High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Peptidome-wide association analysis of Epstein-Barr virus identifies epitope repertoires associated with nasopharyngeal carcinoma.

Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Determining the organ of origin of large pelvic masses in females using multidetector CT angiography and three-dimensional volume rendering CT angiography.

OBJECTIVE: To study the value of tumour feeding arteries and the ovarian vein in determining the organ of origin of large pelvic tumours in females using multidetector CT. METHODS: One hundred and thirty patients with 131 pathologically proven tumours (>6.5 cm) were retrospectively reviewed. Conventional CT images and CT angiography were evaluated, with focus on assessing the value of tumour feeding arteries and the ovarian vein in differentiating ovarian from non-ovarian tumours. RESULTS: For 97 ovarian tumours, the feeding arteries included the ovarian artery (n = 51) and the ovarian branch of uterine artery (n = 64). For 34 non-ovarian tumours, the feeding arteries included the ovarian artery (n = 2), the uterine artery (n = 21), the mesenteric artery (n = 5), and the internal iliac artery (n = 1). The ovarian vein was identified in 86 ovarian tumours and 12 non-ovarian tumours. When the feeding arteries and the ovarian vein were combined to confirm ovarian origin, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.8 %, 84.2 %, 93.8 %, 94.1 %, and 93.9 %, respectively. The accuracy was significantly higher than that of independently using the ovarian vein or the ovarian feeding arteries. CONCLUSION: Combined application of tumour feeding arteries and the ovarian vein is valuable to differentiate large ovarian from non-ovarian tumours. KEY POINTS: • CT is a valuable modality for diagnosing pelvic tumours. • Determining the organ of origin is difficult for large pelvic tumours. • Contrast-enhanced CT and CT angiography are helpful in depicting abdominopelvic vessels. • Tracking tumour-associated vessels can help differentiate large ovarian from non-ovarian tumours.

Evidence map of traditional Chinese exercises.

Objective: This study aimed to assess and visually depict the clinical evidence landscape of traditional Chinese exercises and identify any research gaps and future research needs. Methods: We comprehensively searched seven Chinese and English databases to identify randomized controlled trials (RCTs) and systematic reviews (SRs) evaluating the effects of traditional Chinese exercises from their inception until May 2023. The quality of evidence was assessed via the GRADE approach, and the research topics, intervention effects, and strength of evidence were graphically displayed. Results: This evidence map includes 2,017 studies, comprising 1,822 RCTs and 195 SRs. These studies were conducted globally in various countries. Among the traditional Chinese exercises, Tai Chi and Baduanjin have received the most research attention, with a growing number of publications. When traditional Chinese exercises were compared with the control groups, 88.2% of the included SRs reported significantly positive effects, 4.1% reported unclear effects, and 7.7% reported no significant differences. The findings suggested that traditional Chinese exercises could benefit patients with osteoarthritis, osteoporosis, hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease, stroke, Parkinson's disease, anxiety, and depression. However, the overall quality of the evidence was suboptimal, with 11.3% rated as moderate, 45.6% as low, and 43.1% as critically low. Conclusion: This evidence map visually represents valuable information on traditional Chinese exercises. While most studies have reported significant benefits, the overall quality of evidence is low.

Current status and implementation strategies of patient education in core outcome set development.

OBJECTIVE: Patient participation is essential for Core Outcome Set (COS) development studies. Patient education during participation may help patients better express their views in COS studies. This study aimed to investigate the current status of patient participation and the specified educational information in COS studies. METHODS: We conducted a systematic review of COS development studies. Information on patient participation in COS research, and especially details of patient education, was analyzed. RESULTS: In total, 146 COS development studies were included in this review. Of these, 125 studies (85.6%) mentioned patient participation. Most studies did not provide explicit information on patient participation. Some studies mentioned recruiting patients, but ultimately, none of them responded. Six studies reported conducting patient education through workshops, creating patient forums, or providing videos and slides. However, these studies did not provide details on education. Twenty-three studies used the plain language to explain patient outcomes. CONCLUSION: COS developers are increasingly focusing on patient participation. However, only a few COS studies have explicitly reported conducting measures related to patient education. Further patient education is necessary when they participate in the development of a new Core Outcome Set. PRACTICE IMPLICATION: This article provides implementation strategies related to patient education for future COS development studies.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

A comprehensive predictive model for radiation-induced brain injury in risk stratification and personalized radiotherapy of nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Radiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification. MATERIALS AND METHODS: By performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction. RESULTS: The 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 × 10-34). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27-103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 × 10-2). CONCLUSIONS: The PRS, together with clinical factors, could improve RBI risk stratification and implies personalized radiotherapy.

