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Background: The optimal modality for postoperative analgesia after uniportal video-assisted thoracoscopic surgery (UVATS) for the treatment of lung cancer has not yet been determined. Both ultrasound-guided paravertebral block (PVB) and retrolaminar block (RLB) have been reported to be successful in providing analgesia after UVATS. However, which block technique provides superior analgesia after UVATS is still unclear. This randomized study was designed to compare the postoperative analgesic effects and adverse events associated with ultrasound-guided PVB and RLB after UVATS.Methods: Sixty patients with lung cancer were randomized to undergo ultrasound-guided PVB (group P) or ultrasound-guided RLB (group R). In group P, 30 mL of 0.5% ropivacaine was injected at the T3 and T5 levels via ultrasound-guided PVB (15 mL at each level on the operative side). In group R, 30 mL of 0.5% ropivacaine was injected at the T3 and T5 levels via ultrasound-guided RLB (15 mL at each level on the operative side). The primary outcome was the numerical rating scale (NRS) score within 48 h after surgery. The secondary outcomes were total postoperative sufentanil consumption, time to first analgesic request and adverse events.Results: At 3, 6, 12, 24, 36 and 48 h postoperatively, the NRS score at rest in group P was lower than that in group R (p < 0.05). At 3, 6, 12, 24 and 36 h postoperatively, the NRS score while coughing in group P was lower than that in group R (p < 0.05). The total postoperative sufentanil consumption in group P was significantly lower than that in group R (p < 0.001). Additionally, the time to first analgesic request was longer in group R than in group P (p < 0.0001). The incidence of nausea in group R was higher than that in group P (p < 0.05).Conclusions: In patients with lung cancer undergoing UVATS, ultrasound-guided PVB with 0.5% ropivacaine provides better analgesia and results in less nausea than ultrasound-guided RLB. Compared with ultrasound-guided RLB, ultrasound-guided PVB seems to be a better technique for analgesia in UVATS.Trial Registration: The name of this study is the Effect And Mechanism Of Ultrasound-guided Multimodal Regional Nerve Block On Acute And Chronic Pain After Thoracic Surgery. This study was registered in the Chinese Clinical Trial Registry ( ChiCTR2100044060 ). The date of registration was March 9, 2021. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized by the triad of β-amyloid plaques, neurofibrillary tangles, and neurodegeneration. Genetic mutations and risk factors have been identified that are either causal or modify the disease progression. These genetic and pathological features serve as basis for the creation and validation of mouse models of AD. Efforts made in the past quarter-century have produced over 100 genetically engineered mouse lines that recapitulate some aspects of AD clinicopathology. These models have been valuable resources for understanding genetic interactions that contribute to disease and cellular reactions that are engaged in response. Here we focus on mouse models that have been widely used stalwarts of the field or that are recently developed bellwethers of the future. Rather than providing a summary of each model, we endeavor to compare and contrast the genetic approaches employed and to discuss their respective advantages and limitations. We offer a critical account of the variables which may contribute to inconsistent findings and the factors that should be considered when choosing a model and interpreting the results. We hope to present an insightful review of current AD mouse models and to provide a practical guide for selecting models best matched to the experimental question at hand. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture.Design: A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period.Discussion: Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period.Trial Registration: ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017. [ABSTRACT FROM AUTHOR]

Background: The presence and the prognostic significance of perigastric tumor deposits (TDs) in primary gastric cancer have not been extensively studied. The aim of this study was to evaluate the prognostic significance perigastric TDs in primary gastric cancer.Methods: From 2005 to 2010, 1250 patients underwent R0 gastrectomy at the Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Out of 1250 patients, 132 patients with perigastric TDs were identified. Additionally, 132 patients with staged matched gastric cancer without tumor deposits were selected as a control group.Results: Perigastric TDs were observed in 132 (10.5%) of the 1250 patients with gastric cancer who underwent R0 gastrectomy. There were 94 males (71.21%) and 38 females (28.79%) (2.47:1). The mean age was 57.21 years. Clinicopathologic characteristics between the two groups matched well. There was a significant difference in the overall survival of those with and without TDs by univariate (p<0.05) and multivariate (p < 0.05) survival analysis. The 1-, 3-and 5-year overall survival rates of patients with TDswere69.6%, 39.3%, and 24.2%, respectively, and were significantly poorer than those of the staged matched control group. There was no correlation between the number of TDs and patient survival in patients with gastric cancer (p>0.05); however, when comparing each pT tumor group with the perigastric TD group, the stage T4 survival rate was very similar to that observed in patients with TDs.Conclusions: Perigastric TDs are an independent predictive prognostic factor for gastric cancer and may be appropriately considered a form of serosal invasion. We suggest that TDs should be included in TNM staging system for better outcomes. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Surgical resection remains an important therapeutic strategy for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is the most commonly used method of reducing blood loss during liver parenchymal transection. A major issue with this maneuver is ischemia-reperfusion injury to the remnant liver, and the hemodynamic disturbance it induces in the tumor-bearing liver raises an oncological concern. Given the technical advances in living donor liver transplantation, vascular occlusion in liver resection can be avoided in experienced hands. The aim of this study is to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion. Methods/design: This study will include eligible patients with HBV-related HCC elected for liver resection. Fifty-seven patients will be enrolled in each randomization arm to detect a 20 % difference in the serum level of total bilirubin on postoperative day 5 (80 % power and α = 0.05). The secondary endpoints include procedural parameters, perioperative liver function and inflammatory response, postoperative morbidity and mortality, and long-term outcomes. Patients will be followed for up to 5 years. Data will be statistically analyzed on an intention-to-treat basis. Discussion: This prospective randomized controlled trial is designed to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with vascular occlusion. The clinical implications of these outcomes may change current surgical practice and fill the oncological gaps therein. [ABSTRACT FROM AUTHOR]

