BACKGROUND:Endometrial receptivity is a key factor in embryo implantation in northwest Tibetan cashmere goats,and the expression of genes related to endometrial receptivity and their variable splicing are still unclear. OBJECTIVE:To analyze and explore genes and variable splicing events related to endometrial receptivity in northwest Tibetan cashmere goats. METHODS:On days 5 and 15 of pregnancy(representing pre receptive endometrium group and receptive endometrium group),three northwest Tibetan cashmere goats were randomly selected.Endometrial tissue was collected and stained with hematoxylin and eosin to observe tissue morphology.Immunohistochemical staining was used to detect the expression of endometrial receptive marker proteins leukemia inhibitory factor and vascular endothelial growth factor.After the total RNA was extracted and the quality test was qualified,transcriptome sequencing was performed to search differentially expressed mRNAs,lncRNAs,circRNAs,and miRNAs,perform functional prediction,and analyze alternative splicing mRNAs and lncRNAs related to endometrial receptivity. RESULTS AND CONCLUSION:(1)Compared with the pre receptive endometrium group,the expression levels of leukemia inhibitory factor and vascular endothelial growth factor proteins in the endometrial tissue of the receptive endometrium group were significantly increased.(2)The sequencing results showed that the differentially expressed genes were mostly mRNA and lncRNA genes,including 250 upregulated mRNAs,193 upregulated lncRNAs,135 downregulated mRNAs,and 123 downregulated lncRNAs,which were significantly enriched in the Wnt,Hedgehog,and Hippo signaling pathways.(3)Alternative splicing event analysis uncovered 8 differentially expressed variable splicing transcripts,which were all mRNA transcripts,including 2 downregulated and 6 upregulated,and were significantly associated with vascular endothelial growth factor receptor signaling,cell motility,and embryonic development.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

Objective: To investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and periodontitis and to provide new epidemiologic evidence on the factors affecting periodontitis. Methods: Data on MHR, periodontitis, and other covariates were selected from the NHANES(National Health and Nutrition Examination) database for 3 cycles of subjects in 2009-2010, 2011-2012, and 2013-2014, and a total of 8 456 study subjects were included. The study participants were grouped according to the prevalence of periodontitis (presence or absence), and three regression models (unadjusted covariates, partially adjusted covariates, and fully adjusted covariates) were constructed to analyze the relationship between MHR and periodontitis by using a weighted logistic regression method with stepwise adjustment for confounders. MHR was divided into four groups from Q1 to Q4 according to quartiles from small to large for weighted trend analysis, and the nonlinear relationship between MHR (continuous) and periodontitis was analyzed using a restricted cubic spline with subgroup analysis and sensitivity analysis. Results: All three logistic regression models showed a positive association between MHR and periodontitis (OR = 2.92, 95%CI: 2.14-3.99, P<0.001 (not adjusted); OR = 1.97, 95%CI: 1.39-2.78, P<0.001 (partially adjusted); OR = 1.62, 95%CI: 1.10-2.39, P = 0.017 (fully adjusted)). Trend analysis showed a significantly higher risk of developing periodontitis in the Q4 group compared with the Q1 group in both single (OR = 1.92, 95% CI: 1.58-2.33, P<0.001) and multifactorial analyses (OR = 1.30, 95% CI: 1.03-1.64, P = 0.029). Restricted cubic spline results did not support a nonlinear relationship between MHR and periodontitis (P for nonlinear>0.05), subgroup analysis showed no significant interaction between the covariates and MHR (P>0.05), and sensitivity analysis also showed a positive correlation between MHR and periodontitis (OR = 1.67, 95%CI: 1.31-2.14, P<0.001). Conclusion MHR is positively associated with the risk of developing periodontitis.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.

The patients with skeletal Class Ⅱ high-angle malocclusion are frequently complicated by idiopathic condylar resorption(ICR),which may lead to temporomandibular joint(TMJ)dysfunction and dentofacial deformities.This article reports the diagnosis and treatment process of a 24-year-old female patient with skeletal Class Ⅱ high-angle malocclusion accompanied by ICR.The patient's chief complaints were anterior open bite and TMJ pain,and was diagnosed with ICR through clinical examination and imaging.After stabilizing condylar resorption with occlusal splint therapy,combined orthodontic-orthognathic treatment was performed.The 42-month follow-up revealed:well-aligned dentition with complete closure of diastemas,significant improvement of protrusive facial profile(ANB angle reduced by 4.2°),complete resolution of TMJ pain and clicking,and establishment of stable Class Ⅰ occlusion.Three-dimensional CT demonstrated satisfactory condylar bone remodeling and normalized joint space.Through multidisciplinary treatment,both occlusal function and facial aesthetics were significantly improved.This case demonstrates that orthodontic-orthognathic treatment should be performed after condylar stabilization in ICR patients,and occlusal splint therapy serves as an effective preoperative intervention.

