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Background Pulmonary arterial venous malformation (PAVM) is an abnormal vascular malformation between pulmonary arteries and veins characterized by varying degrees of right-to-left shunts (RLS). Cryptogenic stroke (CS) due to paradoxical embolism (PE) caused by PAVM is relatively rare in the clinic. Case Presentation We report the case of a 54-year-old right-handed woman who presented with sudden-onset left-sided limb weakness for 2 h. A physical examination revealed normal vital signs but weakness in her left upper and lower limbs, graded as 1/5 using the Medical Research Council scale. Her National Institutes of Health Stroke Scale (NIHSS) score was 8, and her modified Rankin scale (mRS) was 4. Brain diffusion-weighted imaging showed acute infarction in the right basal ganglia and the radiation crown but brain magnetic resonance angiography found no obvious abnormality. A transcranial Doppler ultrasound with bubble study (TCD-b) found the rain curtain sign of microbubbles in the left middle cerebral artery, reflecting significant RLS. Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) were conducted to distinguish between intra- and extracardiac shunts. A pulmonary computerized tomography angiogram (CTA) demonstrated a PAVM. We considered the patient had CS due to PE caused by PAVM. Thrombolytic therapy within the time window was performed. Then, transcatheter device occlusion of the arteriovenous fistula was successfully undertaken, and the patient carried on with rehabilitation training. At a 15-month follow-up, there were no catheter-related complications or recurrent stroke, and her NIHSS and mRS scores were both 0. Conclusions PAVM is an important risk factor for PE and CS and should not be ignored as a possible etiology in stroke patients without any other risk factors. CTA of the pulmonary artery is the recommended gold standard for diagnosing and locating a PAVM. Thrombolytic therapy within the time window combined with transcatheter device occlusion of arteriovenous malformation and rehabilitation training may benefit the recovery of patients with CS caused by PE resulting from PAVM. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00275-y.

Purpose Recent studies have confirmed the important role of chronic inflammation in keloid; however, mechanism of chronic inflammation in keloid tissue remains largely unclear, especially the dynamic of infiltrated inflammatory cells. Patients and Methods Tissue and blood samples collected from keloid patients and healthy subjects were studied by immunohistochemistry and flow cytometry. Fibroblasts from keloid scars and normal skin were isolated by enzymic digestion. Results We found that CXCL12 expression was elevated which was correlated with decreased dipeptidyl peptidase-4 (DPP4) expression in keloid scars relative to mature scars. In vitro studies suggested that autocrine transforming growth factor β1 (TGF-β1) in keloid-derived fibroblasts negatively regulated DPP4 expression which inhibited the reduction of extracellular CXCL12 levels by DPP4. Furthermore, immunofluorescence showed that most fibroblasts in keloid scars were DPP4lowTGFβ1high compared with DPP4highTGFβ1low fibroblasts in normal skin tissue, which facilitated extracellular CXCL12 accumulation in fibroblasts in keloid scars. Furthermore, we found that most circulating leukocytes in peripheral blood and tissue-infiltrated inflammatory cells in keloid scars expressed the C-X-C motif chemokine receptor 4 (CXCR4) instead of CXCR7, indicating that the chemotaxis driven by CXCL12 is likely to be mediated mainly by CXCR4. Conclusion Our study indicated that the TGF-β/DPP4/CXCL12 axis may contribute to chronic inflammation in keloid scars by recruiting inflammatory cells through the CXCR4 receptor., Graphical Abstract

Background To compare the efficacy and safety of PSORI-CM01 granules with Yinxieling tablets in patients with chronic plaque psoriasis (CPP), we plan to conduct a multicentre, randomized, double-blinded, double-dummy, controlled trial. This pilot study was conducted to determine the feasibility and the potential of the protocol for the full-scale randomized controlled trial (RCT). Methods This pilot study was conducted in three centers, and compared PSORI-CM01 granules with Yinxieling tablets in patients with CPP during a 12-week treatment and 3-month follow-up period. The primary efficacy endpoint was the decrease of the psoriasis area severity index (PASI) at week 12. The secondary outcome measures included reduction rates of PASI, pruritus scores on the Visual Analogue Scale (VAS), body surface area (BSA), and the Dermatology Life Quality Index (DLQI). Safety was assessed via the incidence of adverse events (AEs) in each treatment group. Results A total of 211 patients were screened, and 63 subjects who met the inclusion criteria were randomised to PSORI-CM01 granule group (N=31) or Yinxieling tablets group (N=32) while 39 subjects finished the study. The primary outcome measure showed a mean decrease of PASI of 2.03 in the PSORICM01 group compared to 0.89 in the Yinxieling group at week 12. Except for the VAS score (t=-2.261, P=0.027), the secondary outcomes showed no significant improvement from baseline in both groups at week 12. No safety or tolerability concerns related to the drugs were observed in either group. Conclusions This pilot study showed that the RCT is feasible for randomization, patient recruitment, and assessment. Major strategies are necessary to reduce the patient dropout rate before conducting the full RCT. In this pilot study, the PSORI-CM01 granule exhibited greater potential for development compared to its original formula (Yinxieling tablets) for the treatment of CPP.

Background: Aphasia is one of the common complications of stroke, and it considerably influences the quality of life of patients. Acupuncture, a therapy used in traditional Chinese medicine for aphasia after stroke, has potential therapeutic effects. We aimed to investigate the therapeutic effect of acupuncture on individuals with poststroke aphasia. Methods: Randomized controlled trials (RCTs) on acupuncture for poststroke aphasia (either alone or combined with other therapies) were included and compared. We conducted a systematic review and meta-analysis by searching databases, such as MEDLINE, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP, and Wanfang, from inception to July 15, 2019. No language restrictions were applied in this study. Results: Fourteen trials involving 936 participants had poor reporting and methodological quality. Our meta-analysis showed that compared to the speech and language therapy (SLT) group, acupuncture combined with SLT could improve the rate of Boston Diagnostic Aphasia Examination (BDAE) (OR: 0.15, 95% confidence interval [CI]: 0.04–0.25, p = 0.005), scores of Aphasia Battery of Chinese (ABC) which includes repeating ability (SMD: 1.46, 95% CI: 1.24–1.69, p < 0.00001), reading ability (SMD: 1.57, 95% CI: 1.25–1.90, p < 0.00001), writing ability (SMD: 1.52, 95% CI: 1.19–1.86, p < 0.00001), naming ability (SMD: 1.40, 95% CI: 1.04–1.76, p < 0.00001), and listening comprehension ability (SMD: 0.57, 95% CI: 0.22–0.92, p = 0.001). All RCTs were considered at high risk of biased assessment. Conclusions: Acupuncture (either alone or combined with SLT) may be effective for poststroke aphasia. In the future, rigorous clinical trials with an accurate method design and high reporting quality are required to validate our results.

