[Deepening the Action on Salt Reduction in China-suggestions on strategy and implementation plan].

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.

[Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement].

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

[A preliminary exploration into the efficacy of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula].

To explore the efficacy and value of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula based on the size of the maxillary sinus perforation and maxillary sinus fistula. A total of 28 patients with maxillary sinus perforation and maxillary sinus fistula who were admitted to the Department of Oral and Maxillofacial Surgery, Stomatology Hospital of Kunming Medical University from July 2017 to May 2020 were included to conduct a prospective case clinical study. After the inflammation in the maxillary sinus was controlled, a proper surgical repair method was selected according to the size of the perforation and fistula based on the double-layer closure technique. The diameter of the perforation and fistula was measured with the assistance of cone-beam CT. After that, the platelet rich fibrin (PRF) repair was performed on the perforation and fistula with 3 mm≤diameter<7 mm in size in 14 patients. The PRF repair and buccal flap repair were performed on the perforation and fistula with 7 mm ≤diameter<15 mm in size in 7 patients. The adjacent buccal pad repair, palatine flap repair, and buccal flap repair were performed on the perforation and fistula with 15 mm≤ diameter<25 mm in size in 4 patients. The nasolabial axial flap repair and nasolabial free flap repair were performed on the perforation and fistula with a diameter ≥25 mm in size in 3 patients. The medical follow-up was conducted in all patients in the 1st, 2nd, and 4th week after surgery, with an overall success rate reaching 96.4% (27/28) after the initial intervention. The relapse of disease occurred in one patient (4.6%) with diabetes and a smoking history in the 2nd week after surgery. Identifying a proper surgical repair method according to the size of the oral and maxillary sinus perforation and maxillary sinus fistula based on the double-layer closure technique can improve the one-time cure rate in these patients under the premise that the inflammation in the maxillary sinus can be controlled.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

[The risk factors of first recurrence in ischemic stroke patients in different periods after first attack].

Objective: To investigate the risk factors of first recurrence in ischemic stroke patients at different periods after first attack. Methods: The subjects were from the screening population of China National Stroke Screening Survey (CNSSS) from 2013 to 2015. The basic demographic information, stroke history, influencing factors and modified Rankin Scale (mRs) scores were collected by using standardized face-to-face questionnaires. A case-control study was conducted to investigate the risk factors of first recurrence in ischemic stroke patients who relapsed for the first time within 12 months, 24 months and 36 months as the case group and non-recurrent ischemic stroke patients as the control group. Further, the subjects were stratified into different subgroups by age, gender and urban-rural distribution to investigate the risk factors of first recurrence in different periods. Results: Diabetes (OR=1.71, 95%CI: 1.08-2.71) and coronary heart disease (OR=1.55, 95%CI: 1.09-2.19) were significantly associated with the risk of first recurrence within 12 months after the first onset of ischemic stroke. The diabetes was significantly associated with the risk of first recurrence within 24 months (OR=1.94, 95%CI: 1.33-2.83) and 36 months (OR=1.64, 95%CI: 1.15-2.34) after the first onset of ischemic stroke. With the increase of mRs score, the risk of first recurrence within 12 months, 24 months and 36 months in ischemic stroke patients increased significantly. In the same period, the risk factors of ischemic stroke recurrence differed in patients with different age, gender and urban-rural distribution. Conclusions: The risk factors of first recurrence in ischemic stroke patients are diverse at different periods after the first onset of ischemic stroke. In different subgroups, the risk factors of first recurrence and the strength of its corresponding association are also different.

[Clinical pathological features of 180 cases with primary esophageal malignant melanoma].

Objective: To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME). Methods: The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis. Results: The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients (P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients (P<0.05). Conclusions: PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

[The epidemiological characteristics and adherence to hypoglycemic agents of ischemic stroke patients with diabetes].

