Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study.

PURPOSE: Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS: This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS: All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION: Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.

Association between workplace health promotion service utilisation and depressive symptoms among workers: a nationwide survey.

OBJECTIVES: Workplace-related factors are associated with the risk of depression. Despite implementation of workplace health promotion (WHP) programmes in China to promote the physical and mental well-being of workers, the relationship between WHP and depression has received limited attention. This study investigated the association between WHP service utilisation and depressive symptoms among workers. STUDY DESIGN: This was a cross-sectional survey. METHODS: A researcher-designed questionnaire was used to collect information on socio-demographic and occupational characteristics, WHP service utilisation, and mental health status. The Lasso method was used for variable selection to achieve dimension reduction, and logistic regression was used to assess the association between WHP service utilisation and depressive symptoms. RESULTS: The analysis included 11,710 workers, of whom 17.0% had depressive symptoms. Lasso regression resulted in 6 of 18 WHP services showing significant negative associations with depressive symptoms, including occupational safety training, mental health services, health check-ups, sports activities, fitness rooms, and healthy canteens. The logistic regression results showed that, after adjusting for sociodemographic and occupational factors, utilisation of these six services was associated with a decreased likelihood of depressive symptoms. The adjusted odds ratio (aOR) was 0.84 (95% confidence interval [CI]: 0.73-0.96) for occupational safety training, aOR: 0.82 (95% CI: 0.68-0.99) for mental health services, aOR: 0.80 (95% CI: 0.71-0.90) for health check-ups, aOR: 0.68 (95% CI: 0.57-0.80) for sports activities, aOR: 0.59 (95% CI: 0.47-0.74) for fitness rooms and aOR: 0.72 (95% CI: 0.59-0.87) for healthy canteens. CONCLUSIONS: Utilisation of WHP services was associated with a lower prevalence of depressive symptoms. Implementation of WHP services and the provision of a supportive workplace environment should be prioritised to benefit the mental health of workers.

[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

[Discrepancy between behavioral-indicated and perceived candidacy for HIV pre-exposure prophylaxis among men who have sex with men in Chengdu, China].

OBJECTIVE: To explore the discrepancy between behavioral-indicated candidacy and perceived candidacy (behavioral-perceived gap) and its associated factors of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM), so as to identify the focus population of PrEP interventions and to design and implement targeted interventions. METHODS: We recruited a sample of 622 HIV-negative MSM who were regular clients of a community-based organization located in Chengdu, China, from November to December 2021. A cross-sectional questionnaire was used to collect the participants' information on social demographics, PrEP-related knowledge and cognitions, and risk behaviors. In this study, behaviorally eligible for PrEP was defined as performing at least one type of high-risk behavior in the past six months, including inconsistent condom use, sex with an HIV-positive partner, confirmed sexual transmitted infections (STI) diagnosis, substance use, and post-exposure prophylaxis (PEP) experience. Logistic regression models were fitted, and multivariate analyses were adjusted for social demographics. RESULTS: Among the 622 eligible participants, 52.6% (327/622) were classified as behaviorally eligible for PrEP. Only 37.9% (124/327) of the participants perceived themselves as appropriate candidates for PrEP and 62.1% (203/207) had discrepancy between behavioral-indicated and perceived candidacy. 85.9% (281/327) had heard of PrEP, and 14.2% (40/281) accessed PrEP information through health care providers. Of the 327 participants eligible for behavior-indicated PrEP use, about half (47.1%) knew how to obtain PrEP medication and 33.0% had a professional PrEP counseling experience. The majority (93.3%) had no or few friends using PrEP. 54.1% scored eight or above in PrEP knowledge level. 66.7% reported having two or more sexual partners in the past six months. After adjusting for age and recruitment channel, we found six factors that were associated with perceived candidacy for PrEP, including PEP use [adjusted odds ratio (ORA)=2.20; 95% confidence interval (CI): 1.33-3.63], PrEP availability (ORA=1.69; 95%CI: 1.06-2.68), a greater number of PrEP-using friends (ORA=4.92; 95%CI: 1.77-13.65), PrEP know-ledge (ORA=2.21; 95%CI: 1.38-3.56), multiple sexual partnership (ORA=1.77; 95%CI: 1.07-2.94), and perceiving a higher risk of HIV infection (ORA=4.02; 95%CI: 1.73-9.32). Substance use during sex and PrEP information channel were not statistically associated with this beha-vioral-perceived gap. CONCLUSION: We observed a high discrepancy between behavioral-indicated and perceived candidacy for PrEP among Chengdu MSM in China. Future PrEP implementation efforts should be made in skills training in assessing HIV infection risk, increasing PrEP knowledge, providing professional PrEP counselling, and fostering PrEP support environment.

