Prior cocaine self-administration does not impair the ability to delay gratification in rats during diminishing returns.

Previous exposure to drugs of abuse produces impairments in studies of reversal learning, delay discounting and response inhibition tasks. While these studies contribute to the understanding of normal decision-making and how it is impaired by drugs of abuse, they do not fully capture how decision-making impacts the ability to delay gratification for greater long-term benefit. To address this issue, we used a diminishing returns task to study decision-making in rats that had previously self-administered cocaine. This task was designed to test the ability of the rat to choose to delay gratification in the short-term to obtain more reward over the course of the entire behavioral session. Rats were presented with two choices. One choice had a fixed amount of time delay needed to obtain reward [i.e. fixed delay (FD)], while the other choice had a progressive delay (PD) that started at 0 s and progressively increased by 1 s each time the PD option was selected. During the 'reset' variation of the task, rats could choose the FD option to reset the time delay associated with the PD option. Consistent with previous results, we found that prior cocaine exposure reduced rats' overall preference for the PD option in post-task reversal testing during 'no-reset' sessions, suggesting that cocaine exposure made rats more sensitive to the increasing delay of the PD option. Surprisingly, however, we found that rats that had self-administered cocaine 1-month prior, adapted behavior during 'reset' sessions by delaying gratification to obtain more reward in the long run similar to control rats.

[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Value of contrast-enhanced ultrasonography in detection of endoleak after endovascular repair of infrarenal abdominal aortic aneurysm].

Objective: To investigate the value of contrast-enhanced ultrasound in detecting endoleak after endovascular repair of infrarenal abdominal aortic aneurysm (EVAR). Methods: The postoperative follow-up data of 102 patients with infrarenal abdominal aortic aneurysm treated with EVAR in Tianjin Medical University General Hospital from August 2015 to December 2021 were retrospectively analyzed. There were 79 males and 23 females, aged 50-91 (69.6±7.6) years old. Using CT angiography (CTA) as the gold standard for diagnosing endoleaks, the effectiveness of contrast-enhanced ultrasound and CDUS in detecting endoleaks was evaluated by paired design chi-square test, and the Kappa value was calculated for consistency test. Patients were divided into groups according to body mass index (BMI), and the number of false-negative endoleaks detected by contrast-enhanced ultrasound in each group was calculated, and its ratio to the actual number of endoleaks was calculated to evaluate whether BMI was related to false-negative ultrasound-enhanced ultrasound. Results: A total of 203 follow-up visits met the inclusion criteria. Endoleaks were detected 36 times (17.7%) by CTA, 31 times (15.3%) by contrast-enhanced ultrasound, 16 times (7.9%) by CDUS, and they all detected type Ⅰ, type Ⅱ and type Ⅲ endoleaks. There was no significant difference between contrast-enhanced ultrasound and CTA in endoleak detection rate and determination of endoleak types (endoleak detection rate: 15.3% vs 17.7%; determination of endoleak types: type Ⅰ 4 vs 4, type Ⅱ 26 vs 31, type Ⅲ 1 vs 1; all P>0.05). CDUS and CTA had statistically significant differences in the detection rate of endoleaks and determination of endoleak types (endoleak detection rate: 7.9% vs 17.7%; determination of endoleak types: type Ⅰ 4 vs 4, type Ⅱ 11 vs 31, type Ⅲ 1 vs 1; all P<0.001). Compared with CTA, contrast-enhanced ultrasound has a sensitivity of 83.3%, a specificity of 99.4%, a Youden index of 0.827, a coincidence rate of 96.6%, a positive predictive value of 96.8%, a negative predictive value of 96.5%, and a Kappa value of 0.875(P<0.001). The two showed excellent diagnostic consistency. All 6 endoleaks not detected by contrast-enhanced ultrasound were type Ⅱ endoleak that did not require treatment, and 3(15.8%) occurred in obese patients with a BMI≥32 kg/m2. Compared with CTA, CDUS had a sensitivity of 38.9%, a specificity of 98.8%, a Youden index of 0.377, a coincidence rate of 88.2%, a positive predictive value of 87.5%, a negative predictive value of 88.2%, and a Kappa value of 0.482 (P<0.001). The two showed moderate diagnostic agreement. The correlation coefficient of the maximum diameter of aneurysms measured by ultrasound and CT was r=0.873(P<0.001). Conclusions: Contrast-enhanced ultrasound is accurate in detecting endoleak after infrarenal EVAR, and its sensitivity to endoleak detection in obese patients with BMI≥32 kg/m2 will be reduced. CDUS is not suitable for detection of endoleak after infrarenal EVAR, but it can be used to monitor the change of the largest diameter of aneurysm after EVAR.

