Objective:To analyze the disease burden of kidney cancer, bladder cancer and prostate cancer and attributed risk factors in China from 1990 to 2019, and provide reference for the development of comprehensive prevention and control strategies.Methods:Based on the Global Burden of Disease Study 2019 platform, we collected the crude and age-standardized incidence rate, age-standardized mortality rate (ASMR), and disability-adjusted life year (DALY) of kidney cancer, bladder cancer and prostate cancer in China from 1990 to 2019. By using the log-linear regression model, trends were analyzed for overall and risk-attributable disease burden by calculating the average annual percentage change (AAPC).Results:From 1990 to 2019, the crude incidence rates of kidney cancer, bladder cancer and prostate cancer showed increasing trends in China, with an AAPC of 5.4% (95% CI: 4.9% - 5.9%), 4.1% (95% CI: 3.9% - 4.2%) and 5.6% (95% CI: 5.3% - 6.0%) (all P<0.001), respectively. Similar trends were found in age-standardized incidence rates with smaller AAPCs. For kidney cancer, the ASMR and age-standardized DALY rate significantly increased, with AAPC of 2.2% (95% CI: 1.5%-2.8%) and 1.5% (95% CI: 1.2%-1.9%) (all P<0.001), while the ASMR of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.7% - -0.5%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). The age-standardized DALY rate of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.8% - -0.4%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). Smoking was responsible for 48.2% of bladder cancer, 18.8% of kidney cancer and 9.8% of prostate cancer in total DALY. The age-standardized DALY rate of kidney cancer caused by smoking and high BMI showed an increasing trend, with AAPC of 3.0% (95% CI: 2.8%-3.2%) and 4.9% (95% CI: 4.7%-5.0%) (all P<0.001), and smoking-attributed age-standardized DALY rates of bladder cancer and prostate cancer decreased gradually with AAPC of -0.4% (95% CI: -0.6% - -0.2%) ( P<0.001) and -0.3% (95% CI: -0.4% - -0.1%) ( P=0.001). Conclusions:In the past 30 years, the disease burden of kidney cancer, bladder cancer and prostate cancer in China increased gradually, while the deaths and DALY of bladder cancer and prostate cancer decreased slightly. We should continue to strengthen the primary prevention strategies for smoking, obesity and other risk factors, and explore the appropriate screening tests and population-based screening strategies.

OBJECTIVE: To investigate the role and underlying mechanism of human myeloid differentiation protein 2 (MD2) in the process of neuronal death induced by lipopolysaccharide (LPS) by establishing an in vitro model of sepsis-associated encephalopathy (SAE) by LPS. METHODS: Healthy C57BL/6J mice at 14-18 days of gestation were selected, and brain cortical tissue was taken from fetal mice. Neurons were stimulated with 0 (control), 1, 5 and 10 g/L of LPS for 24 hours. The release of lactate dehydrogenase (LDH) was detected and the death of neurons was observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukins (IL-6, IL-1β), in order to determine the optimal dose of LPS for establishing an in vitro neuroinflammation model of SAE. The cells were divided into blank control group and LPS group. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) was used to discover apoptosis. Western blotting was used to detect the expression of the relevant protein markers activated caspase-3, necroptosis-associated protein neuronal receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and phosphorylated RIPK3 (p-RIPK3). Immunofluorescence chemical staining was used to detect the expressions of p-RIPK3 and microtubule-associated protein 2 (MAP2) to evaluate the type of cell death and the degree of neuronal death. Western blotting was used to detect MD2 expression. Immunofluorescence chemical staining was performed to observe the expression and distribution of p-RIPK3 and MD2 in neurons to assess whether MD2 was involved in the inflammatory response promoting neuronal death. In addition, the cells were divided into blank control group, LPS group, and MD2 interfering peptide group (LPS+TC group), and the levels of IL-6, IL-1β and LDH were detected to evaluate whether interfering with MD2 can alleviate LPS induced neuroinflammation. RESULTS: 10 g/L LPS induced notable neuronal death, and the release of LDH in neurons stimulated with this concentration for 24 hours was significantly higher than that in the blank control group (relative release: 1.45±0.04 vs. 1.00±0.00, P < 0.01), indicating apoptosis and necroptosis occurred in neurons, and the levels of inflammatory factors IL-6 and IL-1β were remarkable increased [IL-6 (relative level): 1.94±0.04 vs. 1.00±0.00, IL-1β (relative level): 1.53±0.09 vs. 1.00±0.00, both P < 0.01]. Compared with the blank control group, the apoptosis of cells, cleaved-caspase-3 expression, the p-RIPK3/RIPK3 ratio, and p-RIPK3 expression around neurons in the LPS group were significantly increased [cleaved-caspase-3/GAPDH: 1.55±0.10 vs. 1.00±0.00, P < 0.01; p-RIPK3/RIPK3 ratio (relative value): 1.54±0.06 vs. 1.00±0.00, P < 0.05], which suggested that typical apoptosis and necroptosis apoptosis occurred in neurons in the septic environment. Furthermore, MD2 expression was significantly increased in the LPS group compared with the blank control group (MD2/GAPDH: 1.91±0.07 vs. 1.00±0.00, P < 0.01), and MD2 expression around neurons was increased, indicating that LPS-induced MD2 upregulation may play a key role in neuroinflammation and induction of neuronal death in sepsis. In addition, compared with the LPS group, the MD2-interfering peptide could reduce the expression levels of inflammatory factors IL-6 and IL-1β [IL-6 (relative level): 1.16±0.08 vs. 1.94±0.04, IL-1β (relative level): 1.15±0.05 vs. 1.75±0.09, both P < 0.01] and decrease LDH release (relative release: 1.09±0.01 vs. 1.44±0.04, P < 0.05). CONCLUSIONS LPS induced neuronal inflammatory responses via MD2, which ultimately leads to apoptosis and necroptosis. Interfering with MD2 reduces inflammation and inhibits neuronal death.
Mice ; Humans ; Animals ; Sepsis-Associated Encephalopathy ; Caspase 3 ; Interleukin-6 ; Neuroinflammatory Diseases ; Lipopolysaccharides ; Mice, Inbred C57BL ; Cell Differentiation ; Tumor Necrosis Factor-alpha

