Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.

To predict the distribution and habitat of Dermacentor nuttallii in Xinjiang and to under-stand its life cycle history.In this study,Maximum Entropy Modeling(MaxEnt)was used to pre-dict the geographical distribution and adaptation area of Dermacentor nuttallii in Xinjiang,and jackknife test and response curve of environmental variables were used to evaluate the environmen-tal factors affecting the distribution of Dermacentor nuttallii.Dermacentor samples were collected randomly based on predicted sites.The species of Dermacentor was identified by the combination of morphological characteristics and molecular biology.The New Zealand white rabbit was the only blood donor,and the life cycle and biological characteristics of the tick were observed and recorded by the method of earmuffs feeding under natural light in the laboratory.The jackknife test and SPSS analysis results showed that the main environmental variables affecting the distribution of suitable areas of Dermacentor nuttallii were average temperature(Bio1),average daily tempera-ture range(Bio2),seasonal temperature change(Bio4),driest month precipitation(Bio14),precip-itation variation coefficient(Bio15).The response curves of major environmental variables showed that Dermacentor nuttallii had the highest presence probability when Bio1 was 15.58 ℃,Bio2 was 6.19 ℃,Bio4 had a coefficient of variation of 1 500,Bio14 had a coefficient of variation of 20 mm,Bio15 had a coefficient of variation of 23.799 and Bio19 was 69 mm.The prediction results showed that the suitable areas of Dermacentor nuttallii in Xinjiang were Tianshan Mountain range in Junggar Basin,Turpan basin in Altai Mountain valley and some areas south of Tianshan Mountain range,accounting for 50.99％of the total area of Xinjiang.Dermacentor were collected from the predicted area according to MaxEnt model and identified as Dermacentor nuttallii by morphologi-cal and molecular biological methods.The full blood stage was 5.31 d,the degeneration stage was 8.19 d,and the degeneration rate reached 95.5％.If the full blood stage was 8.65 d and the degener-ation stage was 12.86 d,the degeneration rate reached 98％.The full blood stage of adult ticks was 6.75 d,the early egg stage of full blood females was 5.86 d,and the spawning stage of full blood fe-males was 12.5 d.The eggs hatched into young ticks after 25.92 d,and the hatching rate reached 90％.Dermacentor nuttallii took 62-107 d to complete a life history,with an average of 86.06 d.The constructed MaxEnt model has high prediction accuracy and accuracy.According to the varia-ble analysis of the main environmental factors,precipitation and temperature are the main environ-mental factors affecting Dermacentor nuttallii.The study of the whole life cycle of Dermacentor nuttallii in Xinjiang provides the basis for establishing the method of artificial breeding of pure species of Dermacentor nuttallii in Xinjiang.

In order to investigate the mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)on liver bile acid(BAs)and lipid metabolism of dairy cows with fatty liver,A liver lip-id accumulation model was established by isolating primary calf hepatocytes and treating them with high concentration of non-esterified fatty acids(NEFA)in vitro.Then,HMGCR overex-pressed adenovirus(Ad-HMGCR)and overexpressed adenovirus control(Ad-GFP)were added.Hepatocyte triglyceride(TAG)was detected by the kit,lipid droplet changes were detected by lip-id droplet fluorescence,and BAs synthesis,fatty acid synthesis and oxidation factor changes were detected by real-time fluorescence quantitative PCR.The results showed that TAG content and lip-id droplet fluorescence were significantly reduced in Ad-HMGCR+NEFA group compared with Ad-GFP+NEFA group.Real-time fluorescence quantitative PCR results showed that CYP7A1,CYP8B1,CYP7B1 and CYP27A1 of hepatocyte BAs synthesis factors in Ad-HMGCR+NEFA group,BAs transporters ABCC2 and ABCB11 and fatty acid synthesis factors ACC1,FAS and SREBP1C were significantly lower than those in Ad-GFP+NEFA group.The levels of BAs syn-thesis factor FXR and lipid oxidation factor CPT1A in Ad-HMGCR+NEFA group were higher than those in Ad-GFP+NEFA group.The results showed that overexpression of HMGCR could significantly reduce BAs and lipid accumulation in the liver of dairy cows with fatty liver.

