Abstract: With the development of molecular biology, non-coding sRNA has been found to play an important regulatory role in gene expression and protein activity, affecting various biological pathways including mosquito resistance against insecticides. Understanding the molecular regulatory mechanisms of drug resistance is essential for controlling mosquitoes, , of which metabolic resistance being the most critical mechanism, mainly referring to the high expression of metabolic detoxification enzyme-related genes (especially the cytochrome P450 enzyme system) in mosquitoes. On the basis of verification of insecticide resistance-related genes, further research on the correlation between sRNA and mosquito resistance-related genes provides new ideas and directions for further exploring the mechanism of mosquito resistance. The study of mosquito metabolic resistance mechanism is of great significance for the control of vector mosquitoes, drug resistance monitoring and novel insecticide development. This article reviews the progress of research on the resistance genes, sRNAs biosynthesis, genes involved in regulating mosquito metabolic detoxification enzymes and their applications.

Background Retina fixed flat-mount perfused by Evans blue (EB) is a common method for the evaluation of blood-retinal barrier (BRB).However,previous method is inconvenient for some laboratories because the retinal specimen can not be observed by gereral microscope rather than confocal laser scanning microscope after the fixation.Objective This study was to modify the preparing way of flat-mounted retina in order to obtain transparent specimen for the observation of rat retinal vessels and the evaluation of leakage under the ordinary fluorescence microscope.Methods Forty male SD rats were divided into the control group,diabetes mellitus (DM) 1-month group,DM 3-month group and DM 6-month group according to the random number table.Streptozotocinum (STZ) of 2％ dissolved in 0.05 mmol/L sodium citrate-hydrochloric acid buffer was intraperitoneally injected in SD rats to establish DM models,and the equal volume of solvent was injected in the same way in the control rats.One month,three months and six months after injection,EB of 30 g/L was injected via rat femoral vein in the dose of 45 mg/kg.Fifteen minutes after injection of EB,the rats were sacrificed and the retinas were isolated and cut radially to prepare the flat-mounted retinas in PBS immediately and then were dried till the specimens were transparent.The specimens were examined under the fluorescence microscope.The percentage of EB leakage was quantitatively calculated by IPP 6.0 software.All procedures were performed following approval of the institutional animal care and use committee of Tianjin Medical University.Results The retina morphology was normal in the control group,and EB filled the vessels,exhibiting the red fluorescence under the fluorescence microscope.Compared with the control group,retinal background fluorescence was enhanced slightly in the DM 1-month group,and focal leakage of the EB from capillaries and focal dilated vessels were found in the DM 3-month group,further,vascular caliber inequality,retinal hypoperfusion area and a larger number of hyperfluorescence areas were seen in the DM 6-month group.The percentage of leakage area was (0.05 ±0.02) ％,(0.27 ±0.06) ％,(1.17 ±0.18)％ and (4.77 ±0.66)％ in the control group,DM 1-month group,DM 3-month group and DM 6-month group,respectively,showing a significant difference among the four groups (F =795.800,P＜0.001),and the leakage area was obviously larger in the DM 3-month group and DM 6-month group than that in thecontrol group (q'=10.338,q'=43.475,both at P＜0.001).Conclusions Modified EB-perfused retinal wholemount method is easy and helpful for clear visualization of retinal vessel leakage induced by BRB breakdown in the diabetic rats under the common fluorescence microscope.

Objective: To explore aspirin resistance (AR) phenomenon in patients with coronary artery disease (CAD) for secondary prevention and to study the relationships between AR and COX1, COX2, TBXA2R gene polymorphisms. Methods: A total of 2881 CAD patients taken aspirin (100 mg/day) in 7 consecutive days were enrolled. Among them, 2 groups were established as AR group, n=166 and Control group, n=200 aspirin sensitive patients. Platelet aggregation function was induced by arachidonic acid (AA), COX1, COX2 and TBXA2R gene polymorphisms were examined by polymerase chain reaction-restricted fragment length polymorphisms (PCR-RFLP) method. Results: The occurrence rate of AR was 5.76% (166/2881). There were 8 tagSNPs locus in 3 genes as in COX1:(rs3842788), (rs4273915), (rs7866582); in: COX2 (rs3218625); in TBXA2R: (rs2238630), (rs2238631), (rs2238633), (rs3786989). The frequencies of wild type, heterozygous genotype and homozygous genotype were similar between 2 groups. Conclusion: The incidence rate of AR is not high in CHD patients with regular aspirin medication; single nucleotide gene polymorphisms of COX1, COX2 and TBXA2R have no obvious correlation to AR.

