Objective:To understand the willingness of pre-exposure prophylaxis (PrEP) use to prevent HIV infection and related factors in men who have sex with men (MSM) in Yunnan Province.Methods:Cross-sectional study method and snowball sampling method was used to carry out the survey in 14 cities (autonomous prefectures) in Yunnan from April to June 2021. According to national sentinel surveillance program, the sample size was 400 at national sentinel sites and 100 at provincial sentinel sites. The related factors of PrEP use willingness were analyzed by multiple logistic regressions with software SPSS 22.0.Results:A total of 2 450 questionnaires were completed, the rate of having heard of PrEP was 68.5% (1 677/2 449), the willingness rate of PrEP use was 56.7% (1 343/2 368), the willing rate of PrEP use at their own expense was 30.6% (724/2 368), and the willingness rate of free PrEP use was 56.2% (1 330/2 367). The of multivariate logistic analysis results showed that related factors of low willingness to use PrEP included aged 40-49 years and 50 years or above (a OR=2.49 and a OR=4.48), Han ethnic group (a OR=1.47), residence in other provinces (a OR=1.64), education level of senior high school (a OR=1.96) and college or above (a OR=3.49), sample source of bath house (a OR=3.53), online recruiting (a OR=2.53) and voluntary counseling and testing (a OR=1.42), local living time for 3-6 months and 7-12 months (a OR=0.18 and a OR=0.25) ,class 2 and 3 of survey areas (a OR=3.63 and a OR=1.71), having no anal sex with men in the past week (a OR=2.60), having no commercial homosexual behavior in the past six months (a OR=13.32) and self-perceived higer risk for HIV infection (a OR=0.50). Conclusions:There was more than half of MSM with willingness to use PrEP. The health education to promote PrEP use should be strengthen in MSM who had low willingness to use PrEP from underdeveloped areas, in Han ethnic group, with older age, from other provinces, with shorter local living time and self-perceived low risk for HIV infection.

Diabetic wounds are slow to heal， which poses a challenge to the medical field. Being vulnerable to infection， they are a major cause of amputation and even death and thus are costly. Chronic inflammation is an important culprit of the lingering diabetic wounds. NOD-like receptor protein 3 （NLRP3）， apoptosis associated speck-like protein （ASC）， and aspartate-specific proteasezymogen procaspase-1 （pro-Caspase-1）， constitute an intracellular protein complex called the NLRP3 inflammasome. Activated NLRP3 inflammasome can induce the release of pro-inflammatory factors interleukin（IL）-1β and IL-18 and participate in a variety of inflammatory responses. The activation of the NLRP3 inflammasome is associated with several inflammatory diseases. It has been concluded that many factors such as microcirculation disorder of diabetic wounds， accumulation of advanced glycation end products， oxidative stress injury， and long-term infiltration of macrophages can influence NLRP3 inflammasome， which induce persistent inflammation of the wounds. Therefore， solutions to the diabetic wound， such as targeting the NLRP3 inflammasome， reducing its hyperactivation， and inhibiting its overexpression， have emerged. Based on the correlation between the pathological changes of diabetic wounds and NLRP3 inflammasome， this article summarized the research on the methods of reducing NLRP3 inflammasome expression to promote the healing of diabetic wounds， such as regulating diabetic wound oxidative stress， balancing neutrophil extracellular traps （NETs） / NLRP3 inflammasome axis， inducing macrophage M2 polarization， reducing the production of advanced glycation end products， and enhancing autophagy. Moreover， the mechanisms of active constituents of Chinese medicine and compound Chinese medicine prescriptions against NLRP3 inflammasome activation were analyzed. Thereby， this paper is expected to provide new targets for diabetic wound healing and a reference for research the mechanism of Chinese medicine in anti-inflammation and promoting healing.

Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

Objective: To analyze the correlation between the age and the cone-beam CT (CBCT) images of the third and fourth cervical vertebrae in female skeletal class Ⅰ patients aged between 9 and 17 years, and to establish a quantitative evaluation method for calculating the age. Methods: CBCT images of 108 female skeletal class Ⅰ patients aged between 9 and 17 years were collected from Qingdao Stomatological Hospital from September, 2017 to March, 2019. The two-dimensional linear values (AH: height of anterior edge of vertebral body; H: height of middle part of vertebral body; PH: height of posterior edge of vertebral body; AP: width of vertebral body), the two-dimensional linear ratio values (AH/PH, AH/AP, AH/H, H/AP, H/PH, PH/AP) and the three-dimensional volume values of the third vertical vertebrae (C3) and the fourth vertical vertebrae (C4) were measured. By Exponential transformation of measurements and multiple linear regression analysis, the optimal index for evaluating age were screened, and the fitting degree of multiple linear regression equation (R²) and the accuracy of age estimation (SEE) were compared. CBCT images of 27 female skeletal class Ⅰ patients aged from 9 to 17 years were added from Qingdao Stomatological Hospital between April, 2019 and July, 2019, by which the accuracy of the regression equation was verified. Results: Multiple linear regression equation for age estimation based on two-dimensional linear indexes was as follows: Y=-113.928+33.743×e^AH₃^/100+58.844×e^PH₄^/100+20.590×e^AP₄^/100( "e" was a natural constant, e≈2.718), R²=0.745, SEE=1.31. Multiple linear regression equation for age estimation based on two-dimensional linear ratio indexes was as follows: Y=-0.076-2.284×e^AH₃/PH₃+3.227×e^AH₃/AP₃+2.149×e^AH₃/H₃+1.961×e^AH₄/H₄, R²=0.576, SEE=1.70. Multiple linear regression equation of age estimation by the volume index was as follows: Y=-16.828+22.184×e^V₃^{/10 000}, R²=0.555, SEE=1.71. The data of 27 new patients were tested. The CBCT measurement index of C3 and C4 vertebral bodies inferred the fitting degree (R²) and accuracy (SEE) of the equation of the age estimation. The two-dimensional linear value was superior to the two-dimensional linear ratio and the latter was superior to the three-dimensional volume value. The standard error of the estimate about them was 1.74, 2.00 and 2.37, respectively. Conclusions The two-dimensional linear index of CBCT images of C3 and C4 could be used to estimate the age of 9 to 17-year-old female skeletal class Ⅰ patients, and the accuracy of the method was higher than that of two-dimensional ratio index and three-dimensional volume index.

Objective To investigate the guidelines implementation status of preventing gastric aspiration by Neurosurgery Intensive Care Unit (NSICU) nurses, and analyze its effects on gastric aspiration outcomes. Methods Using convenient sampling method, two NSICU of Class Ⅲ hospitals in Beijing from June 2016 to January 2017 were selected to investigate the nursing status of preventing gastric aspiration and analyze its relationship with gastric aspiration outcomes. SPSS 21.0 software was used to analyze the data. Results NSICU nursing routine included assessing the nasal feeding tube position, using the compound chlorhexidine in oral care, and assessing gastric residual volumes (GRVs) per 6 hours. However, only a quarter of bedside elevation angle met the guidelines requirements; 55.9% of the cuff pressure was at a low level. There were statistically significant differences in bedside elevation angle, cuff pressure and enteral nutrition velocity in the comparison of aspiration and non-aspiration patients (χ2=13.848,41.093,33.011;P< 0.001). Conclusions Although guidelines for the prevention of gastric aspiration are being constantly added and updated, a gap between the clinical practice and the guidelines exists. This study suggests that the recommended measures should be more rigorous and detailed in practical clinical work to reduce the incidence of gastric aspiration.