Background: Tauopathy is characterized by neurofibrillary tangles composed of insoluble hyperphosphorylated tau protein. Currently, cellular models that mimic neurofibrillary tangles in vitro are lacking. Previous studies indicate that neurofibrillary tangles form via a prion replication mechanism. In the present work, we establish a seeding based cellular model according to the prion hypothesis. Results: We show that cellular soluble tau can be converted to insoluble tau by seeds from the brain lysate of rTg4510 mice or synthetically generated preformed tau fibrils (PFFs). The cellular insoluble tau exhibits classic features of neurofibrillary tangles. Using genetic and pharmacological methods, we demonstrate that inhibition of autophagy increases whereas enhancement of autophagy reduces insoluble tau in our seeding based cellular model. The insoluble tau can be detected and quantified by thioflavin-S staining, thus allowing us to adapt our cellular model to a high-content image-based screening platform. Conclusions: Our seeding based cellular model reproduces neurofibrillary tangle pathology in vitro and serves as a useful tool for studying tauopathy and identifying tau modulators. [ABSTRACT FROM AUTHOR]

Background: Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Methods: Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Results: Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Conclusions: Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer. [ABSTRACT FROM AUTHOR]

Background: Although male predominance was documented in previous studies on cryptococcal meningoencephalitis (CM), there has been no statistical study about female CM patients despite recently noticeable increase in female prevalence. In the current study, we aimed to investigate the independent gender-specific contributing risk factors for onset of CM and factors related to survival time in female patients by chosen statistical tools.Methods: There have been 108 patients diagnosed with CM from July 1, 1998 to June 30, 2013 in Nanfang Hospital that were included in our study. This 15-year retrospective study compared demographic and clinical features of 31 female patients with 77 males. Multivariate analysis was performed for detection of the contributors to the onset of CM in female patients. The independent variables for multivariate analysis were selected according to statistical significance in univariate analysis. Furthermore, Cox regression model was used to evaluate the factors related to survival length.Results: Use of corticosteroids or other immunosuppressants (32.3% versus 11.7%; p = 0.011) and history of systemic lupus erythematosus (SLE) and other autoimmune diseases (29% versus 3.9%; p < 0.001) were more common in females, but only the history of SLE or other autoimmune diseases was significant (OR 10.59, 95% CI 1.49-74.77, p = 0.02) by multivariate analysis. The ratio of cerebrospinal fluid (CSF) glucose-to-blood glucose was related to the survival time (p = 0.03, 95% CI 0-0.71).Conclusions: The results showed that the history of SLE or other autoimmune diseases rather than chronic use of corticosteroids and/or immunosuppressants was the independent gender-specific contributing risk factor in female CM patients. Therefore, more attention should be made to the prevention of infection from the genus Cryptococcus spp. in female patients with SLE or other autoimmune diseases. In addition, decreased ratio of CSF glucose-to-blood glucose before antifungal therapy predicted the worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Studies have identified prenatal and early childhood conditions as important contributors to weight status in later life. To date, however, few studies have considered how weight status in adulthood is shaped by regional variation in early-life conditions, rather than the characteristics of the individual or their family. Furthermore, gender and life course differences in the salience of early life conditions to weight status remain unclear. This study investigates whether the effect of family background and birth region on adult obesity status varies by gender and over the life course. Methods: We used data from a population-based cohort of 6,453 adults from the Health and Retirement Study, 1992-2008. Early life conditions were measured retrospectively at and after the baseline. Obesity was calculated from self-reported height and weight. Logistic models were used to estimate the net effects of family background and birth region on adulthood obesity risk after adjusting for socioeconomic factors and health behaviors measured in adulthood. Four economic and demographic data sets were used tofurther test the birthplace effect. Results: At ages 50-61, mother's education and birth region were associated with women's obesity risk, but not men's. Each year's increase in mother's education significantly reduces the odds of being obese by 6 % (OR = 0.94; 95 % CI: 0.92, 0.97) among women, and this pattern persisted at ages 66-77. Women born in the Mountain region were least likely to be obese in late-middle age and late-life. Measures of per capita income and infant mortality rate in the birth region were also associated with the odds of obesity among women. Conclusions: Women's obesity status in adulthood is influenced by early childhood conditions, including regional conditions, while adulthood health risk factors may be more important for men's obesity risk. Biological and social mechanisms may account for the gender difference. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningoencephalitis (CM) is the most common opportunistic infection of the central nervous system (CNS). Despite this observation, there have only been a few studies analyzing clinical characteristics as well as cerebrospinal fluid (CSF), electroencephalograph (EEG), and magnetic resonance imaging (MRI) features in CM patients of all ages. Methods: We reviewed the medical records of all patients diagnosed with cryptococcal meningoencephalitis from 1998 to 2013 in the Nanfang Hospital in China and gathered data on the underlying diseases, bird exposure history, and clinical features, including those from CSF, EEG and MRI. Results: CM is more likely to infect adults younger than 60 years old. 71.3% of CM patients were male. Unlike data from other countries, we found that chronic use of corticosteroids or other immunosuppressants (17.59%) was the most frequent risk factor in CM patients rather than HIV infection (1.85%). Clear exposure with bird/ bird droppings before CM onset is obvious in a previous study in CM children. However, our study found that 4.63% CM patients had such an exposure. More importantly, patients with brain tissue damage (p = 0.021) and decreased CSF/blood glucose ratio (p = 0.008) were significantly associated with death, but only the decreased CSF/blood glucose ratio was the contributing factor of prognosis (odds ratio, 0.047; p = 0.025). Decreased CSF/blood glucose ratio was significantly related to the survival length of CM (odds ratio, 0.134; p = 0.033). Conclusions: Our study shows that CM has predilection for young male adults. The chronic use of corticosteroids or other immunosuppressants, rather than HIV infection or bird/bird droppings exposure, was the most frequent risk factor in CM patients in our study. Decreased CSF/blood glucose ratio was both an independent contributing factor to death and was significantly related to the survival length of CM patients. The more decreased the CSF/blood glucose ratio was, the worse prognosis and shorter survival length CM patients had. [ABSTRACT FROM AUTHOR]