Nasal preparations have unique advantages in drug delivery and are widely used in the treatment of local and systemic diseases. Nasal administration of traditional Chinese medicine （TCM） has a long history in China. In recent years， nasal preparations of TCM have attracted wide attention. Based on the information about nasal preparations of TCM from the database of National Medical Products Administration （NMPA）， Yaozh.com and China National Knowledge Internet （CNKI） in the recent 30 years， the formulation， the listed products， commonly used TCM， pharmaceutical excipients， clinical application and safety research of modern nasal preparations of TCM were summarized and expounded. Focusing on many problems in the development of modern nasal preparations of TCM， such as inaccurate dosage of some products， incomplete quality standard system of pharmaceutical excipients， imperfect safety evaluation， lack of research and development of nasal drug delivery devices and so on， the possible solutions and prospects were put forward from the aspects of optimizing the extraction and separation process of TCM， the quality control and application method of pharmaceutical excipients， the development of new dosage forms， the safety evaluation of nasal administration of TCM， and the design and development of nasal administration devices. The aim is to provide ideas for the development of nasal preparations of TCM and provide scientific basis for its sustainable utilization.

Objective:To investigate the curative efficacy of X-ray stereotactic radiotherapy combined with temozolomide in the treatment of recurrent glioma.Methods:48 patients with recurrent glioma treated in Mianyang Central Hospital from January 2018 to January 2019 were retrospectively selected, including 24 patients treated with stereotactic radiotherapy as the control group and 24 patients treated with temozolomide combined with stereotactic radiotherapy as the observation group. The treatment effect, inflammatory factor level, incidence of adverse events and survival rate were compared between the two groups.Results:The complete remission rate and total effective rate in the observation group were significantly higher than those in the control group (66.7% vs 37.5%, 87.5% vs 62.5%) (all P<0.05). There were no significant differences in serum levels of hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) between the two groups before treatment (all P>0.05). After treatment, the serum levels of HGF, TNF-α and IL-17 in observation group was significantly lower than those in control group (all P<0.05). The incidence of adverse events in the observation group was significantly lower than that in the control group ( P<0.05). During follow-up of 6, 12 and 18 months, the survival rate of patients in the observation group was significantly higher than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The combination of X-ray stereotactic radiotherapy with temozolomide in the treatment of recurrent glioma shows better clinical outcome and extended survival rate. To conclude, this combined treatment is recommended in further clinical promotion.

Sepsis is a life-threatening organ dysfunction due to the dysregulation of host responses during infection. Severe systemic inflammatory response syndrome (SIRS) is the primary pathophysiological feature. Despite the classical antibiotic therapies play an important role in sepsis, the emergence of multi-resistant bacteria makes a greater challenge in clinical. Antimicrobial peptides (AMP) which consist of small cationic peptides, can be found in most organisms. As a result of their board-spectrum antibacterial activities and immunoregulatory functions, AMPs may have an excellent effect on the treatment of sepsis. In this review, we will discuss the basic role of AMPs in sepsis treatment and their application prospect and the challenges which need to be resolved in order to provide ideas for clinical application of AMPs.

