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Background:. Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC. Methods:. Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C. Results:. CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells. Conclusions:. LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

Background. Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. Methods. Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. Results. The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271–3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345–1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314–1.875, P = 0.013). Conclusion. Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Supplemental Digital Content is available in the text, Background Regulatory policy (RP) is known as a major factor to improve health care system performance. A significant difference in maternal mortality rates (MMRs) was observed between New York city (NYC) and Shanghai (SH), both first-class international metropolises. This study aims to adopt a quantitative evaluation model to analyze whether RP differences contribute to the different MMRs of the two cities. Methods Based on collection of all publicly released policy documents regarding maternal health in the two cities, we assessed and compared the status of their maternal health care RPs from 2006 to 2017 through a series of quantitative indicators as regulatory elements coverage rate (RECR), departmental responsibility clarity rate (DRCR), and accountability mechanism clarity rate (AMCR), based on two characteristics of comprehensiveness and effectiveness of RPs. Pearson correlation analysis, principal component analysis, and linear regression analysis were used to test the relationships between the indicators and MMR in SH and NYC. Results By 2017, disparities of maternal health care RP are found between SH and NYC, from the indicators of RECR (100% vs. 77.0%), DRCR (38.9% vs. 45.1%), and AMCR (29.2% vs. 22.5%). From 2006 to 2017, RECR, DRCR, and AMCR in SH have shown a higher growth of 8.7%, 53.2%, and 45.2%, compared with growth of 25.0%, 12.5%, and 2.9% in NYC. The three indicators were found all negatively correlated with MMR in SH (Coefficients = −0.831, −0.833, and −0.909, and P

Background: Clinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM. Methods: In this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP). Results: In 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP. Conclusions: This study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD. Key words: Clinically amyopathic dermatomyositis; Interstitial lung diseases; Myositis autoantibodies; Tumor-associated antigen

Supplemental Digital Content is available in the text, Objective: Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis Data sources: Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms “endometriosis” and “non-hormonal therapy.” Study selection: Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English. Results: Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies. Conclusions: Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.

Background:. Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group. Methods:. From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61–69 years and ≥70 years). We compared clinical characteristics and outcomes between groups. Results:. Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1–129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P

Background: Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA. Methods: This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months. Results: In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2=3.937, P=0.047), SDAI (χ2=4.666, P=0.031), and CliDR criteria (χ2=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022). Conclusions: The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA. Key words: Rheumatoid arthritis; Remission; Sustained; Intensive; Disease modifying anti-rheumatic drug

Background: The International Prognostic Score (IPS) was developed based on the data of Western advanced Hodgkin lymphoma (HL) patients treated before 1992. Only a few studies ever evaluated the application value of IPS in Chinese population or in patients treated in the contemporary era whose outcomes has improved significantly than before. Methods: We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients, who were admitted to Cancer Hospital Chinese Academy of Medical Sciences from January 1, 1999 to April 30, 2015 and received uniform first-line treatment. The prognostic value of both IPS and the seven IPS factors for freedom-from progression (FFP) and overall survival (OS) was assessed in this population. The statistical methods included Kaplan-Meier methodology, log-rank testing, and Cox proportional hazard regression analysis. Results: With a median follow-up time of 79 months (range, 15–210 months), the 5-year FFP and OS were 78.8% and 86.0% respectively, which improved obviously compared with the original IPS study. The IPS remained prognostic for both FFP (P = 0.041) and OS (P = 0.013), but the range narrowed obviously, with 5-year FFP ranging from 87.2% to 61.5%, 5-year OS ranging from 94.1% to 69.2%, and the separation of survival curves was not as good as before. Only two of the seven IPS factors showed a significant independent prognostic value in the multivariate analysis: Stage IV (for FFP, hazard ratio [HR] = 2.219, 95% confidence interval [CI]: 1.148–3.948, P = 0.016; for OS, HR = 2.491, 95% CI: 1.159–5.355, P = 0.019) and hemoglobin

Background: Recrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing. Methods: One hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing. Results: Kissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone. Conclusions: ISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation. Key words: Bifurcation; In-stent Anchoring; Percutaneous Coronary Intervention

Hirayama disease is a rare disease characterized by juvenile-onset of asymmetric amyotrophy, of which etiology has not been clarified. The aim of our study was to investigate the clinical and neurophysiologic characteristics of Hirayama disease.Neurophysiological tests, including nerve conduction studies (NCS), F-wave and routine electromyography (EMG), were performed in seventy-three patients with Hirayama disease. EMG was selectively performed on upper and lower extremities, sternocleidomast and thoracic paravertebral muscles according to the clinical features of the patients.Abnormal NCS parameters, including decreased compound muscle action potentials or delayed distal motor latency, were found in 34.2% (25/73) and 12.3% (9/73) of the patients, respectively. A total of 24.6% (18/73) of the patients showed decreased F-wave frequency. EMG demonstrated the presence of neurogenic lesions in all patients with spontaneous potentials, prolonged duration or augmentation of amplitude in motor unit potentials (MUPs), or a single pattern of MUP recruitment. About 17.8% (13/73) of the patients showed neurogenic lesions, mostly in the C7-8 level of the cervical cord, only in the upper extremity of affected side, whereas 35.6% (26/73) of the patients possessed lesions in the upper extremities bilaterally. A total of 46.6% (34/73) of patients exhibited abnormalities in the lower extremities, sterno- cleidomast or thoracic paravertebral muscle. Changes in motor NCS were significantly correlated with muscle strength.EMG detects diffused subclinical neurogenic lesion in a high proportion of patients with Hirayama disease. Results of our study challenge the hypothesis that Hirayama disease is a type of cervical myelopathy.

