Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.

Drug-induced long QT syndrome (LQTS) has become an important clinical research topic, and the occurrence of acquired long QT syndrome (acLQTS) is mainly caused by drug inhibition of the human ether-α-go-go related gene (hERG) channel. The hERG gene encodes the α subunit of the fast-activating delayed rectifying potassium ion channel (Ikr), which plays an important role in the process of action potential phase 3 repolarization and is also the target of most antiarrhythmic drugs. The purpose of this study was to investigate the effect of hydroxyrutaecarpine (HRU) on the hERG channel and to evaluate its cardiotoxicity. The whole cell patch clamp technique was used to detect the effects of HRU on the current and kinetics of the hERG channel, and to confirm the binding site on the hERG channel. PCR was used to determine the effect of HRU on hERG mRNA expression. Western blotting was used to detect the effects of HRU on the expression of hERG protein and transcription factor Sp1. Immunofluorescence was used to confirm the effects of HRU on localization and expression of hERG protein and transcription factor Sp1. Studies have shown that transient HRU can inhibit hERG current and shorten the inactivation time constant. Its binding sites to the hERG channel are F656 and Y652. After incubation for 24 h, HRU can reduce the expression of hERG protein, inhibit the hERG current, reduce the level of hERG mRNA, and reduce the expression of transcription factor Sp1 in the nucleus and hERG protein in the cytoplasm. Immunofluorescence experiments also showed the same results suggesting that the inhibition of Sp1 expression by HRU is the cause of the decreased expression of hERG mRNA. In conclusion, the acute inhibition of HRU accelerates the channel inactivation process and reduces the inactivation time constant by binding to the F656 and Y652 sites in the hERG channel, thus reducing the hERG current. In addition, HRU also inhibits the expression of hERG protein, mainly by inhibiting the expression of transcription factor Sp1, the transcription function of hERG channel protein is down-regulated, so that the hERG protein is reduced.

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.
Humans ; Laser Therapy ; Male ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms ; Risk ; Watchful Waiting

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na⁺ concentration, blood K⁺ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na⁺ concentration, blood K⁺ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.
Aged ; Diuretics/therapeutic use* ; Furosemide/therapeutic use* ; Heart Failure/drug therapy* ; Humans ; Male ; Middle Aged ; Stroke Volume ; Ultrafiltration

Objective: At present, though the laparoscopic delta-shaped anastomosis and overlapping delta-shaped anastomosis have been gradually applied to complete laparoscopic radical resection of left hemicolon cancer, the comparative evaluation of their efficacy has not been mentioned in the published literatures. This study aims to explore the safety, feasibility and short-term efficacy of overlapping delta-shaped anastomosis (ODA) in totally laparoscopic left hemicolectomy. Methods: A retrospective cohort study was performed. The clinical and pathological data of patients who underwent totally laparoscopic left hemicolectomy at Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from May 2017 to October 2020 were retrospectively analyzed. The case inclusion criteria were as follows: (1) age of 18-75 years; (2) body mass index (BMI) of 18.5-30 kg/m(2); (3) descending colonic and proximal sigmoid colonic adenocarcinoma was confirmed by preoperative colonoscopy and pathology. The exclusion criteria: (1) multiple primary colorectal cancers; (2) uncontrolled or poorly controlled diabetes mellitus, immune system diseases, or hematological diseases; (3) severe intestinal obstruction; (4) left transverse colonic or splenic flexure colonic adenocarcinoma; (5) distant metastasis of liver, lung and other viscera determined by enhanced computed tomography in the chest, abdomen and pelvis. According to the above criteria, a total of 115 patients with left hemicolon cancer were enrolled. All the patients underwent totally laparoscopic left hemicolectomy. Patients who underwent laparoscopic traditional delta-shaped anastomosis were selected as the control group. Patients who underwent laparoscopic ODA were selected as the ODA group. Effects of these two laparoscopic reconstruction methods on postoperative recovery and perioperative complications were analyzed and compared. Results: A total of 60 patients were enrolled in the ODA group, including 32 males and 28 females, with mean age of (57.3±10.4) years and body mass index (BMI) of (25.0±3.1) kg/m(2). While mean 55 patients were enrolled in the control group, including 31 males and 24 females, with mean age of (56.7±9.9) years and BMI of (24.4±2.9) kg/m(2). There was no statistically significant differences between the two groups in gender, age, BMI, American Society of Anesthesiologist (ASA) classification, TNM staging, preoperative abdominal surgery history, neoadjuvant chemotherapy and nutritional status (levels of hemoglobin, lymphocyte count, prealbumin, and albumin) (all P>0.05). All the patients in both groups received R0 resection without conversion to open laparotomy or conversion to extra-abdominal anastomosis. The digestive tract reconstruction time of the ODA group was significantly shorter than that of the control group [(15.1±1.7) minutes vs. (15.9±2.4) minutes, t=-2.053, P=0.042]. There were no statistically significant differences in the total operation time, intraoperative blood loss, length of skin incision, tumor size, proximal and distal margins, harvested lymph nodes, postoperative first ambulatory time, and postoperative hospital stay (all P>0.05). However, the time to the first flatus and the first defecation in the ODA group was significantly shorter as compared to control group [(1.5±0.5) days vs. (1.7±0.5) days, t=-2.028, P=0.045; (3.1±0.6) days vs. (3.4±0.7) days, t=-2.095, P=0.039], indicating faster intestinal function recovery in patients with ODA. The morbidity of postoperative complication was 6.7% (4/60) in the ODA group and 7.3% (4/55) in the control group and no significant difference was found (χ(2)=0.016, P=0.898). Two cases of incision infection, 1 case of lung infection, and 1 case of intra-abdominal infection occurred in the ODA group, while 3 cases of lung infection and 1 case of intra-abdominal infection occurred in the control group. All these complications were resolved after conservative treatment, and no secondary operation was performed due to complications. Conclusion: Compared with the traditional delta-shaped anastomosis, ODA is associated with a faster recovery of postoperative intestinal function without increasing the morbidity of postoperative complications, and has the satisfactory short-term efficacy.
Adolescent ; Adult ; Aged ; Anastomosis, Surgical ; Colectomy ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

