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OBJECTIVE To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). METHODS In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement. RESULTS Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. CONCLUSION Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up.

Objective: We aimed to explore the feasibility of evaluating the comparative effectiveness and safety of electroacupuncture (EA) relative to manual acupuncture (MA) for the treatment of knee osteoarthritis (KOA). Methods: A multicenter randomized controlled clinical trial was conducted in Beijing from September 2017 to January 2018. A total of 60 participants with KOA were randomly allocated to either EA ( n = 30) or MA ( n = 30) groups. Participants in the EA group were treated with EA at six to seven local traditional acupuncture points or ah shi points, and two to three distal points. Participants in the MA group had the same schedule as the EA group except that the electrical apparatus featured a working power indicator without actual current output, constituting a sham EA procedure, in order to blind participants. Both groups received 24 sessions over 8 weeks. The primary outcome was response rate, defined as a change of ⩾50% from baseline in the total scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after 8 weeks. Secondary outcomes included pain, stiffness, function, quality of life, and acupuncture-related adverse events (AEs) at 4 and 8 weeks. Results: Of 60 participants randomized, 53 (88%) completed the study. Response rates were 43% for the EA group and 30% for the MA group by the intention-to-treat analysis. Although significant differences were observed in WOMAC pain, stiffness, and function scores within both groups, between-group differences at 8 weeks did not reach statistical significance (odds ratio = 1.75 (95% confidence interval = 0.593–5.162)). Rates of AEs were low and similarly distributed between groups. Conclusion: Both EA and MA interventions in KOA were feasible and appeared safe. Whether or not EA may have a stronger impact on pain and function requires further evaluation through larger, adequately powered, randomized controlled trials. Trial registration number: NCT03274713.

To evaluate the clinical effect of acupuncture for the improvements in various dyspeptic symptoms of postprandial distress syndrome.The secondary analysis on the data of a multi-center randomized controlled trial (RCT) was conducted. 278 patients with postprandial distress syndrome were randomized into an acupuncture group (138 cases) and a sham-acupuncture group (140 cases). In the acupuncture group, acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), Zusanli (ST 36), etc. In the sham-acupuncture group, 6 sites, neither located on meridians nor belonged to meridian acupoints, were selected and punctured shallowly. The duration of treatment was 20 min each time, 3 times a week, for 4 weeks totally in the two groups. The follow-up visit lasted for 12 weeks. The scores of dyspeptic symptoms were compared between the two groups before treatment, during treatment (in week 1, 2, 3 and 4) and during follow-up (in week 8, 12 and 16) separately.Besides the scores of early satiety and vomiting in the sham-acupuncture group in week 1, the scores of the other dyspepsia symptoms during treatment and follow-up were all reduced in the two groups as compared with those before treatment (Acupuncture remarkably relieves postprandial fullness, early satiety, upper abdominal bloating and belching in patients with postprandial distress syndrome.

Background Postprandial distress syndrome (PDS) has a considerable impact on quality of life. Our previous pilot trial suggested that acupuncture might be a potential treatment option for PDS. We will conduct this large trial to determine the efficacy of acupuncture versus sham acupuncture for PDS. Methods/design A total of 280 eligible patients who meet the Rome IV criteria for PDS will be randomly allocated to either the acupuncture group or the sham acupuncture group. Each patient will receive 12 sessions over four weeks. The primary outcomes will be the response rate of overall treatment effect (OTE) and the elimination rate of all three cardinal symptoms (postprandial fullness, upper abdominal bloating, and early satiation) at four weeks after randomization. Secondary outcomes will include assessments of the severity of dyspepsia symptoms and disease-specific quality of life at weeks 4, 8, and 16 after randomization. All patients who receive randomization will be included in the intent-to-treat analysis. Discussion The finding of this trial will provide high-quality evidence on the efficacy of acupuncture for treatment of PDS. Results of this research will be published in peer-reviewed journals. Trial registration ISRCTN Registry, ISRCTN12511434. Registered on 31 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3051-3) contains supplementary material, which is available to authorized users.

