IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.

[Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis].

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

[Study on the distribution pattern of allergen sIgE in patients with respiratory allergic diseases in a hospital in Shanxi Province].

To explore the allergen sensitization status of patients with respiratory allergic diseases in Shanxi Province, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases. It is a cross-sectional study, a total of 1 680 patients with allergic rhinitis and/or asthma diagnosed at the Department of Allergic Reaction of Shanxi Bethune Hospital from July 2021 to June 2023 who underwent allergen sIgE testing and/or skin prick test were retrospectively enrolled.There were 772 males and 908 females.The age range was 3 to 88 years. The median age was 35 years.There were 108 cases in the child group (≤12 years old), 102 cases in the adolescent group (13-17 years old), 819 cases in the youth group (18-40 years old), 498 cases in the middle-aged group (41-65 years old), and 153 cases in the elderly group (>65 years old). There were 333 cases in the allergic rhinitis group, 827 cases in the allergic asthma group, and 520 cases in the allergic rhinitis with asthma group. There were 1 254 urban patients and 426 rural patients.There were 253 cases in the northern Shanxi region, 1 195 cases in the central Shanxi region, and 232 cases in the southern Shanxi region. Statistical analyses were performed using the χ 2 test or Fisher's exact probability method to compare the differences in allergen sIgE positivity rates by sex, age, disease, living environment, and geography. The results showed that 1 027 patients (61.1%) were positive for at least one allergen sIgE, with Artemisia having the highest rate of positivity (603/1 680, 35.9%), followed by ragweed (302/1 680, 18.0%) and dust mite combinations (245/1 680, 14.6%). The number of individuals with single-allergen sIgE positivity was 357 (357/1 027, 34.8%), with the highest number of single-allergen sIgE positive results associated with Artemisia (114/357, 31.9%). The number of multiple-allergen sIgE positive results was 670 cases (670/1 027, 65.2%), with the highest number of patients having 2 allergen sIgE positive results (243/670, 36.3%). The overall positivity rate for allergen sIgE was significantly higher among males than among females (65.7% vs. 57.3%, χ2=12.405, P<0.001). Overall positivity for inhalant allergen sIgE was higher in the child and adolescent groups (88.0% vs. 88.2% vs. 59.8% vs. 40.2% vs. 19.0%, χ2=223.372, P<0.001), and food allergen sIgE positivity was highest in the child group (54.6% vs. 36.3% vs. 26.0% vs. 18.9% vs. 21.6%,χ2=66.383,P<0.001). The sIgE positivity rate of inhalant allergens was significantly higher in the allergic rhinitis group and the allergic rhinitis with asthma group than in the allergic asthma group, except for cockroaches and molds (P<0.05). The overall positive rate of allergen sIgE was significantly higher among urban patients than among rural patients (66.2% vs. 46.2%, χ2=53.230, P<0.001). The difference in the overall positive rate of allergen sIgE among patients from different regions was not statistically significant (56.1% vs. 62.0% vs. 62.1%, χ2=3.140, P=0.208). The sIgE positivity of dust mite combinations was significantly higher in the central Shanxi region and the southern Shanxi region than in the northern Shanxi region (15.5% vs. 18.1% vs. 7.1%,χ2=14.411, P=0.001). In conclusion, artemisia was the most important sensitizer for respiratory allergic diseases in Shanxi Province. The types of allergens and positivity rates were different for different sexes, ages, diseases, living environments, and regions. Therefore, patients with allergic diseases should be tested for allergens to help with the diagnosis, treatment and prevention of allergic diseases.

Evidence for causal effects of sleep disturbances on risk for osteoarthritis: a univariable and multivariable Mendelian randomization study.