[An investigation on the nutritional status and support of in-patients with common variable immunodeficiency].

The study aimed to reveal for the first time the clinical characteristics, nutritional and metabolic status and support of hospitalized patients with common variant immunodeficiency disease (CVID), and provide reference to improve the long-term nutritional management for such patients. This is a retrospective cross-sectional study. Through searching the electronic medical record system of Peking Union Medical College Hospital, the study included 33 consecutive in-patients with CVID diagnosed in Jan 2016 to Jun 2021, with the male to female ratio of 16∶17. All their medical data, nutritional assessment and intervention retrospectively summarized and analyzed. Data with normal distribution were described using (x¯±s), and analyzed with independent sample t-test. Data with non-normal distribution were compared with non-parametric test. The results showed that the median onset-age of the included patients was 22 (10.0,36.5) years old, and the median duration was 9.0 (2.0,16.0) years. All patients had recurrent infections involving various systems (33/33), with development of autoimmune diseases (8/33) and lymphoproliferative disease or malignancy (9/33) in some cases among them. The nutritional risk screening 2002 (NRS 2002) scores revealed that 85.19% of adults had an NRS 2002≥3 points, and 33.33% of children had a BMI-for-age z score<-2. Weight loss occurred in 66.67% of patients (22/33), while 87.88% (29/33), 69.70% (23/33) and 81.82% (27/33) of patients respectively had anemia, hypoalbuminemia and decreased prealbumin. Among 22 patients with micronutrients status evaluated, 77.27% (17/22), 22.73% (5/22) and 31.82% (7/22) of patients respectively had lowered serum iron, folate deficiency and vitamin B12 insufficiency. Six patients underwent 25-OH-VD3 measurement, and were all testified to have vitamin D deficiency. Among all patients with nutritional risk, 56.00% of them underwent nutritional support: oral nutritional supplements (14 cases), enteral feeding (4 cases) and parenteral nutrition (5 cases). In conclusion, the condition of malnutrition was prevalent in patients with CVID, but was under-recognized and undertreated to some degree.

[Evolution and regional differences in the supportive environment for influenza vaccination among the elderly population in China].

Seasonal influenza leads to a significant disease burden, and older people infected with influenza are susceptible to various complications. Influenza immunization can prevent infection effectively and significantly reduce the risk of complications and severe cases. Creating a supportive environment for vaccination is crucial in advancing the influenza vaccination rate among the elderly population. In China, the present environment for supporting influenza vaccinations among the elderly is primarily comprised of policies for free vaccination and expense reimbursement, which exhibit noteworthy regional variations across cities and regions. This study systematically analyses the supportive environment and regional disparities associated with influenza vaccination among the elderly in China. It aims to comprehend the opportunities for influenza prevention and control resulting from the current background of influenza vaccination and to identify potential health inequality challenges caused by regional differences. The findings should inform the introduction of relevant national policies and programs to protect the health and well-being of the elderly population.

[China guideline for the screening and early detection of prostate cancer (2022, Beijing)].

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

[Cardiometabolic disease patterns among elderly patients with colorectal cancer in China].

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

[The 498th case: rash, fever and hematuria].