Harmful substances are produced during the metabolism of alcohol in the human body, which causes liver disease.The mechanism of oxidative stress is the main pathogenesis of alcoholic liver disease, which plays a major role in the occurrence and development of alcoholic liver disease.Alcohol-induced oxidative stress mediated by reactive oxygen species(ROS)/reactive nitrogen species(RNS) brings about liver disease via apoptotic signaling pathway and MAPK signaling pathway, and alleviates liver disease through Nrf2 signaling pathway.In this paper, the studies on the mechanism of oxidative stress in alcoholic liver disease are reviewed.

Objective To investigate the incidence,pathogenetic factors,prognosis and correlation factors of acute kidney injury(AKI) in the hospitalized elderly patients. Methods The clinical data of 4781 elderly patients (aged 65 years and over) in our hospital from June 2008 to December 2009 were collected in this study using the hospital information system(HIS).The patients with AKI were picked out and were retrospectively analyzed. Results Among 4781patients,515cases (10.8％) suffered from AKI and the incidence of AKI increased with growing age. Single factorial analysis of etiology showed that infections (39.2％) was the most common causes of AKI.Multifactorial analysis revealed that the major causes of AKI were infections (81.0％),followed by hypovolemia (67.2 ％ ),nephrotoxic drugs (64.1％ ),cardiovascular diseases (32.3 ％),respiratory failure(17.7％) and neoplasm (9.5％). Multivariate logistic analysis and cox proportional hazard models indicated multiple organ dysfunction syndrome(MODS),gastrointestinal bleeding,mechanical ventilation and malnutrition were independent risk factors inducing end events such as dialysis or death and influencing time of live. Conclusions There is high incidence of AKI in the elderly hospitalized patient.Infections,hypovolemia,nephrotoxic drugs and cardiovascular diseases are the common causes of AKI.Active treatment of primary diseases,early diagnosis and prevention are beneficial for improving the prognosis of AKI.

Objective:To observe whether there was a chronic light damage after the irradiation of 650 nm semiconductor laser (power 2 mW) in chicken cone-rich-retina and discuss the safety of this laser for retina.Methods:Sixty 1-month-old chicken reared under natural light were divided into a normal control group, an irradiation 3-min group, an irradiation 6-min group and an irradiation 30-min group by using a random number table and 15 for each group.The chicken eyes were irradiated with 650 nm laser for different duration according to a grouping.Relative retina area was measured with optical coherence tomography (OCT) at 1 month (2-month-old chicken), 3 months (4-month-old chicken) and 6 months (7-month-old chicken) after laser irradiation.Chickens were sacrificed by overdose anesthesia and the histopathology of chiken retina was examined by hematoxylin-eosin staining.The apoptosis of the retinal cells was evaluated by TUNEL staining.Chicken retinal homogenate was prepared, and the content of malondialdehyde and activity of superoxide dismutase (SOD) in the retina were detected by TBA method and NBT method, respectively.Western blot was employed to detect the expression of L/M opsin and rhodopsin in the retina.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results:In 2-month-old chicken, the molar concentration of malondialdehyde in retina was significantly higher in the irradiation 30-min group compared with the normal control group ( P<0.05). In 4-month-old chicken, the molar concentration of malondialdehyde was statistically higher in the irradiation 6-min group and the irradiation 30-min group in comparison with the normal control group ( P=0.026, 0.003). In 7-month-old chicken, the concentrations of retinal malondialdehyde in the irradiation 3-min group, irradiation 6-min group and irradiation 30-min group were statistically higher than those of the normal control group( P=0.038, 0.032, <0.01). In 7-month-old chicken, the SOD activity and the relative expression of rhodopsin in the retina of the irradiation 30-min group were statistically reduced incomparison with the normal control group (SOD: [140.20±5.99][nmol/s·mg] vs.[160.57±3.13][nmol/s·mg]); Rhodopsin: 0.392±0.065 vs.0.566±0.072) (both at P<0.05). OCT showed that there was no significant difference in relative retinal area within 6 months among the four groups.Histopathological examination showed that the thickness of the retina in each irradiation group was close to the normal control group.TUNEL staining showed that the retinal cells were regularly arranged, and no TUNEL positive staining cells were found in all of the groups. Conclusions:Irradiation of a 650 nm semiconductor laser (2 mW) in chicken's eyes for 6 minutes is safe for retina within 6 months.The lasser irradiation 30 minutes for 6 months results in an increase of free radical content in the retina and a decrease in rhodopsin, suggesting the presence of photo damage.