Objective:To seek any relationship between the single nucleotide polymorphisms (SNPs) of the apolipoprotein E (ApoE) gene and blood lipid sensitivity to high-intensity interval training (HIIT).Methods:Two hundred and thirty Han Chinese college students (104 males and 126 females) who were not majoring in sports were recruited to perform a 28-minute high-intensity interval workout three times per week for 12 weeks. Before and after the intervention, blood levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were measured. The subjects′ DNA was genotyped to obtain SNP loci, and a linear regression model was constructed to quantify any association between ApoE genotypes and phenotypes.Results:(1) A total of 21 SNP loci were identified associated with ApoE genes, one of which (rs7412) was found to be correlated with the training effect on blood lipids. (2) The initial TT and LDL-C values of carriers of the T allele of gene rs7412 (individuals with the CT + TT genotypes) were, on average, significantly lower than those of CC genotype individuals. However, no significant differences in the initial TG and HDL-C values among different genotypes were observed. (3) After the training the average LDL-C levels among the ApoE rs7412 polymorphic groups had changed significantly, with a significantly greater decrease observed among the carriers of the T allele compared with those of CC genotype.Conclusions:ApoE polymorphism may be significantly associated with TT and LDL-C values in Han Chinese youth, with carriers of the T allele tending to display lower levels than those of CC genotype. The polymorphism of ApoE gene rs7412 may be related to LDL-C reduction through HIIT, with carriers of the T allele more sensitive to such training.