A 50-year-old man was admitted to the Department of Rheumatology at Peking Union Medical College Hospital with rash for 6 months, and fever and hematuria for 5 months. The main clinical manifestations included fever, fatigue, purpura, hematuria and thrombocytopenia. He was positive for antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and rheumatoid factor (RF), and had low complement levels. Initial blood culture, echocardiography and chest CT showed no signs of infection. Diagnosis of connective tissue disease was made initially. His disease improved under treatment with glucocorticoids and immunosuppressive agents, but relapsed when glucocorticoids were tapered. After admission, the diagnosis was reconsidered, and infective endocarditis was finally diagnosed with repeated positive blood cultures and vegetations detected by transesophageal echocardiography. Amoxicillin and clavulanate potassium were initiated, and surgery was performed. His symptoms finally recovered gradually.

[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

[Perspectives on recent monkeypox outbreak in non-endemic areas].

Monkeypox is a rare infectious disease caused by the monkeypox virus, which used to occur endemically in central and western Africa. As of 25th May, a total of 219 recently confirmed cases of monkeypox have been reported from 19 non-endemic countries. This outbreak unusually takes place in non-endemic areas for monkeypox virus and has exhibited features of high risk of human-to-human transmission. Onset of multiple human monkeypox cases may be related to the decreased level of herd cross-immunity after the cessation of smallpox vaccination. Moreover, behavioral patterns in specific populations may account for the human-to-human transmission in this outbreak. Currently, possibility of global epidemic of monkeypox is extremely low, but China should be cautious about risks of importation of monkeypox cases. The key to prevention and control is to establish a surveillance system to identify suspicious cases and close contacts as soon as possible.

[Overweight and obesity status and its associated factors among primary and secondary school students in China rural middle and western regions].

Objective: To analyze the overweight and obesity status of students in the national pilot counties of the Nutrition Improvement Program for Rural Compulsory Education Students in 2019 and its associated factors. Methods: In 2019, a multi-stage cluster random sampling method was used to select about 40 students from each grade in primary and secondary schools in China's central and western regions where the Nutrition Improvement Program for Rural Compulsory Education Students was implemented. The height and weight of the children were measured using height or weight scales. The school questionnaire and county questionnaire were used to investigate the associated factors. A Chi-square test was used for comparison between groups. The logistic regression analysis was used to analyze the associated factors. Results: In 2019, the prevalence of overweight and obesity among rural primary and secondary school students aged 6-15 years in central and western China 2019 was 11.5%. It was higher for boys (13.1%) than that for girls (9.8%), higher in central (14.3%) than that in the west (9.9%) and higher for elementary school students (12.4%) than that for secondary school students (9.5%, all P<0.001). The logistic regression showed that boys (OR=1.388), primary school students (OR=1.271), students without other dietary subsidies(OR=1.037), schools in rural areas (OR=1.133), schools with enterprise-based feeding mode (OR=1.043), schools without the provision of lunch (OR=1.143), schools without the provision of dinner (OR=1.122), and schools without providing drinking water (OR=1.015) were positively associated with overweight and obesity among students (P<0.05). Schools with snack shops (OR=0.952) were negatively associated with overweight and obesity among students (P<0.001). Conclusion: A certain proportion of primary and secondary school students in rural areas of central and western China are overweight and obese. The prevalence is not only related to children's gender, school section and county area but also related to school meals, whether schools provide drinking water and other factors.

[Exploration on teaching reform of cancer epidemiology course].

This study aims to explore optimized teaching mode of cancer epidemiology for undergraduates, and provide scientific ideas and basis for improving teaching quality. Non-randomized concurrent control study was used. Undergraduates, enrolled in 2018, from the department of preventive medicine in A and B medical universities were selected as research objects. Traditional teaching mode was used for cancer epidemiology course in A medical university, and innovative teaching mode named "one core, four dimensions" was adopted in B medical university. After the course, questionnaire method was used to investigate self-cognition of students, teaching satisfaction and class preparation time of teachers in B Medical University. The post-class test method was used to compare the students' grades of cancer epidemiology in the two universities. The results indicated that among the 58 students of B medical university, 94.83% (55/58) students were familiar with common types of epidemiological studies and 86.21% (50/58) mastered the evaluation indicators of screening research. Among the nine teaching faculties from B medical university, seven reported that the new teaching plan helped students to learn frontier knowledge of cancer epidemiology, and eight reported the new teaching model was conducive to the interaction between teachers and students. The text score of students in B medical university was 50.34±4.90, significantly higher than that in A medical university (46.21±4.91, t=5.20, P<0.001). The optimized teaching mode of cancer epidemiology is highly praised by students and teachers, which has the potential to improve students' grasp of cancer epidemiology, the ability to combine theory with practice, and the teaching effect of cancer epidemiology.

