Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial.

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.

Development and Validation of a Nomogram for Predicting Second Surgery in Patients with Concomitant Esotropia.

INTRODUCTION: This study developed and validated a nomogram for predicting the risk of second surgery in patients with concomitant esotropia (CE) based on a cohort in Beijing. METHODS: In this retrospective cohort study, the inpatient and outpatient medical records of 419 patients with CE who underwent surgery at the Peking University First Hospital between January 1, 2005 and December 31, 2009 were collected. A total of 357 CE cases were included. For those cases 70% were randomly assigned to the training set (n = 234) and 30% to the validation set (n = 123). Demographic and clinical variables were ascertained at hospital admission and discharge and screened using multivariate Cox proportional hazards regression analysis to construct predictive models and generate a 1-, 4-, and 8-year overall survival nomogram. This nomogram provided an estimate of the risk of second surgery in patients with surgically treated CE. Internal validation was conducted using the concordance index (C-index) and calibration curve for the training and validation sets. RESULTS: Six independent prognostic factors were identified, namely age at surgery, age at onset, amblyopia, deviation angles, surgical amount, and deviation angles 1 week after surgery, and these were entered into the nomogram. The proposed nomogram showed favorable discrimination and accuracy in the training and validation sets. The C-indexes of the training and validation sets were 0.84 (95% CI 0.79-0.89) and 0.80 (95% CI 0.78-0.82), respectively. CONCLUSIONS: The proposed nomogram can serve as a predictive tool for prognostic evaluation of CE surgery.

Tissue metabolomics identified new biomarkers for the diagnosis and prognosis prediction of pancreatic cancer.

Pancreatic cancer (PC) is burdened with a low 5-year survival rate and high mortality due to a severe lack of early diagnosis methods and slow progress in treatment options. To improve clinical diagnosis and enhance the treatment effects, we applied metabolomics using ultra-high-performance liquid chromatography with a high-resolution mass spectrometer (UHPLC-HRMS) to identify and validate metabolite biomarkers from paired tissue samples of PC patients. Results showed that the metabolic reprogramming of PC mainly featured enhanced amino acid metabolism and inhibited sphingolipid metabolism, which satisfied the energy and biomass requirements for tumorigenesis and progression. The altered metabolism results were confirmed by the significantly changed gene expressions in PC tissues from an online database. A metabolites biomarker panel (six metabolites) was identified for the differential diagnosis between PC tumors and normal pancreatic tissues. The panel biomarker distinguished tumors from normal pancreatic tissues in the discovery group with an area under the curve (AUC) of 1.0 (95%CI, 1.000-1.000). The biomarker panel cutoff was 0.776. In the validation group, an AUC of 0.9000 (95%CI = 0.782-1.000) using the same cutoff, successfully validated the biomarker signature. Moreover, this metabolites panel biomarker had a great capability to predict the overall survival (OS) of PC. Taken together, this metabolomics method identifies and validates metabolite biomarkers that can diagnose the onsite progression and prognosis of PC precisely and sensitively in a clinical setting. It may also help clinicians choose proper therapeutic interventions for different PC patients and improve the survival of PC patients.

Blended learning model via small private online course improves active learning and academic performance of embryology.

While blended learning has been growing in popularity in recent years, the effectiveness of this procedure remains controversial. In this report, we assess the effectiveness of blended learning of embryology within international medical students. The participants were international medical students taking embryology in the Bachelor of Medicine and Bachelor of Surgery program. The blended learning group (BLG) consisted of students (n = 43) in the 2018-2019 academic year, taught with blended learning model via a customized small private online course (SPOC). The control traditional teaching group (TTG) consisted students (n = 48) in the 2017-2018 academic year, taught with traditional teaching model. Academic performance, including mean scores and passing ratios on the final exam of two groups were compared and analyzed with a t-test. In addition, a questionnaire directed toward evaluating student's perceptions with the blended learning was administered to students in BLG. The majority of students in BLG actively participated in online self-study activities and discussion in face-to-face class sessions. The mean score and passing ratio were significantly greater than those of students in TTG (p < 0.01). Results from the questionnaire revealed that the majority of BLG students felt that this method was beneficial for their learning of human embryology. The blended learning model, that integrates SPOC with face-to-face class lectures proved a more effective means for the teaching of embryology than the traditional lecture-based teaching model. This blended learning method may serve as a feasible model that can be readily applied for use in other medical courses.