Objective:To investigate the effects of fluoride exposure on kidney injury in rats and the sirtuin 3 (SIRT3)-fork head protein O3a (FOXO3a)-tensin homolog induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (PARKIN) pathway.Methods:Twenty-four 4-week-old SD rats (clean grade, body mass 100 - 150 g) were selected and divided into three groups according to the randomized numeric table: control group, low fluoride group, and high fluoride group, with eight rats in each group (half male and half female). The control group was given free access to tap water (fluoride ion concentration < 0.5 mg/L), while the low fluoride and high fluoride groups were given free access to tap water and sodium fluoride solutions with fluoride ion concentrations of 5.0 and 50.0 mg/L, respectively, for a period of 180 days. The formation of dental fluorosis in rats was observed and recorded, and the femur, urine and blood samples of rats were collected to measure bone fluoride, urinary fluoride, and blood fluoride levels, and to detect kidney function related indicators (serum uric acid, creatinine, and urea nitrogen contents). Morphological changes of renal tissues stained with hematoxylin-eosin (HE) were observed under a light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of renal SIRT3, FOXO3a, PINK1, PARKIN, microtubule associated protein 1 light chain 3 (LC3), autophagy receptor protein (P62), respectively.Results:Seven and one rats in the low and high fluoride groups were found to haveⅠdegree dental fluorosis, while zero and seven rats were found to haveⅡdegree dental fluorosis. Compared with the control group, rats in the low and high fluoride groups had higher levels of bone fluoride (μg/g: 1.18 ± 0.06, 2.16 ± 0.07 vs 0.52 ± 0.05), urinary fluoride (mg/L: 4.43 ± 0.11, 7.46 ± 0.09 vs 2.58 ± 0.14), blood fluoride (μg/ml: 0.77 ± 0.06, 1.68 ± 0.10 vs 0.52 ± 0.08), serum uric acid (μg/ml: 61.01 ± 4.17, 103.92 ± 5.43 vs 28.68 ± 2.91), creatinine (μg/ml: 74.82 ± 9.61, 132.05 ± 5.35 vs 22.38 ± 4.11), and urea nitrogen (μg/ml: 13.36 ± 1.27, 14.55 ± 0.34 vs 0.29 ± 0.07, P < 0.05). Under the light microscope, the kidneys of the control group showed tight and orderly arrangement of renal tubules and glomerular cells, with complete and clear cell contours. The low fluoride group was similar to the control group and no significant abnormalities were observed. The high fluoride group showed abnormal glomerular structure and atrophy, with some areas of renal tubules showing epithelial cell edema and unclear intercellular boundaries. The results of qRT-PCR assay showed that compared with the control group, the low and high fluoride groups had lower mRNA expression levels of SIRT3 (0.82 ± 0.03, 0.58 ± 0.02 vs 1.00 ± 0.08), P62 (0.75 ± 0.07, 0.28 ± 0.09 vs 1.00 ± 0.07, P < 0.05), and higher mRNA expression levels of FOXO3a (1.35 ± 0.04, 3.01 ± 0.23 vs 1.00 ± 0.08), PINK1 (1.58 ± 0.09, 3.28 ± 0.09 vs 1.00 ± 0.07), PARKIN (1.51 ± 0.04, 1.67 ± 0.10 vs 1.00 ± 0.05), LC3 (1.74 ± 0.07, 2.38 ± 0.18 vs 1.00 ± 0.08, P < 0.05). The results of Western blotting showed that compared with the control group, the low and high fluoride groups had lower protein expression levels of SIRT3 (0.91 ± 0.01, 0.55 ± 0.03 vs 1.00 ± 0.01), P62 (0.94 ± 0.27, 0.66 ± 0.38 vs 1.00 ± 0.19, P < 0.05), and higher protein expression levels of FOXO3a (1.14 ± 0.03, 1.22 ± 0.05 vs 1.00 ± 0.02), PINK1 (1.46 ± 0.03, 1.56 ± 0.03 vs 1.00 ± 0.05), PARKIN (1.98 ± 0.02, 2.33 ± 0.11 vs 1.00 ± 0.06), LC3 (4.10 ± 0.58, 4.93 ± 0.33 vs 1.00 ± 0.13, P < 0.05). Conclusion:Exposure to fluoride can cause renal tissue injury in rats, with downregulation of SIRT3 and P62 expression levels, and upregulation of FOXO3a, PINK1, PARKIN, and LC3 expression levels.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Retinopathy of prematurity(ROP), an abnormal vascular proliferative retinopathy of prematurity, is a serious condition that can lead to retinal detachment or blindness. With the development of neonatal medicine, the survival rate of low birth weight and low gestational age infants has been increasing, as well as the incidence of ROP. Therefore, studying ROP's pathogenesis and influencing factors is of great clinical importance. Numerous studies have been conducted on the risk factors for ROP, including gestational age, oxygen intake, mode of delivery, neonatal bronchopulmonary dysplasia, and the use of surfactants. At present, it is widely accepted both at home and abroad that preterm birth, low birth weight, and high oxygen concentration after birth are independent risk factors for ROP. In recent years, more and more scholars have found that abnormalities in blood indicators in preterm infants may be associated with the development of ROP. This article reviews the effects of platelets, haemoglobin, blood glucose, inflammatory cells, and lipids on ROP, providing a reference for identifying and preventing risk factors for ROP.

Rapidly increasing intraocular pressure(IOP)is a typical manifestation of acute angle-closure glaucoma and an important cause of ocular tissue damage, vision loss and even blindness in glaucoma patients. The sharp increase of intraocular pressure in a short period of time in acute angle-closure glaucoma will cause characteristic damage to the structure and function of retina, choroid and optic nerve. Currently, the diagnosis and evaluation of the course of glaucoma is largely dependent on the state of high IOP, changes in the optic nerve and visual field damage, but irreversible damage to the fundus has already been made in glaucoma patients by this time. The microstructural changes in the posterior segment of the eye are more sensitive to high IOP and often appear before optic nerve and visual field damage, which can indicate the damage of high IOP to the eye earlier. Through the evaluation of the imaging characteristics of the posterior segment of the eye, the morphological characteristics that affect the prognosis of glaucoma can be explored, which is clinically important for the early diagnosis of glaucoma.

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.