Modified transcrestal sinus floor elevation with concomitant implant placement in edentulous posterior maxillae with residual bone height of 5 mm or less: a non-controlled prospective study.

The aim of this study was to describe a modified transcrestal sinus floor elevation (mTSFE) technique and to evaluate its clinical effectiveness and reliability when residual bone height is severely reduced. Forty-three maxillary edentulous patients who met the inclusion criteria were enrolled. All patients underwent the mTSFE technique; 66 dental implants were inserted simultaneously. Patient-reported outcomes were assessed 2 weeks after surgery. Prosthetic crowns were placed 6 months after surgery. Radiographic analyses and clinical analyses were conducted to assess the clinical effectiveness and feasibility of mTSFE during a follow-up period of 2-8 years. The mean vertical bone increase after surgery was 8.09 mm, and it decreased to 6.56 mm at 6 months after surgery. Two cases of membrane perforation occurred during surgery and one implant was lost in the third year after surgery; the survival rate at the implant level was 98.48%. No severe postoperative complication was reported and the subjective feeling of patients was acceptable. This mTSFE technique could simplify the operative procedure and might be helpful to reduce intraoperative trauma, as well as to alleviate postoperative discomfort.

[Significance of molecular classification in fertility-sparing treatment of endometrial carcinoma and atypical endometrial hyperplasia].

Objective: To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy. Methods: A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed. Results: (1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype (P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR (P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions: Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Prevalence and potential risk factors of chronic pruritus among community middle-aged and older population in Beijing, China.

BACKGROUND: Chronic pruritus is a common problem among older adults, with a significant impact on their quality of life. However, it is under-studied epidemiologically, especially among Chinese older adults. OBJECTIVE: The aim of this study was to identify the prevalence and explore the risk factors of chronic pruritus among the middle-aged and older adults in Beijing, China. METHODS: A total of 929 participants aged ≥35 years from six communities in Beijing, China, were interviewed. The survey collected the demographic characteristics, the experience of chronic pruritus (>6 weeks), chronic disease history, the level of physical activities and sleep quality. A population-based case-control study was conducted, including 178 chronic pruritus cases and 697 controls. A multivariate logistic regression model was performed to explore the risk factors of chronic pruritus. Additionally, a random forest algorithm was used to rank the importance of potential risk factors and analyse the overall interpretation of risk factors. RESULTS: The prevalence of chronic pruritus was 19.48% (181/929) among the Beijing middle-aged and elderly population. The findings indicated that older adults aged 65 years old or above, male, with college or higher degree, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease and osteoarthritis/rheumatism, and middle or low sleep quality were associated with the increased risk of chronic pruritus respectively. Physical activity level (≥3000 Met) was associated with a decreased risk of chronic pruritus. The rank according to the most contribution of chronic pruritus risk was sleep quality, education, physical activity level, osteoarthritis/rheumatism, age and gender. CONCLUSION: Prevalence of chronic pruritus was high among the Chinese middle-aged and elderly population. Age, gender, high education, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease, osteoarthritis /rheumatism and poor sleep quality may serve as risk factors of chronic pruritus. Moderate and high physical activity levels may serve as protective factors of chronic pruritus risk.

[Current situation of screening, prevention and treatment of bleeding esophageal varices in cirrhotic portal hypertension in Tibet region: a multicenter study].

Objective: To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region. Methods: Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively. Results: 511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective ß-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment. Conclusion: Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Rapid and robust antibody Fab fragment crystallization utilizing edge-to-edge beta-sheet packing.

Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call "Crystal Kappa", enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

[Clinical outcomes of simultaneous bilateral endoscopic surgery for bilateral upper urinary tract calculi].