Background. Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain. Aims. To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor. Methods. We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger’s test. Results. Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias. Conclusions. Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.

Background Although nonpharmacological interventions (NPI) for irritable bowel syndrome (IBS) have been applied clinically, their relative efficacy and safety are poorly understood. Aim To compare and rank different NPI in the treatment of IBS. Methods Five electronic databases were searched from their inception to January 12, 2020. Data of included publications were analyzed using network meta-analysis (NMA). Quality of endpoints were assessed by tools of the Cochrane Handbook and the GRADEpro software. Pooled relative risk or standardized mean difference with their corresponding 95% confidence intervals were used for statistical analysis. Surface under the cumulative ranking curve (SUCRA) probability value was conducted to rank the examined interventions. Sensitivity analysis was performed to verify the robustness of results and test the source of heterogeneity. Results Forty randomized controlled trials with 4196 participants were included in this NMA. Compared with routine pharmacotherapies and placebo, acupuncture and cognitive behavioral therapy (CBT) had better efficacy in relieving IBS symptoms. Based on the SUCRA values, acupuncture ranked first in improving overall clinical efficacy and avoiding adverse effects. CBT ranked first in lowering the scores of IBS symptom severity scale, self-rating anxiety scale and self-rating depression scale. Conclusion This study confirmed the efficacy and safety of NPI for improving IBS symptoms, which to some extent recommended several interventions for clinical practice.

Purpose Menopause modifies women’s lipid profiles. However, the fact that it is still unclear whether high-density lipoprotein-cholesterol (HDL-C) levels decrease in postmenopausal women necessitated a systematic review and meta-analysis. Methods The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched and 498 articles published between 1987 and 2020 were retrieved. Studies reporting HDL-C, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels in both postmenopausal and premenopausal populations were included. The quality of the included studies was assessed using the Cross-Sectional/Prevalence Study Quality tool. The standard mean difference (SMD) and 95% confidence interval (CI) were estimated using random effects models. A meta-regression analysis and subgroup analysis were performed to identify potential modifiers. Egger’s test and funnel plots were constructed to evaluate publication biases. Results Lipid profiles from 18 cross-sectional studies and two cohort studies including 5652 postmenopausal women and 7825 premenopausal women were meta-analyzed. HDL-C levels were not significantly different between the postmenopausal and premenopausal women (SMD = − 0.053, 95% CI − 0.171 to 0.066, p = 0.383) and were not affected by country, publication year, study quality in the meta-regression analysis, or significant publication bias. Higher LDL-C, TC, and TG levels were detected in postmenopausal women than in premenopausal controls. Conclusion Unlike increased LDL-C, TC, and TG levels, HDL-C levels in pre- and postmenopausal women were not different in this first meta-analysis of lipid profiles in premenopausal and postmenopausal women. Prospective studies with large populations examining HDL-C levels and functions in women with different menopausal statuses are essential in the future. Trial registration number None.

The role of histone deacetylases (HDACs) in lung cancer has been extensively studied. Inhibition of HDAC activities have been used as a new cancer treatment strategy. To date, many HDAC inhibitors have been shown to induce apoptosis and inhibit tumorigenesis. Chidamide (CS055) is a new member of HDAC inhibitors. In China, Chidamide has been approved for the treatment of relapsed or refractory peripheral T-cell lymphoma. However, the efficacy of Chidamide in non-small cell lung cancer remains unclear. In this study, we used lung cancer primary cells and investigated the effects of Chidamide combined with paclitaxel on lung cancer. We found that Chidamide combined with paclitaxel effectively inhibited the expression and activity of HDAC in primary lung cancer cells, induced their apoptosis and blocked cell cycle. Chidamide combined with paclitaxel may therefore provide a new promising therapeutic treatment for lung cancer.

Background Diabetes mellitus is associated with risk of sudden sensorineural hearing loss (SSNHL). Systemic and intratympanic corticosteroids are the two primary treatments for SSNHL in patients with diabetes mellitus. The benefit of intratympanic compared to systemic treatment is the reduced systemic steroid exposure and associated systemic adverse effects. Intratympanic corticosteroid administration may have potential benefits over standard systemic therapies. Methods/design The proposed study is a prospective, randomized superiority trial. A total of 96 patients (48 in each group) will be randomized into the experimental or control group. Patients in the experimental group will receive four 1-mL doses of 40 mg/mL of methylprednisolone over a 1-week period, with a dose administered every 2 days via tympanic membrane injection into the middle ear. The control group will be administered intravenous methylprednisolone (1 mg/kg/day, maximal dose 60 mg/day) for 5 days. The primary outcome for this study is the change in hearing threshold from the first audiogram to the 30-day follow-up audiogram. Secondary outcome measures will include pure-tone average (PTA) at 90-day follow up, visual analog tinnitus scale, visual analog vertigo scale, visual analog aural fullness scale, fasting blood glucose and 2-h postprandial blood glucose during treatment, and the change in glycosylated hemoglobin (HbA1C) levels. Vital signs and otological physical examination will be performed at each follow-up visit. Discussion The efficacy and safety of intratympanic methylprednisolone compared to intravenous methylprednisolone will be investigated in patients with diabetes mellitus and SSNHL. This trial may provide strong evidence for the efficacy and safety of intratympanic corticosteroid treatment and important clinical information for the treatment of patients with diabetes mellitus and SSNHL. Trial registration ChiCTR, ChiCTR1800015954. Registered on 2 May 2018, Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=25326.

Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.

Background Opposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia. Methods This will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention. Discussion The aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia. Trial registration Chinese Clinical Trial Registry ChiCTR1900028138. Registered on 13 December 2019.