Postprandial distress syndrome (PDS) is the most common subtype of functional dyspepsia. Acupuncture is commonly used to treat PDS, but its effect is uncertain because of the poor quality of prior studies.To assess the efficacy of acupuncture versus sham acupuncture in patients with PDS.Multicenter, 2-group, randomized clinical trial. (ISRCTN registry number: ISRCTN12511434).5 tertiary hospitals in China.Chinese patients aged 18 to 65 years meeting Rome IV criteria for PDS.12 sessions of acupuncture or sham acupuncture over 4 weeks.The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms: postprandial fullness, upper abdominal bloating, and early satiation after 4 weeks of treatment. Participants were followed until week 16.Among the 278 randomly assigned participants, 228 (82%) completed outcome measurements at week 16. The estimated response rate from generalized linear mixed models at week 4 was 83.0% in the acupuncture group versus 51.6% in the sham acupuncture group (difference, 31.4 percentage points [95% CI, 20.3 to 42.5 percentage points];Lack of objective outcomes and daily measurement, high dropout rate, and inability to blind acupuncturists.Among patients with PDS, acupuncture resulted in increased response rate and elimination rate of all 3 cardinal symptoms compared with sham acupuncture, with sustained efficacy over 12 weeks in patients who received thrice-weekly acupuncture for 4 weeks.Beijing Municipal Science and Technology Commission.

Background Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci. Methods The study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR). Results A significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112–1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122–1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140–1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202–2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005–1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033–3.070, P = 0.037). There was no difference in LTL between controls and patients. Conclusions Our results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.

Background: Evidence for treating postprandial distress syndrome with acupuncture is limited. Aim: We aimed to evaluate the feasibility of verum acupuncture versus sham acupuncture in patients with postprandial distress syndrome. Methods: A total of 42 eligible patients were randomly allocated to either verum acupuncture or sham acupuncture groups in a 1:1 ratio. Each patient received 12 sessions over 4 weeks. The primary outcome was the response rate based on the overall treatment effect (OTE) 4 weeks after randomization. Secondary outcomes included dyspepsia symptom severity and adverse events. Results: In each group, 19 patients (91.5%) completed the study. Thirteen patients receiving verum acupuncture and seven patients receiving sham acupuncture were classified as responders according to OTE (61.9% vs 33.3%; rate difference 28.6%; p = 0.06). Dyspepsia symptom severity at the end of treatment also differed significantly between verum acupuncture and sham acupuncture groups (5.9 units vs 3.7 units; between-group difference 2.2 (95% CI, 0.2–4.2); p = 0.04). No serious adverse events occurred. Conclusion: Four weeks of acupuncture may represent a potential treatment for postprandial distress syndrome. The treatment protocol and outcome measures used in this trial were feasible. Since this was a pilot study, the efficacy of acupuncture still needs to be determined by a larger, adequately powered trial.

Supplemental material, supplementary_Table_1 for Acupuncture for postprandial distress syndrome: a randomized controlled pilot trial by Jian-Feng Tu, Jing-Wen Yang, Li-Qiong Wang, Yang Zheng, Li-Wen Zhang, Yong-Ting Li, Xin Zhang, Guang-Xia Shi, Jun Wang, Jing-Jie Zhao, Yi Du, San-San Chen, Lu Cheng and Cun-Zhi Liu in Acupuncture in Medicine

To observe the effect of the small needle knife through the Zusanli(ST 36) on behavior and hippocampal expression of NLRP3 and IL-1β in myalgia comorbid depressed rats.The rat models of myalgia comorbid depression were prepared by intraperitoneal injection of acute reserpine. Twenty-four SD male rats were randomly divided into control group, model group, small needle knife group and amitriptyline group, 6 rats in each group. The open field behavior and mechanical pain threshold of each group were detected. The thermal pain threshold was detected by intelligent hot plate test. The expression of NLRP3 and IL-1β in hippocampus of rats was detected by Western blotting.Compared with the model group, the mechanical pain threshold of the foot was significantly improved in the small needle knife group (Small needle knife can improve the pathological state of myalgia comorbid depression caused by reserpine in rats. The mechanism may be related to the inhibition of NLRP3 inflammasome and IL-1β expression in central hippocampus.

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA.This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation.This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals.ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.

Background Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. Methods/design This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. Discussion This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. Trial registration ClinicalTrials.gov, NCT03274713. Registered on 20 November 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3138-x) contains supplementary material, which is available to authorized users.