OBJECTIVE: To discuss the efficacy and safety of simultaneous bilateral endoscopic surgery (SBES) for bilateral upper urinary tract calculi, and to summarize the initial experience. METHODS: Patients diagnosed with bilateral upper urinary tract calculi who underwent SBES in the Department of Urology, Beijing Chao-Yang Hospital from January 2019 to January 2020 were enrolled retrospectively. The demographic and clinical data of the patients were recorded, and the operation status, stone free rate (SFR) and peri-operative complications were analyzed. The primary end point was SFR, and second end point was peri-operative complications. RESULTS: A total of 23 patients underwent SBES, of which SBES was completed in 19 patients (12 males, and 7 females). The mean age was (41.3±12.0) years. Fourteen patients underwent modified supine position surgery and 4 patients in prone split-leg position. There was no statistical difference in the demographic and baseline clinical data of the patients in different positions. One patient underwent right percutaneous nephrolithotomy (PCNL) and left endoscopic combined intra-renal surgery (ECIRS) in the prone split-leg position, while 18 patients received simul-taneous surgery with PCNL and contralateral retrograde intra-renal surgery (RIRS). The mean anesthesia and operation time was (128.7±26.5) min and (70.7±20.3) min, respectively, which was significantly longer in the patients with prone split-leg position than in the patients with modified supine position, anesthesia time in the patients with prone split-leg position and modified supine position: (148.4±20.4) min vs. (121.6±25.3) min, respectively, t=－2.121, P=0.049, while the operation time in the patients with prone split-leg position and modified supine position: (86.4±21.1) min vs. (65.1±17.4) min, respectively, t=－2.222, P=0.040. There was no significant difference between the two groups in indwelling of nephrostomy [prone split-leg position and modified supine position: (2.6±0.9) d vs. (2.1±1.0) d, respectively; t=－0.880, P=0.391] and the length of hospital stay [prone split-leg position and modified supine position: (6.0±2.7) d vs. (5.2±1.8) d, respectively; t=－0.731, P=0.475]. One month after the operation, the SFR was 78.9%, and 3 patients had minor peri-operative complications (Clavien-Dindo grades Ⅰ/Ⅱ) without any serious complications (Clavien-Dindo grades Ⅲ/Ⅳ/Ⅴ). CONCLUSION: The simultaneous bilateral endoscopic surgery would decrease the operation time and anesthesia exposure under the premise of ensuring the SFR, which is helpful to reduce the risk of peri-operative complications, especially to the patients who can not tolerate the second-stage or long-time operation.

[Endoscopic combined ultrasound-guided access vs. ultrasound-guided access in endoscopic combined intrarenal surgery].

OBJECTIVE: To compare the outcomes of endoscopic combined ultrasound-guided access (EUGA) with the conventional ultrasound-guided access (UGA) to achieve percutaneous renal access in endoscopic combined intrarenal surgery (ECIRS). METHODS: A retrospective review of 53 patients undergoing ECIRS to treat upper urinary tract calculi between January 2017 and October 2019 was con-ducted. All of the cases were of complex upper urinary tract stones larger than 2 cm in diameter. The com-plex stone situations, such as multiple renal calyces calculi or staghorn calculi necessitated ECIRS. Under general anesthesia, the patients were placed in the galdakao-modified supine valdivia (GMSV) position, thus allowing both antegrade and retrograde accesss. The patients were divided to UGA and EUGA groups according to the protocol of achieving percutaneous renal access. In 28 cases, endoscopic combined ultrasound-guided accesss were obtained. Puncture and dilation were performed under direct flexible ureteroscopic visualization, while percutaneous renal access of 25 cases were performed with the conventional technique employing ultrasound guidance. Demographic and perioperative information, such as stone burden, presence of hydronephrosis and number of calyces involved was compared. Primary outcomes included total operative time, renal access time, repeat puncture, hemoglobin level, perioperative complications, and stone-free rate. RESULTS: No major intra-operative complication was recorded in all the 53 ECRIS. No significant difference was observed between the groups in age and gender. There was no significant difference in body mass index[BMI (29.21±3.14) kg/m2 vs.(28.53±2.56) kg/m2], stone burden (37.68±6.89) mm vs. (35.53±6.52) mm, number of calyces involved 2.72±0.68 vs. 2.86±0.71, presence of hydronephrosis (56.0% vs. 46.4%), total operative time (93.0±12.2) min vs. (96.8±14.2) min, hemoglobin level reduction (6.56±2.16) g/L vs. 97.54±2.64) g/L, stone-free rate (92.0% vs. 92.8%), hospital stay (5.52±0.59) d vs. (5.64±0.62) d, perioperative complication rate (8.0% vs. 7.2%). Two patients in EUGA group experienced perioperative complications (one urinary tract infection and one hematuria) while two patients in UGA group experienced perioperative urinary tract infection. None in both groups received blood transfusion. The patients undergoing EUGA had shorter renal access time [(4.0±0.7) min vs. (6.8±2.6) min, P < 0.01] and less repeat puncture (0 vs. 4 cases, P < 0.05). CONCLUSION: EUGA is an optimal technique to establish percutaneous renal access in ECIRS, which minimizes access time and repeated procedures.