Extraction and profiling of proteins in yellow powder from sweet potato starch wastewater using response surface methodology and proteomic approach.

Sweet potato starch industry produce generous high soluble solid wastewater containing various biochemicals such as proteins. The wastewater could be spray dried into a product called yellow powder (YP). Proteins in the YP were recovered and profiled in this study. The extraction conditions were optimized on dependent variables of YP material-water ratio, pH, and temperature using response surface methodology (RSM). Maximum protein yield (61.2%) using RSM were observed at a material-water ratio of 50 (mg/L), pH 9.5, and extraction temperature of 30℃. Subsequently, a total of 25 proteins were identified by proteomic analysis, which mainly were sporamins, ß-amylase, starch phosphorylase, polyphenol oxidase, and superoxide dismutase. The extraction and profiling of proteins from YP would contribute to a comprehensive utilization and added value of the wastewater produced by sweet potato starch processing industry. PRACTICAL APPLICATION: This study reported the recovery (61.2%) of proteins and protein profile of yellow powder (byproducts) from sweet potato starch wastewater. These information could contribute to the valorization a yellow powder into high-value ingredients.

Landscape of Dysregulated Placental RNA Editing Associated With Preeclampsia.

Dysregulated RNA editing is well documented in several diseases, such as cancer and neurodegenerative diseases. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown. Here, we have systematically profiled RNA editome on the placentae, 9 from patients with early-onset severe preeclampsia (EOSPE) and 32 from normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The RNA editing events at 2 microRNA binding sites in 3'-untranslated region of the LEP mRNA were generated, which could inhibit the microRNA-induced mRNA downregulation of LEP in placenta-derived cell line, consistent with the observation in the placentae of preeclampsia patients. These results demonstrate the association of dysregulated placental RNA editing with preeclampsia, and providing a resource for further study on the role of RNA editing in the pathogenesis of this disease.

Ampelopsin alleviates sevoflurane-induced cognitive dysfunction by mediating NF-κB pathway in aged rats.

BACKGROUND: Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancer patients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. PURPOSE: This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. METHODS: We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. RESULTS: We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. CONCLUSION: miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice.

miR-300 mitigates cancer-induced bone pain through targeting HMGB1 in rat models.

BACKGROUND: Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancer patients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. OBJECTIVE: This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. METHODS: We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. RESULTS: We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. CONCLUSION: miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice.

NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats

Abstract Purpose: To evaluate the role of CX3CL1 and NF-κB in the lumbar disc herniation induced neuropathic pain. Methods: After LDH induced by implantation of autologous nucleus pulposus (NP) on the left L5 nerve root was established, mechanical thresholds and thermal hyperalgesia were tested at relevant time points during an observation period of 28 days. Expression of CX3CL1 and NF-κBin the dorsal root ganglion (DRG) were performed by using Western blotting and RT-PCR. Results: Implantation of autologous nucleus pulposus (NP) induced neuropathic pain, associated with increased mRNA and protein expression of CX3CL1 in the DRG. Moreover, intrathecal injection of neutralizing antibody against CX3CL1 could attenuates LDH-induced persistent pain hypersensitivity. Interestingly, NF-κB activation in the DRGs were found in LDH-induced neuropathic pain. Furthermore, NF-κB downregulation by p65 inhibitor PDTC markedly alleviated LDH-induced mechanical allodynia and thermal hyperalgesia in rat. Importantly, CX3CL1 neutralizing antibody (10 μg/10 μl, i.t.) reduces p-p65 protein level in DRG Conclusions: CX3XL1 could regulate LDH-induced neuropathic pain through NF-κB pathway. Targeting CX3CL1 and NF-κB may represent a potential treatment for neuropathic pain caused by LDH.

