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 observe the effects of vaporized perfluorocarbon (PFC) combined with exogenous pulmonary surfactant (PS) inhalation on rabbit models of acute lung injury (ALI).Methods Thirty-two New Zealand rabbits were randomly divided into four groups: ALI group, combination treatment group, PFC group, and PS group (each groupn = 8 rabbits). The rabbit model of ALI was induced by the whole lung normal saline lavage. After modeling, in the combined group, 3 mL/kg vaporized perfluorooctyl bromide/dipalmitoylphosphatidylcholine (PFOB/DPPC) emulsion was inhaled, the rabbits in PFC and PS groups were treated with vaporized PFOB emulsion and vaporized DPPC emulsion 3 mL/kg inhalation respectively, and in the ALI group was given the same amount of vaporized normal saline inhalation. In each group, before modeling for 30 minutes (basic value), after modeling for 1 hour and after treatment at 0 minute, 30 minutes, 2 hours, 4 hours, the respiratory rate (RR), oxygenation index (OI), dynamic lung compliance (Cdyn) were observed, and the lung coefficient (LI) and lung permeability index (LPI) were calculated; the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the lung tissue was collected and the lung pathological changes were observed under macroscopic and microscopic observation.Results Aftermodeling, the levels of OI, Cdyn were quickly lowered, RR became significantly elevated, and there were obvious edema, hemorrhage and exudation in lung tissue of ALI group. The levels of OI were significantly increased in combined group and PFC group compared with the level in ALI group after treatment at 0 minute initially [mmHg (1 mmHg = 0.133 kPa): 231.0±16.7, 221.4±19.0 vs. 189.5±21.0, both P < 0.05], while the level of OI in PS group was increased significantly until 4 hours after treatment, being higher than that in ALI group (mmHg: 297.0±20.7 vs. 243.3±36.7,P < 0.05); RR was decreased significantly in combined treatment group at 30 minutes after treatment compared with that in ALI group (bpm: 151.1±13.3 vs. 178.5±32.0,P < 0.05), while the RR in PFC group and PS group were not increased significantly until 4 hours after treatment being higher than that in ALI group (bpm: 129.3±14.3, 133.1±13.9 vs. 157.5±32.5, bothP < 0.05). Compared to ALI group, the three treatment groups resulted in significant improvement in Cdyn right at 0 minute (mL/cmH2O: 1.64±0.10, 1.45±0.10, 1.43±0.09 vs. 0.57±0.05, allP < 0.05), their LPI, LI and inflammatory cytokines were significantly decreased [LPI (×10-5): 4.21±0.42, 4.76±0.55, 4.87±0.49 vs. 5.56±0.52, LI: 8.04±0.58, 8.90±0.88, 9.22±0.71 vs. 10.85±0.73, TNF-α (ng/L): 50.05±4.91, 56.18±5.54, 63.60±5.96 vs. 73.60±5.27, IL-1β (ng/L): 34.27±4.55, 40.29±5.03, 48.13±6.38 vs. 54.71±4.26, allP<0.05], and pulmonary edema, congestion and inflammatory cell infiltration were obviously ameliorated (pathological scores: 3.74±0.58, 4.50±0.75, 5.29±0.72 vs. 6.13±0.72, P < 0.05). Cdyn levels were increased significantly in combined treatment group at 0 minute, 30 minutes, 4 hours after treatment compared with thosein PFC and PS group, but there were no significant differences between PFC and PS group. Levels of LI, LPI, inflammatory factors and pathological scores were decreased significantly in combined treatment group compared with those in PFC and PS group, the degrees of improvement of inflammatory factors and pathological scores in PFC group were more obvious than those in PS group (allP < 0.05).Conclusions PFOB combined with DPPC inhalation can provide greater oxygen delivery, reduce the pro-inflammatory cytokines, supplement PS and influence its distribution on the surface of lung, which might lead to a marked and sustained improvement in oxygenation, pulmonary function and amelioration of lung edema and inflammatory reaction in saline lavage induced lung injury of rabbits.

Objective To study the changes of PI3K/Akt/GSK3β signaling pathway during resuscitation with neck cooling in order to explore the relationship between the protective effect of neck cooling and the phosphorylation of PI3K/Akt and GSK3β.Methods Thirty rabbits were randomly(random number) divided into five groups, and models of cadiac arrest were induced by ventricular fibrillation(VF, the positive electrode in the right ventricle and negative pole on the apex of heart) for 4 min.In sham group,a electrode was placed into right ventricle without electric current conducted, and CA was not induced.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.In normothermia treat group(NT group),resuscitation was carried out to restoration of spontaneous circulation(ROSC),and the rabbits were sacrificed and specimens were taken at 24 hours after modeling.In intra-arrest therapeutic hypothermia group (IATH group), rapid neck cooling was initiated at the same time with CPR,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.Rabbits were sacrificed and specimens were taken at 24 hours after modeling.In recovery period cooling + LY294002 group(PATH+LY294002 group), LY294002 was injected intra-ventricularly at 20 minutes before resuscitation.Rapid neck cooling was started at the same time with CPR,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.In post-arrest therapeutic hypothermia group (PATH group), rapid neck cooling was begun after CPR for 1 hour,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.Animals were sacrificed by using overdose anesthetic drug.Western blot was used to detect the level of Akt p-Akt GSK-3β p-GSK-3β (ser9) protein, and TUNEL was used to observe apoptosis of tissues in each group.Multiple comparisons were performed with one-way analysis of variance (ANOVA).Results Compared with Sham group, Akt (Thr-308) phosphorylation (P-AKT) and P-GSK-3β levels in the brain neuron cytoplasm in 24 hours after CPR resuscitation in NT group was significantly reduced, and showed a gradual reduction trend (P<0.05);the P-AKT and P-GSK-3β levels in the brain neuron cytoplasm in 24 hours after CPR resuscitation in IATH group were significantly enhanced compared with NT group (P<0.05);the levels of these two kinds of protein at one hour after resuscitation in PATH group were significantly enhanced compared with NT group (P<0.05), but lower in IATH group.Intra-ventricularly injection of LY294002 made the effect of hypothermia lost, indicating that LY294002 inhibited the phosphorylation of Akt.Apoptosis cells were significantly reduced in IATH group and normothermia theatment group compared with PATH group and LY294002 group(P<0.05).Conclusions Neck cooling can reduce apoptosis in rabbit brain cells after recovery, and the protective effect on brain is best in intra-arrest therapeutic hypothermia group.LY294002 specifically block the PI3K/Akt pathway, and the protective effect of cooling on the brain can be abolished,indicating hypothermia protects the neurological function via activation of PI3K/Akt pathway.Neck cooling protects the neurological function by activating PI3K/Akt/GSK-3β, promoting the Akt activation, and increasing the expression of P-GSK3β.Specific Akt inhibitor LY294002 inhibits Akt phosphorylation of brain tissue recovery and further inhibit the phosphorylation of GSK-3β, thus abolishing protective effect of cooling on neurological function.