[Epidemiological characteristics and serum antibody detection of a COVID-19 aggregated outbreak in vaccinated population].

An epidemiological investigation was conducted on a cluster epidemic of COVID-19 in the vaccinated population in Beijing in 2022, and serum samples were collected from 21 infected cases and 61 close contacts (including 20 cases with positive nucleic acid in the isolation observation period). The results of antibody detection showed that the IgM antibody of two infected persons was positive, and the IgG antibody positive rates of patients who were converted, not converted to positive and infected persons were 36.84% (7/19), 63.41% (26/41) and 71.43% (15/21), respectively. About 98.78% of patients had been vaccinated with the SARS-CoV-2 inactivated vaccine. The positive rate of IgG antibody in patients immunized with three doses of vaccine was 86.00% (43/50), which was higher than that in patients with one or two doses [16.12% (5/31)]. The antibody level of M (Q1, Q3) in patients immunized with three doses was 4.255 (2.303, 7.0375), which was higher than that in patients with one or two doses [0.500 (0.500, 0.500)] (all P values<0.001). The antibody level of patients who were vaccinated less than three months [7.335 (1.909, 7.858)] was higher than that of patients vaccinated more than three months after the last vaccination [2.125 (0.500, 4.418)] (P=0.007). The positive rate and level of IgG antibody in patients who were converted to positive after three doses were 77.78% (7/9) and 4.207 (2.216, 7.099), respectively, which were higher than those in patients who were converted after one or two doses [0 and 0.500 (0.500, 0.500)] (all P values<0.05).

[Epidemiological characteristics of incident cases and risk factors of hepatitis C infection in Beijing City from 2004 to 2021].

Objective: To analyze the epidemiological characteristics and related factors of hepatitis C in Beijing City from 2004 to 2021. Methods: Descriptive epidemiological method and Joinpoint regression were used to analyze the trend and other epidemiological characteristics of hepatitis C in Beijing City from 2004 to 2021 in National Notifiable Disease Reporting System. According to a 1∶1 matched case-control study design, logistic regression was used to investigate the risk factors of hepatitis C infection in 2021. Results: From 2004 to 2021, the reported incidence of hepatitis C in Beijing City ranged from 2.37/100 000 to 10.46/100 000. The reported cases were mainly aged 30-60 years, and most of them were chronic. The reported incidence of hepatitis C showed an initial increase from 2004 to 2006 (APC=45.37%, 95%CI:-1.56%-114.69%), and declined after 2006 (APC=-9.21%, 95%CI:-10.70%-7.70%). Logistic analysis showed that history of surgery (OR=1.84, 95%CI: 1.08-3.14) and previous blood transfusion (OR=34.22, 95%CI: 8.05-145.41) were risk factors for hepatitis C infection. Conclusion: The reported incidence of hepatitis C in Beijing City increases first and decreases later. It currently remains at a low level. The risk factors of infection are surgery and blood transfusion history. Safe blood supply and preventing iatrogenic transmission should be focused on the prevention of hepatitis C transmission.

[A follow-up study on the pain changes trend and effects in patients diagnosed with herpes zoster in Beijing City].

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q1, Q3) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

Presence and clinical significance of acellular mucin pools in resected rectal cancer with pathological complete response after pre-operative chemoradiotherapy.