Background: Post-stroke shoulder-hand syndrome (SHS) is a common complication after stroke. To date, there is still a lack of consistently effective and good patient compliance methods for SHS. Methods: Fifty patients with SHS were included in this study. Patients in the control group received rehabilitation training (RT) for 2 weeks; each session was 30 min, 1 time per day, and 5 times per week. Patients in the observation group were additionally given Bo's abdominal acupuncture (BAA) with the same frequency and duration. The primary outcome was the change value in the VAS score from baseline to 2 weeks. The secondary outcomes measured were motor function of the upper limb, shoulder range of motion, ADL, and swelling volume. Results: Compared with baseline values, the mean VAS score at 2 weeks was reduced by 3.68 in the observation group and by 1.92 in the control group, with a difference between the two groups of 1.84 (P < 0.001); the mean MBI score at 2 weeks increased by 10.44 in the observation group and by 4.79 in the control group, with a difference between the two groups of 5.84 (P = 0.032); the mean swelling volume at 2 weeks decreased by 9.64 in the observation group and by 3.29 in the control group, with a difference between the two groups of 6.48 (P < 0.001). BAA-related adverse events were not found during the study. Conclusions: BAA combined with RT is superior to RT alone in improving shoulder pain, swelling, and ADL in post-stroke SHS patients. Trial Registration: ChiCTR2100045464 (www.chictr.org.cn).

Germline copy number variant (gCNV) has been studied as a genetic determinant for prognosis of several types of cancer, but little is known about how it affects non-small cell lung cancer (NSCLC) prognosis. We aimed to develop a prognostic nomogram for NSCLC based on gCNVs. Promising gCNVs that are associated with overall survival (OS) of NSCLC were sorted by analyzing the TCGA data and were validated in a small Chinese population. Then the successfully verified gCNVs were determined in a training cohort (n = 570) to develop a prognostic nomogram, and in a validation cohort (n = 465) to validate the nomogram. Thirty-five OS-related gCNVs were sorted and were reduced to 15 predictors by the Lasso regression analysis. Of them, only CNVR395.1 and CNVR2239.1 were confirmed to be associated with OS of NSCLC in the Chinese population. High polygenic risk score (PRS), which was calculated by the hazard effects of CNVR395.1 and CNVR2239.1, exerted a significantly higher death rate in the training cohort (HR = 1.41, 95%CI: 1.16–1.74) and validation cohort (HR = 1.42, 95%CI: 1.13–1.77) than low PRS. The nomogram incorporating PRS and surrounding factors, achieved admissible concordance indexes of 0.678 (95%CI: 0.664–0.693) and 0.686 (95%CI: 0.670–0.702) in predicting OS in the training and validation cohorts, respectively, and had well-fitted calibration curves. Moreover, an interaction between PRS and asbestos exposure was observed on affecting OS (Pinteraction = 0.042). Our analysis developed a nomogram that achieved an admissible prediction of NSCLC survival, which would be beneficial to the personalized intervention of NSCLC.

Background: Treatment of melasma is challenging because its pathogenesis is unclear and it is prone to recurrence. We performed a meta-analysis to evaluate the efficacy and safety of laser and laser compound therapy for melasma.Methods: We searched the Cochrane, Embase, and Medline databases for all relevant studies published from inception to July 2018. All randomized controlled trials of melasma describing treatment with lasers or laser compound therapy were included.Results: A total of 346 patients were enrolled in nine RCT studies. Laser therapy and laser compound therapy had better PGA (MD: 1.96 (95% CI: 0.17, 3.75); I2 = 0%) and mMASI scores (MD: -1.57 (95% CI: -3.08, -0.05); I2 = 19%) than drug and laser therapy, respectively. Four studies were assessed to be of low risk of bias. Subgroup analysis was consistent with the results of the meta-analysis, reflecting the reliability of our results.Linking evidence to action: The results of this meta-analysis provide evidence that laser and laser compound therapy can improve the area and severity of melasma. Further high-quality clinical studies should be carried out in the future to confirm this conclusion. Abbreviations: MASI: Melasma Area and Severity Index; mMASI: modified Melasma Area and Severity Index; PGA: patient global assessment; MI: melasma index.

Background Postherpetic neuralgia (PHN) refers to pain which remains after the healing of rashes from herpes zoster. Previous literatures have shown that acupuncture has potential benefits for PHN, but evidence remains lacking. Thus, we have performed a systematic review and meta-analysis to identify the effectiveness of acupuncture in the treatment of PHN. Methods Six databases were searched for randomized controlled trials (RCTs) to assess the effects of acupuncture on PHN. After selecting the studies, extracting the data, and assessing study quality, meta-analysis was performed on several of the studies with RevMan 5.3. The GRADE (Grading of Recommendations Assessment Development and Evaluation) system was used to assess the overall quality of the evidence. Results Acupuncture helps relieve pain intensity (standardized mean difference [SMD]: -1.78, 95% confidence interval [CI]: -2.36 to -1.21). For other intervention types, electroacupuncture (SMD: -1.28, 95% CI: -2.51 to -0.05), fire needle (SMD: -2.23, 95% CI: -2.62 to -1.84), bloodletting and cupping (SMD: -2.46, 95% CI: -2.95 to -1.97) have better effects on pain intensity relief. To date, no study has reported on the onset of pain relief time. The Hamilton Anxiety Scale score (SMD: -18.94, 95% CI: -37.37 to -0.52) was lower for the acupuncture group than for the control group. It was also found that acupuncture can improve quality of life (QOL) (SMD: 3.78, 95% CI: 2.50 to 5.06). The quality of evidence for acupuncture for PHN pain intensity was moderate according to the GRADE system. Conclusion Acupuncture may reduce pain intensity, relieve anxiety and improve quality of life in patients with PHN. Further randomized trials with larger sample sizes and of higher methodological quality are needed to confirm these results.

Background This study evaluates the reporting quality of randomized controlled trials (RCTs) on acupuncture use for the treatment of postherpetic neuralgia and explores related factors. Methods The following six databases PubMed, Embase, Cochrane Library, VIP, CNKI, and SinoMed, were systematically searched from their inception to December 2018. RCTs using acupuncture as an intervention for postherpetic neuralgia were selected and incorporated in this study. The reporting quality was assessed based on the CONSORT statement and the STRICTA guidelines. Regression analyses were also conducted on pre-specified study characteristics searching for factors associated with reporting quality. Results A total of 137 RCTs were included in this study. The CONSORT based median OQS was 12 (minimum 3, maximum 29). Of the items comprised in the statement, ten were sufficiently reported (reported in over 70% of trials). The remaining fifty-five items were poorly reported (reported by fewer than 5% of trials). The STRICTA based median OQS was 9 (minimum 2, maximum 15). The results showed that eight of the comprised items were well reported (reported in over 70% of trials), and only three were incompletely reported (reported in fewer than 20% of trials). Based on the CONSORT statement related analysis, a post-2010 publication (β coefficient 2.394, 95% confidence interval [CI] 1.168–3.620) and funding (β coefficient 4.456, 95% CI: 3.009–5.903) represented independent and significant predictors of a high overall reporting quality. However, only a funding source (β coefficient 1.305, 95% CI 0.219–2.391) was associated with an increased OQS based on STRICTA analysis. Conclusion The findings indicated that RCTs on acupuncture for PHN generally had a sub-optimal reporting quality, a situation that improved for those published after 2010 or with funding sources. Therefore, rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies.