Background: We have demonstrated previously that NFKB1 single nucleotide polymorphism (SNP) rs4648068 GG homozygote was associated with the increased risk of gastric cancer in Chinese Han population. In this study, we constructed the recombinant plasmid pGL3-AA, pGL3-GG, pGL3-AA-NFKB and pGL3-GG-NFKB to investigate the function of rs4648068 by cell biology experiments. Methods: Quantitative real-time PCR was used to detect NFKB1 SNP rs4648068 genotype in the patients with gastric cancer. Anti-NF-B1 p50 polyclonal antibodies were used for immunohistochemical analysis of the tissue specimens. The subsection of NFKB1 containing the promoter site and adjacent three consecutive exons were obtained by PCR technique and subcloned into the vector pGL3-Basic. Dual-Luciferase reporter assay was used to detect the transcriptional activity of the constructed promoter. Effects of transcription factor NFKB1 on C/EBPß expression were determined by chromatin immunoprecipitation and Western analysis. Furthermore, proliferation and invasion ability of the transduced cell were also measured and compared. Results: Intensive staining for p50 expression was observed in the tissues of GG genotype patients, compared with those of GA group and AA genotype patients. The transcriptional activity of rs4648068 (A > G) by dual-Luciferase reporter assay suggested that the luciferase activity of homozygote group (pGL3-GG) was greater than that of the control (pGL3-AA), especially at the stimulation of LPS. We found that the luciferase activity was also influenced by pGL3-GG levels. The effects of NFKB1 rs4648068 were enhanced by rs4648065 on the transduced cells. The interaction between NFKB1 promoter nucleotide sequence and C/EBPß was regulated by the functional SNP rs4648068 in SGC-7901 cells. Our data indicated that the transduction of pGL3 expression plasmid pGL3-GG-NFKB improved the proliferation and motility of gastric cancer cells. Correspondingly, the homozygote GG of SNP rs4648068 strengthened the transcriptional activity of NFKB1 and influenced the cell biological activity. Conclusion: The transcriptional activity of NFKB1 was associated with SNP rs4648068, and this functional SNP site has the important effects on cell proliferation and motility. [ABSTRACT FROM AUTHOR]