Completed Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) 2013 Checklist: items addressed in this clinical trial protocol. (DOC 120 kb)

Members of the Data and Safety Monitoring Board. (DOC 17 kb)

Functional Dyspepsia Trial Cumulative Protocol Amendments. (DOC 14 kb)

Completed Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist. Items addressed in this clinical trial protocol. (DOCX 54 kb)

Background Tuberculosis, one of the deadliest infectious diseases worldwide, is difficult to diagnose. As long noncoding RNAs (lncRNAs) were demonstrated to be promising biomarkers, we aimed to identify lncRNAs in plasma as potential biomarkers for tuberculosis. Methods We analyzed a GEO dataset (GSE94907) to identify the differential lncRNAs in serum exosomes between active tuberculosis (ATB) patients and healthy controls. To search for promising candidates that can be used for tuberculosis diagnosis, we excluded low-abundance lncRNAs using a cutoff value of FPKM >5. Four lncRNAs were selected for validation using real-time quantitative PCR in 69 ATB patients and 69 healthy individuals. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of these lncRNAs for ATB. Results Integrated analysis of the GEO dataset and NONCODE database identified nine dysregulated lncRNAs in ATB patient serum exosomes. Compared with the heathy controls, NONHSAT101518.2, NONHSAT067134.2, NONHSAT148822.1 and NONHSAT078957.2 were significantly downregulated in ATB patient plasma. ROC curve analysis suggests that these four lncRNAs can discriminate ATB from healthy individuals with high specificity and sensitivity. Conclusion We identified four differentially expressed lncRNAs in ATB patient plasma that can be used as potential diagnostic biomarkers of ATB.

Patients with major depressive disorder (MDD) may experience a series of emotional and mental problems accompanied by characteristic clinical symptoms. Depressive patients often have emotional recognition disorders, but the reasons remain unclear. Though a great many functional abnormalities have been observed in the brains of depressed patients, such abnormalities are not often related to clinical symptoms. Currently in Traditional Chinese Medicine (TCM), syndrome differentiation for the MDD mainly consists of excess pattern (EP), and deficiency pattern (DP). EP and DP emphasize balance-regulation thought processes, and are widely used in diagnosis of diseases including depression, anxiety, insomnia, and other emotional disorders. We hope that syndrome differentiation in TCM can combine clinical symptoms and brain function more effectively. The present study investigated altered patterns and different association of brain activation in MDD patients with EP and DP during a facial emotion discrimination task with fMRI.A total of 45 patients (20 with EP and 25 with DP) and 18 normal controls participated in this study. Whole-brain functional scans were collected for each subject. Different patterns of brain activation and association during the facial emotion discrimination task were analyzed statistically.Comparing all the MDD patients with the normal controls, there were no significant differences for sad vs. neutral condition or for happy vs. neutral condition (corrected p 0.05). One-way ANCOVA showed significant differences in the left inferior frontal gyrus, the left insula, and the left caudate for sad vs. neutral condition across the DP, EP and NC groups (corrected p 0.05). The whole brain activation comparison for sad vs. neutral condition between the EP MDD subtype and the DP MDD subtype further verified these differences in the left insula and left inferior frontal gyrus, discovering that these regions showed increased activation in EP MDD subtype compared with the DP MDD subtype (corrected p 0.05). There were no significant differences in brain activation between each MDD subtype and the normal controls.Disparities in sad face processing exist between MDD patients with different TCM syndrome types, suggesting that TCM syndrome differentiation may provide a biological basis for negativity bias in depression, and may determine both symptom formation and social dysfunction.

Objective: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. Design: Pilot randomized controlled trial. Setting: Three teaching hospitals in China. Subjects: Patients with knee osteoarthritis (Kellgren grade II or III). Interventions: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. Main measures: The primary outcome was response rate—the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. Results: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. Conclusion: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

Background Postprandial distress syndrome (PDS) is referred to as meal-related functional dyspepsia (FD) and causes a reduced quality of life (QoL) for patients. Several randomized controlled trials (RCTs) have suggested that acupuncture is an effective treatment for FD, but few studies were particularly for PDS. This pilot study was designed to determine the feasibility and efficacy of acupuncture in patients with PDS characterized by postprandial fullness and early satiation according to the Rome III criteria. Methods This is a multi-center, two-arm, blinded (participants), pilot RCT. Forty-two participants who meet the inclusion criteria will be randomly assigned to the verum acupuncture group or minimal acupuncture group in a 1:1 ratio. Both treatments consist of 12 sessions of 20 min duration over four weeks (three sessions per week). The primary outcome measurement is the proportion of persons who improve as assessed using the global outcome by the overall treatment effect (OTE) at end-of-treatment (EOT) (four weeks after randomization). Global assessment at weeks 8 and 16 after randomization is one of the secondary outcomes. The other secondary outcomes including symptoms, disease-specific QoL, and depression and anxiety will be assessed at weeks 4, 8, and 16 after randomization. Discussion This pilot study will help determine the feasibility and efficacy of acupuncture in patients with PDS. Trial registration ISRCTN Registry, ISRCTN18135146. Registered on 7 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2285-9) contains supplementary material, which is available to authorized users.

