Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

Viral hepatitis has been causing big threat to public health globally. The number of annual deaths caused by hepatitis surpassed the deaths caused by AIDS, tuberculosis, and malaria. World Health Organization (WHO) issued the global health sector strategy on viral hepatitis 2016-2020 (GHSS) to control its epidemic. It established the Strategies and Technical Advisory Committee on HIV, viral hepatitis, and sexually transmitted infections (STAC). This paper summarizes the GHSS goals and the keynote of the 2020 STAC meeting, analyzes the challenges and opportunities faced by China in eliminating viral hepatitis, and provides the comments on the papers on this issue, which could guide further actions.

Objective:To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program.Methods:A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys.Results:A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%).Conclusions:The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.

Objective    By establishing a set of evaluation system for thoracoscopic clinical function and applicability, to evaluate and compare the advantages and disadvantages of different brands of thoracoscopes, and to provide some suggestions for the innovation and upgrade of thoracoscopes, especially for the domestic thoracoscopes. Methods    The project coordination team initially formulated the evaluation index system for the clinical function and applicability of thoracoscope by querying literature and brainstorming. The Delphi expert consultation method was used to distribute questionnaires to the selected experts. Experts provided scores which were based on the importance of each indicator, and clarified the basis of their judgment and the familiarity with the evaluation indicators. After two rounds of screening by Delphi method, a thoracoscopic clinical function and applicability satisfactory questionnaire was formed. The appropriate sample for pre-investigation was selected, and the reliability and validity were tested. The index composition was adjusted based on the results of the test to form a final evaluation scale. Results    The project coordination team initially formulated 24 thoracoscope-related evaluation indicators. After two rounds of experts consultation, the item "brightness adjustment" was deleted without any additional entries. The positive coefficients of the experts in the first round and the second round were 100.0% and 80.0%, respectively. The two rounds of authoritative coefficients were 0.86 and 0.90, and the coordination coefficients were 0.272 (P<0.001) and 0.523 (P<0.001), respectively. A total of 140 questionnaires were issued in this pre-investigation. The recovery rate was 100.0% and the effective rate was 90.0%. The Cronbach's α value of the scale was 0.936, and the Spearman-Brown split-half reliability coefficient was 0.972. The factor analysis finally extracted 3 common factors. The total variance of the cumulative interpretation was 70.9%. The three common factors were named "operation related", "image related" and "device related". Conclusion    The evaluation index system developed in this study has good reliability and validity, and can be used as a tool to evaluate the clinical function and applicability of thoracoscopes.

Objective:To explore the feasibility and safety of minimally invasive surfactant administration (MISA) in preterm neonates with respiratory distress syndrome (NRDS).Methods:In this multicenter prospective randomized controlled trial, 92 preterm infants with gestation age ≤30 weeks and diagnosed with NRDS were enrolled in 8 level Ⅲ neonatal intensive care units (NICU) in Beijing-Tianjin-Hebei Region from 1 st July 2017 to 31 st December 2018. They were randomly assigned to minimally invasive surfactant administration (MISA) group or endotracheal intubation surfactant administration (EISA) group according to random number generated by computer. Infants in both groups received calf pulmonary surfactant preparation at a dose of 70-100 mg/kg. The data of demography, perinatal situation, medication administration, complications, clinical outcomes in the two groups were compared with Chi-square test, Student′s t-test, Mann-Whitney U test or Fisher′s exact test. Results:Among the 92 preterm infants, 53 were males, 39 were females; 47 were in the MISA group (25 males), and 45 were in the EISA group (28 males). The gestational age and birth weight were (29.5±1.2) weeks and (1 271±242) g in all patients, (29.5±1.4) weeks and (1 285±256) g in the MISA group, and (29.6±0.9) weeks and (1 255±227) g in the EISA group. The duration of surfactant infusion and the length of whole procedure in the MISA group were significantly longer than that in the EISA group (60 (18, 270) s vs. 50 (30, 60) s, Z=3.009, P=0.003; 90 (60, 300) s vs. 60 (44, 270) s, Z=3.365, P=0.001). For the outcomes, the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and bronchopulmonary dysplasia (BPD) were lower in the MISA group than in the EISA group (36% (17/47) vs. 67% (30/45), χ 2=8.556, P=0.003; 26% (12/47) vs. 47% (21/45), χ 2=4.464, P=0.035). Conclusions:Minimally invasive surfactant administration is applicable in preterm infants ≤30 weeks gestational age with NRDS. Although the length of whole procedure is longer than route endotracheal administration, the benefit of decreasing the incidences of hsPDA and BPD outweighs this demerit.