Objective To understand HIV incidence in community residents and epidemiological characteristics of newly detected HIV infection cases in Dali,Yunnan province.Methods A cohort study was conducted among 146720 community residents who were tested to be HIV negative during 2010-2011,they were followed-up from June 1,2014 to May 31,2015.Results A total of 136356 community residents received follow up (92.9％).The follow-up time was 0.23-5.40 years (medium:3.43 years),cumulatively 459675 person years,and 78 people were found to be HIV positive.The incidence rate of HIV infection was 0.170/1000 person years.The incidence rate was 0.037/1000 person years in age group 15-29 years,0.288/1000 person years in age group 30-44 years,0.210/1000 person years in age group 45-59 years,0.204/1000 person years in age ≥60 years;0.213/1 000 person years in males,0.130/1000 person years in females;0.248/1000 person years inHan ethnic group,0.149/1000 person years in Minorities;0.194/1000 in people with education level ≤junior middle school,0.046/1000 person years in people with education level ＞ junior middle school;0.070/1000 person years in the unmarried,0.194/1000 person years in the married and 0.425/1000person years in the divorced/widowed.Cox proportional hazards regression analysis showed that being male (HR=l.731),aged 30-44 years (HR=13.158),aged 45-59 years (HR=10.329),aged ≥60years (HR=8.291),unmarried (HR=3.162) and divorced/widowed (HR=2.689) were the risk factors for HIV infection,while the education level ＞ junior middle school (HR=0.132) was the protective factor for HIV infection.Conclusions By medium 3.43 years follow up,the cohort study showed that incidence rate HIV infection was 0.170/1000 person years in the community residents in Dali.Male,middle aged and old people,people with low education level,the unmarried and the divorced/widowed had relatively higher risk to be infected with HIV,Close attention should be paid to the prevention and control of AIDS in these populations.

The main constituents of a typical medicinal herb,Polygonum muMflorum (Heshouwu in Chinese),that induces idiosyncratic liver injury remain unclear.Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats,whereas the solo treatment cannot induce observable injury.In the present work,using the constituent "knock-out" and "knock-in" strategy,we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats.Results indicated a significant elevation of plasma alanine aminotransferase,aspartate aminotransferase,and liver histologic changes,whereas other separated fractions failed to induce liver injury.The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats.Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract.Furthermore,the isolated cis-,and not its trans-isomer,displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats.Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples.In addition,plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats.All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu.Considering that the cis-trans isomerization of transSG was mediated by ultraviolet light or sunlight,our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

Objective To explore the high-risk factors of tracheobronchial aspiration of gastric contents of patients in Neurosurgical ICU, so as to provide basis for aspiration prevention as well as related complications.Methods The prospective cohort study was conducted during the patients with mechanical ventilation who were continuously enrolled. The general information and condition of 74 patients from two tertiary hospitals were recorded and their tracheal secretions were collected. The content of pepsin A in airway secretions was determined whether there is an aspiration.Results The incidence rate of aspiration in 74 patients was 39.2%. The chi-square test results showed that the angle of backrest elevation, the rate of enteral nutrition pump, diameter of nasogastric feeding tube, gastric residual volume, airbag pressure, Glasgow score and the use of sedatives were all related to the occurrence of aspiration (χ2/F =30.771, 16.845, 11.471, 9.212, 6.582, 15.664, 11.722, 18.312;P<0.05). Logistic regression analysis indicated five risk factors related to aspiration, including bed elevation angle, rate of enteral nutrition pump speed, airbag pressure, whether the use of sedatives and gastric residual volume. AUC of risk score calculation is 0.994,RR=1.979 (1.351,2.900). The risk of patients whose AUC score≥10 was double of patients whose AUC score<10.Conclusions To reduce the incidence of aspiration of gastric contents, for patients without contraindications, angle of backrest greater than 30 degrees, maintaining cuff pressure between 20 and 30 cmH2O, nasogastric feeding rate< 25 ml/hour, small bowel feeding rate<45 ml/hour, and GRVs ≥50 ml, gastric feedings and enteral nutrition are recommended; pay attention to patients usingsedative drugs, can also reduce the aspiration rate of gastric contents.