A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-sequencing analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve values as 0.662 [95% confidence interval (CI) = 0.614–0.711] and 0.624 (95% CI = 0.522–0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio = 1.48, 95% CI = 1.05–2.08). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE led to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC.

Background: A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. Methods: We employed RNA-Seq analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined diagnostic and prognostic value of a promising lncRNA in four datasets. Findings: We identified several dysregulated lncRNAs and found that those up-regulated lncRNAs in NSCLC were mostly tumor-suppressive, while down-regulated lncRNAs were most oncogenic. The most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, and its expression was also correlated with prognosis. Clinic treatment decreased serum exosomal linc01125 in NSCLC patients. Linc01125 functions to inhibit cancer growth and metastasis. Acting as a competing endogenous RNA, linc01125 sponges several microRNAs (miRs) to regulate gene expression such as TNFAIP3 via binding miR-19b-3p. Notably, oncogenic transformation of 16HBE leads to decreased linc01125 in cells but increased linc01125 in cells-derived exosomes. Linc01125 expression in exosomes was also highly correlated with that in tumor-associated exosomes. Linc01125 could be loaded into exosomes in vitro and in vivo, which did not dampen tumor development. Interpretation: Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting prognosis of NSCLC. Funding: National Natural Scientific Foundation of China, Guangzhou Science and Technology Program Pearl River Nova projects, The National Key Research and Development Program of China, Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the institutional review board of Guangzhou Medical University.

Background/aims Traditional Herbal Medicines (THM) have been being used for gastroesophageal reflux disease (GERD) for a long time, but clinical evidence is still scarce. We evaluated different THM prescriptions for GERD in adults. Methods Data added to nine online databases from their inception to November 30, 2019, were systematically searched. All relevant randomized controlled trials (RCTs) were included and were combined with Bayesian network analysis. The Cochrane Collaboration's risk of bias tool and GRADE profiler version 3.6 were respectively employed to evaluate the quality of evidence of outcomes. Results Seventeen publications involving 1441 participants were retrieved. The results of our analysis suggested that Jianpi therapy+proton pump inhibitors (PPIs) and Ligan Hewei therapy respectively ranked first in overall clinical efficacy and efficacy under gastroscope; Ligan Hewei therapy+PPIs was the optimum intervention in the improvement of acid regurgitation and heartburn. Conclusion This research indicates that Ligan Hewei therapy and Jianpi therapy, or these therapies separately combined with PPIs, should be recommended as appropriate complementary and alternative treatments based on the specific characteristics of GERD. However, additional well-designed RCTs with high methodological quality are still needed for future research.

Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.

Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics. ispartof: BLOOD ADVANCES vol:4 issue:7 pages:1539-1553 ispartof: location:United States status: published

Aim of the Study. Hot flashes impair the quality of life of breast cancer survivors. Nonhormonal management is an important consideration. The objective of this network meta-analysis (NMA) is to compare the therapeutic efficacy and safety of nonhormonal hot flash treatments for breast cancer survivors. Materials and Methods. We conducted a systematic literature search in PubMed, Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP up to May 2018. Randomized controlled trials (RCTs) reporting nonhormonal hot flash treatments for breast cancer survivors were included. Primary outcome measurements were hot flash frequency and hot flash score of posttreatment. The methodological quality of each study was assessed with Cochrane’s risk of bias tool. Results. 16 RCTs involving 2,349 participants were included. The nonhormonal therapies used in the included studies were classified as follows: lifestyle changes, mind-body techniques, dietary/supplements, SSRIs/SNRIs, other medications, and other therapies. Pairwise meta-analysis showed that the general effect of nonhormonal management was statistically more effective than no treatment/placebo/sham in reducing hot flash frequency (SMD = −0.60, 95% CI [−1.13, −0.06]; P=0.03)) and hot flash score (SMD = −0.38, 95% CI [−0.68, −0.08]). For hot flash frequency, results from the NMA showed that there was no statistically significant difference between any two of the nonhormonal treatments. Another NMA result indicated that acupuncture (other therapies) was 16.05 points more effective in reducing hot flash scores than no treatment/waitlist (SMD = −16.05, 95% CI [−30.2, −1.99]). These results were statistically significant. Acupuncture was also ranked the optimal nonhormonal therapy for both hot flash frequency and hot flash score. The safety analysis showed that there were few related adverse events during acupuncture and that drug related adverse reactions could have also occurred in studies using drug interventions Conclusions. This network meta-analysis comparing nonhormonal treatments suggested that acupuncture might be more effective in improving hot flashes for breast cancer survivors. A pronounced placebo response was found during hot flash treatments. The evidence of safety for nonhormonal therapies was also insufficient. Therefore, at present, we cannot make confirmative recommendations of nonhormonal hot flash management for breast cancer survivors. This study is registered with PROSPERO (CRD42018082008).

Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China. Inclusion criteria: Serum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR ≥ 105, 60–104 (reference), 30–59, and 2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30–59 ml/min/1.73 m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02–1.38, P = 0.022) and eGFR 2 (AOR: 1.41, 95% CI:1.12–1.78, P = 0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.

ObjectiveClinical guidelines are designed to optimise patient care and provide efficient approaches for therapy. Epilepsy is a chronic brain disorder that continues to experience a considerable treatment gap due to non-standard recommendations. We assessed the reporting quality of clinical practice guidelines on epilepsy over the past 5 years to generate a reporting specification for this study.SettingSeven databases were searched in May 2018 focusing on the period from 2013 to 2018. These included Medline, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang and Chinese Science and Technology Journal Database (VIP). Reporting quality of epilepsy guidelines was assessed by two independent authors using the Reporting Items for practice Guidelines in HealThcare (RIGHT) approach. Spearman’s correlation was used to assess inter-rater reliability.ParticipantsParticipants with epilepsy or seizure, not limited by age, gender, course of disease or cause of epilepsy, were included.InterventionsThere were no limitations with regard to intervention.Primary and secondary outcome measuresThe outcome was the ability of the RIGHT tool to measure reporting quality.ResultsTwelve relevant guidelines were included in this study. The reporting quality was not high in any of the included guidelines. The highest reporting quality included a ‘yes’ proportion of 77.1%, whereas the worst included a corresponding proportion of 37.1%. Overall evaluation results showed that 16.7% of the included guidelines were of high quality, 75% were of medium quality and 8.3% were of low quality. The correlation between the two estimators was credible (ρ>0.7).ConclusionsAppraisal of these guidelines using the RIGHT tool revealed that the quality of reporting varied among guidelines. Items that exhibited low quality in most included guidelines were healthcare questions, rationale/explanation for recommendations, quality assurance, funding source(s) and role(s) of the funder, and limitations of the guideline. Thus, these aspects should receive greater attention in future guideline reporting.