For patients with locally advanced rectal cancer (LARC), a pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) does not necessarily indicate a cure. Acellular mucin pools are often seen in patients with pCR. However, the clinical significance of acellular mucin pools in this group of patients remains unknown. This was a retrospective analysis of 225 LARC patients who achieved pCR following CRT and total mesorectal resection from 2011 to 2018. The outcomes of 5-year disease-free survival (DFS), 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) were compared in patients with versus without acellular mucin pools. Among 225 pCR patients, acellular mucin pools could be identified in 56 (24.9%) patients, and recurrence occurred in 30 (13.3%) patients at 5 years. Distant recurrence was seen in 13 (23.2%) patients with acellular mucin pools and in 17 (10.1%) patients without acellular mucin pools. Patients with acellular mucin pools versus those without had poorer DFS (76.8 versus 89.9%, P = 0.010) and OS (87.5 versus 97.0%, P = 0.004) at 5 years. The presence of acellular mucin pools was the independent parameter that remained significant for DFS [hazard ratio (HR) = 3.904; 95% confidence interval (CI) = 1.342-11.356; P = 0.047] and OS (HR = 3.850; 95% CI = 1.214-12.213; P = 0.022) on multivariate analysis. A total of 17 patients demonstrated acellular mucin pools in primary tumour and lymph nodes. Subgroup analysis demonstrated that pCR patients with acellular mucin pools in primary tumour and lymph nodes were more likely to develop distant metastasis compared to pCR patients with acellular mucin pools only in primary tumour (47.1 versus 12.8%, P = 0.005). In summary, acellular mucin pools in LARC patients with pCR after CRT might represent a sign of invasive tumour biology and significantly shorten the prognosis of patients, especially in patients with acellular mucin pools in lymph nodes.

[The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells].

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

[Effects of parity on nutrition and health status of Chinese women of childbearing age].

Objective: To analyze effects of parity on women's nutrition and health status. Methods: This study was based on the data bank of "Chinese Nutrition and Health Surveillance of Children and Adolescents Aged 0-17 years old and Lactating Mothers from 2016 to 2017". Using a multi-stage stratified random sampling method, 17 771 women at 0 to 24 months postpartum from 31 provinces in Mainland China were included in this study. Questionnaires were used to collect data on women's general demographic characteristics, parity, mode of delivery, pre-pregnancy weight, pre-delivery weight, diseases before and during pregnancy, postpartum hemorrhage. Current body height, body weight, waist circumference, and blood pressure were measured. Blood hemoglobin, blood glucose and blood lipids were detected. Pre-pregnancy BMI, gestational weight gain, postpartum weight retention, postpartum BMI, the rates of anemia, hypertension, diabetes, and dyslipidemia were calculated. Survey sample weights were calculated according to the sampling design and number of children under 2 years old from the sixth population census data of China. Effects of parity on the observational indicators after adjusting for confounding factors were analyzed by multivariate linear regression and multivariate logistic regression. Results: The age of 17 771 women was (29.5±5.0) years old, 12.2% (2 172) were over 35 but less than 40 years old, and 3.2% (563) were over 40 years old; the women with one parity, two parities, and three parities accounted for 47.3% (8 413), 48.5% (8 620) and 4.2% (738), respectively; urban women accounted for 49.9% (8 875), and rural women accounted for 50.1% (8 896). The results from multivariate linear regression showed that the pre-pregnancy BMI of women with two and three parities was 0.55 kg/m2 and 0.76 kg/m2 higher than women with one parity, respectively; the results of multivariate logistic regression showed that the OR(95%CI) of pre-pregnancy anemia was 1.45(1.04-2.02) for women with three parities compared with women with one parity, and the OR(95%CI) of anemia during pregnancy for women with two parities was 1.20(1.06-1.35) compared with women with one parity. Conclusion: Parity is associated with pre-pregnancy BMI and risk of anemia before and during pregnancy in women of reproductive age.

[An investigation on serum antibody level of varicella-zoster virus in healthy population in Beijing].

Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²trend=7.32, Ptrend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.

[A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China].

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Optimal reference genes for real-time quantitative PCR and the expression of sigma factors in Acidithiobacillus caldus under various conditions.

AIMS: Acidithiobacillus caldus is an important sulphur-oxidizing bacterium that plays crucial roles in the bioleaching industry. This study aims to analyse the optimal reference gene for real-time quantitative PCR (RT-qPCR) under different conditions and investigate the transcription levels of the sigma factor genes in the stress response. METHODS AND RESULTS: We selected six housekeeping genes and analysed them via RT-qPCR using two energy resources, under four stress conditions. Three statistical approaches BestKeeper, geNorm, and NormFinder were utilized to determine transcription stability of these reference genes. The gapdH gene was the best internal control gene using elemental sulphur as an energy resource and under heat stress, map was the best internal control gene under pH and osmotic stress, era was the best internal control gene for the K2 S4 O6 energy resource, and rpoC was the best internal control gene under Cu2+ stress. Furthermore, the expressional levels of 11 sigma factors were analysed by RT-qPCR in the stress response. CONCLUSIONS: Stable internal control genes for RT-qPCR analysis of A. caldus were determined, and the expression patterns of sigma factor genes of A. caldus were investigated. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of the optimal reference gene and analysis of transcription levels of sigma factors in A. caldus can provide clues for reference gene selection and the study of sigma factor function.