Background: To investigate the risk of hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with HBV carrier state during treatment of disease-modifying antirheumatic drugs (DMARDs) and the use of antiviral prophylaxis in real-world clinical practice. Methods: Consecutive RA patients with HBV carrier state were included. Clinical data including liver evaluation, HBV infection evaluation and the use of antiviral prophylaxis were recorded. Results: Fifty-three RA patients with HBV carrier state were screened and 36 patients were qualified for analysis. Thirty-six percentage of patients developed HBV reactivation and 17% developed HBV hepatitis together with reactivation, one of which developed decompensate cirrhosis. Only 50% of patients accepted lamivudine although all patients were recommended antiviral prophylaxis with entecavir or tenofovir and only 31% continued during DMARDs therapy. Seventy-one percentage of patients who discontinued antiviral prophylaxis developed HBV reactivation 3 ~ 21 months after discontinuation. Logistic regression analyses showed discontinuation of antiviral prophylaxis (OR: 66, p = 0.027), leflunomide (OR: 64, p = 0.011) and past history of hepatitis (OR: 56, p = 0.013) were risk factors of HBV reactivation. Past history of hepatitis (OR: 10, p = 0.021) was also risk factor of HBV hepatitis together with reactivation. Conclusion: Our results suggest poor patient acceptance and discontinuation of antiviral prophylaxis should not be ignored for Chinese RA patients with HBV carrier state in real-world clinical practice. Discontinuation of antiviral prophylaxis, past history of hepatitis and LEF might increase risk of HBV reactivation for RA patients with HBV carrier state during DMARDs therapy. [ABSTRACT FROM AUTHOR]

Background: The 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism. Methods: The MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA-seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis. Results: A novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets. Conclusion: Our results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy. [ABSTRACT FROM AUTHOR]

Background Nonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk. Findings Ion mobility analysis was performed on 78 individuals with obesity undergoing weight loss surgery. All individuals had standard of care liver biopsies performed during surgery. Patients with NASH had significantly smaller peak LDL diameter (P = 0.02, 219.0 Å vs. 222.6 Å), and levels of IDL2 (P = 0.01, 104. nmol/L vs. 133.4 nmol/L) and HDL2b (P = 0.05, 676.7 nmol/L vs. 880.1 nmol/L) compared to those without NASH. NASH patients had significantly higher LDL-IVb levels than those without NASH (P = 0.02, 49.0 nmol/L vs. 37.1 nmol/L). The inverse association of LDL peak diameter with NASH remained significant after adjustment for diabetes (P = 0.02). HDL2b levels were inversely correlated with hepatocyte ballooning and NASH and these remained significant after adjustment for diabetes (P = 0.0017 and P = 0.007, respectively). IDL2 levels were inversely correlated with NASH, hepatocyte ballooning and fibrosis stage but these were not significant after adjustment for diabetes. Conclusions The lipoprotein subfraction profile in subjects with NASH is characterized by small peak LDL diameter, reduced HDL2b levels and elevated LDL-IVb levels. These changes may contribute to the increased CVD seen in patients with NASH. [ABSTRACT FROM AUTHOR]

Background: Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. Methods/Design: The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. Discussion: The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. [ABSTRACT FROM AUTHOR]

Background Whether acupuncture is effective for relieving perimenopausal syndrome has been controversial recently. In this article, we report the protocol of a randomized controlled trial using acupuncture to treat perimenopausal syndrome, aiming to answer this controversy. Design A multicenter randomized controlled trial with two parallel arms is underway in China. Two hundred and six women with perimenopausal syndrome will be randomly assigned to a treatment group using acupuncture plus auricular acupressure (AA group) and a control group using Climen® (Bayer Healthcare Company Limited, Guangzhou, China), a 28-day sequential hormone replacement therapy, in a 1:1 ratio. Participants in the AA group will receive three acupuncture sessions per week in the first 4 weeks and two sessions per week in the following 8 weeks, for a total of 28 sessions over 12 weeks. Auricular points will be plastered by Semen Vaccariae twice per week for a consecutive 12 weeks, with both ears used alternately. The Climen® control group is prescribed a tablet containing estradiol valerate 2 mg/day for the first 11 days, and a tablet containing estradiol valerate 2 mg/day plus cyroterone acetate 1 mg/day for the following 10 days. The total treatment period of the control group is three cycles. The post-treatment follow-up period will last 24 weeks. The primary outcome is the Menopause Rating Scale (MRS) assessed at baseline and 4, 12, 16, 24 and 36 weeks after randomization. The secondary outcomes are Menopause-Specific Quality of Life, average hot flash score during 24 hours, serum estradiol, follicle-stimulating hormone and luteinizing hormone level. The first two secondary outcomes are measured at the same point as the MRS. Other secondary outcomes are measured at baseline and 12, 24 weeks after randomization. Discussion The results of this trial, which will be available in 2015, will clarify whether acupuncture is effective to relieve perimenopausal syndrome. [ABSTRACT FROM AUTHOR]