Background Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. Methods We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini–Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. Results We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. Conclusion Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice. Electronic supplementary material The online version of this article (10.1186/s12877-018-0864-6) contains supplementary material, which is available to authorized users.

Introduction: Patients with amnesic mild cognitive impairment (aMCI) are more likely to develop Alzheimer disease than corresponding age normal population. Because Alzheimer disease is irreversible, early intervention for aMCI patients seems important and urgent. We have designed a pilot multicenter, randomized, parallel controlled trial to assess the efficacy and safety of acupuncture on aMCI, explore the feasibility of acupuncture in the treatment of aMCI, so as to provide a reference for large-sample clinical trials in the next stage.

Background: Postpartum subinvolution of the uterus is a more common condition after cesarean section. Auricular acupressure (AA) is widely used for the treatment of postpartum diseases. However, few studies have explored the effects of AA as a treatment of uterine involution following cesarean section to date. This study aimed to assess the efficacy and safety of AA for uterine involution after cesarean section. Methods: A total of 109 women who underwent cesarean section participated in this study. They were randomly allocated to either real AA or sham AA in a 1:1 ratio by a computer program. For 3 days, the real AA and sham AA groups received treatment 3 times daily. A series of assessments at 42 days after cesarean section, namely on the uterine size, the incidence of hydrometra, the first anal exsufflation time, bleeding volume at 6 hours, bleeding volume at 6–24 hours along with other general assessments were carried out. Results: A total of 89 women completed the study. The uterine size at 42 days after a cesarean section was 6.3 cm smaller in the real AA group than in the sham AA group (P

OBJECTIVE We conducted this study to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in advanced non-small cell lung cancer (NSCLC) patients who underwent chemotherapy. DESIGN This was a prospective, open-label, randomized controlled trial. NSCLC patients at stage IIIA, IIIB, or IV were randomly assigned to either TCM plus chemotherapy or chemotherapy alone. The comprehensive TCM treatment consisted of Kang Ai injection, herbal decoction, and Zhenqifuzheng capsules. The primary endpoint was quality of life (QOL) measured by the Functional Assessment of Cancer Therapy-Lung version 4.0. The secondary endpoints were chemotherapy completion rate, tumor response, and adverse events. All assessments were done at baseline, the third week, and the sixth week. RESULTS Thirty-nine participants were randomly assigned to the treatment group and 36 to the control group. The QOL scores were significantly improved in the treatment group compared with those of the control group in social well-being (cycle 1, P = .048; cycle 2, P = .015), emotional well-being (cycle 1, P = .047; cycle 2, P = 4.29E-05), and functional well-being (cycle 1, P = .030; cycle 2, P = .003), while the QOL scores in the above 3 domains declined in the control group (P

// Dongfang Tang 1 , Lu Yue 2 , Ruyong Yao 3 , Lin Zhou 4 , Yuqin Yang 4 , Liming Lu 4 and Wen Gao 1 1 Department of Thoracic Surgery, Huadong Hospital Affiliated to FuDan University, Huadong, China 2 Department of Oncology of the Qingdao Municipal Hospital, Qingdao, China 3 Central Laboratory of the Affiliated Hospital of Medical College Qingdao University, Qingdao, China 4 Central Laboratory of Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, China Correspondence to: Wen Gao, email: gaowenchest@163.com Keywords: lung cancer, IDO signaling, p53, metastasis Received: February 10, 2017 Accepted: March 29, 2017 Published: April 25, 2017 ABSTRACT In present study, we are to clear demonstrate the genetic evidence of IDO signaling’s impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo . As results, we reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the up-regulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis. The over-expression of IDO1 significantly encouraged the metastasis and invasion of lung cancer cells, and IDO1 could promote metastasis formation in vivo . Furthermore, we further found that p53 could attenuate IDO signaling in lung cancer cell migration partly. In conclusion, these results demonstrate that the IDO signaling’s impact on invasion and metastasis and the suppressive effect of p53 on IDO1 in lung cancer, present one novel therapeutic strategy for early metastatic lung cancer in clinical.

// Liming Lu 1 , Leiyu Shi 2 , Jingchun Zeng 3 and Zehuai Wen 1, 4 1 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China 2 Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA 3 Guangzhou University of Chinese Medicine, Guangzhou, China 4 National Center for Design Measurement and Evaluation in Clinical Research, Guangzhou University of Chinese Medicine, Guangzhou, China Correspondence to: Zehuai Wen, email: wenzh@gzucm.edu.cn Keywords: aspirin, breast cancer, dose-response Meta-analysis Received: January 17, 2017 Accepted: February 20, 2017 Published: March 17, 2017 ABSTRACT Background: Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established. Results: The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 ( P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). Methods: We searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Conclusion: Our study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer.

BACKGROUND Photodynamic therapy (PDT) has emerged as the effective new method to treat acne vulgaris. However, no meta-analysis has been published on PDT for acne vulgaris currently. OBJECTIVE The current meta-analysis and systematic review were carried out to assess the safety and effect of PDT on treating acne vulgaris. METHODS The electronic databases, including EMBASE, Cochrane Library, and MEDLINE, were systemically retrieved to identify relevant articles for meta-analysis. The primary outcome included mean percentage reduction in the inflammatory lesion count (MPRILC), while the secondary outcome included the total effective response (TER). RESULTS Altogether 13 randomized controlled trials (RCTs) involving 701 subjects had been enrolled into the current meta-analysis. PDT had certain effect on acne vulgaris in terms of the outcomes of MPRILC (MD: 15.97, 95% CI: 11.93 to 20.00, P

Objectives: This study evaluates the efficacy of Chinese herbal medicines after percutaneous coronary intervention (PCI). Background: PCI is the primary treatment for coronary atherosclero...