Diaphragm ultrasound in the diagnosis of respiratory dysfunction in patients with amyotrophic lateral sclerosis.

OBJECTIVE: In this study, we aimed to select the best diaphragm ultrasonography (DUS) parameter as an alternative index for the diagnosis of lung function impairment in amyotrophic lateral sclerosis (ALS). METHODS: Twenty-nine patients with ALS and 15 healthy subjects were enrolled in the study. DUS, lung function tests, phrenic nerve conduction study and arterial blood gas analysis were performed. RESULTS: Patients with respiratory dysfunction had a significantly lower level of ΔTmax than those without (P=0.039). Significant correlations (P<0.05) were found between forced vital capacity (FVC) and Tdi-ins (r=0.665, P<0.0001) and ΔTmax (r=-0.748, P<0.0001) and Δins-exp (r=0.627, P<0.0001) and ΔTdi (r=0.485, P<0.0001). Receiver Operating Curves analysis demonstrated that ΔTmax (AUC=0.76, P=0.044) had a better overall accuracy for detection of respiratory dysfunction compared with Tdi-ins (AUC=0.27, P=0.067), Δins-exp (AUC=0.312, P=0.139), and ΔTdi (AUC=0.38, P=0.359). CONCLUSION: ΔTmax is the most valuable DUS index in the diagnosis of diaphragmatic dysfunction. SIGNIFICANCE: DUS can provide functional and structural information of diaphragm and help to diagnose diaphragmatic dysfunction in ALS.

[Construction of professional competency model of center for disease prevention and control].

Objective: Analyze and contruct the post competency model of professionals in centers for disease prevention and control in Beijing, so as to provide information for cultivation and construction of public health personnel, and the human Resource Management in relevant institutions. Methods: Cross-sectional research method was used, and based on literature research, functional analysis and referring to Hay Group Competency Dictionary and McClellan Competency Dictionary, the post competency dictionary was established after the unified discussion of the subject group. Hierarchical cluster sampling method was used to investigate an online survey on competency factors of professionals in centers for Disease prevention and Control in Beijing, and factor analysis was conducted on the survey data. Results: The competency model of professionals in centers for disease prevention and control in Beijing was composed of six factors, which are Public health practical operation skills and norms, public health emergency response thinking and deductive and inductive ability, professional quality and professional ethics, communication, coordination ability and team spirit, medicine humanities knowledge and health management and guidance. Conclusions: This competency model is basically in line with the job responsibilities of professionals in centers for disease prevention and control in Beijing. However, it can only reflect the post competence and ability of the middle and junior technical personnel for practice, so which should belongs to the category of basic competence.

[Association between dietary vitamin A intake and gestational diabetes mellitus in the first trimester].