[The role of three-dimensional speckle tracking imaging derived parameters on predicting outcome of hypertrophic cardiomyopathy patients with MYH7 mutations].

Objective: To evaluate the cardiac functional changes in hypertrophic cardiomyopathy(HCM) patients with ß-myosin heavy chain gene (MYH7) mutations by three-dimensional (3D) speckle tracking imaging(3D-STI) and conventional echocardiography modalities, and then to explore the potential predictors of adverse cardiovascular events in these patients. Methods: A consecutive series of 192 HCM patients admitted in our center from October 2014 to October 2016 were genetically screened to identify MYH7 mutations in this retrospective study. A total of 43 HCM patients with MYH7 mutations were enrolled. The patients were divided into events group(n=13) and no event group(n=30) according to the presence or absence of adverse cardiovascular events(primary and secondary endpoints). All patients were followed up to January 2019 after comprehensive evaluation of 3D-STI, two-dimensional and Doppler echocardiography. The adverse cardiovascular events were recorded. Results: The median follow up time was 1 012 (812, 1 330) days. During follow-up, 13 patients (30.2%) reached endpoints: 6 cases of the primary endpoints(2 cases of sudden cardiac death(SCD), 3 cases of survival after defibrillation, and 1 case of appropriate implantable cardioverter-defibrillator(ICD) discharge); 7 cases of the second endpoints(5 cases of heart failure hospitalization, 1 case of syncope and cardioversion due to supraventricular tachycardia, and 1 case of end-stage HCM). Patients with adverse cardiovascular events had higher prevalence of syncope and risk of SCD, enlarged left atrial volume index(LAVI) and reduced 3D left ventricular global longitudinal train (3D-GLS), as compared to those without adverse events(all P<0.05). The multivariate Cox regression analysis showed that reduced 3D-GLS(HR=0.814, 95%CI 0.663-0.999, P=0.049) was an independent predictor for adverse cardiovascular events. The cutoff value of 3D-GLS≤13.67% was linked with significantly increased risk of adverse cardiovascular events in this patient cohort(AUC=0.753, 95%CI 0.558-0.948, sensitivity 86%, specificity 69%, P<0.05). The Kaplan-Meier analysis indicated that the patients with the 3D-GLS≤ 13.67% faced higher risk of death than those with 3D-GLS>13.67%. Conclusion: 3D-GLS is useful on predicting adverse cardiovascular events in HCM patients with MYH7 mutations.

Efficacy and safety of Jessner's solution peel in comparison with salicylic acid 30% peel in the management of patients with acne vulgaris and postacne hyperpigmentation with skin of color: a randomized, double-blinded, split-face, controlled trial.