Antiangiogenesis is a promising field of cancer therapy. Endostar, a novel recombinant human endostatin, is one of the few approved drugs acting as angiogenesis inhibitors of cancer in China. However, there are few clinical studies about Endostar in gastrointestinal cancer. This pilot study aimed to evaluate the efficacy and safety of the combination of Endostar and chemotherapy in patients with metastatic colorectal and gastric cancers.From March 2007 to October 2009, 23 patients were enrolled. Patients received Endostar intravenously at a dose of 15 mg daily from day 1 to 14 and day 1 to 7 when combined with 3- and 2-week chemotherapy regimens, respectively, which were determined according to patients' previous chemotherapy history. Treatment was repeated until disease progression, unacceptable toxicity or patients' refusal.Seven, six and ten patients received Endostar as first-, second- and third-line therapy, respectively. A total of 75 cycles were administered. Twenty-one patients were assessable for responses. The overall response rate and disease control rate were 19.0% and 47.6%, respectively. All the four partial responses were among patients receiving Endostar as first-line therapy, whose response rate was 57.1%. The median time to progression and overall survival were 2.6 months (95%CI, 2.0 - 3.2 months) and 10.3 months (95%CI, 3.9 - 16.7 months), respectively. Toxicity was tolerable, with grade 3-4 toxicities observed for leucopenia (30.4%), neutropenia (34.8%), thrombocytopenia (17.4%) and anemia (13.0%). Three patients (13.0%) encountered transient sinus bradycardia with spontaneous remission.Endostar combined with chemotherapy is well-tolerated in patients with metastatic colorectal and gastric cancers, and it is relatively effective as a first-line therapy.

Thrombin is a multifunctional serine protease that plays a crucial role in hemostasis following tissue injury. In addition to its procoagulation effect, thrombin is also a potent mesenchymal cell mitogen, therefore it plays important roles in the local proliferation of mesenchymal cells in the tissue repair process. Reactive oxygen species (ROS) can induce some human cells to proliferate at lower rates while at higher concentrations they promote cells to undergo apoptosis or necrosis. Accumulative evidence suggests that thrombin can induce some cells to produce ROS. Based on these observations, we provide a hypothesis that thrombin can stimulate human lung fibroblasts to produce ROS, which play an important role in human lung fibroblast proliferation.ROS were detected in fibroblasts at 30 minutes and 60 minutes following thrombin (20 U/ml) exposure using flow cytometry. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) was assayed in lung fibroblasts using a commercial kit following treatment with thrombin at different concentrations. NADPH oxidase and the extracellular regulated kinase1/2 (ERK1/2) signaling pathway were detected by Western blotting after thrombin stimulation to lung fibroblasts.Thrombin, at 20 U/ml, stimulated human lung fibroblasts (HLF) to generate ROS in a time dependent manner. The ratio of GSH/GSSG in fibroblasts treated with thrombin showed a significant decrease. NADPH oxidase was activated and the ERK1/2 signal pathway was involved in the proliferation process of fibroblasts treated with thrombin.The activation of NADPH oxidase by thrombin leads to the production of ROS, which promotes fibroblasts proliferation via activation of the ERK1/2 signaling pathway.

We conducted a prospective, multicenter investigation of incidence, management and outcome of neonatal acute respiratory disorders (NARD), and evaluated related perinatal risk factors and efficacy of respiratory therapies in neonatal intensive care units (NICUs) in a Chinese neonatal network.Data were prospectively collected in 2004 - 2005 from infants with NARD defined as presence of respiratory distress and oxygen requirement during the first 3 days of life.A total of 2677 NARD was classified (20.5% of NICU admissions). There were 711 (5.44%) with respiratory distress syndrome (RDS), 589 (4.51%) pulmonary infection, 409 (3.13%) meconium aspiration syndrome, 658 (5.03%) aspiration of amniotic fluid and 239 (1.83%) transient tachypnoea. Meconium aspiration syndrome had the highest rate with fetal distress, transient tachypnoea from cesarean section, and RDS with maternal disorders. Assisted mechanical ventilation was applied in 53.4% of NARD, and in above five disorders with 84.7%, 52.3%, 39.8%, 24.5%, and 53.6%, respectively. Corresponding mortality in these disorders was 31.4%, 13.6%, 17.8%, 4.1% and 5.0%, respectively. Surfactant was provided to 33.9% of RDS. In all RDS infants, the survival rate was 78.8% if receiving surfactant, and 63.4% if not (P0.001).This study provided NICU admission-based incidence and mortality of NARD, reflecting efficiency of advanced respiratory therapies, which should be a reference for current development of respiratory support in NICU at provincial and sub-provincial levels, justifying efforts in upgrading standard of care in emerging regions through a collaborative manner.

BACKGROUND: Postprandial hypotension (PPH) occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose (alpha-glucosidase inhibitor), a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment. METHODS: Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days: screening day and intervention day. Blood pressure and heart rate (HR) were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction (EF) and fractional shortening (FS) were measured by two dimensional echocardiography. RESULTS: Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure (SBP, DBP, MAP) (all P < 0.05) were significantly attenuated after taking acarbose during breakfast, so were MAP (P < 0.05) during lunch, DBP (P < 0.05) and MAP (P < 0.05) during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction (ADR) was 9%. CONCLUSION: Acarbose is effective and safe in the treatment of elderly patients with PPH.