Background Chronic stable angina pectoris (CSAP) is a common cardiovascular condition that endangers a patient's life quality and longevity. As demonstrated in several clinical trials, acupuncture is attested to be effective for CSAP. Current trials are not adequate enough to provide highquality evidence for clinical decision making, as a result of inadequate methodology design and small sample size. Notably, stark controversy toward acupoint specificity also exists in the clinical acupuncture trials for CSAP. Therefore, we designed the present study as a randomized controlled trial primarily to investigate the effectiveness of acupuncture in addition to routine care among patients with CSAP. Meanwhile, we examined whether acupoint on the disease-affected meridian (DAM) is superior to either acupoint on the nonaffected meridian (NAM) or non-acupoint (NA), to further investigate the meridian-based characteristics of acupoint specificity. Methods/Design This study was a multicenter, assessor and statistician blinded, randomized controlled trial in China. In this study, 404 participants in sum will be randomly assigned to four groups through central randomization in a 1:1:1:1 ratio. The whole study period is 20 weeks including a 4-week baseline period, a 4-week treatment period and a 12-week follow-up. Participants in the DAM group receive acupuncture stimulation at acupoints on the diseaseaffected meridian, and three different control groups will undergo acupuncture stimulation at the NAM, the non-acupoint and no intervention respectively, in addition to basic treatment. Participants in the acupuncture groups will receive 12 sessions of acupuncture treatment over 4 weeks, while the wait-listed (WL) group would receive free acupuncture treatment after the completion of the study. The outcome measures in this trial include the frequency of angina attack during 4 weeks as the primary outcome and eight other secondary outcomes. Discussion This trial will provide new and relatively high-quality evidence in acupuncture treatment for CSAP. Moreover, this trial may further validate the meridian-based characteristics of acupoint specificity by comparing the strength of acupoints on the disease-affected meridian versus that of the non-affected meridian, to further inspire optimization of acupuncture therapy for CSAP. Trial registration Clinical Trials.gov NCT01686230 [ABSTRACT FROM AUTHOR]

Background Many patients with gastric gastrointestinal stromal tumor (GIST) and synchronous gastric cancer have been described, most in single case studies. We retrospectively investigated the clinicopathologic features and prognostic effects of gastric GIST in patients with synchronous gastric cancer. Methods The study enrolled 170 patients with gastric GIST, who had undergone complete surgical resection (R0) from January 2000 to December 2011. Forty-two patients had synchronous gastric cancer (CA Group), whereas 128 did not (Non-CA Group). The clinicopathologic features and potential prognostic factors in the two groups were compared. Results Patients in the CA Group had more obvious symptoms, but a lower rate of preoperative diagnosis of gastric GIST (P <0.05). The two groups differed significantly in gender, age, greatest tumor diameter, risk stratification, tumor-associated ulcers, and CD117 and CD34 expression (P <0.05 each). Univariate analysis showed that age, risk stratification, postoperative oral imatinib and synchronous gastric cancer were predictive factors of survival (P <0.05). Cox regression analysis showed that risk stratification, postoperative oral imatinib and synchronous gastric cancer were independent predictors of survival (P <0.05). Stratified analysis showed that the 5-year overall survival rate was lower in patients with synchronous gastric cancer than in those without synchronous gastric cancer. Conclusions Gastric GIST with synchronous gastric cancer had a lower rate of preoperative diagnosis, with correct diagnosis often missed. Survival, however, depended primarily on the gastric cancer. [ABSTRACT FROM AUTHOR]

Background Although cardiac cancer of the remnant stomach and primary cardiac cancer both occur in the same position, their clinical characteristics and outcomes have not been compared previously. The objective of this study was designed to evaluate the prognosis of cardiac cancer of the remnant stomach in comparison with primary cardiac cancer. Methods In this retrospective comparative study, clinical data and prognosis were compared in 48 patients with cardiac cancer of the remnant stomach and 96 patients with primary cardiac cancer who underwent radical resection from January 1995 to June 2007. Clinicopathologic characteristics, survival times, mortality, and complications were analyzed. Results The 5-year survival rate was significantly higher in patients with primary cardiac cancer than in those with cardiac cancer of the remnant stomach (28.4% vs. 16.7%, P = 0.035). Serosal invasion, lymph node metastasis and tumor location were independent prognostic factors for survival. Subgroup analysis, however, showed similar survival rates in patients with primary cardiac cancer and cardiac cancer of the remnant stomach without serosal invasion (25.0% vs. 43.8%, P = 0.214) and without lymph node metastasis (25.0% vs. 38.8%, P = 0.255), as well as similar complication rates (20.8% vs. 11.5%, P = 0.138). Conclusion Although the survival rates after radical resection in patients with cardiac cancer of the remnant stomach were poorer than in those with primary cardiac cancer, they were similar in survival rates when patients without serosal invasion or lymph node metastasis. Therefore, early detection is an important way to improve overall survival in cardiac cancer of the remnant stomach. [ABSTRACT FROM AUTHOR]