Background: NLRP3 inflammasome is an inflammatory mediator. The expression of NLRP3 inflammasome is associated with the development of various tumors and is closely related to the prognosis of tumors. However, the role of NLRP3 inflammasome in laryngeal squamous cell carcinoma (LSCC) remains unclear. This study aim to investigate the influence of NLPR3 inflammasome expression in LSCC, and especially the NLRP3 inflammasome expression level and the prognosis of LSCC after surgery in a Chinese population.Methods: We used quantitative real-time PCR and immunohistochemical (IHC) staining to calculate the mRNA (20 patients, fresh tissue) and protein expression (104 patients, paraffin tissue microarray) levels of the NLRP3 inflammasome (NLRP3/IL-18/IL-1β/ASC/caspase-1), respectively. We also analyzed the relationship between NLRP3 inflammasome expression levels and LSCC cancer tissues compared with adjacent normal tissues and the clinical features of LSCC. Kaplan–Meier survival curves of overall survival (OS) and disease-free survival (DFS) in LSCC patients were compared and analyzed under different expression levels of the NLRP3 inflammasome.Results: Our results indicated that the mRNA expression of the NLRP3 inflammasome was higher in LSCC cancer tissues compared with adjacent normal tissues (p < 0.001). The IHC staining score also demonstrated that the expression of the NLRP3 inflammasome was higher than in the adjacent normal tissues (p < 0.001). The NLRP3 inflammasome expression also exhibited a close relationship with the clinicopathological characteristics (especially the stage of LSCC) of LSCC. Univariate Cox regression analysis and multivariate Cox regression analysis revealed that both NLRP3 and IL-1β had an increased risk of LSCC progression (p < 0.05). The Kaplan–Meier log rank test (OS and DFS) demonstrated that high expression of NLRP3/IL-18/IL-1β/ASC was statistically different than the low expression group (p < 0.05) of LSCC patients after surgery.Conclusion: The high expression group of the NLRP3 inflammasome (NLRP3/IL-18/IL-1β/ASC) had a poorer prognosis (OS and DFS) than the low expression group of LSCC patients 5 years after surgery. The NLRP3 inflammasome (NLRP3/IL-18/IL-1β/ASC) may be used as an auxiliary indicator to predict LSCC patient prognosis after surgery.

Background. Whether traditional Chinese medicine preparation combined therapy can improve the efficacy of chemotherapy is controversial. This meta-analysis evaluates the efficacy of traditional Chinese medicine preparation combined with chemotherapy. Method. Three databases were searched from inception through August 2018. Eligible randomized controlled trials (RCTs) involving the combined treatment of chemotherapy and traditional Chinese medicine preparation compared to chemotherapy alone for treating cancer were retrieved. The methodological quality of the included RCTs was assessed with Cochrane Collaboration’s risk of bias assessment tool. Meta-analysis was adopted to make comprehensive comparisons between the experimental and control groups. Results. Four RCTs were included in this review, comprising 256 subjects. The majority of the RCTs were judged as being of poor methodological quality. Meta-analysis showed that the combination of traditional Chinese medicine preparation and chemotherapy appeared to be more effective than chemotherapy alone, for the treatment of cancer, as assessed by the disease control rate (RR: 1.41, 95% CI: 1.11 to 1.79) and the objective response rate (RR: 2.71, 95% CI: 1.28 to 5.77). There were no statistically significant differences between the groups in terms of bone marrow suppression (RR: 0.88, 95% CI: 0.57 to 1.37) or gastrointestinal reaction (RR: 1.12, 95% CI 0.75 to 1.69). Conclusions. Traditional Chinese medicine preparation combined with chemotherapy may improve objective response rates and disease control rates more than chemotherapy alone. The evidence that combined traditional Chinese medicine preparation can reduce the side effects of chemotherapy is insufficient. More rigorous randomized controlled trials are needed to confirm these conclusions.

Exercise may effectively reduce side effects caused by chemotherapy. However, no meta-analyses of exercise during or postchemotherapy for cancer patients have been definitely performed to guide clinical practice.To evaluate and summarize available scientific evidence to provide recommendations of an exercise intervention for cancer patients undergo chemotherapy.A systematic review and meta-analysis were performed with databases searching of MEDLINE, Cochrane Library, and Embase from their inception to October 15, 2017. Literature was selected to identify randomized controlled trials of exercise during or postchemotherapy for cancer patients. Risk-of-bias assessment was performed by two reviewers independently. Data were analyzed using the Cochrane Collaboration's RevMan 5.3 (Review Man, Copenhagen, Denmark).A total of 10 trials with 838 participants were included in our study. Exercise could have a beneficial effect in cancer patients undergo chemotherapy in the outcome of physical fitness (MD: 0.16, 95% CI: 0.08-0.25, p .01 and MD: 2.46, 95% CI: 1.44-3.47, p .01) and depression (MD: -1.36, 95% CI: -2.68 to -0.04, p = .04), but not in FACT-G, FACT-B, anxiety, weight, and BMI (all p .05). Exercise sequence (during or postchemotherapy) did not influence the effect of exercise for cancer patients undergo chemotherapy. In total, six studies were assessed as an overall low risk of bias. Subgroup analyses and sensitivity analyses reached results similar to those of the meta-analyses, which reflected our results were reliable and robust.Exercise seems to have a beneficial effect on physical fitness and depression, but not on quality of life, anxiety, weight, and BMI. More specific and detailed description of the implementation of exercise programs should be proposed in the future.

