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Introduction The chronic neuropathic pain associated with postherpetic neuralgia (PHN) can last for several months or even many years, seriously affecting the affected person’s work, sleep, mood, and daily life activities. In generaly, current treatments for PHN are at best limited and unsatisfactory, and adverse reactions are common, especially in elderly patients. Electroacupuncture (EA) is widely used clinically to manage painful diseases, but there remains a lack of evidence to support the effectiveness of EA on PHN. This study is designed to assess the efficacy and safety of EA on PHN, and to provide evidence-based medical evidence for EA treatment of PHN. Methods This multicenter, prospective, randomized controlled trial will recruit 448 patients with PHN at seven clinical centers. Multicenter stratified variable block randomization will be used, and the eligible patients will be randomly allocated in a ratio of 1:1 to the EA group or sham EA group. The EA group will receive 4 weeks of EA treatment, given as 30-min treatment sessions, once daily, 5 times per week, for a total of 20 treatments; the sham EA group will receive sham EA treatment under the same conditions. Planned Outcomes The primary outcome measure is the 11-point Numeric Rating Scale pain score at week 4. The secondary outcome measures, including mechanical pain threshold, pain area of PHN, average number of pain episodes, the short-form McGill Pain Questionnaire 2, Zoster Brief Pain Inventory, the Depression, Anxiety, and Positive Outlook Scale, Patient Global Impression of Change, safety of EA, and use of concomitant medications, among others. The primary analysis of the outcomes will be the mixed-effect model with repeated measurement between groups on an intent-to-treat population. Trial Registration Clinicaltrials.gov identifier: NCT04560361. Registered 23 September 2020 (https://clinicaltrials.gov/ct2/show/NCT04560361?term=NCT04560361&draw=2&rank=1). Supplementary Information The online version contains supplementary material available at 10.1007/s40122-021-00283-8.

Many articles have reported that Rab1A was overexpressed in a variety of human cancers and involved in tumor progression and metastasis. However, the biological function and molecular mechanism of Rab1A in nasopharyngeal carcinoma (NPC) remained unknown until now. Here we found that Rab1A overexpression is a common event and was positively associated with distant metastasis and poor prognosis of NPC patients. Functionally, Rab1A depletion inhibited the migration and EMT phenotype of NPC cells, whereas Rab1A overexpression led to the opposite effect. Furthermore, we reveal an important role for Rab1A protein in the induction of radioresistance via regulating homologous recombination (HR) signaling pathway. Mechanistically, Rab1A activated Wnt/β-catenin signaling by inhibiting the activity of GSK-3β via phosphorylation at Ser9. Then Wnt/β-catenin signaling induced NPC cells radioresistance and metastasis through nuclear translocation of β-catenin and transcription upregulation of HR pathway-related and EMT-related genes expression. In general, this study shows that Rab1A may serve as a potential biomarker for predicting prognosis in NPC patients. Targeting Rab1A and Wnt/β-catenin signaling may hold promise to overcome NPC radioresistance.

Aims Acupuncture is frequently recommended as a complementary therapy for infertility. However, whether acupuncture can prevent early ovarian hyperstimulation syndrome has not been examined and its potential mechanisms are not well understood. Main methods Forty rats were randomized into four groups: Control, Ovarian Stimulation Model, Acupuncture, and Human Chorionic Gonadotropin (HCG). Serum estradiol, progesterone, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured by enzyme-linked immunosorbent assay. Pituitary ER mRNA and ERβ expression were detected by real-time PCR and western blotting respectively. The pathology of rat ovaries were observed by light microscopy. Key findings We observed significantly lower estradiol levels in the Acupuncture group than in the Model group and increased LH levels in the HCG group than in Model and Acupuncture groups. Testosterone and FSH levels were significantly lower in the Acupuncture group than in the HCG group. Western blotting showed significantly lower pituitary ERβ expression in the Model group than in the Control group and higher expression in the Acupuncture group than in the Model group. Real-time PCR showed lower pituitary ER mRNA expression in the Acupuncture group than in the Model group. Hematoxylin and eosin staining showed a lower proportion of atretic follicles in Acupuncture and HCG groups than in Model and Control groups. Instead, Acupuncture and HCG groups showed growing and mature follicles. Significance Our results demonstrate a relationship between acupuncture and the hypothalamic-pituitary-gonadal axis, and the potential mechanism underlying the preventative effects of acupuncture on the incidence of early ovarian hyperstimulation syndrome.

