Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials.

BACKGROUND: SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD. RESULTS: In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors. CONCLUSIONS: SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.

Impact of high-intensity interval training on cardiorespiratory fitness, body composition, physical fitness, and metabolic parameters in older adults: A meta-analysis of randomized controlled trials.

High-intensity interval training (HIIT) can effectively increase peak oxygen consumption, body composition, physical fitness, and health-related characteristics of adults; however, its impact in the older population remains highly debated. This review and meta-analysis aimed to evaluate the effects of high-intensity interval training on cardiorespiratory fitness, body composition, physical fitness, and health-related outcomes in older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until July 2020) for randomized trials comparing the effect of HIIT on physical fitness, metabolic parameters, and cardiorespiratory fitness in older adults. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies; Stata 14.0 software was used for statistical analysis. HIIT significantly improved the maximum rate of oxygen consumption (VO2peak) as compared to a moderate-intensity continuous training (MICT) protocol (HIIT vs. MICT: weighted mean difference = 1.74, 95% confidence interval: 0.80-2.69, p < 0.001). Additional subgroup analyses determined that training periods >12 weeks, training frequencies of 2 sessions/week, session lengths of 40 min, 6 sets and repetitions, training times per repetition of >60 s, and rest times of <90 s were more effective for VO2peak. This systematic review and meta-analysis showed that HIIT induces favorable adaptions in cardiorespiratory fitness, physical fitness, muscle power, cardiac contractile function, mitochondrial citrate synthase activity, and reduced blood triglyceride and glucose levels in older individuals, which may help to maintain aerobic fitness and slow down the process of sarcopenia.

Investigation of mean glandular dose in diagnostic mammography in China.

A survey of 420 exposures of mammography was performed with the parameters recorded. Entrance skin air kerma (ESAK) was measured and the mean glandular dose (MGD) was calculated according to the Dance's formula. Correlation analysis showed that several factors could affect the MGD level. Mann-whitney test and Non-parametric ANOVA analyses were used to compare the MGD level grouped by view type and radiographic systems. No significant difference was found in MGD between the craniocaudal (CC) group and the mediolateral oblique (MLO) group. The MGD level was higher in the CR group than in the other two groups. MGD was positively correlated with the compressed breast thickness (CBT). MGD varied with the half value layer (HVL) and increased first then decreased. The mean MGD level in China is about 1.6 mGy and is lower than the guidance level in the International Basic Safety Standards (IBSS).

Monotonicity, concavity, and convexity of fractional derivative of functions.

The monotonicity of the solutions of a class of nonlinear fractional differential equations is studied first, and the existing results were extended. Then we discuss monotonicity, concavity, and convexity of fractional derivative of some functions and derive corresponding criteria. Several examples are provided to illustrate the applications of our results.

(2E,4E)-2-Cyano-5-dipropyl-amino-N,N-dimethyl-penta-2,4-dienamide.

In the title compound, C(14)H(23)N(3)O, the n-propyl group is disordered over two orientations with an occupancy ratio of 0.778 (3):0.222 (3). In the crystal, mol-ecules are linked by pairs of weak C-H⋯O inter-actions into inversion dimers with an R(2) (2)(14) graph-set motif.

[Application of wavelet neural networks model to forecast incidence of syphilis].

OBJECTIVE: To apply Wavelet Neural Networks (WNN) model to forecast incidence of Syphilis. METHODS: Back Propagation Neural Network (BPNN) and WNN were developed based on the monthly incidence of Syphilis in Sichuan province from 2004 to 2008. The accuracy of forecast was compared between the two models. RESULTS: In the training approximation, the mean absolute error (MAE), rooted mean square error (RMSE) and mean absolute percentage error (MAPE) were 0.0719, 0.0862 and 11.52% respectively for WNN, and 0.0892, 0.1183 and 14.87% respectively for BPNN. The three indexes for generalization of models were 0.0497, 0.0513 and 4.60% for WNN, and 0.0816, 0.1119 and 7.25% for BPNN. CONCLUSION: WNN is a better model for short-term forecasting of Syphilis.

[Risk factors for patent ductus arteriosus in neonates].

OBJECTIVE: To identify the risk factors for patent ductus arteriosus (PDA) in neonates. METHODS: Fifty infants with PDA and 100 infants without PDA were enrolled. Chi-square test, Student's t test and the linear correlation analysis were used to study the clinical data. Logistic regression analysis was used to investigate the independent risk factors for PDA. RESULTS: The prevalence of PDA was negatively correlated with the gestation age (r=-0.03, P<0.05) and birth weight (r=-0.04, P<0.05). Oxygen inhalation was a protective factor for the development of PDA. Fetal distress, meconium-stained amniotic fluid, oligohydramnios, cord entanglement, 1 minute Apgar score <8, maternal infection and hypoxic-ischemic encephalopathy were the independent risk factors for the development of PDA. CONCLUSIONS: The incidence of PDA can be reduced by preventing maternal infection, premature birth, low birth weight and hypoxia.

[Public health situation and needs assessment after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the public health situation and needs in Anxian after Wenchuan earthquake so as to make an effective strategy for disease control and prevention. METHODS: 69 concentrated settlements with 100 residents were investigated. Probability proportion to size was adopted for sampling of 2200 residents from 687 scattered households (about 440 000 scattered residents). The content of this survey included drinking water, food hygiene, environment sanitation, planning immunity and medical health service, disease surveillance and so on. SPSS 16.0 was used for data analysis, and statistical interpretation was used to describe the results. RESULTS: 90.9% (31/66) resettled residents in Anxian lived in tents, 7.6% (5/66) lived in the movable-plate house, 93.3% (621/666) scattered households lived in tents and 71.9% (446/621) of them lived in tents which were built by residents themselves; the rate of drinking water disinfection in resettlement sites and scattered households were 97.1% (66/68) and 94.6% (650/687); 12.8% scattered residents had mouldy or food; 50% of resettlement sites raised animals; 43.6% (17/39) medical station didn't have bacterin inoculation service; 66.7% (10/15) lacked sufficient disinfection equipment; register rate was 50.0% (33/66) and report rate of symptoms and infectious diseases was 56.1% (37/66). CONCLUSION: There was still some risk of enteric and vector-borne diseases in Anxian, therefore, some tailored measures should be very important.

[Mental health assessment among scattered residents after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the mental health status of residents scattered living in Anxian after Wenchuan earthquake so as to provide scientific basis for further mental health intervention. METHODS: A face to face interview was conducted among the scattered residents with designed questionnaire, which had three parts of the physical and emotional reaction, the relax methods and the social care and supports expected. Two-stage probability proportional to size (PPS) sample method was performed to sample 2184 from 0.44 million scattered residents in Anxian. On the basis of statistical description, mental health of different characteristics groups was compared. RESULTS: Three main symptoms of posttraumatic stress disorders in 2184 residents (11.23+/-3.44) were higher than the 103 fire victims in Hunan in 2003 (10.06+/-3.26), three factor scores of SCL-90 (5.76+/-1.74) were higher than normal in 1998 repair mode (n=23 891) (4.72+/-1.44), and the statistical difference was observed (t=10.77, P<0.05; t=706.04, P<0.05). Comparing the mental health of different groups, some significant differences were found by age, gender and education background. CONCLUSION: The earthquake disaster brought prevalent physical and emotional reaction. Elderly people, female, junior students need mental intervention immediately. Therefore, strengthen the mental education and assistance (especially in high risk groups) would be of more significance.