Comparative effectiveness of phlegm-heat clearing Chinese medicine injections for AECOPD: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingkailing (QKL), Reduning (RDN), Xiyanping (XYP), Tanreqing (TRQ) and Yuxingcao (YXC) injections are all phlegm-heat clearing Chinese medicine (CM) injections composed of the extract from traditional CM materials. Evidence from clinical studies and animal experiments indicates that the above CM injections are effective supplementary therapy for acute exacerbation chronic obstructive pulmonary disease (AECOPD), and clinicians are faced with a difficult choice on the optimal phlegm-heat clearing CM injection for AECOPD. AIM OF THE STUDY: This systematic review and Bayesian network meta-analysis aimed to evaluate the comparative effectiveness of five commonly used phlegm-heat clearing CM injections for COPD. MATERIALS AND METHODS: A pairwise and network meta-analyses were performed to assess the effectiveness of QKL, RDN, TRQ, XYP and YXC on AECOPD. Randomized controlled trials (RCTs) were identified by searching English and Chinese databases. The primary outcome was lung function (forced expiration volume [FEV1] and forced vital capacity [FVC]), blood gas analysis index was secondary outcome measure. Winbugs and Stata 15.0 software were used for data analysis. RESULTS: A total of 57 RCTs were included. The pairwise analyses showed that each of the injections combined with routine treatment were superior to routine treatment alone [FEV1: QKL, MD 0.20, 95% CI (0.06, 0.35); RDN, MD 0.24, 95% CI (0.08, 0.40); TRQ, MD 0.24, 95% CI (0.19, 0.29); XYP, MD 0.26, 95% CI (0.20, 0.32); YXC MD 0.73, 95% CI (0.06, 1.41)]. The network meta-analysis provided the following rank of lung function improvement: FEV1: YXC > TRQ > XYP > RDN > QKL; FVC: YXC > TRQ > QKL > RDN > XYP. RDN and YXC ranked highest in blood gas analysis index. RDN was the highest ranked injection for effectiveness, followed by QKL, TRQ, XYP, then YXC. Most of the injections appeared safe, with severe adverse events rarely reported. CONCLUSION: This study suggests that YXC and TRQ are the most effective therapies in treating AECOPD patients. RDN and YXC are more effective in the alleviation of clinical symptoms. Given that the safety of YXC is controversial, TRQ and RDN may be preferable as phlegm-heat clearing CM injections in the adjuvant treatment of AECOPD.

Whole-Exome Sequencing Study of Familial Nasopharyngeal Carcinoma and Its Implication for Identifying High-Risk Individuals.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals with a family history suffer elevated NPC risk, requiring effective genetic counseling for risk stratification and individualized prevention. METHODS: We performed whole-exome sequencing on 502 familial NPC patients and 404 unaffected relatives and controls. We systematically evaluated the established cancer predisposition genes and investigated novel NPC susceptibility genes, making comparisons with 21 other familial cancers in the UK biobank (N = 5218). RESULTS: Rare pathogenic mutations in the established cancer predisposition genes were observed in familial NPC patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), and BRCA1 (0.80%). Additionally, 6 novel susceptibility genes were identified. RAD54L, involved in the DNA repair pathway together with ERCC2, MUTYH, and BRCA1, showed the highest frequency (4.18%) in familial NPC. Enrichment analysis found mutations in TP63 were enriched in familial NPC, and RAD54L and EML2 were enriched in both NPC and other Epstein-Barr virus-associated cancers. Besides rare variants, common variants reported in the studies of sporadic NPC were also associated with familial NPC risk. Individuals in the top quantile of common variant-derived genetic risk score while carrying rare variants exhibited increased NPC risk (odds ratio = 13.47, 95% confidence interval = 6.33 to 28.68, P = 1.48 × 10-11); men in this risk group showed a cumulative lifetime risk of 24.19%, much higher than those in the bottom common variant-derived genetic risk score quantile and without rare variants (2.04%). CONCLUSIONS: This study expands the catalog of NPC susceptibility genes and provides the potential for risk stratification of individuals with an NPC family history.