BACKGROUND: Hepatocellular carcinoma, also called malignant hepatoma, is a primary malignancy of the liver. Despite regular surveillance conducted in high‐risk populations, most people with hepatocellular carcinoma are diagnosed at an advanced stage. Consequently, only a minority of people with the disease are suitable for surgical resection when diagnosed. OBJECTIVES: To compare the beneficial and harmful effects of transcatheter arterial chemoembolisation (TACE) followed by three‐dimensional conformal radiotherapy (3‐DCRT) versus TACE alone in adults with primary hepatocellular carcinoma, considered unsuitable for surgical resection. SEARCH METHODS: We searched The Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index – Science up to 31 May 2018. We checked reference lists for all included studies and related reviews for further relevant articles. SELECTION CRITERIA: We included all randomised clinical trials comparing TACE followed by 3‐DCRT versus TACE alone in people with primary hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as suggested by Cochrane. We presented the results of the fixed‐effect model in the absence of statistical heterogeneity. Otherwise, we reported the results from the random‐effects model meta‐analysis. We assessed risk of bias of the included trials using bias risk domains and presented the review results incorporating the methodological quality of the trials using GRADE. Our main conclusions were based on the analysis up to three years' follow‐up. MAIN RESULTS: We identified eight randomised clinical trials (632 participants) that fulfilled our inclusion criteria. All eight trials were at high risk of bias, and we rated the evidence as low to very low certainty. The mean age ranged from 16 years to 78 years. The proportion of men ranged from 60% to 75% and the proportion of people with stage III primary hepatocellular carcinoma ranged from 22% to 85%. The median follow‐up duration was 12 months (2 months to 38 months). TACE followed by 3‐DCRT compared with TACE alone may have reduced all‐cause mortality at three years' follow‐up (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.88; 552 participants; 7 trials; low‐certainty evidence). TACE followed by 3‐DCRT compared with TACE alone may reduce the proportion of participants without tumour response (complete response plus partial response) (RR 0.49, 95% CI 0.39 to 0.61; 632 participants; 8 trials; low‐certainty evidence). Data, from one trial on health‐related quality of life, favoured the TACE followed by 3‐DCRT group, but the provided data were ill‐defined (very low‐certainty evidence). None of the trials reported serious adverse events. The results on non‐serious adverse events were as follows: TACE followed by 3‐DCRT compared with TACE alone showed no difference in the results for proportion of participants with leukopenia (RR 1.12, 95% CI 0.92 to 1.34; 438 participants; 5 trials; very low‐certainty evidence) and serum transaminases elevation (RR 1.67, 95% CI 0.66 to 4.27; 280 participants; 4 trials; very low‐certainty evidence). However, the proportion of participants with total bilirubin elevation was larger in the TACE followed by 3‐DCRT group than in the TACE alone group (RR 2.69, 95% CI 1.34 to 5.40; 172 participants; 2 trials; very low‐certainty evidence). The rate of participants with serum alpha‐fetoprotein (AFP) without decline or normalisation was significantly lower in the TACE followed by 3‐DCRT group than in the TACE group, but these data were from one trial only (Chi² = 7.24, P = 0.007; very low‐certainty evidence). AUTHORS' CONCLUSIONS: TACE followed by 3‐DCRT may be associated with lower all‐cause mortality and increased tumour response, despite the increased toxicity expressed by a higher rise of total bilirubin. Our review findings should be considered with caution because of the methodological weaknesses in the included trials, resulting in low‐ to very low‐certainty evidence. Data on serious adverse events and health‐related quality of life are lacking. We are also very much uncertain in the results of the reported non‐serious adverse events. High‐quality trials are needed to assess further the role of TACE followed by 3‐DCRT for unresectable hepatocellular carcinoma.

and purpose Acupuncture has gained increasing attention in the treatment of insulin resistance (IR). This study systematically reviews the efficacy of acupuncture on clinical IR outcomes.Cochrane Central Register of Controlled Trials, Embase, Medline (via OVID), China National Knowledge Infrastructure (CNKI), Wan Fang and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials (RCTs) of patients with IR treated by acupuncture. Meta-analysis was performed by RevMan 5.3.With acupuncture, the homeostasis model assessment of insulin resistance (homa-IR) significantly decreased (mean difference (MD) = -1.04, 95% confidence interval (CI) -1.37 to -0.71; P 0.00001), as did fasting blood glucose (FBG) (MD = -0.56, 95% CI -0.88 to -0.25; P = 0.0005), 2 h postprandial blood glucose (2hPG) (MD = -0.91, 95% CI -1.62 to -0.20; P = 0.01), and fasting insulin (FINS) (MD = -3.23, 95% CI -4.14 to -2; P 0.00001). Meanwhile, the insulin sensitivity index (ISI) (MD = 0.36, 95% CI 0.18 to 0.53; P 0.0001) increased, and fewer adverse events occurred.Acupuncture may improve homa-IR, ISI, FBG, 2hPG and FINS with fewer adverse events than other treatments, making it a viable treatment for IR.

Hyperlipidemia, defined as elevated lipid levels, is the primary and major risk factor for atherosclerotic cardiovascular disease. Several studies have evaluated the effects of Chinese medicine (CM) on hyperlipidemia. However, due to the varied designs and methods of these studies, data synthesis has been difficult, restricting the practical value of the findings. Developing a core outcome set (COS) could solve these methodological concerns. In this paper, we report a protocol to develop a COS for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia). The development of COS-CM-Hyperlipidemia will include four stages: (1) a systematic review to identify potential important outcomes—a study advisory group, composed of core stakeholders of hyperlipidemia, will be set up afterwards to evaluate the identified outcomes and a candidate outcome set will be developed accordingly; (2) a panel of experts will be invited to conduct a three-round Delphi survey, so that the experts’ opinions on the importance of outcomes for treating hyperlipidemia with CM will be collected; (3) a consensus meeting with clinicians, patients, and other key stakeholders will be conducted to finalize the items and definitions; and (4) COS-CM-Hyperlipidemia will be promoted and updated. The development of this COS will improve the design and operation of CM trials on hyperlipidemia, keeping them in compliance with international standards, as well as the comparability and utility of their results. The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.comet-initiative.org/studies/details/983 . Registered on 25 April 2017.

Introduction According to clinical observations, traditional Chinese exercise (TCE) has a potential impact on patients with chronic heart failure (CHF). However, these findings still lack comprehensive assessment, therefore, a systematic review and meta-analysis were conducted to assess the overall efficacy of TCE for CHF. Methods We searched the PubMed, Embase, Cochrane Library, CNKI and SinoMed databases from their inception to March 30, 2020. We included only published English and Chinese full-text articles on randomized controlled trials (RCTs) involving TCE compared with conventional therapy (usual care, conventional treatment or medical treatment) for CHF. Two reviewers independently conducted risk assessments for bias, and the data were analysed using the Cochrane Collaboration's RevMan v.5.3. Results The study included 22 trials conducted in hospitals with 1646 participants, and only one study was assessed as having a low risk of poor methodological quality. The comprehensive results indicated that compared to the conventional therapy, TCE effectively improved peak VO2 (MD = 0.85 ml/kg/min; 95% CI =0.32-1.38 ml/kg/min; P =0.002), reduced NT-proBNP (MD =-14.08 pg/ml; 95% CI =-17.88 to -10.28 pg/ml; P Conclusion TCE may be beneficial for patients with CHF to improve their prognosis, and it appears to be relatively safe. The intensity and follow-up time of a TCE intervention appear to influence its effect. However, due to methodological weaknesses in the included trials, more RCTs of high quality with larger samples are needed to verify the role of TCE in CHF rehabilitation.

