Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.

Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.

When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.