Amyloid deposits are one of the hallmark pathological lesions of Alzheimer's disease (AD). They can be visualized by thioflavin-S, silver impregnation, Congo red staining, and immunohistochemical reactions. However, that amyloid deposits generate blue autofluorescence (auto-F) has been ignored. Here, we report that visible light-induced auto-F of senile plaques (SPs) was detected and validated with conventional methods. Brain slices from APP/PS1 (amyloid precursor protein/presenilin 1) transgenic mice were mounted on slides, rinsed, coverslipped and observed for details of the imaging and spectral characteristics of the auto-F of SPs. Then the slices were treated with the above classic methods for comparative validation. We found that the SP auto-F was greatest under blue-violet excitation with a specific emission spectrum, and was much easier, more sensitive, and reliable than the classic methods. Because it does not damage slices, observation of auto-F can be combined with all post-staining techniques in slices and for brain-wide imaging in AD.

Objective To study the association, clinical presentation, and diagnosis and treatment of bile duct cancer as a late complication of biliary-enteric anastomoses for benign diseases. Methods A retrospective study was carried out on 5 patients and the medical literature was reviewed. Results They were 3 males and 2 females. The average age was ( 66. 0 ± 0. 7 ) years. The average time period was ( 14. 0 ± 6. 1 ) years after biliary-enteric anastomosis. The clinical presentations included right upper quadrant pain, fever, chills and jaundice. CA19-9, CT and MRI were valuable in diagnosis. There were two patients with distal and three patients with perihilar cholangiocarcinomas (type IIIa, n=2, and type IV, n=1). Local resection with lymphadenectomy was carried out in one patient. Another patient underwent pancreaticoduodenectomy. The remaining three patients only underwent percutaneous transhepatic cholangial drainage ( PTCD). The 2 patients who underwent surgery died of progressive tumor disease at 8 and 13 months postoperatively. The other three patients who underwent palliative biliary drainage died within 6 months of PTCD. There was no significant difference between the two types of treatment ( P ＞0. 05). Conclusions Chronic cholangitis caused by reflux and bacterial infection was properly a predisposing factor leading to late development of bile duct cancer after biliary-enteric anastomosis for benign diseases. Patients treated with biliary-enteric anastomosis should be closely monitored for late development of cholangiocarcinoma. Some procedures such as choledochoduodenostomy and jejunum interposition choledochoduodenostomy should be abandoned because of their poor outcomes and severe complications. Proper indications of biliary-enteric anastomosis should strictly be followed and the Oddi's sphincter should be protected if possible to prevent late development of bile duct cancer.

Objective To present the initial clinical experience of robot-assisted thoracoscopic esophagectomy for patients with esophageal cancer and to analyze the short-term outcomes of these patients. Methods Between February 2016 and December 2017, 148 patients with esophageal carcinoma underwent robotic esophagectomy and two-fields lymph node dissection. There were 126 males and 22 females at average age of 62.0±8.0 years. Demographic data, intraoperative characteristics and short-term surgical outcomes were collected and analyzed. Results 106 patients underwent McKeown esophagectomy and 42 patients underwent Ivor-Lewis esophagectomy. The mean operation time was 336.0±76.0 min, the mean intraoperative blood loss was 130.0±89.0 ml, the mean number of lymph nodes removed was 21.0±8.0 and the mean length of postoperative hospital-stay was 12.0±7.2 days. Postoperative complications included anastomotic fistula (n=8, 5.4%), pulmonary infection (n=13, 8.7%), hoarseness (n=23, 15.5%), tracheoesophageal fistula (n=1, 0.7%), chylothorax (n=4, 2.7%) and incision infection (n=2, 1.4%). There was no intra-operational massive hemorrhage or in-hospital mortality. Conclusion Both robot-assisted McKeown and Ivor-Lewis esophagectomy are safe and feasible with good early outcomes.