Corrigendum: A Chinese medicine formula (Bushen Huoxue Tongluo) for the treatment of chronic subjective tinnitus: a study protocol for a pilot, assessor-blinded, randomized clinical trial.

[This corrects the article DOI: 10.3389/fphar.2022.844730.].

A Chinese Medicine Formula (Bushen Huoxue Tongluo) for the Treatment of Chronic Subjective Tinnitus: A Study Protocol for a Pilot, Assessor-Blinded, Randomized Clinical Trial.

Background: Tinnitus is a common problem worldwide. There is still no effective method to cure it. Traditional Chinese medicine (TCM) may be a potentially effective treatment approach for tinnitus. However, there is still no clinical trial with scientifically rigorous methodology to evaluate the treatment effect of TCM for tinnitus. Therefore, we propose a pilot study to inform the feasibility of a future full-scale RCT to establish the efficacy of TCM formula for tinnitus. Objectives: The aim of this study is to determine the feasibility of a full-scale RCT and explore whether a TCM formula (BHT) has an additional effect on improving tinnitus when compared to informative counseling alone. Design: An assessor-blinded, randomized, controlled clinical trial is used. Participants: Twenty-four patients with chronic subjective tinnitus will be enrolled. Interventions: The patients will be allocated randomly to receive a TCM formula (BHT, Bushen Huoxue Tongluo) and informative counseling or informative counseling alone. The oral BHT herbal granules will be taken twice per day continuously for 8 weeks. Main outcome measures: The primary outcomes include recruitment rate, intervention completion rate, and data completion rate to evaluate the feasibility. The secondary outcomes include Tinnitus Handicap Inventory, tinnitus functional index, tinnitus sensation level, self-rated visual analogue scale on tinnitus loudness and annoyance, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and adverse event. The outcome measures will be collected at baseline, end of treatment, and 4-week follow-up. Discussion: This trial is currently ongoing and is recruiting patients. The expected study results will find some preliminary evidence about the clinical effectiveness of BHT on chronic tinnitus and will also determine if it is feasible to conduct a full-scale RCT of BHT and identify the necessary changes to the protocol if possible.

Meta-analysis with zero-event studies: a comparative study with application to COVID-19 data.

BACKGROUND: Meta-analysis is a statistical method to synthesize evidence from a number of independent studies, including those from clinical studies with binary outcomes. In practice, when there are zero events in one or both groups, it may cause statistical problems in the subsequent analysis. METHODS: In this paper, by considering the relative risk as the effect size, we conduct a comparative study that consists of four continuity correction methods and another state-of-the-art method without the continuity correction, namely the generalized linear mixed models (GLMMs). To further advance the literature, we also introduce a new method of the continuity correction for estimating the relative risk. RESULTS: From the simulation studies, the new method performs well in terms of mean squared error when there are few studies. In contrast, the generalized linear mixed model performs the best when the number of studies is large. In addition, by reanalyzing recent coronavirus disease 2019 (COVID-19) data, it is evident that the double-zero-event studies impact the estimate of the mean effect size. CONCLUSIONS: We recommend the new method to handle the zero-event studies when there are few studies in a meta-analysis, or instead use the GLMM when the number of studies is large. The double-zero-event studies may be informative, and so we suggest not excluding them.

[Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis].

OBJECTIVES: This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically. METHODS: We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment. CONCLUSIONS: The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.

Harms and benefits of adoptive immunotherapy for postoperative hepatocellular carcinoma: an updated review.

The harms and benefits of adoptive immunotherapy (AIT) for patients with postoperative hepatocellular carcinoma (HCC) are controversial among studies. This study aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. Electronic databases were systematically searched to identify randomized controlled trials (RCTs) and cohort studies evaluating adjuvant AIT for patients with HCC after curative therapies. Recurrence and mortality were compared between patients with or without adjuvant AIT. Eight RCTs and two cohort studies involving 2,120 patients met the eligibility criteria and were meta-analyzed. Adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year [risk ratio (RR) 0.64, 95%CI 0.49-0.82], 3 years (RR 0.85, 95%CI 0.79-0.91) and 5 years (RR 0.90, 95%CI 0.85-0.95). Similarly, adjuvant AIT was associated with significantly lower mortality at 1 year (RR 0.64, 95%CI 0.52-0.79), 3 years (RR 0.73, 95%CI 0.65-0.81) and 5 years (RR 0.86, 95%CI 0.79-0.94). Short-term outcomes were confirmed in sensitivity analyses based on RCTs or choice of a fixed- or random-effect meta-analysis model. None of the included patients experienced grade 3 or 4 adverse events. Therefore, this update reinforces the evidence that adjuvant AIT after curative treatment for HCC lowers risk of recurrence and mortality.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling.

BACKGROUND: Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. METHODS: Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). RESULTS: Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). CONCLUSIONS: This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux.

A rethink of fusion surgery for lumbar spinal stenosis.

Lumbar spinal stenosis is one of the most common spinal disorders in elderly patients, how to choose decompression alone or decompression plus fusion is still controversial. It was reported that the rate of decompression alone for lumbar stenosis was decreased, whereas the rate of decompression plus fusion was increased recently. Two recent multicenter RCTs papers published in the same issue of N Engl J Med compare the outcomes of decompression alone or decompression plus fusion for lumbar spinal stenosis currently. We combined the results from these two studies using the Stata software, we found that the decompression plus fusion had a significantly more blood loss and longer operative time. And no significant difference was found in the parameters of length of hospital stay, SF-36 Physical Component Summary, Oswestry Disability Index, Visual analogue scales of back pain and leg pain between decompression alone group and decompression plus fusion group. Therefore, based on the current evidence, we advocate a rethink on the decompression plus fusion trend chosen by surgeons, the indications of fusion should be restricted to the lumbar stenosis patients accompanied with spinal instability or deformity.

CD133+ subpopulation of the HT1080 human fibrosarcoma cell line exhibits cancer stem-like characteristics.

The cancer stem cell (CSC) theory holds that a minority population within tumors possesses stem cell properties of self-renewal and multilineage differentiation capacity and provides the initiating cells from which tumors are derived and sustained. However, verifying the existence of these CSCs has been a significant challenge. The CD133 antigen is a pentaspan membrane glycoprotein proposed to be a CSC marker for cancer-initiating subpopulations in the brain, colon and various other tissues. Here, CD133+ cells were obtained and characterized from the HT1080 cell line to determine the utility of this marker for isolating CSCs from human fibrosarcoma cells. In this study, CD133+ cells were separated from HT1080 cells using magnetic beads and characterized for their proliferation rate and resistance to chemotherapeutic drugs, cisplatin and doxorubicin, by MTS assay. Relative expression of tumor-associated genes Sox2, Oct3/4, Nanog, c-Myc, Bmi-1 and ABCG2 was measured by real-time polymerase chain reaction (PCR). Clonal sphere formation and the ability of CD133+ cells to initiate tumors in BALB/c nude mice was also evaluated. We found that CD133+ cells showed a high proliferation rate, increased resistance to chemotherapy drugs and overexpression of tumor-associated genes compared with these features in CD133- cells. Additionally, CD133+ cells were able to form spherical clusters in serum-free medium with high clonogenic efficiency, indicating a significantly greater tumor-initiating potential when compared with CD133- cells. These findings indicate that CD133+ cells identified within the HT1080 human fibrosarcoma cell line possess many CSC properties and may facilitate the development of improved therapies for fibrosarcoma.