Objective: To investigate the epidemiological characteristics and adherence to hypoglycemic agents of the ischemic stroke patients combined with diabetes. Methods: The study recruited 23 044 ischemic stroke cases from 2013-2015 screening period of China National Stroke Screening Survey. Standardized questionnaires were used to obtain information on demographic data, stroke history, the presence of influence factors, as well as the type of stroke, diagnosis date, frequency, chronic diseases history and hypoglycemic therapy. We used logistics model to investigate the possible risk factors of ischemic stroke combined with diabetes, and calculated the population attributable risk proportion (PARP). We also investigate the adherence to hypoglycemic agents. Results: The mean age of 23 044 ischemic stroke patients was (64.99±9.42) years old, 50.91% were males (11 731). In ischemic stroke patients, 21.52% had diabetes. According to the results of logistics model, ischemic stroke patients with hypertension, dyslipidemia, atrial fibrillation or family history of stroke had higher risk to combine with diabetes, their Odds Ratios (OR) were 2.18 (1.87-2.55), 1.99 (1.78-2.23), 1.64 (1.39-1.92) and 1.19 (1.06-1.33). Considering the prevalence of each influence factor in ischemic stroke patients, atrial fibrillation had the highest PARP (95%CI) of 62.65% (61.27%-63.76%). In ischemic stroke patients combined with diabetes, 70.73% (3 463/4 896) had taken hypoglycemic agents. Conclusion: There still were a large number of ischemic stroke patients combined with diabetes and a low rate of adherence to hypoglycemic agents.

[Investigation on influencing factors of blood indexes of interventional radiology workers].

Objective: To analyze the influencing factors of blood indicators indexes of interventional radiology workers, and provide a theoretical basis for radiological occupational health monitoring, radiation protection monitoring and risk assessment. Methods: In March 2020, a total of 500 interventional radiology workers (interventional group) and 200 non-interventional radiology workers (control group) who underwent an occupational health examination in Liaoning Center for Disease Control and Prevention from 2018 to 2019 were selected as the subjects. The general information, occupation related information, blood routine, fasting blood glucose and thyroid stimulating hormone test results of the subjects were collected. The differences in the levels and abnormal detection rates of blood indexes between the two groups were compared. And the influencing factors of blood indexes of the intervention riodiology workers were analyzed. Results: The lymphocyte count of interventional group[2.10 (1.70, 2.50) ×10(9)/L] was lower than that of control group[2.20 (1.80, 2.60) ×10(9)/L], the difference was statistically significant (P<0.05) . The white blood cell count and lymphocyte count of interventional workers in the service age≤13 years were higher than those of service age≥28 years group, and fasting blood glucose was lower than those of service age ≥28 years group (P<0.05) . The detection rate of abnormal fasting blood glucose of interventional radiology workers in the service age ≤13 years group was lower than that of the service age 14-27 years and service age ≥28 years (P<0.05) . The lymphocyte count and platelet count of interventional radiology workers in annual effective dose<0.5 mSv group was higher than that of annual effective dose≥1 mSv group (P<0.05) . The results of multi-factor linear regression analysis showed that service age, annual effective dose and female gender were the influencing factors of lymphocyte count of interventional radiology workers (b=-0.008, -0.110, -0.167, P<0.05) . Conclusion: Long-term low-dose radiation exposure had certain influence on the lymphocyte count of interventional radiology workers. Service age, annual effective dose and gender are the influencing factors of lymphocyte count in interventional radiology workers. It should be reinforced to the radiological protection monitoring and risk assessment on interventional radiology workers.

Chimeric antigen receptor signaling: Functional consequences and design implications.

