Toxoplasmosis is caused by the intracellular protozoan Toxoplasma gondii. It is anopportunistic zoonosis in warm-blooded animals and humans, with a worldwide distribution. Toxoplasma gondii dense granule protein 16 (TgGRA16) can modulate some functions in host cells and is considered a significant virulent factor of the parasite. The present study reports sequence variation in TgGRA16 gene among T. gondii strains from different hosts and geographical locations, and the construction of phylogenetic relationships of these T. gondii strains based on sequences of TgGRA16, and analysis of B cell epitopes in TgGRA16. Our results showed that all TgGRA16 gene sequences were 1518 bp and the C+G contents ranged from 52.17% to 52.59%. Sequence variation in the TgGRA16 gene was 0-1.51%. Phylogenetic analysis revealed that TgGRA16 gene sequence could not be used to differentiate the different T. gondii genotypes. Six B cell epitopes were predicted in TgGRA16. These results indicated that TgGRA16 gene is not an ideal marker for studying genetic relationships of T. gondii isolates, but may represent a good vaccine candidate against toxoplasmosis.

BACKGROUND/AIMS: There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. METHODS: Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. RESULTS: The GRR and SPR were improved by noise stress compared with control (P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and malondialdehyde in gastric mucosa homogenate were increased by noise stress (P < 0.05). CGRP and superoxide dismutase activity in both of blood plasma and gastric mucosa homogenate were significantly decreased (P< 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde (P < 0.05). CONCLUSIONS: Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones.
Animals ; Gastric Mucosa ; Gastrointestinal Hormones* ; Gastrointestinal Motility* ; Hydrocortisone ; Injections, Intraperitoneal ; Intestine, Small ; Malondialdehyde ; Melatonin* ; Motilin ; Noise* ; Oxidative Stress* ; Plasma ; Rats* ; Superoxide Dismutase ; Ulcer*

OBJECTIVE: To explore the relationship between physiological parameters changes and severe heatstroke induced by 5-km armed cross-country training. METHODS: A total of 521 male officers and soldiers from a special team who participated in the summer training of 5-km armed cross-country training from year 2016 to 2017 were enrolled. All trainees participated in 5-km armed cross-country training in high temperature and humidity environment of ambient temperature > 32 centigradeand (or) relative humidity > 65%. The trainees were divided into two groups according to the incidence of severe heatstroke in the course of training. The age, enlistment time, constitution score, body mass index (BMI), external environment (ambient temperature, relative humidity, wind speed, heat index) of trainees of the two groups, and the change rates of arterial blood oxygen saturation (SaO₂), body temperature, pulse and blood pressure within 5 minutes after the 5-km armed cross-country training were compared between the two groups. The risk factors of severe heatstroke were screened by two classified Logistic regression analysis, and the predictive value of various risk factors of severe heatstroke was analyzed by the receiver operator characteristic curve (ROC). RESULTS: In 521 trainees of 5-km armed cross-country training, 29 trainees suffered from severe heatstroke accounting for 5.57%. There was no significant difference in the age, enlistment time, constitution score, BMI, or external environment during 5-km armed cross-country training between severe heatstroke group and non-severe heatstroke group. Compared with those without severe heatstroke, the descending rates of body temperature, pulse, blood pressure and SaO₂ increased rate within 5 minutes after 5-km armed cross-country training of severe heatstroke trainees were significantly decreased [temperature descending rate: (0.67±0.30)% vs. (1.43±1.28)%, pulse descending rate: (7.53±5.21)% vs. (13.48±8.07)%, blood pressure descending rate: (9.28±6.84)% vs. (19.42±7.73)%, SaO₂ increased rate: (0.51±0.39)% vs. (1.50±1.43)%, all P < 0.01]. Two classification Logistic regression analysis showed that the temperature descending rate [odds ratio (OR) = 0.485, 95% confidence interval (95%CI) = 0.289-0.817], pulse descending rate (OR = 0.903, 95%CI = 0.845-0.965), blood pressure descending rate (OR = 0.841, 95%CI = 0.790-0.896), and SaO2 increased rate (OR = 0.421, 95%CI = 0.250-0.711) were the risk factors for severe heatstroke during 5-km armed cross-country training (all P < 0.01). ROC curve analysis showed that temperature descending rate [area under ROC curve (AUC) = 0.659, 95%CI = 0.604-0.714], pulse descending rate (AUC = 0.730, 95%CI = 0.762-0.900), blood pressure descending rate (AUC = 0.831, 95%CI = 0.659-0.801), SaO₂ increased rate (AUC = 0.711, 95%CI = 0.655-0.767) could be used for the incidence of severe heatstroke prediction during 5-km armed cross-country training (all P < 0.01), and the predicted value was the same. CONCLUSIONS Under the same conditions, the severe heatstroke during 5-km cross-country training is closely related to the descending rates of body temperature, pulse, and blood pressure as well as SaO₂ increased rate within 5 minutes after the training, whose predictive values for severe heatstroke were the same.
Blood Pressure ; Heart Rate ; Heat Stroke ; Hot Temperature ; Humans ; Male ; Risk Factors