OBJECTIVE: To disentangle whether sleep disturbances have a causal effect on the risk of osteoarthritis (OA) using genetically based approaches. METHOD: We performed univariable and multivariable Mendelian randomization (MR) analyses using publicly released genome-wide association studies summary statistics to estimate the causal associations of sleep disturbances with OA risk. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas complementary methods including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were applied to detect and correct for the presence of pleiotropy. RESULTS: There were 228 independent instrumental variables (IVs) for insomnia and 78, 27 and 8 IVs for sleep duration, short sleep duration and long sleep duration, respectively. Univariable MR analysis suggested that genetically determined insomnia or short sleep duration exerted a causal effect on overall OA in an unfavorable manner (Insomnia: OR = 1.22, 95%CI = 1.15-1.30, P = 8.05 × 10-10; Short sleep duration: OR = 1.04, 95%CI = 1.02-1.07, P = 2.20 × 10-3). More compelling, increasing genetic liability to insomnia or short sleep duration was also associated with OA risk, after accounting for effects of insomnia or short sleep duration on body mass index, type 2 diabetes and depression individually, and in a combined model considering all three confounders. CONCLUSIONS: Findings suggested consisted evidence for an adverse effect of increased insomnia or short sleep duration on OA risk. Strategies to mitigate sleep disturbances may be one of the cornerstones protects against OA.

Resolvin D2 promotes host defense in a 2 - hit model of sepsis with secondary lung infection.

In the development of sepsis, there is early, massive inflammation which can lead to multiple organ failure. Later there is an immunosuppressed phase where the host is susceptible to secondary infections or is unable to clear existing infection. Specialized Pro-resolving Mediators (SPMs) are endogenously produced lipids which resolve infection by decreasing bacteria load and reducing systemic inflammatory response. There has been little work studying if SPMs given late, can promote host defense. We examined if an SPM, Resolvin D2 (RvD2) could promote host defense in a 2-hit mouse model of cecal ligation and puncture (CLP) sepsis and secondary Pseudomonas aeruginosa lung infection. RvD2 given 48 h after mild CLP (1st hit), increased gene expression of Toll-like receptor-2 (TLR-2) and alveolar macrophage/monocyte phagocytic ability compared to CLP mice given saline vehicle. In this model, RvD2 did not affect plasma IL-6 or IL-10. These effects induced by RvD2, lowered lung bacterial load and decreased mortality after the secondary infection of Pseudomonas aeruginosa (2nd hit). Splenic T-cell numbers were also increased in RvD2 treated mice compared to saline vehicle treated animals. The results suggest that RvD2 promoted mechanisms of host defense in a 2-hit model sepsis and secondary lung infection.

Predicting lung adenocarcinoma invasiveness by measurement of pure ground-glass nodule roundness by using multiplanar reformation: a retrospective analysis.

AIM: To explore the value of roundness measurement based on thin-section axial, coronal, and sagittal section computed tomography (CT) images for predicting pure ground-glass nodule (pGGN) invasiveness. MATERIALS AND METHODS: A total of 168 pGGNs in 155 patients (44 male, 111 females; mean age, 55.74 ± 10.57 years), and confirmed by surgery and histopathology, were analysed retrospectively and divided into pre-invasive (n=72) and invasive (n=96) groups. Photoshop (CS6) software was used to measure pGGN roundness based on conventional axial section, as well as coronal and sagittal sections generated by multiplanar reformation, from thin-section (1-mm-thick) CT lung images. RESULTS: pGGN roundness values, measured in axial, coronal, and sagittal thin-section CT sections from the pre-invasive group were 0.8 ± 0.049, 0.816 ± 0.05, and 0.818 ± 0.043, respectively, while those in the invasive group were 0.745 ± 0.077, 0.684 ± 0.106, and 0.678 ± 0.106; differences between the two groups were significant (all p<0.001). Binary logistic regression analysis showed that roundness values based on coronal and sagittal sections (p<0.001) were better than those from axial sections (p>0.05) in predicting pGGN invasiveness, with odds ratio (OR) values of 14.858 and 23.315, respectively. ROC analysis showed that evaluation of roundness measured in sagittal sections was better at predicting pGGN invasiveness than when coronal sections were used (AUC 0.870 versus 0.832). CONCLUSION: Roundness is useful for predicting pGGN invasiveness, with measurements from coronal and sagittal sections better than those from conventional axial sections, with sagittal section images having the best predictive value.

[The prevention and therapy of corneal ulcers in patients with large-area thermal burns].

