ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Endodontic microsurgery is an important treatment for endodontic disease and maxillary sinusitis of endodontic origin of maxillary posterior teeth. However, endodontic microsurgery is challenging due to the close proximity between the maxillary posterior teeth and the maxillary sinus, which may lead to complications of mucosal perforation of the maxillary sinus floor. Endodontic microsurgery combined with maxillary sinus floor elevation is considered as a solution, namely natural tooth-related maxillary sinus floor elevation. The evaluation and design of natural tooth-related maxillary sinus floor elevation are closely related to local anatomic relationships. This article provides a systematic review of the anatomical considerations of endodontic microsurgery, namely natural tooth-related maxillary sinus floor elevation in the maxillary posterior region in terms of maxillary posterior teeth, alveolar ridge of the maxillary posterior region, and maxillary sinus. The literature review showed that a minimum of 3 mm of the root apex must be removed during endodontic microsurgery to eliminate the majority of apical ramification, lateral canals, and severe root curvatures. The height and thickness of alveolar ridge bone are important indicators for evaluating and designing endodontic microsurgery for maxillary posterior teeth. Maxillary sinus floor mucosa, maxillary sinus ostium, the proximity between maxillary posterior teeth and the maxillary sinus floor, maxillary sinus septa, posterior superior alveolar artery, and greater palatine artery, and possible maxillary sinus cysts are the main maxillary sinus-related considerations. When the maxillary sinus floor is below the line between the buccal and palatal roots, when the root apices contact or protrude into the maxillary sinus floor, or when the apical lesion is directly connected to the maxillary sinus mucosa, natural tooth-related maxillary sinus floor elevation is applicable. Anatomical considerations should be emphasized throughout endodontic microsurgery and natural tooth-related maxillary sinus floor elevation in the maxillary posterior region. Further studies are required to investigate the clinical design and difficulty assessment of natural tooth-related maxillary sinus floor elevation in different local anatomical relationships.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Tooth resorption is the degradation of dental hard tissue due to the continuous action of odontoclasts. External cervical resorption refers to the cervical resorption of a tooth due to destruction and/or defects of the periodontal ligament or subepithelial cementum. In this paper, we report a case of maxillary central incisor with external cervical resorption after dental trauma and orthodontic treatment. The resorption site and morphology of the affected tooth were thoroughly analyzed by cone beam computed tomography prior to the operation. Dental operating microscope and layered external repair with composite resin and bioceramics ensured a perfect restoration of the resorption, and the vital pulp was preserved. The 6-year follow-up indicated a favorable treatment effect.
Humans ; Composite Resins ; Cone-Beam Computed Tomography ; Incisor/surgery* ; Maxilla ; Microsurgery/methods* ; Tooth Resorption/etiology*

Objective To investigate whether omeprazole(OME)can enhance the sensitivity of epithelial ovarian cancer(EOC)cells to cisplatin(DDP)by inhibition of autophagy and to elucidate its possible mechanism.Methods Color in situ hy-bridization(CISH)and immunohistochemistry were applied to detect the expression of miR-214-3p and autophagy specific mark-ers p62 in EOC tissues,respectively.Pearson analysis showed the correlation between miR-214-3p and p62 expression levels in EOC.The half concentration(IC50)of DDP was determined by CCK-8 method.The mRNA expressions of miR-214-3p and multi-drug resistance gene 1(MDR1),the protein levels of p-gp and p62 were measured by using real-time quantitative PCR(qRT-PCR)and Western blot,respectively.Results In 43 cases,the expressions of miR-214-3p and p62 were 53.5％(23/43)and 60.5％(26/43)in patients with ovarian carcinoma,respectively.miR-214-3p was downregulated in platinum-relatively resistant OC tissue(P＜0.05).On the contrary,p62 was upregulated in platinum-relatively resistant OC tissue(P＜0.01).In ovarian cancer,the negative expression of miR-214-3p was closely related with p62(r=0.238,P＜0.05).After OME(150 μmol/L)pre-treatment,varying degrees of decrease was observed in cisplatin IC50 OV2008 and C13K cells,especially cisplatin resistant strain C13K(P＜0.01).After DDP treatment,qRT-PCR results revealed that the expression of miR-214-3p was decreased,the mRNA and protein expressions of MDR1 were greatly increased,and the protein levels of p62 were increased in C13K and OV2008 cells,compared to the blank control C13K and OV2008 cells(all P＜0.01).Compared with the blank control C13K and OV2008 cells,the IC50 of DDP was decreased after pretreatment with OME(150 μmol/L).The sensitivity of C13K and OV2008 cells to DDP was increased after OME(150 μmol/L)pretreatment,the relative expression of miR-214-3p was significantly increased,the expression of MDR1 protein and mRNA was decreased,and the expression of p62 protein was decreased(all P＜0.05).Conclu-sion OME pretreatment might enhance the sensitivity of ovarian cancer cells to DDP by downregulating miR-214-3p mediated autophagy.

Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.

Objective To explore the influence of IL-6 secreted by cancer-associated fibroblasts(CAFs)on pro-moting the proliferation and invasion of ovarian cancer cells and the possible mechanisms.Methods CAFs and normal ovarian fibroblasts(NFs)were isolated and cultured respectively from epithelial ovarian cancer and normal ovarian epithelial tissues.Cell markers alpha-smooth muscle actin(α-SMA),E-cadherin were detected by West-ern blot and immunofluorescence.CAFs and normal ovarian fibroblasts(NFs)were collected and cultured,and their supernatants were used to establish an indirect co-culture system with ovarian cancer SKOV3 cells,including SKOV3 cells alone(SKOV3)group,SKOV3 combined with the supernatants of NFs(NFs)group and SKOV3 combined with the supernatants of CAFs(CAFs)group.Cell immunochemistry was used to detect the expression of alcohol dehydrogenase 1B(ADH1B)in SKOV3 cells co-cultured with the supernatant of CAFs or NFs.Before and after treatment with the methylation inhibitor 5-aza-2'-deoxycytidine(5-Aza-dC),methylation-specific PCR(MSP),Reverse transcription quantitative real-time PCR(RT-qPCR),enzyme-linked immunosorbent assay(ELISA),and Western blot were used to detect the mRNA level and methylation status of ADH1B,and the phos-phorylation level of signal transducers and activators of transcription 3(p-STAT3).The cell counting kit-8(CCK-8)method and Transwell assay were used to investigate the effects of the IL-6 inhibitor LMT-286 and recombinant human interleukin-6(rhIL-6)on cell proliferation and invasion.Results The protein levels of α-SMA was highly expressed,however,CAFs and NFs cells almost lacked the E-cadherin protein.Compared with the SKOV3 and NFs groups,CAFs group exhibited significantly downregulated mRNA and protein expression of ADH1B.After treatment with 5-Aza-dC,ADH1B methylation was partially reversed,and the mRNA and protein expression of ADH1B increased in all groups.The phosphorylation level of STAT3 proteins was significantly reduced in CAFs group,while there were no significant changes in SKOV3 and NFs groups.Intervention with LMT-286 and rhIL-6 only inhibited or promoted the proliferation and invasion of cells in CAFs group,while there were no significant changes in SKOV3 and NFs groups.Conclusion CAFs can enhance the methylation of ADH1B in ovarian cancer cells via IL-6/STAT3 pathway,and may promote the proliferation and invasion.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.