The present study investigated the inhibitory effect of curcumin on human breast cancer MCF-7 cells and investigated the potential underlying molecular mechanisms. MCF-7 cells were cultured with curcumin at different concentrations and time points. The effects of curcumin treatment on breast cancer cell proliferation were studied using a MTT assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to assess the mRNA and protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) and inhibitor of NF-κB-α (IκBα). The proliferation of MCF-7 cells in the group treated with curcumin was markedly decreased compared with the control, with the greatest inhibitory effect at a concentration of 20 µM. The expression of Bax mRNA was increased and Bcl-2 mRNA expression was decreased compared with the control. Additionally, protein expression of NF-κB and IκB was increased. The data indicate that curcumin is able to inhibit breast cancer cell proliferation, possibly by regulating the NF-κB signaling pathway.

The aim of the present study was to evaluate the effects of programmed cell death 4 (PDCD4) on cell proliferation and apoptosis, and to elucidate the potential role of the Jun N-terminal kinase (JNK)/c-Jun pathway in human bladder cancer (BCa) cells. Mixed BCa cells were transfected with plasmids containing PDCD4 (PDCD4-pcDNA3). The sensitivity to cisplatin was analyzed using cell viability, invasion/migration, apoptosis, flow cytometry, wound healing and Transwell assays at different transfection times. Furthermore, epithelial-to-mesenchymal transition (EMT) markers were detected by immunofluorescence staining, and the protein expression of c-Jun, and phosphorylated Jun N-terminal kinase (p-JNK) and c-Jun (p-c-Jun, Ser-73) were also tested using western blotting. It was observed that BCa cell proliferation and invasion and tumor growth were significantly inhibited, whereas apoptosis was enhanced in PDCD4-transfected cells treated with cisplatin compared with controls. Moreover, the western blotting and immunofluorescence results demonstrated that PDCD4 upregulated the expression of epithelial cell markers, but downregulated the expression of mesenchymal cell markers. Furthermore, overexpression of PDCD4 reduced the protein levels of p-JNK and p-c-Jun. Taken together, the findings of the present study indicate that PDCD4 enhances the sensitivity of BCa cells to cisplatin, partially via regulation of the JNK/c-Jun pathway, and reverses EMT. In conclusion, the results of the present study suggested that PDCD4, a nuclear/cytoplasmic shuttling protein with multiple functions, plays an important role in the development and progression of human BCa.

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.* (PDF 192Â kb)

Trial registration: Acupuncture for postprandial distress syndrome (PDS). (PDF 23Â kb)

The aim of the current study was to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial infarction (AMI). AMI was induced in mini‑swine by ligating the left anterior descending coronary artery, and BMSCs (1x107) were injected via a sterile microinjection into the ischemic area. Six months postoperatively, electrocardiograph‑gated single photon emission computed tomography revealed that the myocardial filling defect was reduced and the left ventricular ejection fraction was improved in the BMSC group compared with the control group (P

Telomeres play an important role in the maintenance of genomic stability/integrity and are synthesized by the RNA-dependent polymerase telomerase. Progressive telomere shortening contributes to both in vitro and in vivo aging, and telomere length dynamics and telomerase expression profile in human tissues during extrauterine life have been well characterized. However, little is known about these changes in the early stage of gestation. In the present study, we determined telomere length and the expression of telomerase core units (telomerase reverse transcriptase, hTERT, and telomerase RNA component, hTERC) in human fetus tissues from 6 to 11 weeks of gestational age. A sharp decline in telomere length occurred between 6 and 7 weeks of gestational age, and a relatively stable or slightly shortened telomere length was thereafter maintained until birth. The inverse correlation between TERT or TERC expression and gestational age was steadily observed in these fetus tissues. Taken together, there is a rapid reduction followed by a slow erosion of telomere length in human fetus from gestational age 6-11 weeks, while hTERT and hTERC expression decreases steadily during this period. The present findings not only contribute to better understandings of telomere/telomerase biology in human embryonic development, but also are implicated in telomere/telomerase-related diseases or problems.

The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell (BMSC) transp1antation on lung and heart damage in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). The animals were randomly divided into 3 groups: control, PAH and BMSC implantation groups. Structural changes in the pulmonary vascular wall, such as the pulmonary artery lumen area (VA) and vascular area (TAA) were measured by hematoxylin and eosin (H&E) staining, and the hemodynamics were detected by echocardiography. Two weeks post-operation, our results demonstrated that sublingual vein injection of BMSCs significantly attenuated the pulmonary vascular structural and hemodynamic changes caused by pulmonary arterial hypertension. The mechanism may be executed via paracrine effects.