Objective: To evaluate the characteristics of ocular injury in patients with severe extensive thermal burns, and to explore the effective methods to prevent and treat corneal ulcers related to severe burns. Methods: A retrospective case series study. Between 2010 and 2019, Sixteen severe thermal burn patients with burn sizes>70% of the total body surface area involving the ocular region were admitted to the Burns and Plastic Surgery Division of Chinese PLA General Hospital, and consult with Ophthalmology Division. There were deep second-degree to fourth-degree burns in the eyelids. In the eleven surviving patients, 22 eyes presented ectropion. Eyelid full-thickness skin grafting (EFTSG) combined with or without tarsorrhaphy was performed in 20 eyes due to severe corneal exposure. Two eyes received partial blepharorrhaphy because of mild ectropion. The ocular manifestations and treatment outcomes were reviewed and assessed. Results: The majority of the patients were youth, and the average age was (36.8±10.4) years. The burn area was 84.0%±9.1% of the body surface area. Corneal ulcers secondary to lagophthalmos occurred at (35.1±15.6) days after burning in 75% (24/32) of eyes. Perforation was found in 18.8% (6/32) of eyes. Among the 22 operated eyes, the corneal ulcer was repaired in all 9 eyes receiving EFTSG with tarsorrhaphy, whereas ectropion recurred in 8 of 11 eyes only receiving EFTSG, and 4 eyes underwent further surgery due to corneal epithelial defects. Conclusions: In patients with severe large-area thermal burns, corneal ulcers are common complications. Prevention of corneal exposure is vital because the treatment of corneal ulceration is difficult due to eyelid deformity, inflammation and the absence of donor skin. Timely full-thickness skin grafting and blepharorrhaphy are effective approaches to preventing exposure keratopathy. To severe ulcers occur, conjunctival flap or Tenon's capsule covering combined with eyelid EFTSG and tarsorrhaphy is useful to rescue visual function.

Lipoxin A4 promotes reduction and antibiotic efficacy against Pseudomonas aeruginosa biofilm.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients. P. aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen. We have previously shown that a Specialized Pro-resolving Mediator (SPM), Lipoxin A4 (LxA4) is a quorum sensing inhibitor which can reduce P. aeruginosa virulence. In this study, we examined the direct actions of LxA4 and RvD2 on P. aeruginosa biofilm formation and virulence gene expression. The influence of LxA4 on antibiotic efficacy and the combined effects on biofilm formation were also investigated. LxA4 and RvD2 reduced P. aeruginosa biofilm formation and virulence gene expression. LxA4 increased ciprofloxacin inhibition on biofilm formation but did not affect ciprofloxacin's action on non-adherent bacteria. On the other hand, LxA4 increased bacterial killing action of imipenem but did not affect imipenem's action on biofilm. We also found that LxA4 can increase ciprofloxacin's bacterial killing ability in established biofilm. Together these results suggest that LxA4 has direct effects on P. aeruginosa biofilm formation and can increase antibiotic efficacy directly.

[An epidemiological survey on clinical features, self-management and cognitive level of elderly asthmatics in China].

Objective: To investigate the prevalence of asthma among the elderly people in China and to analyze the clinical features, self-management and cognitive level of elderly asthma patients. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the last epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) and seven regions (north, northeast, southern china, east, south, southwest and northwest) in China from February 2010 to August 2012. 2 034 were diagnosed as asthma. The elderly patients aged ≥65 years were selected from the 2 034 asthma patients. The clinical characteristics, comorbidities, the status of asthma control and self-management and insights of the disease in elderly asthma patients were analyzed. Results: Among the 2 034 asthma patients, 584 (28.7%) were elderly asthmatics aged ≥65 years old and 1 450 (71.3%) were<65 years old. In the elderly asthma group, Early-onset asthma accounted for 439 (75.2%) and 145 (24.8%) were late-onset. The common clinical manifestations of elderly asthma patients were: chest distress 395 (67.6%), wheezing 304 (52.1%), cough 298 (51.0%). Common comorbidities of elderly asthmatics were: chronic obstructive pulmonary disease 144 (24.7%), allergic rhinitis 122(20.9%), gastroesopheal reflux disease (GERD) 114(19.5%), allergic conjunctivitis 86 (14.7%), eczema 82 (14.0%), chronic bronchitis 76 (13.0%). The Asthma Control Test (ACT) scores of elderly asthmatics and non-elderly asthmatics were (18.5±3.2) and (21.7±3.4) respectively. There was a significant difference between the two groups (P=0.042). Of the elderly asthmatics, only 13 (2.2%) patients monitored daily using a peak flow meter. 93 (15.9%) patients aware that asthma was characterized by chronic airway inflammation. 64 (11.0%) asthmatics understood that the treatment goal. Conclusions: The clinical manifestations of elderly asthmatics are atypical, especially paroxysmal wheezing. Asthma in elderly people causes more comorbidities and mortality. The self-management and cognitive level of patients with asthma needs to be improved.