Systematic Review and Meta-Analysis of Diagnostic Accuracy of miRNAs in Patients with Pancreatic Cancer.

BACKGROUND: It is reported that miRNAs are aberrantly expressed in patients with pancreatic cancer. However, the diagnostic value of miRNAs in pancreatic cancer remains controversial. The meta-analysis was to access diagnostic accuracy of miRNAs in pancreatic cancer. METHODS: PubMed, Scopus, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WANFANG Data, China Biomedical Literature Database (CBM), and VIP databases were retrieved up to June 30, 2016, to collect articles concerning the diagnosis of miRNAs in pancreatic cancer. The methodological quality of each study was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). This meta-analysis was conducted using RevMan5.0, MetaDiSc 1.4, and Stata 12.0 software. RESULTS: There are 40 articles including 109 studies. The pooled SEN was 0.81 (95% CI, 0.80-0.82), the pooled SPE was 0.78 (95% CI, 0.77-0.79), the pooled +LR was 3.32 (95% CI, 2.92-3.80), the pooled -LR was 0.27 (95% CI, 0.24-0.31), the pooled DOR was 14.56 (95% CI, 11.55-18.34), and pooled AUC was 0.86 (95% CI, 0.84-0.88). DISCUSSION: This meta-analysis demonstrated that miRNA makes a significant impact in the pancreatic cancer diagnosis with a high SEN and SPE, particularly using multiple miRNAs.

A prognostic model for lung adenocarcinoma patient survival with a focus on four miRNAs.

There is currently no effective biomarker for determining the survival of patients with lung adenocarcinoma. The purpose of the present study was to construct a prognostic survival model using microRNA (miRNA) expression data from patients with lung adenocarcinoma. miRNA data were obtained from The Cancer Genome Atlas, and patients with lung adenocarcinoma were divided into either the training or validation set based on the random allocation principle. The prognostic model focusing on miRNA was constructed, and patients were divided into high-risk or low-risk groups as per the scores, to assess their survival time. The 5-year survival rate from the subgroups within the high- and low-risk groups was assessed. P-values of the prognostic model in the total population, the training set and validation set were 0.0017, 0.01986 and 0.02773, respectively, indicating that the survival time of the lung adenocarcinoma high-risk group was less than that of the low-risk group. Thus, the model had a good assessment effectiveness for the untreated group (P=0.00088) and the Caucasian patient group (P=0.00043). In addition, the model had the best prediction effect for the 5-year survival rate of the Caucasian patient group (AUC=0.629). In conclusion, the prognostic model developed in the present study can be used as an independent prognostic model for patients with lung adenocarcinoma.

Medical image classification via multiscale representation learning.

Multiscale structure is an essential attribute of natural images. Similarly, there exist scaling phenomena in medical images, and therefore a wide range of observation scales would be useful for medical imaging measurements. The present work proposes a multiscale representation learning method via sparse autoencoder networks to capture the intrinsic scales in medical images for the classification task. We obtain the multiscale feature detectors by the sparse autoencoders with different receptive field sizes, and then generate the feature maps by the convolution operation. This strategy can better characterize various size structures in medical imaging than single-scale version. Subsequently, Fisher vector technique is used to encode the extracted features to implement a fixed-length image representation, which provides more abundant information of high-order statistics and enhances the descriptiveness and discriminative ability of feature representation. We carry out experiments on the IRMA-2009 medical collection and the mammographic patch dataset. The extensive experimental results demonstrate that the proposed method have superior performance.

Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals.

Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals.To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors.A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis.The application rates of Kaplan-Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate, misleading of the reported results, or difficult to interpret.There are gaps in the conduct and reporting of survival analysis in studies published in Chinese oncology journals, severe deficiencies were noted. More endorsement by journals of the report guideline for survival analysis may improve articles quality, and the dissemination of reliable evidence to oncology clinicians. We recommend authors, readers, reviewers, and editors to consider survival analysis more carefully and cooperate more closely with statisticians and epidemiologists.