Introduction Pulmonary hypertension (PH) is a rapidly progressive and fatal disease. In recent years, despite drug treatment made significant progress, the prognosis of patients with advanced PH remains extremely poor. The authors implanted bone marrow-derived mesenchymal stem cells (BMSCs) intravenously into the PH model rats and observed the effect of MSCs on right ventricular (RV) impairments. Methods BMSCs were isolated, cultured from bone marrow of rats and stained with the cross-linkable membrane dye in vitro. One week after, a PH model was induced by subcutaneous injection of monocrotaline, the animals were randomly divided into 4 groups (n = 20 in each group): I, control; II, MSCs implantation; III, PH and IV, PH + MSCs implantation. Two weeks after MSCs implantation, the authors observed the MSC survival and transformation by immunofluorescence microscopy. On the other hand, RV hypertrophy and the elevation of systolic pressure were detected by echocardiography. Result Three weeks after monocrotaline injection, RV systolic pressure, mean right ventricular pressure and mean pulmonary arterial pressure were significantly elevated in group III than in group I and II ( P 0.05) but significantly lower in group IV than in group III ( P 0.05). These results showed that implantation of MSCs could improve RV impairments caused by experimental PH. Histochemical results confirmed that transplanted MSCs were still alive after 2 weeks and part of the cells could differentiate into pulmonary vascular endothelial cells. Conclusion Intravenous implantation of MSCs could significantly reduce or even reverse the progression of MCT-induced PH, improve cardiac function and hemodynamics.

A new type of tissue-engineered bone was constructed by seeding hVEGF165 gene-modified endothelial progenitor cells into the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds. These were implanted into the segmental femoral defects of rats to explore the promotion of angiogenesis and osteogenesis. The bone marrow of Sprague Dawley rats was cultured and proliferated, and the endothelial progenitor cells were transfected with Ad5–hVEGF165–EGFP. The gene-modified endothelial progenitor cells were seeded into the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds; the growth was observed by scanning electron microscope, and the proliferation was evaluated by methyl thiazolyl tetrazolium assay. In vivo, 80 Sprague Dawley rats were divided randomly into four groups; segmental femoral defects (5 mm) were made and allografted: group A with hVEGF165/endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), group B with mock endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), group C with endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), and group D with scaffolds only. Radiographic, histological, and microvessel density tests were performed to evaluate the angiogenic and osteogenic ability. Reverse transcription polymerase chain reaction and western blot results showed that the target gene was expressed by endothelial progenitor cells. The scanning electron microscope findings and methyl thiazolyl tetrazolium assay revealed that endothelial progenitor cells were attached and proliferated within the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds. The average radiographic score and capillary density were the highest in group A, and those in groups B and C were higher than that of group D. The histology showed osteogenesis and scaffold degradation in group A, with less in groups B and C and little in group D. The hVEGF165 gene-modified endothelial progenitor cells, which promoted angiogenesis and osteogenesis in bone-defected areas and the hVEGF165/endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid) composites, may have potential application in repair of segmental bone defects.

Objective -The objective of this study was to explore the relationship between increased plasma osteoprotegerin (OPG) levels and acute coronary syndrome (ACS). Methods - Plasma OPG levels from 85 subjects undergoing coronary artery angiography in three different groups, including ACS (n = 45), stable angia pectoris (SAP) (n = 20) and normal coronary artery (NCA) (n = 20), were detected by ELISA. Twenty-two ascending aorta specimens were surgically taken from 8 ACS, 7 SAP and 7 NCA patients, and OPG mRNA expression in the specimens was detected by RT-PCR. In addition, 10 coronary artery sections each were selected from autopsy archives for the presence of vulnerable atherosclerosis plaques (VP), stable plaques (SP) or no plaques (NP) and OPG protein expression in the sections was detected by immunohistochemistry. Results - Plasma OPG concentrations in the ACS group were significantly higher than those in the SAP or NCA group. The levels of plasma OPG in the 1-, 2- and 3-vessel disease subgroups of ACS were increasingly higher (P

Objective: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. Materials and Methods: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. Results: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies ( P

Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012 ), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.