OBJECTIVE: Antibiotics and retinoids have been used for acne vulgaris for decades. Though effective, each has its own drawbacks. Chemical peels have been used for treatment of acne vulgaris with inadequate clinical evidence. We sought to determine the efficacy and safety of Jessner's solution (JS) in comparison with salicylic acid (SA) 30% in the management of acne vulgaris and postacne hyperpigmentation in patients with colored skin. METHODS: A total of 36 subjects (94.5% Fitzpatick Type IV-V) were recruited in this randomized double-blinded, split-face, controlled trial. Each side of the face was randomly assigned for treatment with either JS or SA. Subjects were treated once fortnightly for a total of three sessions. Lesion counting, Michaelsson acne score (MAS), photographs, and postacne hyperpigmentation index (PAHPI) were used to objectively assess the improvement. Complications were assessed during each visit. Statistical analysis was conducted using SPSS v22.0. Significance was set at P = 0.05. RESULTS: At the end of therapy, significant reduction in inflammatory, noninflammatory lesions, MAS, and PAHPI scores (P < 0.001, respectively) were noted in comparison to baseline. Mixed model analysis revealed no significant outcome difference between the two groups. Patients who reported good and very good outcome were 76.4% (JS) and 85.3% (SA). Burning, stinging sensation, and exfoliation were the common complications reported. Postinflammatory hyperpigmentation was reported only once in the JS arm. CONCLUSION: Both JS and SA were equally effective in the treatment of acne vulgaris and reducing postacne hyperpigmentation in patients with colored skin.

Down-regulation of long noncoding RNA PGM5-AS1 correlates with tumor progression and predicts poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: Growing studies have shown that long non-coding RNAs (lncRNAs) have critical regulatory roles in tumorigenesis. Recently, a newly identified lncRNA, Homo sapiens PGM5 antisense RNA 1 (PGM5-AS1), was found to be dysregulated in several tumors. However, its roles in clear cell renal cell carcinoma (ccRCC) have not been investigated. The aim of the present study was to clarify the clinical significance of PGM5-AS1 in ccRCC patients. PATIENTS AND METHODS: The PGM5-AS1 expression levels were evaluated in 182 primary ccRCC patients using quantitative real-time PCR assays. The associations between expression of PGM5-AS1, clinicopathological parameters, and prognosis of ccRCC were examined using Chi-square test, Kaplan-Meier assays, and multivariate assays. RESULTS: The expressions of PGM5-AS1 in cancer specimens were lower than those in matched non-tumor specimens from the ccRCC patient (p<0.05). Downregulation of PGM5-AS1 was closely associated with more advanced clinical features, including lymph nodes metastasis (p=0.007) and distant metastasis (p=0.037). A clinical study revealed that ccRCC patients with lower PGM5-AS1 expressions had substantially shorter overall survival (OS) and disease-free survival (DFS) than patients with higher PGM5-AS1 expressions. Further multivariate assays demonstrated that PGM5-AS1 was identified as an independent prognostic factor for patients with ccRCC. CONCLUSIONS: Down-regulation of PGM5-AS1 in ccRCC tissues had a strong association with unfavorable outcomes and PGM5-AS1 might be a potential tumor suppressor.

[Effects of occupational noise exposure on asymmetric hearing loss in automobile manufacturing workers].

Objective: To investigate the characteristics of asymmetric hearing loss in automobile manufacturing workers and the effect of occupational noise exposure on asymmetric hearing loss. Methods: A cross-sectional approach was used in this study. From March 2017 to February 2018, Subjects (7066) from four complete vehicle factories were given a pure tone audiometry (Hearing thresholds were measured at frequencies of 0.5, 1, 2, 3, 4 and 6 kHz in each ear) and were required to complete a health-related information questionnaire. According to the inclusion criteria, a total of 6339 workers were selected. The mean hearing thresholds for the left and right ears at overall frequencies were compared using the repeated means analysis of variance (ANOVA) test. The threshold differences at each frequency were compared using paired t tests. Results: The overall mean left minus right threshold difference across all frequencies was determined to be 0.58 dB, which met statistical significance (P<0.01) . Hearing threshold in the left ear was statistically significantly higher compared with the right ear at each frequency. The differences between binaural threshold shifts at each frequency among subjects with a asymmetry in terms of worse left ear and worse right ear were at the range of 6.17-9.87 dB and 6.39-10.92 dB, respectively. Hearing threshold in the left ear was statistically significantly higher compared with the right ear at only 2, 3 kHz of subjects with high-frequency hearing threshold shifts (HFHTs) more than 25 dB. Hearing threshold in the left ear was statistically significantly higher compared with the right ear at only 3 kHz of subjects with high-frequency hearing threshold shifts (HFHTs) more than 30 dB. With the increase of HFHTs, the proportion of subjects with a asymmetry at 2 and 3 kHz of more than 10 dB in terms of worse left ear and worse right ear increased. Conclusion: The average hearing threshold of the left ear across overall frequencies is higher compared with the right ear, the proportion of the cases with a higher left ear hearing threshold is higher that that of the cases with a higher right ear hearing threshold. As hearing loss caused by occupational noise exposure getting worse, the proportion of the cases with a higher left ear hearing threshold and the cases with a higher right ear hearing threshold may tent to be the same.

