Effects of transcutaneous electrical acupoint stimulation on early postoperative pain and recovery: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Background: Previous studies have indicated beneficial outcomes of transcutaneous electrical acupoint stimulation (TEAS), but high-quality and comprehensive meta-analyses are lacking. The aim was to quantitatively analyze the efficacy and safety of perioperative TEAS on postoperative pain and recovery. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched through July 2022. Randomized controlled trials (RCTs) that examined the perioperative application of TEAS in adults compared with sham-TEAS and/or non-TEAS were eligible. Cumulative analgesic consumption within 24 h and rest pain scores at 2, 6, 12, and 24 h postoperatively were the two co-primary outcomes. Results: Seventy-six RCTs (n = 9,665 patients) were included. Patients treated with TEAS experienced a reduction in clinical importance in cumulative analgesic (morphine equivalent) consumption (WMD: -14.60 mg, 97.5% CI: -23.60 to -5.60; p < 0.001) and a reduction in statistical importance in rest pain scores at multiple time points within the first 24 postoperative hours. The secondary outcome analysis also identified clinically significant recovery benefits to TEAS during the first 24 h after surgery. Furthermore, TEAS could effectively reduce opioid-related side effects and did not increase serious side effects. Conclusion: This article describes current evidence about TEAS intervention on early postoperative pain and recovery. The results support the effectiveness of TEAS, but more high-quality evidence of clinical applicability is also needed. Systematic review registration: PROSPERO (CRD42021249814).

[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

Contrasting effects of music therapy and aromatherapy on perioperative anxiety: A systematic review and meta-analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

[Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress].

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1ß, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway].

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 µmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Does the last 20 years paradigm of clinical research using volatile organic compounds to non-invasively diagnose cancer need to change? Challenges and future direction.

PURPOSE: Volatile organic compounds (VOCs) have shown great potential as novel biomarkers for cancer detection; however, comprehensive quantitative analysis is lacking. In this study, we performed a bibliometric analysis of non-invasive cancer diagnosis using VOCs to better characterise international trends and to predict future hotspots in this field, and then we focussed on human studies to analyse clinical characteristics for presenting the current controversies and future perspectives of further clinical work. METHODS: Publications, from 2002 to 2022, were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to generate network maps and identify the annual publications, top countries, authors, institutions, journals, references, and keywords. Then, we further screened clinical trials, and the key information was extracted into Microsoft Excel for further systematical analysis. RESULTS: Six hundred and forty-one articles were identified to evaluate research trends, of which 301 clinical trials were selected for further systematical analysis. Overall, the annual publications in this area increased, with an overall upward trend, while the quality of clinical research remains remarkably uneven. CONCLUSION: The study of non-invasive cancer diagnosis using VOCs would continue to be an active field. However, without stringent clinical design criteria, most suitable acquisition and analysis devices and statistical approaches, a list of exclusive, specific, reliable and reproducible VOCs to identify a disease and these VOCs appearing in a breath at detectable levels at early stage disease, the clinical utility of VOC tests will be difficult to have any breakthroughs.

Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications.

Lung cancer is one of the most common malignant tumors worldwide, with high morbidity and mortality due to significant individual characteristics and genetic heterogeneity. Personalized treatment is necessary to improve the overall survival rate of the patients. In recent years, the development of patient-derived organoids (PDOs) enables lung cancer diseases to be simulated in the real world, and closely reflects the pathophysiological characteristics of natural tumor occurrence and metastasis, highlighting their great potential in biomedical applications, translational medicine, and personalized treatment. However, the inherent defects of traditional organoids, such as poor stability, the tumor microenvironment with simple components and low throughput, limit their further clinical transformation and applications. In this review, we summarized the developments and applications of lung cancer PDOs and discussed the limitations of traditional PDOs in clinical transformation. Herein, we looked into the future and proposed that organoids-on-a-chip based on microfluidic technology are advantageous for personalized drug screening. In addition, combined with recent advances in lung cancer research, we explored the translational value and future development direction of organoids-on-a-chip in the precision treatment of lung cancer.

Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development.

Allosteric modulation is a direct and effective method for regulating the function of biological macromolecules, which play vital roles in various cellular activities. Unlike orthosteric modulators, allosteric modulators bind to sites distant from the protein's orthosteric/active site and can have specific effects on the protein's function or activity without competing with endogenous ligands. Compared to traditional orthosteric modulators, allosteric modulators offer several advantages, including reduced side effects, greater specificity, and lower toxicity, making them a promising strategy for developing novel drugs. Indole-fused architectures are widely distributed in natural products and bioactive drug leads, displaying diverse biological activities that attract the interest of both chemists and biologists in drug discovery. Currently, an increasing number of indole-fused compounds have exhibited potent activities in allosteric modulation. In this review, we provide a brief summary of examples of allosteric modulators based on the indole-fused complex architecture, highlighting the strategies for drug design/discovery and the structure-activity relationships of allosteric modulators from the perspective of medicinal chemistry.

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.

Regulated cell death (RCD) is a critical and active process that is controlled by specific signal transduction pathways and can be regulated by genetic signals or drug interventions. Meanwhile, RCD is closely related to the occurrence and therapy of multiple human cancers. Generally, RCD subroutines are the key signals of tumorigenesis, which are contributed to our better understanding of cancer pathogenesis and therapeutics. Indole alkaloids derived from natural sources are well defined for their outstanding biological and pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, and 3,3'-diindolylmethane, which are currently used in the clinic or under clinical assessment. Moreover, such compounds play a significant role in discovering novel anticancer agents. Thus, here we systemically summarized recent advances in indole alkaloids as anticancer agents by targeting different RCD subroutines, including the classical apoptosis and autophagic cell death signaling pathways as well as the crucial signaling pathways of other RCD subroutines, such as ferroptosis, mitotic catastrophe, necroptosis, and anoikis, in cancer. Moreover, we further discussed the cross talk between different RCD subroutines mediated by indole alkaloids and the combined strategies of multiple agents (e.g., 3,10-dibromofascaplysin combined with olaparib) to exhibit therapeutic potential against various cancers by regulating RCD subroutines. In short, the information provided in this review on the regulation of cell death by indole alkaloids against different targets is expected to be beneficial for the design of novel molecules with greater targeting and biological properties, thereby facilitating the development of new strategies for cancer therapy.

Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions.

HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC.

[Visualized analysis of knowledge map for traditional Chinese medicine prevention and treatment of pulmonary nodules based on CiteSpace].

This study aims to analyze the current status and development trend of the prevention and treatment of pulmonary nodules(PN) with traditional Chinese medicine(TCM) based on knowledge map and to provide both references and suggestions for future research directions. CNKI, Wanfang, VIP, and SinoMed were searched for relevant papers from the inception to December 31, 2021. Eligible articles were included according to the inclusion and exclusion criteria. The line chart was drawn based on the annual publication volume of articles, and the research interests of this field were learned. The knowledge maps of prevention and treatment of PN with TCM were drawn in CiteSpace 5.8.R1, and the authors, institutions, contents, and hotspots were analyzed. A total of 122 articles were included and the line chart demonstrated that the annual publication volume has been rising since 2018. According to the knowledge maps, the most prolific author was ZHANG Xiao-mei and there were four main research teams. Beijing University of Chinese Medicine and its affiliated hospitals were in a leading position in this field. The main research contents were disease, pathogenesis, and treatment, and the hotspots were data mining and TCM syndrome. The research on prevention and treatment of PN with TCM has become an increasing field of interest in recent years. In the future, the cross-regional cooperation and communication between research teams and institutions should be strengthened for more real-world studies and basic studies about the prevention and treatment of PN with TCM, so that the high-level evidence can be obtained and the underlying mechanisms of TCM formulae in the treatment of PN be clarified.