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.
Humans ; Neuroendocrine Tumors ; Pituitary Neoplasms/pathology* ; Pituitary Hormones ; Growth Hormone/metabolism* ; Keratins

Objective: Data from the surveillance program was collected, to analyze the situation of hospitalization and cases of death with recorded causes, in Shenzhen, from 1995 to 2014. Situation of hospitalization and causes of deaths were studied in Shenzhen which had been a fast-developing city with growing number of immigrants so as to provide reference for decision-making on related prevention and control strategies. Methods: Data on hospitalizations and deaths collected from the surveillance program, were classified by both International Classification of Diseases (ICD)- 9 and ICD-10. A database was constructed with methods on related descriptive and trend analysis. Results: Around 6.3 million inpatients were seen in the past two decades in Shenzhen. The top five diseases for hospitalization were pregnancy childbirth and puerperium complications, respiratory diseases, injury and poisoning, digestive system diseases and circulatory system diseases, that accounting for 68.4% of all the hospitalization burden. The number of inpatients increased annually, with an 11 times increase during the past two decades. Proportions for pregnancy childbirth and puerperium complications, circulatory system diseases and urinary system diseases all showed increasing (χ(2)=53 806.94, 6 893.95 and 15 383.14, P<0.01), while proportions for injuries and poisoning, respiratory diseases, digestive system diseases showed a declining trend (χ(2)=131 480.09,1 711.84 and 11 367.66, P<0.01). Number of cumulative inpatient deaths exceeded 60 000, with the top five causes as malignant tumor, circulatory system diseases, injury and poisoning, respiratory system diseases and digestive system diseases, that accounting for 82.28% of all the inpatient deaths. Deaths due to circulatory system diseases, injury and poisoning increased and then decreased. Malignant tumor and respiratory diseases-induced deaths showed an increasing trend (χ(2)=1 546.48, 309.55, P<0.01), while induced deaths from disease of the other systems showed slight changes. The overall case fatality rate showed an annual decline (χ(2)=4 378.63, P<0.01), from 2.23% in 1995 to 0.74% in 2014, with mortality attribute to tumor, circulatory system disease decreased significantly. Conclusions: Shenzhen had been under an ageing transition, with relatively young population living in the city. Chronic diseases such as tumor gradually had become the major causes for heavy hospitalization burden on the population of Shenzhen.
Cardiovascular Diseases/epidemiology* ; Cause of Death ; China/epidemiology* ; Female ; Global Burden of Disease ; Hospitalization/statistics & numerical data* ; Humans ; Neoplasms/epidemiology* ; Pregnancy ; Pregnancy Complications/epidemiology* ; Respiratory Tract Diseases/epidemiology*