The Initial Response to a Pandemic: Anesthesiology Experiences from China at the Onset of COVID-19.

This article documents experiences from frontline anesthesia providers in Wuhan, China, mainly from the anesthesiologists in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Those experiences offer valuable insight into the processes used to optimize the emergency response system, and the medical resources and emergency allocation, as well as providing information on the role anesthesiologists played in managing the pandemic.

Comparative Effectiveness and Safety of Seven Qi-Tonifying Chinese Medicine Injections for AECOPD Patients: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) imposes a large burden on economy and society worldwide. In addition to western medicine, multiple kinds of qi-tonifying Chinese medicine injections have been widely used in China as adjunctive treatments. Previous small-sample clinical trials have proven their efficacy in the treatment of AECOPD. However, data on comparative effectiveness and safety of qi-tonifying injections are limited. We conducted this network meta-analysis to compare the efficacy and safety of 7 commonly used qi-tonifying injections in patients with AECOPD. METHODS: Literature search was conducted through electronic databases, including PubMed, the Cochrane Library, EMBASE, CINAHL, AMED, CBM, CNKI, Wanfang database, and VIP database. Randomized clinical trials (RCTs) exploring the efficacy of any of these 7 qi-tonifying injections were included. The primary outcome was lung function (FEV1 and FVC). R 4.0.0 and STATA 12.0 were adopted to perform the network meta-analysis using Bayesian statistics. RESULTS: A total of 36 RCTs involving 2657 participants were included. The results of network meta-analyses indicated that Chuankezhi injection (CKZ) combined with routine treatment (RT) was superior to other qi-tonifying injections combined with RT in terms of FEV1 improvement (MD = 0.63, 95% CI: 0.22, 1.04). For improving FVC, Shengmai injection (SGM) combined with RT showed the greatest therapeutic effect (MD = 0.38, 95% CI: 0.13, 0.61). Moreover, SGM combined with RT revealed the best estimates for response rate (MD = 4.00, 95% CI: 1.34, 13.63). The main adverse events in this study were gastrointestinal reactions and injection site reactions. No serious adverse events were reported. CONCLUSION: In this network meta-analysis, SGM and CKZ were potential best adjunctive therapies in the treatment of AECOPD.

Real-World Effects of Chinese Herbal Medicine for Idiopathic Membranous Nephropathy (REACH-MN): Protocol of a Registry-Based Cohort Study.

Introduction: Some encouraging findings of Chinese herbal medicine (CHM) in management of idiopathic membranous nephropathy (IMN) obtained in the setting of clinical trials are hard to validate in the daily clinical practice due to a complicated treatment scenario of CHM in practice. The primary objective of this registry is to provide a description of treatment patterns used in management of IMN and assess clinical remission in daily practice in a Chinese population sample with IMN. Methods and analysis: This is a prospective, multicenter cohort which will comprise 2000 adults with IMN regardless of urinary protein levels that will be recruited from 11 nephrology centers across China. The participants will be followed for up to at least 2 years. Primary outcome is composite remission (either complete remission or partial remission) 24 months after enrolment. The secondary outcomes are complete remission, partial remission, time to remission, no response, relapse, proteinuria, annual change of glomerular filtration rate, antibodies against PLA2R, and composite endpoint of 40% reduction of glomerular filtration rate, doubling of serum creatinine, end-stage renal disease, and death. Propensity score analysis will be used for matching and adjustment. Ethics and dissemination: This study has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2020-094-01). Results of the study will be published in both national and international peer-reviewed journals, and presented at scientific conferences. Investigators will inform the participants as well as other IMN patients of the findings via health education. Study registration: ChiCTR2000033680 (prospectively registered).

