Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Objective:To investigate the prevalence and the risk factors of Helicobacter pylori( H. pylori) infection in Qinghai Province with a multi-center cross-sectional study. Methods:From May to December in 2021, stratified sampling was conducted in Xining City, Haidong agricultural district, Hainan Tibetan Autonomous Prefecture, Haibei Tibetan Autonomous Prefecture and Yushu Tibetan Autonomous Prefecture by 20 centers, including the Affiliated Hospital of Qinghai University, Qinghai Red Cross Hospital and Qinghai Renji Hospital, etc. A questionnaire survey was carried out among the individuals undergoing routine health checkups. The questionnaire included general information, lifestyle and family history, etc. 13C-urea breath test was performed to diagnose H. pylori infection. Chi-square test, trend Chi-square test, segmentation method and multivariate logistic regression analysis were performed for statistical analysis. Results:The infection rate of H. pylori in Qinghai area was 53.6% (2 531/4 724). The age distribution of infection was statistically significant ( χ2=15.95, P=0.007), the infection rate in individuals aged 15 to<30 was higher than that of individuals aged 60 to< 75 (57.6%, 626/1 086 vs.49.5%, 231/467), and the difference was statistically significant ( χ2=8.83, P=0.003). With the increase of age, the infection rate decreased in female over 30 years old ( χ2trend=5.89, P=0.015). There were statistically significant differences in H. pylori infection rate among different ethnic groups ( χ2=28.13, P<0.001); the infection rate of Tibetan population was higher than that of Han population (62.9%, 313/498 vs. 51.5%, 1 804/3 503), and the difference was statistically significant ( χ2=22.56, P<0.001). The H. pylori infection rate in people living at an altitude >3 500 m was higher than that of people living at an altitude between 1 500 m and 3 500 m (61.8%, 327/529 vs. 52.5%, 2 204/4 195), and the difference was statistically significant ( χ2=16.25, P<0.001). Compared with those without corresponding habits, the infection rate of H. pylori was higher in smokers (62.1%, 1 081/1 740 vs. 48.6%, 1 450/2 984), in people who had the habit of eating hand grabbed mutton (55.4%, 967/1 744 vs. 52.5%, 1 564/2 980), raw garlic (55.5%, 968/1 744 vs. 52.4%, 1 563/2 980), spicy food (55.6%, 1 471/2 647 vs. 51.0%, 1 060/2 077), sweet food (55.2%, 1 187/2 149 vs. 52.2%, 1 344/2 575), the infection rate of tea drinkers was lower (50.5%, 1 135/2 247 vs. 56.4%, 1 396/2 477), and the differences were statistically significant ( χ2=80.94, 3.89, 9.63, 4.36, 4.13 and 16.19, all P<0.05). The results of logistic regression analysis indicated that Tibetan ( OR=1.379, 95% confidence interval (95% CI) 1.120 to 1.699), the Hui people ( OR=1.362, 95% CI 1.117 to 1.662), living at an altitude over 3 500 m ( OR=1.355, 95% CI 1.107 to 1.657), smoking ( OR=1.847, 95% CI 1.629 to 2.094), and spicy food ( OR=1.224, 95% CI 1.084 to 1.382) were independent risk factors of H. pylori infection (all P<0.05). Conclusions:The infection rate of H. pylori in Qinghai Province is higher than the average level in inland China. The infection rate of people with different ages, nationalities, altitudes of residence, occupations, living and eating habits were different. The infection rate of female over 30 years old is decreasing year by year. The infection risk is high in Hui people and Tibetan, spicy food lovers, smokers and people living at an altitude >3 500 m.

Objective:To discuss the diagnostic value of the quantitative analysis of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant subpleural lung lesions.Methods:A total of 299 cases of ultrasound-guided percutaneous lung puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2019 to June 2019 were selected and divided into benign group and malignant group. The time-intensity curve (TIC) parameters of CEUS before puncture in both groups were reviewed and compared with the corresponding pathological results, including the arrival time (AT), the AT intensity, the time to peak intensity (TTP), and maximum intensity (IMAX) of the lesions, the net enhancement of intensity of the lesions, the reduced-by-half intensity and the reduced-by-half time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio. The receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) and the optimal cut-off point were calculated.Results:Among the quantitative parameters of CEUS, there were statistically significant differences between the benign group and malignant group in terms of the AT, AT intensity, TTP, the reduced-by-half intensity and time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio ( P<0.05); while there was no statistically significant difference between the benign group and malignant group in terms of the IMAX and the net enhancement of intensity of the lesions ( P>0.05). The AUC of time ratio was the largest (0.845); the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 86.2%, 79.3%, 84.3%, 92%, and 68%, respectively, when the time ratio was at or above 51.89%. Conclusion:Multiple TIC parameters of CEUS quantitative analysis have shown significant differences in differentiating benign and malignant subpleural lung lesions, especially, the parameter of time ratio can provide a basis for clinical differential diagnosis.

Objective:To discuss the diagnostic value of the quantitative analysis of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant subpleural lung lesions.Methods:A total of 299 cases of ultrasound-guided percutaneous lung puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2019 to June 2019 were selected and divided into benign group and malignant group. The time-intensity curve (TIC) parameters of CEUS before puncture in both groups were reviewed and compared with the corresponding pathological results, including the arrival time (AT), the AT intensity, the time to peak intensity (TTP), and maximum intensity (IMAX) of the lesions, the net enhancement of intensity of the lesions, the reduced-by-half intensity and the reduced-by-half time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio. The receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) and the optimal cut-off point were calculated.Results:Among the quantitative parameters of CEUS, there were statistically significant differences between the benign group and malignant group in terms of the AT, AT intensity, TTP, the reduced-by-half intensity and time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio ( P<0.05); while there was no statistically significant difference between the benign group and malignant group in terms of the IMAX and the net enhancement of intensity of the lesions ( P>0.05). The AUC of time ratio was the largest (0.845); the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 86.2%, 79.3%, 84.3%, 92%, and 68%, respectively, when the time ratio was at or above 51.89%. Conclusion:Multiple TIC parameters of CEUS quantitative analysis have shown significant differences in differentiating benign and malignant subpleural lung lesions, especially, the parameter of time ratio can provide a basis for clinical differential diagnosis.