Objective: To investigate the relationship between dietary vitamin A intake and its sources in the first trimester and gestational diabetes mellitus (GDM). Methods: A prospective study was conducted to select women at 6-14 weeks of gestation in an obstetric clinic of a maternal and child health care medical institution in Chengdu in 2017. The types and quantities of food during the first trimester were collected by 3-day 24-hour dietary recalls. Dietary vitamin A intake was calculated based on the Chinese Food Composition Table (2018), and it was divided into animal and plant vitamin A intakes according to its food sources. An oral glucose tolerance test was performed at 24-28 weeks of gestation to diagnose GDM according to the Chinese guidelines for diagnosis and treatment of gestational diabetes mellitus (2014). According to the estimated average requirement (EAR) and recommended nutrient intake (RNI), dietary vitamin A intake was divided into low-level group (RNI). Animal and plant vitamin A intakes were divided into four groups (Q1-Q4) according to the quartile method, respectively. The association between dietary vitamin A intake, its different sources of vitamin A intake and GDM in the first trimester was analyzed by log-binomial regression models. Results: A total of 1 298 valid samples were finally included. The average dietary vitamin A intake, animal and plant vitamin A intakes in the first trimester were 341.1 (227.8-501.0) µgRAE/d, 139.3 (69.6-195.3) µgRAE/d and 184.2 (99.4-301.1) µgRAE/d, respectively. After adjusting for confounding factors, log-binomial regression analysis showed that the risk of GDM in high-level group of dietary vitamin A intake was lower than that in low-level group [RR (95%CI):0.53 (0.36-0.80)]. Pregnant women in the highest quartile of animal vitamin A intake had a lower risk of GDM than those in the lowest quartile [RR (95%CI):0.66 (0.47-0.95)]. No relationship between plant vitamin A intake and GDM was found. Conclusion: Dietary vitamin A intake in the first trimester is associated with the occurrence of GDM, and higher intake than RNI may reduce the risk of GDM. Higher vitamin A intake from animal-derived food is associated with decreased risk of GDM.

[Survey on source of infection of the first local outbreak caused by SARS-CoV-2 Alpha variant in China].

Objective: To investigate the epidemiological characteristics and the chain of infection of a local outbreak, which was the first outbreak caused by severe acute respiratory syndrome corona virus 2 Alpha variant in China and occurred in Daxing district, Beijing. Methods: Epidemiological investigation and big data technology were used to verify the exposure points of the cases. Close contacts were traced from the exposure points, and their human and environmental samples were collected for nucleic acid tests. Serum samples were collected from key persons for antibody detection. Results: A total of 33 corona virus disease 2019(COVID-19) cases were reported in the local outbreak, from January 17, 2021 to January 29, 2021 in Daxing district, Beijing, and there was epidemiological association in 32 cases. Except for one case who was infected in the workplace, other cases were all infected in the community and family. All cases involved 14 families, of which 6 families were all infected. The attack rate of all family members was 69%(33/48), and the secondary attack rate was 56%(19/34). There was no obvious source of infection found after the investigation of entry-exit personnel and goods. Conclusion: The first outbreak caused by severe acute respiratory syndrome corona virus 2 Alpha variant in China is found and handled in time, and thus the scope of influence is limited, but the family clustering characteristics are more obvious than previous outbreaks.

[Interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats].

Objective: To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats. Methods: In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-ß1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1ß) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results: Compared with the negative control group, SiO2 model group had a significant decrease in the body weight of rats (P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α, IL-1ß were all significantly increased (P<0.05) . Compared with the SiO2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly (P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α and IL-1ß were significantly decreased (P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased (P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased (P<0.05) . Conclusion: Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.

Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients.

A combination of pegylated interferon-alpha (peg-IFN-α) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear. Forty NA-experienced CHB patients were enrolled into this study. The frequencies of peripheral blood natural killer (NK) cells, dendritic cells (DCs), CD4+ T cells, CD8+ T cells, T helper (Th) cells, regulatory T cells (Treg ), B cells and follicular T helper (Tfh) cells were evaluated by flow cytometry. Seven of the 40 patients converted to peg-IFN-α combined with NA treatment, while the other 33 continued to NA therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56bright NK cells in the combination treatment group increased significantly compared with the NA treatment group, whereas the CD56dim NK cells were decreased. In the NA treatment group, the proportions of CD4+ TN , CD8+ TN , CD19+ B and cytotoxic T lymphocyte antigen-4 (CTLA-4)+ CD4+ T cells were increased, while the proportions of CD4+ TEM , CD8+ TEM , CD25+ CD4+ Treg , CD25high CD4+ Treg , CD127low CD25+ Treg , programmed cell death 1 (PD-1)+ CD4+ T, PD-1+ CD8+ T, CTLA-4+ CD8+ T, CCR4+ CD25+ Treg and CCR4+ CD25high Treg cells were decreased after therapy. For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56bright NK cells.