Short-Term Outcomes of Patients With COVID-19 Undergoing Invasive Mechanical Ventilation: A Retrospective Observational Study From Wuhan, China.

Background: COVID-19 has spread rapidly worldwide. Many patients require mechanical ventilation. The goal of this study was to investigate the clinical course and outcomes of patients with COVID-19 undergoing mechanical ventilation and identify factors associated with death. Methods: Eighty-three consecutive critically ill patients with confirmed COVID-19 undergoing invasive mechanical ventilation were included in this retrospective, single-center, observational study from January 31 to March 15, 2020. Demographic, clinical, laboratory, radiological, and mechanical ventilation data were collected and analyzed. The primary outcome was 28-day mortality after endotracheal intubation. The secondary outcomes included the incidences of SARS-CoV-2-related cardiac, liver, and kidney injury. Results: Seventy-four out of 83 (89.2%) patients achieved oxygen saturation above 93% after intubation. Forty-nine out of 83 (59%) patients died and 34 (41%) patients survived after 28 days of observation. Multivariable regression showed increasing odds of death associated with cardiac injury (odds ratio 15.60, 95% CI 4.20-74.43), liver injury (5.40, 1.46-23.56), and kidney injury (8.39, 1.63-61.41), and decreasing odds of death associated with the higher PaO2/FiO2 ratio before intubation (0.97, 0.95-0.99). PaO2/FiO2 ratio before intubation demonstrated a positive linear correlation with platelet count (r = 0.424, P = 0.001), and negative linear correlation with troponin I (r = -0.395, P = 0.008). Conclusions: Cardiac, liver, and kidney injury may be associated with death for critically ill patients with COVID-19 undergoing invasive mechanical ventilation. The severity of pre-intubation hypoxia may be associated with a poorer outcome of patients with COVID-19 undergoing invasive mechanical ventilation. Larger, multi-institutional, prospective studies should be conducted to confirm these preliminary results.

Protocol of the Development of a Core Outcome Set for Ischemic Stroke in Clinical Trials of Chinese Medicine.

Background. Ischemic stroke (IS) seriously impacts the quality of life of survivors. Chinese medicine (CM) has been developed for more than 2000 years and plays a key role in the treatment of ischemic stroke. Many Chinese medicine clinical trials have been conducted; however, the heterogeneity of outcome measurements and reporting limits implications of the findings in clinical practice and health policy development. Therefore, it is important to develop a core outcome set (COS) that should be used and reported in trials for ischemic stroke treated by Chinese medicine. This protocol describes the process of developing the IS-CM-COS. Methods and Analysis. The development of the COS will involve the following four steps: (1) A list of outcomes reported in the registered and published Chinese medicine trials of ischemic stroke will be extracted by conducting a systematic literature review. (2) An additional outcome list will be collected by semistructured interview to patients with ischemic stroke. (3) A two-round Delphi survey will be performed to prioritize and condense the outcomes. (4) In the consensus meeting, a final recommended COS will be developed. Discussion. The COS could improve the reliability and consistency of outcome reporting. We hope that this IS-CM-COS will be used in the future Chinese medicine trials for the treatment of ischemic stroke and improve research quality. Trial Registration. This study was registered with the Core Outcome Measures in Effectiveness Trials Initiative (http://www.comet-initiative.org/studies/details/1282).

Acupuncture combined with speech rehabilitation training for post-stroke dysarthria: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The evidence of Acupuncture combined with speech rehabilitation training for post-stroke dysarthria is insufficient and there is no consensus on its efficacy. METHODS: We searched seven Chinese and English medicine databases for randomized controlled trials (RCTs) from their inception to November 2019. The primary outcome measure was the clinical response rate, assessed with the Frenchay Dysarthria Assessment (FDA) tool. We assessed risk of bias using the Cochrane risk-of-bias tool. We used GRADE to assess the certainty of evidence (CoE). RESULTS: Thirty studies were included in this systematic review, 23 of which were pooled in meta-analysis. Acupuncture combined with speech rehabilitation training is likely beneficial for was response rate (n = 1685; RR = 1.37; 95% CI [1.29, 1.46], P < 0.01, I 2 = 34%; 17 studies, low CoE) compared to speech rehabilitation treatment alone. CONCLUSION: The combination of acupuncture and speech rehabilitation training may improve total response rate of stroke patients with dysarthria. However, more RCTs with rigorous study design and validated outcome measures are needed to confirm the evidence.