The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA) . The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P

Introduction Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupuncture is a popular form of complementary medicine for musculoskeletal conditions, although the evidence is inconclusive. Our objective is to evaluate the efficacy of traditional Chinese acupuncture for pain relief and function improvement in mild-to-moderate knee osteoarthritis (TCAKOA) participants. Methods/analysis 42 patients will be recruited who have been diagnosed with mild-to-moderate KOA and randomly allocated in equal proportions to traditional Chinese acupuncture or minimal acupuncture. They will receive acupuncture for 24 sessions over 8 weeks. The primary end point is success rate, which will be calculated according to a change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain and function scores at 8 weeks. Secondary end points include pain and function measurement, global change, the quality of life and the use of non-steroidal anti-inflammatory drugs (Celebrex, Pfizer) at 8, 16 and 26 weeks. Ethics and dissemination Ethical approval of this study has been granted by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (permission number: 2016BL-010-02). Written informed consent will be obtained from all participants. Outcomes of the trial will be disseminated through peer-reviewed publications. Trial registration number ISRCTN14016893; Pre-results.

The aim of the present study was to investigate the association of human leukocyte antigen (HLA) gene polymorphism and clinical phenotypes of patients with mesangial proliferative glomerulonephritis (MsPGN). The genotyping of HLA-A, HLA-B and HLA-DRB1 alleles was detected in 1,536 consecutive MsPGN patients during the previous five years and 2,027 age- and gender-matched healthy individuals by using the polymerase chain reaction-sequence-specific primers method. The clinical and pathological data of the patients were collected and the genotype frequencies (GF) and odds ratio (OR) were analyzed. The allele frequencies of HLA-A*23, A*25, B*15, B*40, B*53 and DRB1*18 were significantly higher in MsPGN patients than in the controls (P

The aim of the present study was to determine the protection of allogeneic bone marrow mesenchymal stem cells (BMSCs) on an ischaemia/reperfusion (I/R)‑induced acute kidney injury (AKI) rat model and to investigate the underlying mechanisms. The BMSCs were isolated and cultured from adult Sprague‑Dawley (SD) rats and the I/R‑induced AKI model was established by bilateral clamping of renal pedicles for 60 min. Following successfully establishing the AKI model, 1x106 BMSCs were administered by intrarenal injection. All animals were randomly divided into four groups (n=10 in each): 1 (sham control), 2 (I/R), 3 (I/R+culture medium) and 4 (I/R+BMSCs). Serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured in all four groups at 24 and 72 h. Three days post‑surgery, the level of inflammatory factors, including interleukin‑6 (IL‑6), tumour necrosis factor‑α (TNF‑α) and vascular endothelial growth factor (VEGF) in the kidney was analysed by quantitative polymerase chain reaction. Three days following surgery, mRNA expression levels of IL‑6 and TNF‑α were significantly lower, however, the expression level of VEGF was significantly higher in group 4 compared with groups 2 and 3 (P

To investigate chronic hepatitis B (CHB) patients infected with the antiviral-resistant rtA181 mutation hepatitis B virus (HBV) who have been unresponsive to general therapy to determine the effects of individualized therapy.Fifty-four patients with confirmed rtA181 mutation and who experienced virological breakthrough during nucleus(t)ide analogue (NUC) treatment were enrolled in this prospective cohort study. Their serum levels of HBV DNA, hepatitis B surface antigen (HBsAg), and alanine transaminase (ALT) were tested. Each patient was genotyped by pyrosequencing for 10 mutation sites in the HBV P gene that have been previously correlated to NUC efficacy. Each patient's antiviral therapy and response history was analyzed in regard to their particular mutation pattern. The serological index was determined for carriers of the rtA181T/V mutation. The secondary individualized treatment included adding/switching to entecavir (ETV; group A) or adding telbivudine (LdT; group B) upon confirmation of drug resistance. Effect of individualized treatment was analyzed by T test and Mann-Whitney U test for continuous variables with normal or skewed distributions, respectively. Categorical variables were analyzed by the Chi-squared ( x² ) or Fisher's exact tests.The rtA181T mutation was found in 64.8% (35/54) of patients with rtA181 mutation HBV. The most frequent previously administered medications were adefovir dipivoxil (ADV) and lamivudine (LAM). Multi-site rtA181 mutations occurred more frequently in the patients with multi-NUCs history (57.6%) than in those with single NUCs history (28.6%) (x²=4.342, P less than 0.05). Serum HBV DNA level at virological breakthrough was lower than that at baseline of the first antiviral treatment (5.66+/-1.01 vs. 6.75+/-0.81 log10 copies/ml; t=-4.210, P less than 0.01). The serum HBsAg level was higher in carriers of the rtA181T mutation than in carriers of the rtA181V mutation (3.80+/-0.45 vs. 3.46+/-0.60 log10 IU/ml; t=2.109, P less than 0.05). In patients with serum HBV DNA more than or equal to 6 log10 copies/ml at viral breakthrough, 100% (8/8) of patients in the secondary treatment group A and 75% (3/4) patients in the secondary treatment group B exhibited virological response at week 24 after intervention. Undetectable HBV DNA was achieved in three patients of group A and one patient of group B. In patients with serum HBV DNA less than 6 log10 copies/ml at viral breakthrough, 100% (14/14) of patients in group A and 71.4% (5/7) of patients in group B exhibited biological response at week 24 after intervention. The serum HBV DNA level decreased to undetectable levels in 12 patients of group A and four patients of group B.The rtA181 mutation pattern correlates with previous antiviral therapy response. In addition, multi-site rtA181 mutations occur more frequently in patients with a history of multi-NUCs therapy. Adding or switching rtA181 carriers to ETV produces a more robust virological suppression than adding LdT.