Objective:To investigate the effects of SINC, a novel secreted protein of Chlamydia psittaci, on the apoptosis of host cells and the regulatory role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway in it. Methods:HeLa cells were treated with recombinant SINC. The expression of Bax and Bcl-2 at protein level and the phosphorylation of ERK1/2 were analyzed by Western blot. Hoechst 33258 staining was used to detect the apoptosis of HeLa cells after SINC stimulation. Moreover, HeLa cells were pretreated with MEK1/2 inhibitor U0126 (50 μmol/L), and then stimulated with different concentrations of SINC for different time. Flow cytometry was used to detect the changes in cell apoptosis rates and Western blot was performed to detect the expression of Bax and Bcl-2 at protein level.Results:Treating HeLa cells with 10 μg/ml of SINC for 18 h resulted in down-regulated Bax and up-regulated Bcl-2 at protein level. Besides, the ratio of Bax/Bcl-2 was the lowest and a significant increase in the ratio of phosphorylated ERK1/2 (p-ERK1/2) to ERK1/2 was observed. Hoechst 33258 staining showed that the number of apoptotic bodies decreased significantly after stimulating HeLa cells with 5, 10 and 15 μg/ml of SINC. In the presence of MEK1/2 inhibitor U0126, the expression of Bcl-2 at protein level was down-regulated, while the expression of cleaved PARP was significantly up-regulated. Flow cytometry showed a significantly enhanced apoptosis of HeLa cells.Conclusions:SINC can inhibit the apoptosis of HeLa cells through activating the MAPK/ERK signaling pathway.

Tooth ankylosis is a clinical condition where the tooth cementum directly fuses with the surrounding alveolar bone,leading to functional and aesthetic defects.The etiology involves genetic,metabolic,and local stimulation factors.The diagnosis of tooth ankylosis requires a combination of clinical manifestations and imaging examinations to improve the diagnostic accuracy.The treatment of tooth ankylosis presents significant challenges.Orthodontic treatment combined with other disciplines offers a new,comprehensive treatment approach,integrating traditional orthodontic techniques with osteotomy,distraction osteogenesis,orthodontic bone traction,corticotomy,dislocation,and autologous tooth transplantation techniques.The treatment of tooth ankylosis requires the cooperation of multiple disciplines,and the experts from orthodontics,oral surgery,and oral medicine collaborate to develop the optimal treatment plan.This comprehensive treatment method achieves better outcomes compared with traditional treatments.This review discusses the etiology,diagnosis,and orthodontic combined multidisciplinary treatment methods of tooth ankylosis,analyzes the advantages and disadvantages of various treatment options,evaluates the efficacy and risks,and provides new perspectives for the treatment of tooth ankylosis.

Objective:To investigate the effects of wza gene deletion in Klebsiella pneumoniae on capsule formation ability and bacteriophage sensitivity. Methods:The wza deletion mutant strain was constructed through a temperature-sensitive plasmid-mediated homologous recombination. The growth curves of W14 and Δ wza were detected by measuring the optical density OD 600. In order to analyze the effect of gene wza on bacterial capsule formation, wild-type strain W14 and Δ wza mutant strain were detected by transmission electron microscope, and their capsule contents were measured by quantifying the uronic acid contents. The plaque assay was used to detect bacterial sensitivity to bacteriophage in wild-type strain W14 and Δ wza mutant strain. The t test was used to compare whether there were differences in the contents of uronic acid in the capsules of wild-type strain W14 and Δ wza mutant strain. Results:The PCR results revealed that the Δ wza mutant strain was successfully constructed. Compared with wild-type strain W14, the growth curves of Δ wza on the solid plates demonstrated a slightly slower growth. However, no difference in growth was observed among wild-type strain W14 and Δ wza mutant strains in LB broth. The transmission electron microscope results showed that wza gene deletion resulted in the loss of capsule in bacteria. The uronic acid content assay suggested that the capsule content was significantly decreased in Δ wza mutant strain (45.963±2.795) μg/ml compared with wild-type strain W14 (138.800±5.201) μg/ml. There was a statistical difference between the two groups ( t=27.233, P<0.001). The plaque assay indicated that bacteria lost its sensitivity to bacteriophage when gene wza was deleted. Conclusion:Deletion of the wza gene impairs bacterial capsule formation ability and can affect bacterial sensitivity to bacteriophage phiW14.