Objective: To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population. Methods: All participants were selected from a prospective cohort study based on a rural population from Henan province, China. Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality. Restricted cubic spline models were used to detect the dose-response relation. Results: Among the 5 461 hypertensive patients, a total of 31 048.38 person-years follow-up was conducted. The median of follow-up time was 6 years, and 589 deaths occurred during the follow-up period. Compared to normal weight group (18.5 kg/m(2)%CI: 0.37-1.87), 0.81 (95%CI: 0.67-0.97), and 0.72 (95%CI: 0.56-0.91), respectively. The dose-response analysis showed a nonlinear, reverse "S" shaped relationship (non-linearity P<0.001). Conclusion: Overweight or obese might have a protective effect on all-cause mortality in hypertensive population, which supports the "obesity paradox" phenomenon.
Adult ; Asian People/statistics & numerical data* ; Blood Pressure/physiology* ; Body Mass Index ; Cause of Death ; China/epidemiology* ; Humans ; Hypertension/mortality* ; Middle Aged ; Mortality ; Obesity/mortality* ; Overweight ; Prospective Studies ; Risk Factors ; Young Adult

Objective: To study the modification effect of age on the association between body mass index and the risk of hypertension. Methods: People age ≥18 years old were selected by clusters, from a rural area of Henan province. In total, 20 194 people were recruited at baseline during 2007 and 2008, and the follow-up study was completed from 2013 to 2014. Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI. Results: During the 6-year follow-up period, 1 950 hypertensive persons were detected, including 784 men and 1 166 women, with cumulative incidence rates as 19.96%, 20.51%, and 19.61%, respectively. Compared with those whose BMI<22 kg/m(2), the RRs of hypertension were 1.09 (0.93-1.27), 1.17 (1.01-1.37), 1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-, 24-, 26- and ≥28 kg/m(2), respectively. In young and middle-aged populations, the risk of hypertension gradually increased with the rise of BMI (trend P<0.05). However, in the elderly, the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05). Conclusion: The effect of BMI on the incidence of hypertension seemed to depend on age. Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations, to prevent the development of hypertension.
Adolescent ; Age Factors ; Aged ; Asian People/statistics & numerical data* ; Body Mass Index ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hypertension/ethnology* ; Incidence ; Logistic Models ; Male ; Middle Aged ; Risk Factors ; Rural Population

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
Apoptosis ; drug effects ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Humans ; Ligands ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; genetics ; metabolism ; Oximes ; metabolism ; pharmacology ; Protein Conformation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrazoles ; metabolism ; pharmacology ; Retinoid X Receptor alpha ; chemistry ; genetics ; metabolism ; Thiazoles ; metabolism ; pharmacology ; Transcription, Genetic ; drug effects ; Transcriptional Activation ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

Objective: To understand the seasonal distribution of patient hospitalization due to asthma exacerbation in 7 geographic areas in China. Methods: This was a retrospective study which involved patients hospitalized for asthma exacerbation in 29 hospitals throughout 7 geographic areas in the mainland of China (northeast, north, central, east, south, northwest and southwest). The numbers of asthmatic patients and total inpatients of the respiratory department of each hospital were recorded. The monthly ratio of asthmatic patients to the total inpatients in every area was calculated and compared. Results: During the study period, 6 480 patients were admitted for asthma exacerbation, accounting for 3.14% of all the 206 135 patients admitted to the respiratory departments in the 29 hospitals. The ratio of asthmatic patients to total inpatients in the northeast area (5.61%) was highest, and the ratio in east area was lowest (1.97%). Statistical analysis showed that the difference among different areas was significant (P<0.000 1). In most areas, both the number and proportion of hospitalized asthmatic patients peaked in spring (February-April) and autumn (September-October). In the northeast area, east area and south area, the peaks in spring were more obvious, while in the north area and southwest area, the peaks in autumn were more obvious. In the northwest area the peaks occurred in winter (December-January) and summer (June-August), respectively. The differences in hospitalization due to asthma among different months were significant in the northeast, north, and southwest areas (P<0.005). Conclusion: The number of patients hospitalized for asthma exacerbation fluctuated with season in different areas in China. In most areas, more asthmatic patients were admitted to hospitals in spring and autumn.
Asthma ; China/epidemiology* ; Hospitalization/statistics & numerical data* ; Humans ; Retrospective Studies ; Seasons