Objective To explore the mechanism of tumor-associated fibroblasts(CAFs)for regulating proliferation and migration of prostate cancer(PCa)cells.Methods We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa.The proliferation,migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs.We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR.In PCa cell lines C4-2 and LNCAPNC,the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation,migration,invasion,drug resistance,apoptosis and cell cycle were evaluated,and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice.Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes,whose expressions were detected in PCa cells using RT-qPCR and Western blotting.Results The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines,which exhibited significantly enhanced proliferation and migration abilities.Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells,and in C4-2 and LNCAP cells cultured alone,inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation,migration,invasion,and drug resistance.In the tumor-bearing mice,hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice.Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p,and dual luciferase reporter gene confirmed a binding site between them.In C4-2 and LNCAP cells,hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3.Conclusion CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To explore the mechanism of tumor-associated fibroblasts(CAFs)for regulating proliferation and migration of prostate cancer(PCa)cells.Methods We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa.The proliferation,migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs.We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR.In PCa cell lines C4-2 and LNCAPNC,the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation,migration,invasion,drug resistance,apoptosis and cell cycle were evaluated,and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice.Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes,whose expressions were detected in PCa cells using RT-qPCR and Western blotting.Results The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines,which exhibited significantly enhanced proliferation and migration abilities.Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells,and in C4-2 and LNCAP cells cultured alone,inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation,migration,invasion,and drug resistance.In the tumor-bearing mice,hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice.Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p,and dual luciferase reporter gene confirmed a binding site between them.In C4-2 and LNCAP cells,hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3.Conclusion CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Objective To explore the influence of gender on the prognosis of patients with atrial fibrillation(AF)undergoing left atrial appendage occlusion(LAAO).Methods All non-valvular AF patients who were admitted in our hospital and underwent LAAO from August 2014 to August 2021 were enrolled and grouped according to gender.Their general information,including gender,age,comorbid underlying diseases,and results of transthoracic echocardiography and transesophageal echocardiography(TEE)were collected.The incidences of device-related thrombosis(DRT),pericardial tamponade,stroke,bleeding,hospitalization for heart failure,and cardiac death were recorded during follow-up.The influence of gender on the prognosis of these patients was analyzed.Results There were totally 673 patients with non-valvular AF were enrolled,including 366 males and 307 females,at a mean age of 68.2±9.4 years.When compared with the male patients,the female ones had a higher CHA2DS2-VASc score(P＜0.01),but smaller proportions of history of stroke,average compression ratio of occluders,and incidence of residual shunt(＜3 mm)after occlusion(P＜0.05).In 45～60 d after surgery,TEE revealed that there were 17 cases of DRT,including 8 males(2.2％)and 9 females(2.9％),though without statistical difference between the groups.Among the 17 DRT cases,1 experienced stroke,and the incidence of stroke was 5.9％in those with DRT and 0.5％without.There were 4 cases of postoperative pericardial tamponade,including 1 in the male group and 3 in the female group(no significant difference),and all of them were improved after pericardial puncture and fluid extraction.During the follow-up period of 40.2±20.5 months,no obvious differences were observed between the 2 groups in terms of stroke,bleeding,hospitalization for heart failure,and cardiogenic death.Conclusion Gender shows no significant effect on the prognosis of patients with non-valvular AF after LAAO.

Objective: Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. Methods: We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. Results: The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. Conclusion The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Background: Senecavirus A (SVA), a member of the family Picornaviridae, is newly discovered, which causes vesicular lesions, lameness in swine, and even death in neonatal piglets. SVA has rapidly spread worldwide in recent years, especially in Asia. Objectives: We conducted a global meta-analysis and systematic review to determine the status of SVA infection in pigs. Methods: Through PubMed, VIP Chinese Journals Database, China National Knowledge Infrastructure, and Wanfang Data search data from 2014 to July 26, 2020, a total of 34 articles were included in this analysis based on our inclusion criteria. We estimated the pooled prevalence of SVA in pigs by the random effects model. A risk of bias assessment of the studies and subgroup analysis to explain heterogeneity was undertaken. Results: We estimated the SVA prevalence to be 15.90% (1,564/9,839; 95% confidence interval [CI], 44.75–65.89) globally. The prevalence decreased to 11.06% (945/8,542; 95% CI, 28.25–50.64) after 2016. The highest SVA prevalence with the VP1-based RT-PCR and immunohistochemistry assay was 58.52% (594/1,015; 95% CI, 59.90–83.96) and 85.54% (71/83; 95% CI, 76.68–100.00), respectively. Besides, the SVA prevalence in piglet herds was the highest at 71.69% (119/166; 95% CI, 68.61–98.43) (p < 0.05). Moreover, our analysis confirmed that the subgroups, including country, sampling year, sampling position, detected gene, detection method, season, age, and climate, could be the heterogeneous factors associated with SVA prevalence. Conclusions The results indicated that SVA widely exists in various countries currently.Therefore, more prevention and control policies should be proposed to enhance the management of pig farms and improve breeding conditions and the environment to reduce the spread of SVA.

BACKGROUND: Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China. METHODS: We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method. RESULTS: The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under five has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased by 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased by 1.75 years when only considered the ten major disease systems (tumors; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly. CONCLUSIONS In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.
Child ; Humans ; Aged ; Cross-Sectional Studies ; Quality of Life ; Life Expectancy ; China/epidemiology* ; Prevalence

OBJECTIVES: International Ovarian Tumor Analysis (IOTA) working group proposed a logistic regression (IOTA LR2) model. It is served as a risk prediction model for benign and malignant adnexal tumors. This study aims to compare the diagnostic efficiency between the IOTA LR2 model and doctors' subjective assessment on diagnosing benign and malignant adnexal mass. METHODS: The ultrasonographic images of 616 adnexal masses were retrospectively analyzed by the senior doctors' group and the junior doctors' group using the IOTA LR2 model and subjective assessment. The postoperative pathological diagnosis was used as the gold standard to compare the diagnostic efficiency of the 2 methods. RESULTS: The area under the curves of subjective assessment and IOTA LR2 model for diagnosing malignant adnexal masses were 0.86 and 0.90 for the senior doctors' group and 0.79 and 0.88 for the junior doctors' group, respectively. The sensitivity and specificity of subjective assessment for diagnosing the malignant adnexal masses were 81.0% and 91.3% for the senior doctors' group and 70.1% and 88.7% for the junior doctors' group, respectively. The sensitivity and specificity of the IOTA LR2 model for diagnosing the malignant adnexal masses were 79.6% and 88.1% for the senior doctors' group, and 79.6% and 81.7% for the junior doctors' group, respectively.There were no significant difference in the sensitivities between the senior doctors' group and junior doctors' group using the IOTA LR2 model and the senior doctors' group using subjective assessment (both P>0.05). CONCLUSIONS The diagnostic efficiency of the IOTA LR2 model is equal to the senior doctors' experiences. This model can help junior doctors to reduce the missed diagnosis of malignant adnexal masses.
Adnexal Diseases/pathology* ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms/diagnostic imaging* ; Retrospective Studies