Background Several studies using acupuncture to treat essential hypertension have been carried out. However, whether acupuncture is efficacious for hypertension is still controversial. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for patients with mild hypertension. Methods/Design This is a large scale, open-label, multicenter, randomized controlled clinical trial with four parallel arms. We will recruit 428 hypertensive patients with systolic blood pressure (SBP) between 140 and 159 mmHg, diastolic blood pressure (DBP) between 90 and 99 mmHg. The participants will be randomly assigned to four different groups (three acupuncture groups and one waiting list group) (1).The affected meridian acupuncture group (n = 107) is treated with acupoints on the affected meridians (2).The non-affected meridian acupuncture group (n = 107) is treated with acupoints on the non-affected meridians (3).The invasive sham acupuncture group (n = 107) is provided with sham acupoints treatment (4).The waiting-list group (n = 107) is not offered any intervention until they complete the trial. Each patient allocated to acupuncture groups will receive 18 sessions of acupuncture treatment over 6 weeks. This trial will be conducted in 11 hospitals in China. The primary endpoint is the change in average 24-hSBP before and 6 weeks after randomization. The secondary endpoints are average SBP and average DBP during the daytime and night-time, and 36-Item Short Form Survey (SF-36), and so on. Discussion This is the first large scale, multicenter, randomized, sham controlled trial of acupuncture for essential hypertension in China. It may clarify the efficacy of acupuncture as a treatment for mild hypertension. Trials registration Clinicaltrials.gov Identifier: NCT01701726. [ABSTRACT FROM AUTHOR]

Background: To explore the safety and feasibility of the transorally inserted anvil (OrVil™) in laparoscopy-assisted total gastrectomy for gastric cancer. Methods: From December 2010 to June 2011, a total of 28 patients underwent laparoscopy-assisted total gastrectomy with a Roux-en-Y-esophagojejunostomy anastomosis with OrVil™. Perioperative treatments, intraoperative data, postoperative complications and hospital length of stay were evaluated. Results: There were no conversions to the open gastrectomy. The mean operation time was 143 minutes and the mean blood loss was 70 ml. Patients resumed an oral liquid diet on postoperative days 4 to 5. Two patients (7%) who suffered postoperative aspiration pneumonia were cured by conservative treatment. The median hospital length of stay was 9.6 days (8 to 11 days), with no inhospital mortalities. The median follow-up time was 14.8 months (12 to 18 months), and postoperative endoscopic examination revealed no anastomosis stenosis in patients who had dysphagia. Conclusion: The use of the OrVil™ is technically feasible and relatively safe for Roux-en-Y reconstruction after laparoscopy-assisted total gastrectomy [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a common malignancy worldwide and a common cause of death from cancer. Despite recent advances in multimodality treatment and targeted therapy, complete resection remains the only treatment that can lead to cure. This study was devised to investigate the technical feasibility, safety and oncologic efficacy of laparoscopy-assisted gastrectomy for advanced gastric cancer without serosa invasion. Methods: A retrospective matched cohort study was performed in south China comparing laparoscopy-assisted gastrectomy and open gastrectomy for advanced gastric cancer without serosa invasion. Eighty-three patients with advanced gastric cancer undergoing laparoscopy-assisted gastrectomy between January 2008 and December 2010 were enrolled. These patients were compared with 83 patients with advanced gastric cancer undergoing open gastrectomy during the same period. Results: There was no significant difference in clinicopathologic characteristics between the two groups. Regarding perioperative characteristics, the operation time and time to ground activities did not differ between the two groups, whereas the blood loss, transfused patient number, time to first flatus, time to resumption of diet, and postoperative hospital stay were significantly less in laparoscopy-assisted gastrectomy than in open gastrectomy (P <0.05). There was no statistically significant difference in postoperative morbidity and mortality. No significant difference in the number of lymph nodes dissected was observed between these two groups. There was no significant difference in the cumulative survival rate between the two groups. Conclusion: Laparoscopy-assisted gastrectomy with D2 lymphadenectomy is a safe and feasible procedure for advanced gastric cancer without serosa invasion. To be accepted as a choice treatment for advanced gastric cancer, well-designed randomized controlled trials comparing short-term and long-term outcomes between laparoscopy-assisted gastrectomy and open gastrectomy in a larger number of patients are necessary. [ABSTRACT FROM AUTHOR]

Retroviruses have an intricate life cycle. There is much to be learned from studying retrovirus-host interactions. Among retroviruses, the primate lentiviruses have one of the more complex genome structures with three categories of viral genes: structural, regulatory, and accessory genes. Over time, we have gained increasing understanding of the lentivirus life cycle from studying host factors that support virus replication. Similarly, studies on host restriction factors that inhibit viral replication have also made significant contributions to our knowledge. Here, we review recent progress on the rapidly growing field of restriction factors, focusing on the antiretroviral activities of APOBEC3G, TRIM5, tetherin, SAMHD1, MOV10, and cellular microRNAs (miRNAs), and the counter-activities of Vif, Vpu, Vpr, Vpx, and Nef. [ABSTRACT FROM AUTHOR]