Conclusion This study indicates that IL-10 promoter polymorphism variants, smoking, and alcohol consumption increase the risk of recurrence and canceration in vocal leukoplakia. Objective This prospective, clinical trial was performed to evaluate the association of interleukin (IL)-10 promoter polymorphism variants and canceration and recurrence rates in vocal leukoplakia (a pre-cancerous laryngeal carcinoma lesion) over a 2-year period. Participants and method Sixty-one post-operative patients with vocal leukoplakia were enrolled in this prospective, observational study and genotyped for the IL-10 promoter gene (IL-10-1082 A/G, -819 T/C and -592 A/C) using pyrosequencing, and responded to a 2-year follow-up survey. Recurrence and canceration rates were used to evaluate the association between the genotype variants and the clinical outcome. Results There was an increased canceration rate in the variant genotype group compared to that in the normal genotype group in the 2-year follow-up period (18.4% vs 0%, p-value = 0.038). Compared with the non-smoker group, the smoker group had a higher recurrence rate of vocal leukoplakia (29.3% vs 5%, p-value =0.044). Likewise, the recurrence rate in the alcohol consumption group was also higher (30.6% vs 8%, p-value =0.034). The percentage of cancerization in the alcohol consumption group was significantly higher than that in the non-alcohol consumption group (19.4% vs 0%, p-value =0.035).

Background Hemiplegia after stroke is one of the main dysfunctions in stroke patients. Acupuncture had been widely used for poststroke spastic hemiplegia (PSSH), but the efficiency was unclear. This study aimed to examine the efficiency and safety of acupuncture for individuals with PSSH. Methods We searched nine databases from their inception to 27th July 2019. Randomized controlled trials (RCTs) of acupuncture for the treatment of PSSH met the screening criteria. The quality of methodology was evaluated by Cochrane's risk of bias tool. RevMan 5.3 was used to perform the meta-analysis. The primary outcome was the Fugl-Myer Assessment (FMA) score, and the secondary outcomes were the Ashworth Scale for Spasticity (ASS) and Barthel Index (BI) scores. To evaluated the safety of acupuncture therapy, researchers scanned the full text to collect adverse events. Results Researchers retrieved 2452 articles in total, after screening, thirty-eight studies with 2628 participants of were included. In this meta-analysis, twenty-seven trials revealed that acupuncture therapy was associated with an increase in FMA scores compared with rehabilitation training (RT) (MD: 8.43, 95% CI, 6.57 to 10.28, p Conclusions This review discovered that acupuncture might be a safe and effective adjuvant therapy for individuals with PSSH. Nevertheless, there were methodological limitations in the included RCTs, and well-designed and large-scale studies should be carried out to confirm our results.

Importance Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking. Objective To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis. Data Sources A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included “(lichen planus or LP) and (prevalence or incidence or epidemiology).” No language restriction was applied. Study Selection Observational descriptive studies investigating the prevalence and incidence of OLP were included. Data Extraction and Synthesis Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence. Main Outcomes and Measures The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using theI2statistic. Results Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462 993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191 963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older. Conclusions and Relevance This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.

Background: Heart failure with reduced ejection fraction (HFrEF) has contributed to an increasing number of deaths and readmissions over the past few decades. Despite the appearance of standard treatments, including diuretics, β-receptor blockers and angiotensin-converting enzyme inhibitor (ACEI), there are still a large number of patients who have progressive deterioration of heart function and, inevitably, end-stage heart failure. In recent years, new medications for treating chronic heart failure have been clinically applied, but there is controversy surrounding drug selection and whether patients with HFrEF benefit from these medications. Therefore, we aimed to compare and rank different new pharmacological treatments in patients with HFrEF. Methods: We performed a network meta-analysis to identify both direct and indirect evidence from relevant studies. We searched MEDLINE, EMBASE, and PsycINFO through the OVID database and CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating new pharmacological treatments in patients with HFrEF published up to September 30, 2018. We included trials of ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) and angiotensin-neprilysin inhibition (LCZ696). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. Based on these items, more than half of the entries were judged as having an overall low to moderate risk of bias; the remaining studies had a high or unclear risk of bias. The outcomes investigated were left ventricle ejection fraction (LVEF %), heart rate (HR) and serum level of B-type natriuretic peptide (BNP). We performed a random-effects network meta-analysis within a Bayesian framework. Results: We deemed 32 trials to be eligible that included 3810 patients and 32 treatments. Overall, 32 (94.1%) trials had a low to moderate risk of bias, while 2 (5.9%) trials had a high risk of bias. The quality of the included studies was rated as low in regard to allocation concealment and blinding and high in regard to other domains according to the Cochrane tools. As for increasing LVEF%, levosimendan was better than placebo (–3.77 (–4.96, –2.43)) and was the best intervention for improving ventricle contraction. As for controlling HR, n3-PUFA was better than placebo (4.01 (–0.44, 8.48)) and was the best choice for regulating HR. As for decreasing BNP, omega-3 was better than placebo (941.99 (–47.48, 1952.89) and was the best therapy for improving ventricle wall tension. Conclusions: Our study confirmed the effectiveness of the included new pharmacological treatments for optimizing the structural performance and improving the cardiac function in the management of patients with HFrEF and recommended several interventions for clinical practice.

Insulin-like growth factor (IGF) signaling plays an important role in tumorigenesis and metastasis. Here, we analyzed insulin-like growth factor (IGF) binding protein-2 (IGFBP2) expression in 81 lung cancer patients and 36 controls consisting of healthy and benign pulmonary lesion participants for comparison, then validated the IGFBP2 expression in additional 84 lung cancer patients, and evaluated the prognostic and chemoresistant significance of IGFBP2 in two cohorts respectively. Next we detected the reversal effect of trichostatin A (TSA) on chemoresistance in cell lines with high IGFBP2 expression. As a result, the mean expression of IGFBP2 in lung cancer patients was significantly higher than that in controls and increased with lung cancer progressed to advanced stage. In addition, high IGFBP2 expression was independently predictive for chemoresistance; over-expressed IGFBP2 enhances cell activity and TSA can reverse the chemoresistance induced by high IGFBP2 expression through enhancing autophagy. Furthermore, multivariate analysis showed that lung cancer patients whose blood IGFBP2 was higher had a poor survival outcome, with a hazard ratio of 8.22 (95%CI 1.78–37.92, P = 0.007) after adjustment for stage, histopathology, EGFR mutation, age, smoking and surgery.

Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD) induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and NOD-like receptor family pyrin domain containing-3 (NLRP3) in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG) and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.