No Association between TNF-α -308G/A Polymorphism and Idiopathic Recurrent Miscarriage: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Conflicting results were reported on the association between the TNF-α -308G/A polymorphism and idiopathic recurrent miscarriage (IRM). Though three meta-analyses have been conducted on this topic, the conclusions were contradictory, and the results may be unreliable as certain crucial conditions were neglected. METHOD: A complete search was conducted in PubMed, Cochrane Library, and Embase, other sources like Google Scholar, ClinicalTrial.gov and reference lists of relevant articles were also retrieved. All candidate articles were accessed and screened using specific inclusion and exclusion criteria. Statistical analyses were performed on data extracted from eligible studies using the STATA 12.0 software and the TSA 0.9 beta software. RESULTS: Eventually, 12 case-control studies from 11 publications (with 1,807 cases and 2,012 controls) were included in this meta-analysis, and no evidence of any significant association was found in the overall analyses between the TNF-α -308G/A polymorphism and IRM risk. However, significant association was shown in Asian population (four studies from three publications) in the dominant model (AA + GA vs. GG), the allelic model (A vs. G), and the heterozygote model (GA vs. GG). CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with IRM risk. Though significant association was found in Asian population, the result needs further confirmation from more studies.

Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer.

MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21's diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma.

[Clinical study on abdominal expanded subdermal vascular plexus skin flaps for repairing dorsal hand scar].

OBJECTIVE: To explore the method and effectiveness of abdominal expanded subdermal vascular plexus skin flaps in repairing dorsal hand scar. METHODS: Between May 2005 and October 2010, 16 cases of dorsal hand scars were treated with the abdominal expanded flaps. There were 13 males and 3 females, aged 22.5 years on average (range, 10-35 years). Defect was caused by burn in 10 cases, hot crush injury in 4 cases, and scald injury in 2 cases. The average scar formation was 21 months (range, 1 year and 6 months to 2 years). The patients had flexion restriction of metacarpophalangeal joint and interphalangeal joint. The scar size ranged from 11 cm x 7 cm to 18 cm x 10 cm. The expander was implanted in abdominal skin and inflated with water regularly at the first stage. After 2 weeks, the expanded pedicled flap was trasferred to repair wounds in which scars were excised. The flap size ranged from 12 cm x 9 cm to 19 cm x 12 cm. After being cut off the pedicle at 14 days, the fingers were divided, and the digital web was formed. The abdominal donor site was directly sutured. RESULTS: All flaps survived. The wound and donor site achieved primary healing. Sixteen cases were followed up 1 year and 2 months to 3 years with an average of 2 years and 3 months. The flaps had soft texture and good flexibility. At last follow-up, hand function was graded as excellent in 13 cases, good in 2 cases, and poor in 1 case with an excellent and good rate of 93.7% according to the total active motion evaluation system. CONCLUSION: Abdominal expanded subdermal vascular plexus skin flap is an effective method to repair large scar of the dorsal hand because it has satisfactory texture, fast rebuilding of blood supply, and large area of survival.

Three-dimensional multimodal image non-rigid registration and fusion in a High Intensity Focused Ultrasound system.

High Intensity Focused Ultrasound (HIFU) has been successfully applied in tumor therapy. For a successful HIFU therapy, it is crucial to localize the tumor region accurately. In this paper, we present a semi-automatic non-rigid registration method for implementing image guided surgery navigation and localization by matching pre-operative CT/MR images and intra-operative ultrasound images. The global motion of the target is modeled by an affine transformation, while the local deformation of the target is described by Free-Form Deformation (FFD) based on B-splines. The results of our experiments on simulated and real data show that the non-rigid registration method based on HPV interpolation (partial volume based on the Hanning windowed sinc function) is effective at restraining local extrema and improves the accuracy of registration results. A preliminary clinical validation of the use of the non-rigid registration method in image guided localization of a HIFU system is also reported.