objective To explore the method and performance of using multiple indices to diagnose sepsis and to predict the prognosis of severe ill patients.Methods Critically ill patients at first admission to intensive care unit (ICU) of Changzheng Hospital, Second Military Medical University, from January 2014 to September 2015 were enrolled if the following conditions were satisfied: ① patients were 18-75 years old;② the length of ICU stay was more than 24 hours; ③ All records of the patients were available. Data of the patients was collected by searching the electronic medical record system. Logistic regression model was formulated to create the new combined predictive indicator and the receiver operating characteristic (ROC) curve for the new predictive indicator was built. The area under the ROC curve (AUC) for both the new indicator and original ones were compared. The optimal cut-off point was obtained where the Youden index reached the maximum value. Diagnostic parameters such as sensitivity, specificity and predictive accuracy were also calculated for comparison. Finally, individual values were substituted into the equation to test the performance in predicting clinical outcomes.Results A total of 362 patients (218 males and 144 females) were enrolled in our study and 66 patients died. The average age was (48.3±19.3) years old. ① For the predictive model only containing categorical covariants [including procalcitonin (PCT), lipopolysaccharide (LPS), infection, white blood cells count (WBC) and fever], increased PCT, increased WBC and fever were demonstrated to be independent risk factors for sepsis in the logistic equation. The AUC for the new combined predictive indicator was higher than that of any other indictor, including PCT, LPS, infection, WBC and fever (0.930 vs. 0.661, 0.503, 0.570, 0.837, 0.800). The optimal cut-off value for the new combined predictive indicator was 0.518. Using the new indicator to diagnose sepsis, the sensitivity, specificity and diagnostic accuracy rate were 78.00%, 93.36% and 87.47%, respectively. One patient was randomly selected, and the clinical data was substituted into the probability equation for prediction. The calculated value was 0.015, which was less than the cut-off value (0.518), indicating that the prognosis was non-sepsis at an accuracy of 87.47%. ② For the predictive model only containing continuous covariants, the logistic model which combined acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) score to predict in-hospital death events, both APACHE Ⅱ score and SOFA score were independent risk factors for death. The AUC for the new predictive indicator was higher than that of APACHE Ⅱ score and SOFA score (0.834 vs. 0.812, 0.813). The optimal cut-off value for the new combined predictive indicator in predicting in-hospital death events was 0.236, and the corresponding sensitivity, specificity and diagnostic accuracy for the combined predictive indicator were 73.12%, 76.51% and 75.70%, respectively. One patient was randomly selected, and the APACHE Ⅱscore and SOFA score was substituted into the probability equation for prediction. The calculated value was 0.570, which was higher than the cut-off value (0.236), indicating that the death prognosis at an accuracy of 75.70%.Conclusion The combined predictive indicator, which is formulated by logistic regression models, is superior toany single indicator in predicting sepsis or in-hospital death events.

Pulmonary embolism (PE) refers to the endogenous or exogenous emboli blocking pulmonary trunk or branches, causing clinical and pathophysiological syndrome of pulmonary circulation disorder, the incidence rate is high. Sometimes PE patients were lack of specific symptoms and signs, or without any symptoms, which often result in misdiagnosis, un-timely diagnosis, and the delay of treatment. A PE case with syncope, vomiting and shock, which was proved to be pulmonary artery trunk and branch wide embolism later, was presented so as to improve the understanding of the disease.