[A survey on clinical characteristics and risk factors of severe asthma in China].

Objective: To investigate the clinical characteristics and risk factors of severe bronchial asthma in Chinese people over 14 years old. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) located in seven regions (north, northeast, east, central China, south, southwest and northwest) of China from February 2010 to August 2012. A total of 2 034 were diagnosed as asthma. The clinical characteristics and related risk factors of patients with severe asthma in China were analyzed. Results: Among all asthma patients, 560 were newly diagnosed, accounting for 27.5% (560/2 034) and the percentage of previously confirmed patients was 72.5% (1 474/2 034). A total of 145 were eligible for severe asthma, accounting for 9.8% (145/1 474) of previously confirmed asthmatics and 7.1% (145/2 034) of all asthmatics. 83.5% (121/145) severe asthmatics had at least one trigger factor. Correlation analysis showed that the risk factors of severe asthma were: smoking (OR=1.543, 95%CI: 1.250-1.814), obesity (OR=2.186, 95%CI: 1.972-2.354), petting (OR=2.135, 95%CI: 1.904-2.283), combined with allergic rhinitis (OR=3.456, 95%CI: 2.721-4.326), gastroesophageal reflux disease (OR=1.842, 95%CI: 1.682-2.140), bronchiectasis (OR=1.665, 95%CI: 1.347-1.912) or chronic obstructive pulmonary disease (OR=1.312, 95%CI: 1.171-1.694). Conclusions: The most common comorbidities in severe asthmatics in China are allergic rhinitis and gastroesophageal reflux disease. The risk factors of severe asthma include obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, bronchiectasis, smoking and petting.

Application Prospects of Virtual Autopsy in Forensic Pathological Investigations on COVID-19.

ABSTRACT: Autopsy of patients who died of infectious diseases is of significance for public health management. Few forensic autopsies have been performed since the outbreak of the corona virus disease 2019 （COVID-19） due to some limitations, thus forensic pathological examination failed to contribute to the prevention and treatment of infectious diseases. Virtual autopsy has unique advantages in the forensic examination of patients who died of infectious diseases. Accumulated virtual autopsy image data are of great value to the study of the pathological mechanism and diagnosis of COVID-19. This article reviews the relationship between imaging changes and pathology of the COVID-19 as well as the application of virtual autopsy in autopsy of patients who died of infectious diseases, in order to provide reference for performing virtual autopsy in the outbreak of COVID-19.

[The impact of male circumcision on the natural history of genital HPV infection: a prospective cohort study].

Objective: To analyze the correlation between circumcision and incidence and clearance of male genital HPV infection. Methods: From May to July 2014, 18-55 year old men who had sexual behavior history were recruited from the general population in Liuzhou, Guangxi to set up a cohort. Totally, 113 circumcised and 560 uncircumcised men were enrolled and interviewed using a questionnaire (including information on demographic characteristics and sexual behaviors), then they were followed-up with 6-month interval for 2 times. On each visit, specimens of male external genitalia were collected and genotyped for HPV DNA. The differences of incidence and clearance of genital HPV infections between circumcised and uncircumcised men were analyzed by Log-rank test. Cox regression was used to analyze the relationship between circumcision and incidence and clearance of HPV infection. Results: The median age (P(25), P(75)) of circumcised and uncircumcised men were 28 (24, 35) and 32 (24, 31), respectively. The incidences of any HPV infections were 9.1 (95%CI: 2.4-15.7) and 8.4 (95% CI: 5.6-11.2) per 1 000 person-months (χ(2)=0.10, P=0.758), respectively. The clearance of circumcised men [136.3 (95%CI: 70.0-202.7) per 1 000 person-months] was higher than that in uncircumcised men [89.6 (95%CI: 65.9-113.3) per 1 000 person-months] (χ(2)=8.19, P=0.004). In multivariate COX regression analysis, compared with uncircumcised men, circumcised men had higher possibility to clear any HPV infections (HR: 2.41, 95%CI: 1.30-4.46). Compared with men having one sexual partner, people having more than 4 sexual partners had lower possibility to clear any HPV infections (HR: 0.49, 95%CI: 0.25-0.96). Compared with 18-25 years old men, men aged 26-35 years old had higher possibility to clear high-risk HPV infections (HR: 2.14, 95%CI: 1.08-4.23). Conclusion: Circumcised and uncircumcised men had similar incidence of genital HPV infection, whereas, men conducted circumcision and having fewer sexual partners could increase the clearance of genital HPV infections.