Urban rail transit systems constructed along demand-oriented corridors will supply the main travel mode to most commuters in their commute trip-chains. However, in residential areas, a long walking distance from home to stop makes travelers take a private mode. To date, the conventional approach has limitations when applied to residential areas, as the radial and tidal characteristics of trips start from rail stations. For the purpose of urban rail transit feeder bus system planning, the positioning and selection of feeder stops are critical to the efficiency of subsequent route arrangement, and a set of stops that mainly affects the average value of walking distance must be selected in the first step. This paper discusses a double circulation method developed to get the required stop-set using an optimal model, given the threshold value of Average Walking Distance (AWD). The subsets selected during the process should make each planning zone have at least one stop that serves commuters, and two questions will be answered: (1) How many required stops should be selected to satisfy the threshold value of AWD? and (2) Which alternative stops can be chosen in the required stop-set? Thus, the outcomes can assure both larger site coverage and less travel time.

Given the rapid evolution of urban morphology and the expansion of urban scale, characteristics of residential daily activities become diverse and change constantly. To do more research on residential activity and travel behavior, a better understanding of family joint tour/activity generation, especially the driving-included-mode joint tour generation should be developed, and this is also essential to the policymaking of transportation. Using descriptive statistics, this paper investigates empirical characteristics of family-joint tours’ frequency and patterns. The effect of several attributes, including individual and household socio-demographics, on the household members’ choice behavior is analyzed by cross tab method. Also, a binary logistic regression model is presented to estimate the likelihood that a family generates joint-tours. Using the travel data collected in a suburban district of Beijing, the empirical results show that family size, age distribution, possession of mobile car, and profession structure affect both the generation of family joint tour and the joint-tour type, such as mandatory tour, maintenance tour, and discretionary tour. Future research should focus on the analysis and modeling of travel mode choice of joint-tours’ participants involving more attributes than those listed above.

By means of the detection of the numbers of CD34(+) cells and eosinophils (EOS), and the level of IL-5 in peripheral blood from normal controls and patients with allergic rhinitis pre- or post-treatment, the role of EOS-stem cells paths for treatment effect in allergic rhinitis (AR) was studied so as to find the convenient and quick indicators which could be used to evaluate the clinical therapeutic effect and adjust the methods of the hormone therapy.There were 2 groups. (1) experimental group: 44 patients, including 24 males and 20 females with a age range of 7 to 68 years old. The patients received the treatment of fluticasone spurt for four weeks. (2) CONTROL GROUP: 30 cases, from normal health examination. The EOS numbers, CD4(+) cell numbers and the IL-5 level were examined in control group as well as before and after therapy in experimental group.The IL-5 level and CD numbers before therapy in experimental group were (88.25 +/- 33.47) ng/L, (9.24 +/- 2.15)/10(5), significantly higher than that after therapy and experimental group which were (44.34 +/- 16.32) ng/L, (6.31 +/- 1.83)/10(5) and (31.24 +/- 8.43) ng/L, (3.47 +/- 1.32)/10(5) respectively. The IL-5 level was positively correlated with the CD34(+) number pre-and post treatment in experimental group (r = 0.64, P0.01; (r = 0.61, P0.01). The EOS number was positively correlated with the level of IL-5 (r = 0.64, P0.01).IL-5 and CD34(+) cells can be regarded as indicators to evaluate the therapeutic effect. The EOS, CD34(+) cells and the level of IL-5 in the peripheral blood are correlated with the pathogenesis of AR, suggesting that there is a related path between the local nasal tissue of AR patients and the marrow.