Drug efficacies on bone mineral density and fracture rate for the treatment of postmenopausal osteoporosis: a network meta-analysis.

OBJECTIVE: Globally, a great number of elderly suffer from osteoporosis, especially postmenopausal women. Osteoporosis results in low bone mineral density (BMD) and high risk of fragility fracture. However, there is no defined strategy to select the most suitable anti-osteoporotic drugs for osteoporosis patients. Therefore, this study aims to select the most effective anti-osteoporotic drug for postmenopausal women with osteoporosis. MATERIALS AND METHODS: Literature search was conducted in PubMed, EMBASE, and the Cochrane Library. Raw data from the related randomized clinical trials were extracted. A pairwise and network meta-analysis model was utilized to assess the efficacy of ten drugs on the percentage change of BMD in the lumbar spine and total hip from baseline to one year of treatment. Risks of vertebral fracture and non-vertebral fracture were evaluated as well. We reported the effect size with a weighted mean difference (WMD) for continuous outcomes and odds ratio (OR) for dichotomous outcomes. All the drugs were ranked based on the surface under the cumulative ranking curve (SUCRA) value. Furthermore, the heterogeneity, consistency and publication bias of enrolled literature were assessed. RESULTS: With regard to lumbar spine BMD, the ten selected drugs all showed significant efficacy compared with placebo. In regard to total hip BMD and vertebral fracture, with the exception of calcitonin, the remaining nine drugs all showed significant efficacy compared with placebo. Six drugs - abaloparatide, alendronate, risedronate, strontium ranelate, teriparatide, and zoledronate - were significantly more effective compared with placebo for the treatment of non-vertebral fractures. As the SUCRA values indicated, abaloparatide performed the best on improving lumbar spine BMD, vertebral fracture and non-vertebral fracture, while denosumab was the best choice to improve total hip BMD. CONCLUSIONS: To sum up, abaloparatide, denosumab, and teriparatide showed the best efficacy for the treatment of postmenopausal osteoporosis, especially abaloparatide.

Circ-VANGL1 promotes the progression of osteoporosis by absorbing miRNA-217 to regulate RUNX2 expression.

OBJECTIVE: This study aims to investigate whether circ-VANGL1 can promote the progression of osteoporosis (OP) by absorbing miRNA-217 to regulate RUNX2 expression. PATIENTS AND METHODS: The serum levels of circ-VANGL1, miRNA-217 and RUNX2 in OP patients and non-OP patients were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Their expression levels in human bone marrow mesenchymal stem cells (hBMSCs) at different time points of osteogenesis differentiation were determined as well. The expression levels of RUNX2 and osteogenic proteins (BSP, OCN, OPN) in hBMSCs were detected by Western blot. Dual-Luciferase reporter gene assay was performed to verify the relationship among circ-VANGL1, miRNA-217 and RUNX2. Alkaline phosphatase (ALP) staining was conducted to evaluate the degree of osteogenic differentiation influenced by circ-VANGL1 and miRNA-217. RESULTS: OP patients presented a higher serum level of miRNA-217 and lower serum levels of circ-VANGL1 and RUNX2 relative to non-OP patients. Circ-VANGL1 accelerated osteogenic differentiation by absorbing miRNA-217 to regulate RUNX2 expression. Moreover, miRNA-217 inhibited osteogenic differentiation by degrading RUNX2 by targeting to RUNX2 3'UTR. The overexpression of circ-VANGL1 upregulated expressions of RUNX2, BSP, OCN, and OPN. Meanwhile, ALP activity increased in hBMSCs overexpressing circ-VANGL1. However, co-overexpression of circ-VANGL1 and miRNA-217 did not alter RUNX2 expression. ALP activity in hBMSCs co-overexpressing circ-VANGL1 and miRNA-217 slightly increased, but had no difference with controls. CONCLUSIONS: Circ-VANGL1 promotes the development of OP via binding to miRNA-217 to downregulate RUNX2 expression.