Background: To evaluate different types of acupuncture treatment for migraine in China from the perspective of health economics, particularly the comparison between treatment of specific acupoints in Shaoyang meridians and penetrating sham acupoints treatment. Methods: Data were obtained from a multicenter, randomized controlled trial of acupuncture treatment in patients with migraine. Four-hundred eighty migraineurs were randomly assigned to 3 arms of treatment with genuine acupoints and 1 arm of penetrating sham acupoints. The primary outcome measurement was the cost effectiveness ratio (C/E), expressed as cost per 1 day reduction of headache days from baseline to week 16. Cost-comparison analyses, differences in the migraine-specific quality of life questionnaire (MSQ), and the incremental cost-effectiveness ratio were taken as secondary outcome measurements. In addition, a sensitivity analysis was conducted. Results: The total cost per patient was ¥1273.2 (95% CI 1171.3-1375.1) in the Shaoyang specific group, ¥1427.7 (95% CI 1311.8-1543.6) in the Shaoyang non-specific group, ¥1490.8 (95% CI 1327.1-1654.6) in the Yangming specific group, and ¥1470.1 (95% CI 1358.8-1581.3) in the sham acupuncture group. The reduced days with migraine were 3.972 ± 2.7, 3.555 ± 2.8, 3.793 ± 3.6, and 2.155 ± 3.7 in these 4 groups (P<0.05 for each genuine acupoints group vs the sham group), respectively, at week 16. The C/Es of the 4 groups were 320.5, 401.6, 393.1, and 682.2, respectively. Results of the sensitivity analysis were consistent with that of the cost-effectiveness analysis. The Shaoyang specific group significantly improved in all 3 MSQ domains compared with the sham acupuncture group. Conclusions: Treatment of specific acupoints in Shaoyang meridians is more cost-effective than that of nonacupoints, representing a dramatic improvement in the quality of life of people with migraine and a significant reduction in cost. Compared with the other 3 groups, Shaoyang-specific acupuncture is a relatively cost-effective treatment for migraine prophylaxis in China. [ABSTRACT FROM AUTHOR]

Background: Patients with periodontitis seek periodontal-orthodontic treatment to address certain functional and aesthetic problems. However, little is known of the effect of periodontitis on orthodontic treatment. Thus, we compared the differences in peptide mass fingerprints of orthodontic patients with and without periodontitis by MALDI-TOF MS using a magnetic bead-based peptidome analysis of saliva samples. In this way, we aimed to identify and explore a panel of differentially-expressed specific peptides. Results: Saliva samples from 24 patients (eight orthodontic patients without periodontitis, eight with periodontitis and another eight with periodontitis but no orthodontic treatment) were analyzed, and peptide mass fingerprints were created by scanning MS signals using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic beads. Nine mass peaks showed significant differences. Orthodontic patients in the group without periodontal disease showed higher mass peaks for seven peptides of the nine, whereas the mass peaks for the other two peptides were higher in the periodontal-orthodontic patients. Besides, these differentially-expressed peptides were sequenced. Conclusions: The elucidated candidate biomarkers indicated interactions between periodontal condition and orthodontic treatment and their contributions to the changes of saliva protein profiles. Our results provide novel insight into the altered salivary protein profile during periodontal-orthodontic treatment, and may lead to the development of a therapeutic monitoring strategy for periodontics and orthodontics. [ABSTRACT FROM AUTHOR]

Background: The application of laparoscopic surgery for advanced gastric cancer (AGC) remains questionable on account of technical difficulty of D2 lymphadenectomy, and there has been few large-scale follow-up results regarding the oncological adequacy of laparoscopic surgery compared with that of open surgeries for AGC. The aim of this study is to evaluate technical feasibility and oncological efficacy of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer without serosal invasion. Methods: From January 2008 to December 2012, 1114 patients with gastric cancer underwent D2 gastrectomy, including 336 T2 and T3 patients in term of depth of invasion. Of all 336 patients, 224 underwent LAG, while open gastrectomy (OG) performed on the other 112 patients. The comparison was based on the clinicopathologic characteristics, surgical outcome, and follow-up results. Results: There are not significant differences in clinicopathological characteristics between the two groups (P > 0.05). The operation time and first ambulation time was similar in the two groups. However, estimated blood loss, bowel function recovery time and duration of hospital stay were significantly less in the LAG group. No significant difference in morbidity and mortality was found between the LAG group and OG group (11.1% vs. 15.3%, P = 0.266; 0.9% vs. 1.8%, P = 0.859). The mean number of resected lymph nodes (LNS) between the LAG group and OG group was similar (30.6 ± 10.1 vs. 30.3 ± 8.6, P = 0.786). Furthermore, the mean number of removed LNS in each station was not significantly different in the distal gastrectomy and total gastrectomy (P > 0.05). No statistical difference was seen in 1 year survival rate (91.5% vs. 89.8% P > 0.05) and the survival curve after surgery between the LAG group and OG group. Conclusion: Laparoscopy-assisted D2 radical gastrectomy is feasible, effective and has comparative oncological efficacy compared with open gastrectomy for advanced gastric cancer without serosal invasion. [ABSTRACT FROM AUTHOR]