Optical rogue waves in coupled fiber Raman lasers.

For coupled linear cavity-random fiber Raman lasers, for the first time, to the best of our knowledge, we demonstrate a new mechanism of emergence of the random pulses, with the anomalous statistics satisfying optical rogue waves' criteria experimentally. The rogue waves appear as a result of the coupling of two Raman cascades, namely, a linear cavity laser with a wavelength of 1.55 µm and a random laser with a wavelength nearly 1.67 µm, along with coupling of the orthogonal states of polarization (SOPs). The coherent coupling of SOPs causes localization of the trajectories in the vicinity of these states, whereas polarization instability drives escape taking the form of chaotic oscillations. Antiphase dynamics in two cascades result in the suppression of low amplitude chaotic oscillations and enable the anomalous spikes, satisfying rogue waves criteria.

Development, validity and reproducibility of a whole grain food frequency questionnaire in Malaysian children.

BACKGROUND: To date, there is no validated whole grain assessment tool for children in any Southeast Asian countries. Hence, there is a need for a valid tool to assess whole grain intake among Malaysian children. This study aimed to develop, validate and test the reproducibility of a food frequency questionnaire (FFQ) in estimating whole grain intake among Malaysian children. METHODS: A total of 392 children participated in the FFQ development and 112 children aged 9-12 years participated in the validation phase; with a subsample of 50 children participating in the reproducibility phase. Three-day diet record (3DR) as the reference method in validation phase. Spearman correlations, mean difference, Bland-Altman plot and cross-classification analyses were used to assess validity. The reproducibility was tested through a repeat administration of the FFQ, with 1 month time interval. Reproducibility analyses involved intra-class correlation coefficient (ICC), Cronbach's alpha and cross-classification analyses. RESULTS: The FFQ consisted of 156 whole grain food items from six food groups. Mean intake of whole grain in FFQ1 and 3DR were correlated well (r = 0.732), demonstrated good acceptance of the FFQ. Bland Altman plots showed relatively good agreement for both the dietary methods. Cross-classification of whole grain intake between the two methods showed that < 9.9% of children were grossly misclassified. Outcomes from ICC (0.989) and Cronbach's alpha (0.995) demonstrated excellent reliability. All the children were classified in the same or adjacent quartile of whole grain intake. CONCLUSIONS: Overall, the findings support the validity of the developed FFQ to appropriately estimate the whole grain intake in Malaysian children. This validated FFQ will be a valuable tool for future studies, to analyses the impact of whole grain consumption with disease relationship among Malaysian schoolchildren.

[The preliminary observation of intralesional rituximab administration in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma].

Objective: To observe the efficacy of intralesional rituximab administration in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). Methods: Retrospective case series study. The clinical and follow-up data of eight patients with POAML in the treatment group from September 2017 to December 2018 at the First Affiliated Hospital of Zhengzhou University were collected and analyzed retrospectively. The patients (3 males and 5 females) were 35 to 83 years old, with a median of 58 years. All patients received surgical treatment (most of the tumor were removed). The diagnosis of mucosa-associated lymphoid tissue lymphoma was confirmed by histopathology and immunohistochemical staining showed CD20+. Examinations such as chest CT, abdominal CT, bone marrow biopsy or positron emission tomography-CT to exclude lymphoma with systemic lesions. Patients with conjunctival POAML were injected through the subconjunctival infiltration. For the lacrimal gland POAML and the orbital POAML, the injection was performed through the periocular space by using a post-bulb syringe needle at multi-points with an interval of 1 cm, before the pressure dressing. All patients were injected 1.5 to 5.0 ml (15 to 50 mg) once every three weeks, 4 to 6 times as a treatment cycle. The injection range included or exceeded the lesion area. Then consider whether to supplement the number of treatments based on the remaining tumor. The patients' treatment doses, drug onset time, tumor regression, local reactions (local pain and swelling), systemic reaction indicators (fever, gastrointestinal reactions, complete blood count and the lymphocyte subsets), and systemic recurrence indicators (serum ß2 microglobulin and lactate dehydrogenase detecting) were recorded. Results: Two patients, including one patient with bilateral lesions, had conjunctival POAML, one patient had lacrimal gland POAML, and five patients had orbital POAML. They received 2 to 7 injections, and the total dose was 45 mg to 280 mg. There were tolerable local pain upon injections in all patients, local redness and swelling in one patient, fever in two patients, mild gastrointestinal reactions in one patient, fatigue in one patient, and palpitation and discomfort in one patient. After close observation or corresponding symptomatic treatment, the symptoms subsided. No special treatment was given. The follow-up time was 9 to 30 months, and the median was 20 months. The lymphomas in all patients were controlled without recurrence. The MRI showed that local lesions disappeared completely in five patients, and the conjunctiva and the extraocular muscle became thickened in three patients. There was no abnormity in complete blood count, serum ß2 microglobulin and lactate dehydrogenase. Conclusion: The intralesional rituximab administration is a simple, effective therapy for localized POAML with no systemic invasion. (Chin J Ophthalmol, 2020, 56: 839-845).