Chimeric antigen receptor (CAR) T cell therapy has transformed the care of refractory B cell malignancies and holds tremendous promise for many aggressive tumors. Despite overwhelming scientific, clinical, and public interest in this rapidly expanding field, fundamental inquiries into CAR T cell mechanistic functioning are still in their infancy. Because CAR T cells are manufactured from donor T lymphocytes, and because CARs incorporate well-characterized T cell signaling components, it has largely been assumed that CARs signal analogously to canonical T cell receptors (TCRs). However, recent studies demonstrate that many aspects of CAR signaling are unique, distinct from endogenous TCR signaling, and potentially even distinct among various CAR constructs. Thus, rigorous and comprehensive proteomic investigations are required for rational engineering of improved CARs. Here, we review what is known about proximal CAR signaling in T cells, compare it to conventional TCR signaling, and outline unmet challenges to improving CAR T cell therapy.

[The association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma].

Objective: To investigate the association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma (ESCC) in China. Methods: From March 2014 to September 2018, ESCC patients from three hospitals (the Affiliated Hospital of Medical College of Shantou University, Shantou Central Hospital in Southern Chaoshan area and First Affiliated Hospital of Zhengzhou University in Northern Taihang Mountain) were selected as a case group; non-esophageal patients who had a physical examination were selected as a control group. The case and control group were paired by age (±5 years) and a 1:1 ration. A total of 1 528 subjects were enrolled including 764 patients in the case group and 764 patients in the control group. About 3-5 ml venous blood samples were collected, and the erythrocyte glutathione reductase activity coefficient (GRAC) was measured to assess the whole blood riboflavin level. A multivariate conditional logistic regression model was used to analyze the association between the GRAC and the risk of ESCC. The association between the GRAC and the prognosis of ESCC was analyzed by using Cox proportional risk regression model based on 288 patients with complete survival data. They were divided into two groups, the high GRAC group (GRAC≥7.87) group and the low GRAC group (GRAC<7.87) according to the strongest correlation between the total survival time, survival outcome and GRAC (GRAC=7.87). Results: Among the 1 528 patients, 958 patients were from Southern Chaoshan area, including 479 patients in the case group with an average age about (59.90±9.34) years and 479 patients in the control group with an average age about (59.55±8.77) years. Other 570 patients were from Northern Taihang Mountain area, including 285 patients in the case group with an average age (58.39±5.19) years and 285 patients in the control group with an average age about (58.74±4.57) years. The multivariate conditional logistic regression showed that the OR (95%CI) of the GRAC and the risk of ESCC was 1.009 (0.998-1.019). The Cox proportional hazard regression model analysis showed that the HR (95%CI) of the high GRAC group was 1.712 (1.034-2.824) compared with the low GRAC group in the 50-70 years group. Conclusion: The whole blood riboflavin level might not be associated with the occurrence of ESCC. The high whole blood riboflavin level would be more beneficial to the prognosis of ESCC patients aged 50-70 years.

[Gender-specific factors of ischemic stroke among atrial fibrillation patients].

Objective: To explore gender-specific factors and their contributions to ischemic stroke among atrial fibrillation (AF) patients. Methods: A case-control study was conducted. The relevant data were obtained from the database of China National Stroke Screening Survey. The cases were first-ever ischemic stroke cases diagnosed from September 2013 to September 2015. Frequency-matched for the age and distribution of city and country, controls were randomly selected by 1∶3 ratio from individuals with AF but without stroke in the program. Altogether, there were 85 male cases (320 controls) and 147 female cases (484 controls). Unconditional logistic regression model was applied for the analysis of relevant factors of the onset of ischemic stroke, and their population-attributable risk proportion [PARP, (95%CI)] was calculated. Results: The age of male subjects in the case group and control group were (65.26±11.20) and (64.83±11.08) years old, and that of females in two groups were (63.63±10.40) and (63.93±10.35) years old. According to the PARP (95%CI), relevant factors of the onset of ischemic stroke in a descending sequence were hypertension history [35.63 (18.64-47.73)], family history of stroke [28.70 (23.63-32.30)]and physical inactivity [15.73 [5.62-23.06)] among male AF patients, and family history of stroke (29.39 (24.21-33.08)), dyslipidemia (22.17 (2.26-36.45)) and smoking [2.09 (0.76-3.24)] among female AF patients. Conclusion: The relevant factors of ischemic stroke were different between male and female AF patients.