Background: C-src is an evolutionarily conserved proto-oncogene that regulates cell proliferation, differentiation and apoptosis. In our previous studies, we have reported that another proto-oncogene, c-erbB2, plays an important role in primordial follicle activation and development. We also found that c-src was expressed in mammalian ovaries, but its functions in primordial follicle activation remain unclear. The objective of this study is to investigate the role and mechanism of c-src during the growth of primordial follicles. Methods: Ovaries from 2-day-old rats were cultured in vitro for 8 days. Three c-src-targeting and one negative control siRNA were designed and used in the present study. PCR, Western blotting and primordial follicle development were assessed for the silencing efficiency of the lentivirus c-src siRNA and its effect on primordial follicle onset. The expression of c-src mRNA and protein in primordial follicle growth were examined using the PCR method and immunohistochemical staining. Furthermore, the MAPK inhibitor PD98059, the PKC inhibitor Calphostin and the PI3K inhibitor LY294002 were used to explore the possible signaling pathways of c-src in primordial folliculogenesis. Results: The results showed that Src protein was distributed in the ooplasmic membrane and the granulosa cell membrane in the primordial follicles, and c-src expression level increased with the growth of primordial follicle. The c-src -targeting lentivirus siRNAs had a silencing effect on c-src mRNA and protein expression. Eight days after transfection of rat ovaries with c-src siRNA, the GFP fluorescence in frozen ovarian sections was clearly discernible under a fluorescence microscope, and its relative expression level was 5-fold higher than that in the control group. Furthermore, the c-src-targeting lentivirus siRNAs lowered its relative expression level 1.96 times. We also found that the development of cultured primordial follicles was completely arrested after c-src siRNA knockdown of c-src expression. Furthermore, our studies demonstrated that folliculogenesis onset was inhibited by Calphostin, PD98059 or LY294002 treatment, but none of them down-regulated c-src expression. In contrast, the expression levels of p-PKC, p-ERK1/2 and p-PI3K in the follicles were clearly decreased by c-src siRNA transfection. Correspondingly, both Calphostin and LY294002 treatment resulted in a decrease in the p-PKC level in follicles, but no change was observed in the PD98059 group. Finally, LY294002 treatment decreased the p-PI3K expression level in the follicles, but no changes were observed in the PD98059 and Calphostin groups. Conclusions: C-src plays an important role in regulating primordial follicle activation and growth via the PI3K-PKC- ERK1/2 pathway. [ABSTRACT FROM AUTHOR]

Background: Vpr is exclusively expressed in primate lentiviruses and contributes to viral replication and disease progression in vivo. HIV-1 Vpr has two major activities in vitro: arrest of cell cycle in the G2 phase (G2 arrest), and enhancement of viral replication in macrophages. Previously, we reported a potent HIV-1 restriction in the human CD4+ CEM.NKR (NKR) T cells, where wild-type (WT) HIV-1 replication was inhibited by almost 1,000-fold. From the parental NKR cells, we isolated eight clones by limiting dilution. These clones showed three levels of resistance to the WT HIV-1 infection: non-permissive (NP), semi-permissive (SP), and permissive (P). Here, we compared the replication of WT, Vif-defective, Vpr-defective, and Vpu-defective viruses in these cells. Results: Although both WT and Vpu-defective viruses could replicate in the permissive and semi-permissive clones, the replication of Vif-defective and Vpr-defective viruses was completely restricted. The expression of APOBEC3G (A3G) cytidine deaminase in NKR cells explains why Vif, but not Vpr, was required for HIV-1 replication. When the Vpr-defective virus life cycle was compared with the WT virus life cycle in the semi-permissive cells, it was found that the Vpr-defective virus could enter the cell and produce virions containing properly processed Gag and Env proteins, but these virions showed much less efficiency for reverse transcription during the next-round of infection. In addition, although viral replication was restricted in the non-permissive cells, treatment with arsenic trioxide (As2O3) could completely restore WT, but not Vpr-defective virus replication. Moreover, disruption of Vpr binding to its cofactor DCAF1 and/or induction of G2 arrest activity did not disrupt the Vpr activity in enhancing HIV-1 replication in NKR cells. Conclusions: These results demonstrate that HIV-1 replication in NKR cells is Vpr-dependent. Vpr promotes HIV-1 replication from the 2nd cycle likely by overcoming a block at early stage of viral replication; and this activity does not require DCAF1 and G2 arrest. Further studies of this mechanism should provide new understanding of Vpr function in the HIV-1 life cycle. [ABSTRACT FROM AUTHOR]