[Trends of asthma control, disease management and perception in China].

Objective: To evaluate the changes of asthma control, disease management and perception in recent years in China. Methods: We conducted 2 multi-center, cross-sectional surveys. Outpatient asthmatic patients from 10 cities in mainland China (2007-2008) and 30 central cities from 30 provinces in China (except Tibet)(2015-2016) were recruited respectively. Data of asthma control, disease management and perception from the 2 surveys were compared for 10 cities which took part in both of the 2 surveys. Chi-square test was used for comparison between groups. Results: The asthma control level improved from 28.7%(839/2 928) in 2007-2008 to 39.2%(533/1 361) in 2015-2016(P<0.01). The rate of emergency visits was 18.2%(248/1 362) in 2015-2016, which was lower than that in 2007-2008(33.9%, 1 032/3 044)(P<0.01). The rate of peak flow meter (PFM) usage was 17.9%(244/1 360) in 2015-2016, which was slightly lower than the PFM usage rate in 2007-2008(21.8%, 660/3 030)(P=0.004). 56.0%(763/1 362) of the patients used inhaled corticosteroid (ICS) + formoterol to control asthma when asthma symptoms deteriorated in 2015-2016, which was higher than the result of 2007-2008(31.8%, 803/2 524)(P<0.01). 71.1%(968/1 361) of the patients in 2015-2016 had a right perception on disease nature, while the result in 2007-2008 was 63.3%(1 889/2 986)(P<0.01). 61.6%(839/1 362) of the patients in 2015-2016 had a right perception on medication choice on daily-use first-line medication for chronic asthma, while the result in 2007-2008 was 51.0%(1 500/2 942)(P<0.01). Conclusion: The current level of asthma control and disease perception in China improved significantly in recent years, while the rate of PFM usage showed no significant improvement. Asthma action plan including PFM monitoring and asthma self-management should be further promoted nationwide.

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5.

Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

[The relationship between smoking status and epidermiology of asthma in people aged over 14 years in China].

Objective: To study the relationship between bronchial asthma and smoking status in Chinese people. Methods: Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012. Asthma was diagnosed based upon case history, clinical signs and lung function test. Smoking status was investigated by questionnaire. Results: Sampling population was 180 099 and 164 215 were valid. A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women. The overall prevalence rate of asthma was 1.24% (2 034/164 215). Smokers were 23.8% (39 137/164 215) in the whole population. Smokers were 34.5% (702/2 034) in asthmatic patients, compared with 23.7% (38 435/162 181) in no-asthmatic population. The incidence of asthma was 1.79% and 1.06% in smokers and non-smokers respectively (P<0.001), suggesting that OR of smoking was 1.70 (95% CI 1.55-1.86, P<0.001). According to asthma control test (ACT) score, the level of asthma control in non smoking group was higher than that in smoking group(43.2% vs 35.3%). The times of hospitalization due to acute exacerbations(0.51 vs 0.41 events/person/year), total hospitalization rate(27.35% vs 20.12%), annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77% vs 24.47%) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients, indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients. Conclusions: The smoking rate in Chinese people over 14 years is still high. The prevalence rate of asthma in smokers is significantly higher than that of non-smokers. The level of asthma control in smokers is significantly worse than that in non smokers.

[Research Progress of Sudden Cardiac Death in Forensic Medicine].

Sudden death （SD） is a special kind of death owing to disease, which severely threatening the lives of community population. As the most common type of SD, sudden cardiac death （SCD） has always been a crucial content of identification and research in forensic pathology. This article reviews the research progress from the aspects of epidemiology, morphology, molecular pathology and virtual anatomy of SCD in forensic medicine, so as to provide a reference for the morphological identification, determination of cause of death, and integrated control of this kind of SD.

Asymmetrical reproductive interference between two sibling species of tea looper: Ectropis grisescens and Ectropis obliqua.