As a natural plant source of artemisinin,a first-line drug against malaria,Artemisia annua directly affects the extraction process of artemisinin and the source of artemisinin. At present,traditional breeding methods combined with tissue culture are often used to breed high-yield artemisinin-containing new varieties of A. annua. However,the breeding method has the disadvantages of low efficiency and continuous selection. In this study,heavy ion beam irradiation technology was used to observe the specific germplasm resources of A. annua,and the morphological characteristics,agronomic traits and artemisinin content were used as indicators to observe the selection materials and materials. The cultivated new varieties were compared with trials and regional trials. In addition,the new variety of A. annua was identified by SRAP molecular marker technology. The results showed that the new variety of A. annua, " Kehao No.1",had an average yield of 235. 0 kg of dry leaf per mu,which was more than 20% higher than that of the control. Especially,the average artemisinin content was 2. 0%,which was 45% higher than that of the control,and the " Kehao No.1" has high anti-white powder disease,high-yield and high-quality new varieties. Therefore,mutagenic breeding of heavy ion beam irradiation can significantly improve the yield and artemisinin content of the " Kehao No. 1" and it has a good promotion value.
Artemisia annua/genetics* ; Artemisinins/analysis* ; Heavy Ions ; Mutagenesis ; Phenotype ; Plant Breeding ; Plants, Medicinal/genetics*

OBJECTIVETo investigate the clinical features, treatment strategy and risk factors affecting the prognosis of elderly patients with non-small cell lung cancer (NSCLC) complicated by chronic obstructive pulmonary disease (COPD).

METHODSWe retrospectively analyzed the data of elderly patietns (>60 years) with newly diagnosed NSCLC complicated by COPD at the Geriatric Institution of General Hospital of PLA between January, 2000 and June, 2015. The clinical data collected included history of smoking, pulmonary function test results, initial treatments, TNM stage, chief complaints, comorbidities and laboratory tests. The Cox proportional hazards regression model was used to explore the prognostic factors in these patients.

RESULTSA total of 200 NSCLC patients were reviewed, of which 107 (53.5%) patients had the co-morbidity of COPD as confirmed by spirometry using bronchodilator test. The median survival of the patients with NSCLC complicated by COPD was 45.8 months with 1-, 3-, 5-, and 10-year survival rates of 80.4%, 55.4%, 41.0% and 20.0%, respectively. Stratification analysis showed that patients with COPD Gold grades 1 and 2 had a significant longer median overall survival (51.7 and 43.1 months, respectively) than those with grade 3/4 (16.9 months; P=0.020 and 0.043, respectively). Univariate and multivariate analyses using Cox proportional hazards regression model showed that an older age, a higher Gold grade, advanced disease stage (stages III and IV), squamous cell carcinoma, nonsurgical initial treatment, coughing and an elevated serum CEA level were independent risk factors for shorter survival of the patients.

CONCLUSIONMultiple prognostic factors can affect the outcomes of elderly patients with NSCLC complicated by COPD, and a higher COPD Gold grade that fails to respond to treatment within 3 months is the independent risk factor for survival of the patients.

Objective To analyze the correlation between neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR) in peripheral blood and the therapeutic effect and prognosis of patients with advanced lung adenocarcinoma treated with tyrosine-kinase inhibitors.Methods Retrospective analysis was utilized to measure the clinical pathological characteristics and follow-up data of 40 cases with advanced lung adenocarcinoma definitely diagnosed by pathology.Correlation analysis was performed by Spearman test,and comparison of the sample rate was measured by the chi square test.Survival analysis was performed by Kaplan-Meier method,Log-rank test was used to compare patients survival difference among different groups.COX regression model was utilized to analyze the prognostic factors of patients with lung cancer.Results Through the ROC curve,the optimal cut-off points of NLR and PLR were calculated to be 3.74 and 205.1 respectively.In NLR<3.74 group,objective response rate(ORR),the median progression-free survival(PFS) and the median overall survival(OS) were 86.9%(20/23),9.02 months and 12.37 months respectively.In NLR ≥3.74 group,ORR,the median PFS and the median OS was ORR were 35.2%(6/17),3.15 months and 5.12 months respectively.Compared with NLR ≥ 3.74 group,NLR<3.74 group had a higher ORR(P=0.036),PFS(P=0.011) and OS(P=0.021),the difference was statistically significant.In PLR<205.1 group,ORR,the median PFS and the median OS was ORR were 85.7%(18/21),9.67 months and 14.35 months respectively.In PLR ≥ 205.1 group,ORR,the median PFS and the median OS was ORR were 42.1%(8/19),3.21 months and 9.25 months respectively.Compared with group PLR ≥ 205.1,PLR<205.1 group had a higher ORR(P=0.045) and PFS(P=0.018),the difference was statistically significant.COX multivariate analysis showed that NLR was an independent prognostic factor for PFS(RR=1.091,95%CI:1.004-1.185,P=0.039) and OS(RR=0.986,95%CI:0.932-1.148,P=0.021).PLR was an independent prognostic indicator of PFS(RR=1.100,95%CI:0.996-1.005,P=0.024).Conclusion NLR and PLR may be independent prognostic factors in patients with advanced lung adenocarcinoma.