Background Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habit without organic disease. A global perspective given by the World Gastroenterology Organization (WGO) points out that IBS can impact the quality of an individual’s daily life, cause socioeconomic problems and potentially impair the patient-physician relationship. It remains a problem to treat IBS due to the complicated pathophysiology. Acupuncture is an alternative therapy recommended for IBS. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for patients with IBS. We also want to explore the correlation between IBS-gene subtypes and acupuncture effect. Methods/design A multicenter randomized controlled trial will be performed in seven hospitals. Six hundred participants will be stratified into two strata (IBS-C or IBS-D). Then, patients within each stratum will be divided into an experimental group and a control group randomly. The experimental group is treated with acupuncture while the control group is treated with Western medicine. All the patients will receive a 6-week treatment and a 3-month follow-up. The primary outcome is the IBS-Symptom Severity Score (IBS-SSS), the secondary outcome is the score of the IBS-Quality of Life (IBS-QoL).The correlation between IBS-gene subtypes and acupuncture effect will be detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Outcome measures (including primary and secondary outcome measures) are collected at baseline,1 week, 2 weeks, 4 weeks, and 6 weeks of the intervention, and 12 weeks after the intervention. Discussion This is a multicenter randomized controlled trial for IBS in China. It may clarify the efficacy of acupuncture as an alternative therapy for IBS. This is the first time ever that the potential mechanism of IBS based on genomics has been investigated. Trial registration Chinese Clinical Trials Register, ID: ChiCTR-IOR-15006259. First registered on 14 April 2015. Electronic supplementary material The online version of this article (10.1186/s13063-018-2922-y) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. Method: This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. Discussion: The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. Trial registration: This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445).

Objective To assess the efficacy and safety of treating post-stroke depression with acupuncture compared to western medicine systematically. Methods Databases were retrieved such as Cochrane Library, PubMed, Web of Sicence, EMbase, CBM, CNKI and WanFang Data so as to look up randomized controlled trials (RCT) of treating post-stroke depression with acupuncture and western medicine, and the time limit for the retrieval spanned from the date of database established to September 2013. By extracting data and evaluating methodological quality of included studies according to inclusion and exclusion criteria, RevMan 5.2 software was applied for Meta-analysis and evidence quality was assessed by adopting the GRADE system. Results A total of 13 RCTs (845 patients with post-stroke depression) were included in this study. It was revealed by Meta-analysis that the differences of the two groups were statistically significant in terms of HAMD scale scores measured at the end of the treatment by comparing the treatment of acupuncture and western medicine [SMD=0.26, 95% CI (0.11, 0.40)], but via susceptibility analysis (excluding low quality studies), the differences were not statistically significant [SMD=-0.06, 95% CI (−0.37, 0.25)], and the reliability of the results was low; in terms of adverse events, the differences were statistically significant [RR= 0.32, 95% CI (0.19, 0.53)], and the risk of adverse events reduced by 68% in the acupuncture group. From the assessment on evidence quality grade based on GRADE system, it was revealed that HAMD scores and adverse events were evidences with fairly low quality. Conclusion Although this system assessment showed that treating post-stroke depression with acupuncture was more effective compared with western medicine, the result was less reliable and quality of evidences was poor. The above-mentioned results need more high-quality randomized controlled trials for further verification.