[Status and related factors on the drinking behavior among primary and secondary students in China rural middle and western regions in 2019].

Objective: To analyze the daily drinking behavior and related factors of primary and middle school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) pilot regions. Methods: Multi-stage stratified random cluster sampling method was used to select one to three national pilot counties in 22 provinces in central and western China where the NIPRCES was implemented in 2019. According to different feeding patterns, two primary schools and two middle schools were selected as key monitoring schools. One or two classes were selected from grade 3 to grade 9. The student questionnaire was used to collect the basic information and daily drinking behavior. Taking whether the drinking water ≥5 cups every day as the dependent variable, multivariate logistic regression model was used to analyze the related factors of drinking behavior among students. Results: A total of 27 374 students were included. On average, primary and middle school students in the regions where NIPRCES was implemented had 3.9 cups of water every day. Logistic regression model showed that boys (OR=1.230, P<0.001), primary school students (OR=1.379, P<0.001), father worked outside the home (OR=1.169, P<0.001), both parents worked outside the home (OR=1.228, P<0.001), non-resident students (OR=1.142, P<0.001), the school in the village (OR=1.638, P<0.001) or township (OR=1.358, P<0.001), school feeding (OR=1.252, P<0.001), the school building with flush toilets (OR=1.384, P<0.001) and the central regions (OR=1.300, P<0.001) students were more likely to drink ≥5 cups water every day. Conclusion: The water consumption of primary and middle school students in the pilot regions of NIPRCES is low, and their drinking behaviors are affected by many factors.

[Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins].

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

[Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats].

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 µg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 µg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 µg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

[CacyBP promotes the proliferation and invasion of non-small cell lung cancer].

Objective: To investigate the effects and the mechanism of Calcyclin-binding protein (CacyBP) on the proliferation and invasion of non-small cell lung cancer (NSCLC) cells. Methods: Six lung cancer tissues and paired normal lung tissues were collected from NSCLC patients who underwent surgical treatment in Jinan Central Hospital during 2016. The expression of CacyBP in these tissues was examined by western blot. The protein and mRNA expression of CacyBP in human bronchial epithelial cells (16HBE), NSCLC cell lines including A549, H1299, H460 and H1975 were examined by western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RNAi and shRNA against negative control (NC) or CacyBP were transfected into A549 cell which were denoted as siNC group, siCacyBP-1 group, sicacyBP-2 group, shNC group and shCacyBP group, respectively. Control and Flag-CacyBP plasmids were transfected into A549 cells which were denoted as NC group and Flag-CacyBP group, respectively. Cell counting kit-8 (CCK-8), plate clone formation assay and flow cytometry assay were used to assess cell proliferation ability and cycle of A549. Wound healing assay and transwell assay were used to assess abilities of A549 cells migration and invasion. The protein expressions of epithelial-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin, Snail1, Vimentin, and phosphorylation of protein kinase B (p-Akt) were examined in CacyBP depleted or overexpressed A549 cells. Results: The CacyBP protein level in NSCLC tissues was 0.41±0.23, significantly higher than 0.11±0.04 in normal lung tissues (P<0.05). The CacyBP protein expression levels in different NSCLC cell lines including A549, H1299, H460 and H1975 were 0.35±0.01, 0.38±0.01, 0.32±0.01 and 0.41±0.01, respectively, which were significantly higher than 0.03±0.01 in 16HBE cells (P<0.05). The result of RT-PCR was consistent with that of western blot. Compared with siNC group (absorbance was 1.54±0.03), siCacyBP-1 group and siCacyBP-2 group showed decreased cell proliferation (absorbances were 1.38±0.04 and 1.34±0.03, P<0.05). The number of cell colony in shNC group was 41.33±3.21, significantly higher than 22.00±3.61 in shCacyBP group (P<0.05). The proportion of G(1) phase in shCacyBP group was (61.35±5.45)%, higher than (49.61±1.54) % in shNC group (P<0.05). The proportion of S phase was (25.41±3.21)%, which was lower than (38.68±0.46)% of shNC group (P<0.05). The cell migration rate of shCacyBP group was (12.67±0.71)%, which was significantly lower than (35.50±2.07)% of shNC group (P<0.05). The numbers of cell migration and invasion in shNC group were 406.33±7.37 and 92.33±8.50, respectively, which were significantly higher than 224.67±10.01 and 66.00±7.94 in shCacyBP group (P<0.05). Compared with siNC group, the expression of epithelial marker E-cadherin was up-regulated, while the expressions of mesenchymal markers including N-cadherin, Vimentin, Snail1 and p-Akt were down-regulated in CacyBP depleted A549 cells. Compared with NC group, overexpression of CacyBP inhibited E-cadherin expression while promoted the expressions of N-cadherin, Snail1, Vimentin and p-Akt, which could be restored by LY294002. Conclusion: CacyBP may promote the proliferation and invasion of NSCLC cells by regulating Akt signal pathway.