[The association of health-related behavior and the risk of stroke in people with hypertension].

Objective: To investigate the association between the combination of different health-related behaviors and the risk of stroke in people with hypertension. Methods: The data in this study were obtained from the China National Stroke Screening Survey (CNSSS). The case group was the people with hypertension who were also diagnosed as the first-ever stroke cases (total stroke and ischemic stroke) during 2013-2014 screening period. Their corresponding controls (1∶3 frequency-matched for age group and urban/rural ratio) were randomly selected from individuals with hypertension without stroke. The information on demographic data, stroke history, influence factors and health-related behaviors (non-smoking, normal body mass index maintenance and physical activity) was obtained using standardized face-to-face questionnaires. Univariate analysis included t-test and Chi-square test. Multivariate analysis included unconditional logistic regression. Results: There were 603 total stroke cases (1 909 controls) and 536 ischemic stroke cases (1 608 controls) in men with hypertension, and 600 total stroke cases (1 800 controls) and 534 ischemic stroke cases (1 602 controls) in women with hypertension. We found that women with three health-related behaviors had lower risk of total stroke (OR=0.29, 95%CI: 0.11-0.79) and ischemic stroke (OR=0.28, 95%CI: 0.10-0.77). Only the combination of non-smoking and physical activity was significantly associated with the decreased risk of total stroke (OR=0.30, 95%CI: 0.11-0.78) and ischemic stroke (OR=0.32, 95%CI: 0.12-0.87). We had not found significant association between the combination of different health-related behaviors and risk of total stroke and ischemic stroke (P>0.05) in men. Conclusion: This study indicated that health-related behavior intervention might be more effectively to prevent stroke in women with hypertension, especially the smoking control and physical activity.

[Clinical applications of transcrestal around detached sinus floor elevation technique using osteotomes and sequential drills with stops].

Sinus floor elevation was needed in 11 patients having 15 implant sites with the residual bone height (RBH) was less than 10 mm in the posterior maxillary region from Feb to May 2017. The RBH ranged from 3.10 to 8.34 mm [averaged (6.18±1.60) mm]. RBH<6 mm was observed in 40% implant sites (6 implant sites) and RBH≥6 mm was observed in 60% implant sites (9 implant sites). The thickness of the sinus floor membrane correspond to the implant site measured by cone beam CT (CBCT) ranged from 0.50 to 4.24 mm [averaged (1.21±0.92) mm]. Sequential drills with stops were used to perforate the cortical bone of the sinus floor firstly, then the transcrestal around detached sinus floor elevation technique (TADSFET) was carried with osteotomes. Anorganic bovine bone was used as the augmentation material.Fifteen implants were placed in 15 implant sites. CBCT pictures showed that there was a smooth and continuous tent-shaped apophysis on each lifted site and no air fluid level was observed in the sinus immediately after operation. The mean elevated height of the 15 implant sites was (7.83±1.57) mm (ranged from 5.94 to 11.01 mm). The mean follow-up time was 7.91 months (7-10 months). The survival rate was 100% during the follow up period.

Characterization of tissue chromogranin A (CgA) immunostaining and clinicohistopathological changes for the 125 Chinese patients with primary small cell carcinoma of the esophagus.

The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological staging system and to clarify the mechanisms of CgA protein in PSCE progression and prognosis.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion.

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy.

Mast cells (MCs) are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration and tumor progression. Dysregulated MC development leads to systemic mastocytosis (SM), a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused MC accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-MC progenitors altering gene expression patterns to favor cell fate choices that enhanced MC specification. In addition, LIN28B-induced MCs appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of MC terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human MC leukemia samples revealed upregulation of LIN28B in abnormal MCs from patients with SM. This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in MC disease.