To systematically analyze the therapeutic efficacy and safety of acupuncture in treating functional constipation (FC). By searching the Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, WanFang databases, the randomized controlled trials (RCTs) comparing acupuncture with Western medication in treating FC were retrieved, from the inception of the databases to September 2013. When the literatures were arranged according to the inclusion and exclusion criteria, and the methodological qualities were evaluated, RevMan 5.2 was adopted for meta-analysis. Ten RCTs were included, covering 1 041 cases of FC. The meta-analysis showed that there was no significant difference in comparing spontaneous bowel movements per week between shallow acupuncture at Tianshu (ST 25) and Western medication [MD=−0.47, 95% CI (−1.28, 0.34)]; there was a significant difference in comparing the spontaneous bowel movements per week between deep acupuncture at Tianshu (ST 25) and Western medication [MD = 0.53, 95% CI (0.13, 0.92)], but the difference was insignificant according to the sensitivity analysis [MD=0.38, 95% CI (−0.03, 0.80)], indicating the low reliability of the conclusion. Regarding the Cleveland clinic score (CCS), the difference between shallow acupuncture at Tianshu (ST 25) and Western medication was insignificant [MD = 0.39, 95% CI (− 1.13, 1.91)]; the difference between deep acupuncture at Tianshu (ST 25) and Western medication was significant [MD=2.64, 95% CI (1.32, 3.97)]. In the evaluation of security, the incidence rate of adverse events in acupuncture treatment (0.31%) was significantly lower than that in Western medication treatment (3.4%). Although the present systematic review showed that deep acupuncture at Tianshu (ST 25) should have better therapeutic efficacy than Western medication, the reliability and quality of the evidences were poor, and thus the above results require proving by more RCTs of higher quality.

To explore the effect of Soothing Gan (肝) and invigorating Pi (脾) (SGIP) acupuncture treatment on the clinical symptoms and quality of life (QOL) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). With a single-blinded randomized control study adopted, 63 patients who met the inclusion criteria were assigned by a random number table to two groups, 31 in the treatment group and 32 in the drug control group. The treatment group received SGIP acupuncture therapy; while the control group was treated orally with pinaverium bromide. The treatment duration of both groups was 28 days. The clinical efficacy was evaluated and compared by scoring patient’s symptom and QOL. A significant difference was found by variance analysis in efficacies between the two groups (P

Objective: Optimization of combining electroencephalography (EEG), short latency somatosensory evoked potentials (SLSEP) and transcranial Doppler (TCD) techniques to diagnose brain death. Methods: One hundred and eleven patients (69 males, 42 females) from the major hospitals of Zhejiang Province were examined with portable EEG, SLSEP and TCD devices. Re-examinations occurred ≤12 h later. Results: The first examination revealed that the combination of SLSEP and EEG led to more sensitive diagnoses than the combination of SLSEP and TCD. Re-examination confirmed this and also revealed that the combination of TCD and EEG was the most sensitive. Conclusion: The results show that using multiple techniques to diagnose brain death is superior to using single method, and that the combination of SLSEP and EEG is better than other combinations.

BACKGROUND An apnea test is essential in the clinical determination of brain death. This study was conducted to analyse complications associated with the apnea test in the determination of the brain death. METHODS On 93 adult patients in coma in Zhejiang Province of China from January 2003 to December 2006, 179 apnea tests were performed as a part of the determination of brain death. Potential risk conditions and complications were analysed during apnea tests. RESULTS During apnea, serious cardiac arrhythmia did not occur in all patients. Complications occurred in 37 of 179 (21%) apnea tests. Hypotension occurred in 30 patients (17%) and it was observed in 8/94 (9%) tests with baseline value of systolic arterial blood pressure not less than 120 mmHg, and 22/85 (26%) less than 120 mmHg (P < 0.05). Severe hypoxaemia occurred in 10 patients (6%) of which 3/138 (2%) tests with baseline value of arterial oxygen pressure not less than 200 mmHg, and 7/41 (17%) less than 200 mmHg (P < 0.05). CONCLUSIONS This study demonstrated that complications occurred mostly in patients with inadequate baseline systolic arterial blood pressure and preoxygenation. Adequate precautions during the apnea tests may reduce the risk of cardiovascular and oxygenation complication.