[The application of scales and characteristics of disability in the common genotypes of Charcot-Marie-Tooth disease].

Objective: To analyze the correlations among different common scales for evaluating the severity of the first-visit Charcot-Marie-Tooth disease (CMT), and explore the cross-sectional characteristics of neurological dysfunction in patients with four common genotypes (CMT1A, CMT1X, CMT2A and MPZ-related CMT) at their first visits. Methods: A total of 117 genetically confirmed CMT patients (aged ≥10 years) from the Department of Neurology of the Third Xiangya Hospital from 2009 to 2019 were included in the study, which consisted of 45 CMT1A, 41 CMT1X, 19 CMT2A, and 12 MPZ-related CMT patients. Clinical data of these patients at first visits were collected and neurological deficits were evaluated by Charcot-Marie-Tooth Neuropathy Score (CMTNS), Charcot-Marie-Tooth Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS) and Functional Disability Scale (FDS). Spearman's correlation was performed to analyze the relationship between CMTNS, CMTES, ONLS and FDS. The age of onset, duration of disease, scores of CMTNS, CMTES, ONLS and FDS were compared among four genotypes. Results: In the 117 CMT patients, the male to female ratio was 1.79/1, and the age of onset was (19±13) years. The duration of disease was 10(3, 15) years, and the scores of CMTNS, CMTES, ONLS and FDS were 11.4±6.2, 8.8±5.7, 2.7±1.4 and 2.6±1.3, respectively. There was a significant correlation between CMTES, ONLS, FDS and CMTNS in the overall CMT patients and four subtypes respectively (r≥0.40, P<0.05). CMTNS, CMTES and ONLS scores of four subtypes showed positive correlations with duration of disease (P<0.05), but FDS scores of CMT1A, CMT1X and MPZ-related CMT patients exhibited no correlation with duration of disease (P>0.05) at their first visits. The age of onset in CMT2A patients was younger than that of the patients with the other three genotypes (P<0.05), furthermore, the scores of four scales in early-onset CMT2A patients were higher than those of adult-onset type CMT2A patients (CMTNS: P=0.031, CMTES: P=0.048, ONLS: P=0.042, FDS: P=0.047). In CMT1X patients, the males had higher scores than those of females for all four scales (CMTNS: P=0.028, CMTES: P=0.014, ONLS: P=0.023, FDS: P=0.002). Conclusions: CMTNS, CMTES and ONLS could be used in natural history studies and clinical trials according to the different clinical situations. In the four genotypes, CMT2A patients have younger age of onset, and the earlier the age of onset, the severer the dysfunction. Moreover, male CMT1X patients relatively have severer neurological dysfunction than female patients.