To investigate the association of thrombin activatable fibrinolysis inhibitor (TAFI) and its encoding gene CPB2 polymorphism in patients with coronary heart disease (CHD).The CPB2 gene polymorphisms of Thr325Ile and Thr147Ala were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients of acute myocardial infarction (n=100), acute angina pectoris (n=110) and a control group (n=190). The antigen (Ag) and activity (Act) of the TAFI were determined by sandwich enzyme link immunosorbent assay specific for human TAFI and chromogenic assay for activated human TAFI in plasma, respectively. The relationship between Thr325Ile and Thr147Ala gene polymorphism and TAFI Ag and Act were also analyzed.Plasma TAFI Act and TAFI Ag in acute myocardial infarction group and acute angina pectoris group (CHD patients group) were both significantly higher than those of the control group. The genotype frequencies of Thr325Ile (C1040T) and Thr147Ala (G505A) were as the following: C1040C (Thr325Thr) 67 (31.9%) and 64 (33.6%); C1040T (Thr325Ile) 109 (51.9%) and 92 (48.4%); T1040T (Ile325Ile) 34 (16.2%) and 34(17.8%); G505G (Ala147 Ala) 75 (35.7%) and 72 (37.8%); G505A(Thr147Ala) 112 (53.3%) and 96 (50.5%); A505A(Thr147Thr)23 (10.9%) and 22 (11.7%), in the CHD patients and control respectively. Chi-square analysis showed no significant difference in the Thr325Ile and Thr147Ala polymorphism distributions (P0.05). In addition, at the 325 position, the TAFI antigen of the Thr325Thr was higher than that of the other genotypes (Thr325Ile and Ile325Ile, P0.05). There was no statistical significance between the TAFI antigen of the Thr325Ile and Ile325Ile (P0.05). No significant correlation was found between the TAFI Act and the Thr325Ile polymorphism. At the position 147, significant correlation between the polymorphism of the Thr147Ala and TAFI Ag and Act was not found.TAFI plays an important role in anti-fibrinolysis. It might be a risk factor for acute myocardial infarction and acute angina pectoris. The Thr325Ile polymorphism had obvious effect on TAFI antigen levels, but the Thr325Ile and Thr147Ala polymorphism had no association with coronary heart disease.

The purpose of this study was to observe the association between chronic glomerulonephritis (CGN) and human leukocyte antigen (HLA) on DNA level in order to identify susceptible and protective genes and to further explain the possible pathogenesis of CGN.1073 renal transplantation patients with Han ethnicity were included in this study. All patients were recruited from three provincial Hospitals during the past ten years. The control group contained 7418 healthy Han volunteer donors from Shandong Hematopoietic Stem Cell Data Bank of China. We collected data about the polymorphism of HLA-I , II and DRB1. Gene frequency (GF), relative risk (RR) and correlation test were analyzed using statistical software. Some patients carrying the susceptible genes were followed up for 1,3 and 5 years, and compared their survival rate respectively.The frequency of HLA-A23, A25,B15, B40, B53 and DRB1 * 18 alleles increased significantly in CGN patients than in controls, showing that they might be the suspicious susceptibility genes of CGN. After the follow-up periods, the prognosis of patients with the susceptible genes was worse than the controls. The frequency of haplotypes of A23-B44-DRB1 * 18, A25-B15-DRB1 * 07, A3-B70-DRB1 * 11, A68-B13-DRB1 * 04, A11-B10-DRB1 * 12 increased significantly in CGN patients than in controls. There were 8 lower frequencies alleles (including A20, A22, A35, A36, A38, B21, B73 and B78) in CGN patients that were not found in the control group. The frequencies of the HLA-A32, A33, B50, B58, B60, B71, DRB1 * 16 alleles decreased significantly in CGN patients than in controls, showing that they might be the protective genes of CGN.Our data showed that there might be corresponding susceptibility and protective genes of CGN in Han population, in Shandong. There was significant association between the five common haplotype and CGN in Shandong population. However, the prognosis of the patients with the susceptibility genes was worse than the controls.

To investigate the factors affecting the survival and to predict the survival time of glioma.Graph method was applied to fit the type of probability distribution of patients' postoperative survival time. As one suitable model, Weibull regression model tested by residual analysis was used to identify prognostic factors for postoperative survival and to predict patients' post-operative survival time.In multivariate analysis of Weibull regression model, following characteristics showed significant influence on postoperative survival time including: sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy. According to predictive value, patients were clustered into three groups. The survival probability of one year for the first group was less than 50% and that of five years for the second group about 50%, for the third group around 80%.Sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy were important risk factors and Weibull regression model might help to predict patients' postoperative survival time.