Background To examine whether electro-acupuncture (EA) could decrease 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), and increase neuro-peptide Y (NPY) in the brain-gut axis (BGA) in D-IBS using rat models. Methods Rats were randomly exposed to unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest, or daily gavage of Senna decoction (6 g/kg) plus chronic restraint stress (for a duration of 2 h, starting from 1 h prior to the gavage) for 2 weeks (ISC). The content of 5-HT, CGRP and NPY in the distal colon, spinal cord, hypothalamus was examined at the end of the treatment. Results 1. The two rat models exhibited similar characteristics, e.g., increased number of fecal pellets expelled in 1 h, decreased sacchar-intake, decreased CRD, elevated 5-HT, CGRP content and decreased NPY in the distal colon, spinal cord, hypothalamus (P

// Jia-hong Wang 1, * , Wei Wei 1, * , Jing Xu 2 , Zhi-xing Guo 3 , Cheng-zuo Xiao 1 , Yong-fa Zhang 1 , Pei-en Jian 1 , Xiao-liang Wu 2 , Ming Shi 1 , Rong-ping Guo 1 1 Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 3 Department of Ultrasonics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Rong-Ping Guo, e-mail: guorp@sysucc.org.cn Keywords: hepatocellular carcinoma, Cripto-1, MMP-9, aggressiveness, prognosis Received: April 20, 2015 Accepted: August 24, 2015 Published: September 05, 2015 ABSTRACT Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Cripto-1 expression was increased in TNM and BCLC stage-dependent manner. Cripto-1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM and BCLC stage. In addition, Cripto-1 was positively correlated with MMP-9 among 205 HCC samples. Patients with Cripto-1 upregulation had poor OS and shorter TTR in low and high aggressiveness groups. Furthermore, Cripto-1 had predictive validity for early and late recurrence in HCC patients. Combination of Cripto-1 and serum AFP was correlated with OS and TTR. In conclusion, Cripto-1 overexpression contributes to aggressiveness and poor prognosis of HCC. Cripto-1/AFP expression could be a potential prognostic biomarker for survival in HCC patients.

We have previously reported that Cezanne could be a prognostic biomarker for survival in hepatocellular carcinoma (HCC) patients. However, the role of Cezanne genes in HCC cells and its response to postoperative adjuvant transcatheter arterial chemoembolization (TACE) in HCC patients remains unknown. In this study, Cezanne expression was detected in human HCC using real-time PCR, western blot and immunohistochemistry. The function of Cezanne in HCC cells was determined by Transwell invasion assays and nude mice metastasis assay. The response of Cezanne in patients who received adjuvant TACE after hepatectomy was evaluated. Functional study demonstrated that interference of Cezanne expression promoted the migration and invasion of HCC cells in vitro and boosted metastasized HCC formation in mice. Upregulation of Cezanne diminished the adhesion and migration of hepatoma cells. Further study indicated that Cezanne might inhibit invasion of HCC cells by inducing epithelial–mesenchymal transition (EMT). In addition, patients with low Cezanne expression had significant improvement in prognosis after receiving adjuvant TACE. In contrast, patients with high Cezanne expression had a poorer response to adjuvant TACE. Moreover, Cezanne status was associated with response to adjuvant TACE in patients subgroup stratified by vascular invasion, tumor size and tumor number. In conclusion, Cezanne may be a novel antioncogene that has a pivotal role in the invasion of HCC and contribute to the selection of patients who may benefit from adjuvant TACE to prevent recurrence.

Sai-Ping Jiang,1 Zheng-Yi Zhu,2 Xiao-Liang Wu,3 Xiao-Yang Lu,1 Xing-Guo Zhang,1 Bao-Hua Wu1 1Department of Pharmacy, the First Affiliated Hospital, 2Department of Pharmacy, Children’s Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China Background: The impact of continuous renal replacement therapy (CRRT) on drug removal is complicated; pharmacist dosing adjustment for these patients may be advantageous. This study aims to describe the development and implementation of pharmacist dosing adjustment for critically ill patients receiving CRRT and to examine the effectiveness of pharmacist interventions. Methods: A comparative study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Patients receiving CRRT in the intervention group received specialized pharmacy dosing service from pharmacists, whereas patients in the no-intervention group received routine medical care without pharmacist involvement. The two phases were compared to evaluate the outcome of pharmacist dosing adjustment. Results: The pharmacist carried out 233 dosing adjustment recommendations for patients receiving CRRT, and 212 (90.98%) of the recommendations were well accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81%) were the most common risk factors for dosing errors, whereas antibiotics (n=168, 72.10%) were the medications most commonly associated with dosing errors. Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per critically ill patient receiving CRRT. Suspected adverse drug events in the intervention group were significantly lower than those in the preintervention group (35 in 27 patients versus [vs] 18 in eleven patients, P