Decreased A20 expression on circulating CD56bright NK cells contributes to a worse disease status in patients with ankylosing spondylitis.

A20, a pivotal anti-inflammatory protein, preserves immune homeostasis and regulates prolonged inflammation. A previous study has shown that A20 expression levels are down-regulated in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS). However, the precise role of A20 in reducing autoimmune disorders needs to be further elucidated. In this study, A20 expression was found to be preferentially reduced on circulating CD56bright natural killer (NK) cells in patients with AS, and its level was negatively correlated with that of proinflammatory cytokines. Further investigation demonstrated that A20 reduces interferon (IFN)-γ and tumour necrosis factor (TNF)-α production in CD56bright NK cells after stimulation with monokines or phorbol myristate acetate (PMA)/ionomycin(P/I). Furthermore, CD56bright NK cells isolated from AS patients promote TNF-α secretion by autologous monocytes, and increasing the A20 expression level partially attenuates this process. More importantly, decreased A20 expression on circulating CD56bright NK cells is associated with worse disease status in patients with AS. Our findings reveal that A20 participates in the pathogenesis of AS by negatively regulating CD56bright NK cells and that its reduced expression contributes to a worsened disease status in patients with AS.

Expression of proteinase-activated receptor-2 and transient receptor potential A1 in vagal afferent nerve of rat after lung schemia-reperfusion injury.

Lung ischemia-reperfusion injury (LIRI) is a common and severe clinical complication. As the injury occurs, the pulmonary afferent nerves play an important role in regulating respiratory functions under pathophysiological conditions. The purpose of this study was to examine expression of proteinaseactivated receptor-2 (PAR2) and transient receptor potential A1 (TRPA1) in pulmonary vagal afferent nerves of LIRI and further to determine molecular mediators linking activation of PAR2 and TRPA1. A rat model of LIRI was used. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were employed to examine pro-inflammatory cytokines (PICs, i.e., IL-1ß, IL-6 and TNF-α), and the protein levels of PIC receptors, PAR2, TRPA1, and intracellular signals. In the results, IL-1ß, IL-6 and TNF-α along with their receptors were amplified in afferent nerves of LIRI rats as compared with control rats. Sensory PAR2 and TRPA1 were also upregulated by LIRI. Blocking PAR2 by infusion of FSLLRY-NH2 attenuated upregulation of TRPA1 via intracellular signals, namely p38-MAPK and JNK. Moreover, blocking individual PIC receptor attenuated PAR2 and TRPA1 in pulmonary vagal afferent nerves. Our data showed specific signaling pathways leading LIRI to activation of PIC signal and activation of PAR2 and TRPA1 in pulmonary vagal afferent nerves via intracellular mediators. Targeting one or more of these signaling molecules may present opportunities to improve the abnormalities in vagal afferent nerve-mediated respiratory functions observed as LIRI occurs.