Protective effect of a hydrogen sulfide donor on balloon injury-induced restenosis via the Nrf2/HIF-1α signaling pathway.

Restenosis is liable to occur following treatment with endovascular interventional therapy. Increasing evidence indicates that hydrogen sulfide (H2S) exhibits numerous physiological properties, including antioxidative and cardioprotective disease properties. Thus, the present study aimed to investigate the anti­restenosis effects of H2S and its protective mechanisms. A balloon dilatation restenosis model was used, in which model Sprague­Dawley rats were treated with sodium hydrosulfide (NaHS: A donor of H2S, 30 µmol/kg) by intraperitoneal injection for 4 weeks. Histological observations of the carotid artery were performed, and H2S production and the expression of Nuclear factor­E2­related factor 2 (Nrf2)/hypoxia­inducible factor (HIF)­1α signaling pathway proteins were measured. In addition, human umbilical vein endothelial cells (HUVECs) were treated with NaHS following the inhibition of Nrf2 or HIF­1α expression. The expression of Nrf2/HIF­1α signaling pathway proteins, tube formation and cell migration were evaluated thereafter. The results demonstrated that NaHS treatment significantly increased H2S production in rats with restenosis, and that neointimal thickness decreased significantly in arteries with restenosis. Furthermore, an increase in H2S production enhanced the nuclear accumulation of Nrf2 and expression of its downstream targets, heme oxygenase­1 and superoxide dismutase, as well as HIF­1α. Similar effects of NaHS on the expression of these proteins were observed in HUVECs. Additionally, these findings indicated that NaHS­induced HIF­1α expression was dependent on Nrf2 expression. NaHS treatment also markedly increased tube formation by upregulating vascular endothelial growth factor expression and cell migration, both of which were mediated by the Nrf2/HIF­1α signaling pathway, and suppressed the migration and proliferation of human vascular smooth muscle cells. Thus, NaHS­mediated H2S production was observed to prevent neointimal hyperplasia, promote activation of the Nrf2/HIF­1α signal pathway, and enhance HUVEC tube formation and migration, thereby exerting protective effects on balloon injury­induced restenosis.

Clinical application of oligo array-CGH for detecting balanced translocations in preimplantation genetic diagnosis.

Array comparative genomic hybridization (array-CGH), which facilitates to detect unbalanced reciprocal translocation and allows screening aneuploidy for chromosomes, has been repeatedly verified to be valid for diagnosis of translocations in preimplantation human embryos. Currently, the main microarrays used for CGH are bacterial artificial chromosome (BAC)-based arrays. Compared with the BAC-based arrays, oligonucleotide (oligo)-based arrays have a relatively higher resolution and optimal coverage particularly in the subtelomeric regions. Herein, we described the clinical application of a newly designed oligo-based array by Agilent in preimplantation genetic diagnosis (PGD) and aneuploidy screening for balanced translocations. In the study, a total of 144 embryos from 9 couples carrying Robertsonian translocations and 5 carrying reciprocal translocations were biopsied on day 3 for array-CGH analysis. Overall, 135 (93.8%) embryos were successfully diagnosed to be free of either aneuploidies or unbalanced fragments. However, the remained 9 (6.2%) embryos failed to be amplified due to failed cell lysis, DNA damage or the absence of nuclei in the biopsied cells. Collectively, 23 embryos were identified as "euploid and balanced" and suitable to be transferred. Finally, 9 embryos of satisfactory quality were transferred to 6 women, among which 4 recipients exhibited positive hCG level. Fortunately, one recipient with positive hCG level has delivered one baby, and two pregnancies were continuing. Our study served as the first clinical application of oligo-based array CGH technology in PGD for both reciprocal and Robertsonian translocations concomitant with comprehensive aneuploidy screening.

Hormones in pain modulation and their clinical implications for pain control: a critical review.

Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.