Objective:To explore the effects of psychological suggestive therapy combined with diet restriction therapy on resilience and glycolipid metabolism in elderly patients with coronary heart disease and type 2 diabetes mellitus.Methods:A total of 200 elderly patients with coronary heart disease and type 2 diabetes mellitus were recruited from June 2017 to March 2019. They were divided into control group and study group according to the random number table method, with 100 cases each. However, during the whole research cycle, some patients affected by various factors dropped out of the study, and the final number of patients was 92 cases in the study group and 87 cases in the control group. The study group received psychological suggestive therapy combined with dietary restriction therapy on the basis of the control group. The psychoelasticity of patients was assessed by concise psychoelasticity scale by physicians trained before and after intervention, and the changes of glucose and lipid metabolism were investigated before and after intervention.Results:After intervention, the scores of resilience (19.39 ± 3.29), self-improvement (16.56 ± 3.00), optimism (15.02 ± 2.50) in the study group were higher than those in the control group (15.97 ± 3.77, 10.58 ± 2.40, 9.20 ± 3.12), with significant differences ( t value was 4.459, 6.762, 6.220, P < 0.05). After intervention, the blood glucose index of the study group was generally better than that of the control group. After intervention, FPG, 2hFPG and HbA1c in the study group were (5.02 ± 0.45) mmol / L, (8.94 ± 1.43) mmol / L, (5.87 ± 0.65)% respectively, and those in the control group were (6.29 ± 1.71) mmol / L, (9.65 ± 1.4) mmol / L, (7.21 ± 1.05)% respectively, with statistically significant differences ( t value was 4.682, 5.214, 5.696, P < 0.05). After intervention, ApoA1, TG, HDL-C and LDL-C were (1.58 ± 0.32)mmol/L, (1.61 ± 0.58)mmol/L, (2.11 ± 0.85)mmol/L, (2.09 ± 0.67) mmol / L in the study group, and in the control group ApoA1, TG, HDL-C and LDL-C were (1.13 ± 0.33)mmol/L, (1.98 ± 0.69)mmol/L, (1.82 ± 0.63)mmol/L, (2.71 ± 0.79) mmol/L respectively ( t value was 3.036-4.256, P < 0.05). Conclusion:Psychological suggestive therapy combined with dietary restriction therapy can effectively improve the resilience of elderly patients with coronary heart disease and type 2 diabetes mellitus, control the level of glycolipid metabolism, stabilize the condition and promote early recovery.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Objective To investigate the relationship between the changes of plasma thromboxane B2 (TXB2),6-keto-prostaglandin 1 α (6k-PGF1 α) and positive platelet α-granule membrane glycoprotein (CD62P) in patients with acute cerebral infarction.Methods 160 patients with acute cerebral infarction (case group) and 80 healthy subjects were enrolled in our hospital from August 2016 to August 2018.The plasma levels of 6k-PGF1α,CD62P and TXB2 were measured and analyzed.Subgroup analysis was performed on patients with cerebral infarction with different trial of org 10172 in acute stroke treatment (TOAST) classification,National Institute of Health Stroke Scale (NIHSS) score,and prognosis outcome.Results The plasma levels of 6k-PGF1α,CD62P and TXB2 in the case group were significantly higher than those in the control group (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in mild,moderate and severe groups were gradually increased (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in patients with small infarction,mid-infarction and large infarction were also gradually increased,with statistically significant difference (P ＜ 0.05);plasma 6k-PGF1 α,CD62P,TXB2 levels in patients with good prognosis were significantly lower than those in poor prognosis group (P ＜ 0.05).Conclusions The levels of plasma TXB2,6k-PGF1α and CD62P in patients with acute cerebral infarction are elevated,and are closely related to the patient's condition and prognosis.

Objective: To explore the value of bioelectrical impedance analysis in evaluating hemodialysis patients′ nutritional status. Methods: Cross-sectional design was employed to evaluate 193 hemodialysis patients′ nutritional status in a Level 3 hospital in Zhuhai, with bioelectrical impedance analysis, modified quantitative subjective global assessment, physical and biochemical measurement. The correlation between each index and the predictive effect of bioelectrical impedance analysis on malnutrition of patients were analyzed. Results: According to bioelectrical impedance analysis, hemodialysis patients′ average muscle mass was (44.06±8.84) kg, body fat rate was (19.81±8.89)%, fat free mass index was (17.70±2.45) kg/m², presumed bone mass was (2.49±0.46) kg, and extracellular water rate was (40.54±3.75)%. The bioelectrical impedance analysis indexes were significantly correlated with most other nutritional evaluation indexes (P<0.05). The muscle mass and bone mass of the malnourished group were lower than that of the well-nourished group (P<0.01). Multivariable logistic regression analysis found that body fat rate (OR=0.94, 95%CI 0.89-0.99), fat free body mass index (OR=0.79, 95%CI 0.66-0.93) were associated with lower risk of malnutrition, age (OR=1.08, 95% CI 1.04-1.12), dialysis age (OR=1.02, 95%CI 1.01-1.04), high sensitive C reactive protein (OR=1.11, 95%CI 1.03-1.23) were associated with higher risk of malnutrition. Conclusion Bioelectrical impedance analysis is a valid measurement on evaluating maintenance hemodialysis patients′ nutritional status. There has a high prevalence of malnutrition in hemodialysis patients. The lower risk of malnutrition is associated with higher body fat rate and higher fat free mass index, and the higher risk of malnutrition is associated with older age, longer dialysis age and higher level of high sensitive C reactive protein.