Lactobacilli are important colonizing bacteria in female reproductive tract， among which Lactobacillus crispatus is closely associated with reproductive tract health and plays a crucial role in maintaining the vaginal microbiota balance. A decrease in the abundance of Lactobacillus crispatus may be correlated with various female reproductive tract diseases， such as bacterial vaginosis and vulvovaginal candidiasis， and it can even lead to adverse pregnancy outcomes such as infertility and embryo arrest. This article provides an overview of the basic characteristics of Lactobacillus crispatus， relationship between the decrease of its quantity and reproductive tract diseases， its ability to inhibit pathogenic bacteria such as Candida albicans and Chlamydia trachomatis， and the anti-inflammatory effects of Lactobacillus crispatus. The aim is to provide references for the use of Lactobacillus crispatus in vaginal therapeutics.

Promoting medical preventive integration and improving its collaborative mechanism is an inevitable requirement for achieving the transformation of China′s medical and health care system from " disease centered" to " people′s health centered" and providing comprehensive and comprehensive health services for the people.This study established a research framework based on the SFIC model on the basis of clarifying the collaborative subjects of medical preventive integration, sorted out the dilemma of medical preventive integration collaborative governance in China from five aspects, including external environment, starting conditions, facilitative leadership, institutional design and collaborative process.In order to break the dilemma of medical preventive integration and promote collaborative governance among multiple subjects, the authors proposed such optimization strategies, including further improving relevant laws, regulations, and policy systems, filling resource gaps, attracting multiple entities to participate, providing reference for promoting China′s medical preventive integration work.

Objective:To analysis the clinical features of patients with acute myocardial infarction (AMI) presenting de Winter pattern on electrocardiogram.Methods:A total of 1 287 patients with AMI admitted to Beijing Luhe Hospital between June 2017 and January 2019 were enrolled in the study. Electrocardiogram and clinical features of 13 patients with AMI presenting de Winter pattern on electrocardiogram were analyzed and compared with anterior wall ST-segment elevation myocardial infarction(STEMI, n=206). Results:Among the 13 patients, 12 were males, aged (52.23±12.55) years old. Compared to patients with anterior wall STEMI, the age in the de Winter group was younger [(52.23±12.55)years vs. (59.79±12.46)years; t=-2.12, P=0.03], and the time from onset to appearing a typical ECG was shorter [109.0 (71.5, 152.0)min vs. 200.5 (120.0, 397.5)min; Z=-3.38, P<0.01]. Three cases showed a shifting between de Winter pattern and typical STEMI ECG: the de Winter ECG pattern progressed to STEMI in 2 cases, 1 case changed from STEMI to de Winter,then converted to STEMI again. The emergency angiography was performed in all 13 patients, angiography showed that proximal left anterior descending branch (LAD) was involved in 11 cases, mid LAD was involved in 1 case, and diffuse spasm occurred in all vessels in 1 case. The de Winter ECG pattern vanished in all patients after primary percutaneous coronary intervention or emergency angiography. Conclusions:The de Winter ECG pattern suggests an acute proximal or mid LAD artery occlusion, and the de Winter ECG pattern can be alternated with STEMI. The de Winter pattern should be recognized and revascularization should be given early.

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.