Ectropis grisescens Warren and Ectropis obliqua (Prout) are two morphologically similar sibling species with overlapping ranges. In this study, manipulative laboratory experiments were conducted to examine the possibility of reproductive interference in sympatric populations of E. grisescens and E. obliqua and the potential consequences of the mating interaction. Our results showed that the presence of males or females of different species could incur mating interference and significant reduction of F 1 offspring. The reduction was not significant relevant to the initial relative abundance of E. grisescens and E. obliqua. Detailed observations of mating opportunity showed that female mating frequencies of both species were not significantly affected by the absolute species density, but the mating success of E. obliqua females with conspecific males depended on species ratio. In addition, adding males to the other species resulted in lower number of offspring suggesting that the males' behaviour might be linked with mating interference. Males of both E. grisescens and E. obliqua could interfere the intraspecific mating of the other species, but the impact of the mating interference differed. These combined data indicated that asymmetric reproductive interference existed in E. grisescens and E. obliqua under laboratory conditions, and the offspring of the mixed species were significantly reduced. The long term outcome of this effect is yet to be determined since additional reproductive factors such as oviposition rate and progeny survival to adulthood may reduce the probability of demographic displacement of one species by the other in overlapping niches.

[A cross-section study of severe asthma in eight provinces of China].

Objective: To analyze the prevalence of severe asthmain China. Methods: The epidemiological data was collected from 2 034 asthmatics who were diagnosed in the last epidemiological survey from 2009 to 2010 in 8 provinces. Results: According to the questionnaire survey, among the 2 034 patients, the previously diagnosed patients accounted for 72.47% (1 474/2 034) and the percentage of newly-diagnosed patients was 27.53% (560/2 034). In those 1 474 previously diagnosed asthmatics, 122 (8.28%) were classified into severe asthma, while 6.00% (122/2 034) of all asthmatics and 0.07% (122/164 215) of total respondents presented as severe cases. Statistically, there was no difference in the prevalence of severe patients between men and women. The morbidity rate of severe asthma was the lowest in the 21-30 year old group and the highest in 61-70 year old group (0.85% and 8.31% respectively). The difference among ages was statistically significant (χ2=18.791, P=0.005). In addition, the prevalence rates of severe asthma were also significantly diverged among patients with different education background(χ2=24.639, P<0.000 1). A negative relation was found between education level and the proportion of severe cases. Moreover, the morbidity of severe asthma in smoking patients and non-smoking patients were significantly different as well (χ2=7.447, P<0.05). Compared with asthma patients who do not smoke, smokers were more likely to suffer severe asthma (OR=1.663, 95% CI 1.150-2.404). Conclusions: The prevalence rate of severe asthma in China is similar to that in other countries.Elderly patients have higher risk of severe asthma. Smoking is considered as a risk factor for severe asthma.

[Effect of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury].

OBJECTIVE: To explore the role of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury. METHODS: According to the random digital table, a total number of 32 Wistar rats were divided into 4 groups: sham burn (group A), burn group (group B), 12-week post burn recovery group (group C), and 12-week post burn recovery plus a second burn injury group (group D). In group A and group B, lung tissues were harvested on post burn day 4. After received first burn injury 12 weeks, the group C and group D received separately a second sham burn injury and burn injury. Lung tissues were harvested on post burn day 4 after the second burn injury. All tissues were examined for cells apoptosis by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). Pulmonary fibrosis was assessed by Masson trichrome staining and Sirius red staining. The protein expression levels of cleaved Caspase-3, Bax and Bcl-2 were assessed by Western blot. RESULTS: Both Masson trichrome staining and Sirius red staining showed obvious pulmonary fibrosis in group C and group D. The apoptosis rates of group B, C and D were significantly higher than that in group A ((15.50±3.30)%, (7.88±3.10)%, (15.88±3.23)% vs (2.10±1.07)%, all P<0.05). Compared to group A, cleaved Caspase-3 levels were significantly higher in group B, C and D ((0.59±0.11), (0.33±0.08), (0.73±0.13) vs (0.16±0.05), all P<0.05). The ratio of Bax/Bcl-2 in group B, C and D also increased significantly ((2.08±0.30), (0.83±0.09), (1.54±0.12) vs (0.64±0.05), all P<0.05). CONCLUSION: Severe burn injury can induce pulmonary fibrosis and mitochondrial apoptosis may play an important role in the development of pulmonary fibrosis.