Preoperative Oral Gabapentin in the Management of Postoperative Catheter-Related Bladder Discomfort in Adults: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of preoperative oral gabapentin in preventing postoperative Catheter-Related Bladder Discomfort (CRBD) in surgical patients. Methods: Randomized controlled trials in which gabapentin was used for the prevention of CRBD in surgical patients with transurethral catheterization were evaluated. The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 2, and 6 h after surgery, and secondary outcomes included the incidence of any grade CRBD, postoperative pain, and adverse events. Pooled risk ratios (RRs) and mean difference (MD), 95% confidence intervals (CIs), and P values were estimated using fixed and random effects statistical models. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the levels of certainty for key results. Results: A total of 6 randomized controlled trials involving 679 participants were included in the meta-analysis. Gabapentin significantly reduced the risk of moderate-to-severe CRBD at 0, 1, 2, and 6 h (0 h: RR = 0.19, 95% CI: 0.11 to 0.31, p < 0.00001; 1 h: RR = 0.40, 95% CI: 0.25 to 0.66, p < 0.001; 2 h: RR = 0.38, 95% CI: 0.26 to 0.56, p < 0.00001; 6 h: RR = 0.20, 95% CI: 0.11 to 0.38, p < 0.00001). The overall incidence of CRBD at 1 h showed no statistical difference between the two groups (RR = 0.55, 95% CI: 0.30 to 1.00, p = 0.05). The risk of CRBD was significantly reduced in the gabapentin group at 0, 2, and 6 h after surgery (0 h: RR = 0.59, 95% CI: 0.46 to 0.74, p < 0.0001; 2 h: RR = 0.62, 95% CI: 0.51 to 0.75, p < 0.00001; 6 h: RR = 0.66, 95% CI: 0.52 to 0.83, p < 0.001). In addition, gabapentin was associated with low postoperative pain intensity without significant side effects. Conclusion: Preoperative oral gabapentin as an adjunct to surgery is effective in decreasing the risk and severity of CRBD over a short time after surgery, and it can decrease postoperative pain without significant side effects. Overall, the level of certainty was moderate to low. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021228171.

Gabapentin has Longer-Term Efficacy for the Treatment of Chronic Pelvic Pain in Women: A Systematic Review and Pilot Meta-analysis.

INTRODUCTION: Gabapentin has potential analgesic benefits in patients with neuropathic pain, such as post-herpetic neuralgia and diabetic peripheral neuropathy neuropathic pain. However, its efficacy in women with chronic pelvic pain (CPP) remains contradictory. In the present study, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain the efficacy of this treatment. METHODS: We systematically reviewed RCTs published in PubMed, Embase, the Cochrane Library, Web of Science, and Google Scholar databases, up to July 2021. These articles compared gabapentin with placebo or any other active treatment for CPP in women, with 'the change in pain scores from the baseline during the first 3 and 6 months of treatment' taken as the primary outcome. We considered reductions equivalent to 1.0 cm for primary outcomes to be clinically important. RESULTS: Four studies, comprising 469 participants, were included in our meta-analysis. Results revealed that the gabapentin group had significantly higher change in pain intensity scores from baseline to 3 months [weighted mean difference (WMD) - 0.61 cm; 95% confidence interval (CI) - 0.97 to - 0.25; I2 = 0%; p = 0.0009] and 6 months (WMD - 1.38 cm; 95% CI - 1.89 to - 0.88; I2 = 0%; p < 0.00001), relative to the control group. The difference of 6-month pooled result was more clinically important. Results from analysis of secondary outcomes showed that gabapentin had no beneficial efficacy during the first 3 months of treatment. Although gabapentin treatment was associated with a higher risk of dizziness and somnolence, no statistically significant differences were observed with regards to the total incidence of adverse events. CONCLUSIONS: Overall, gabapentin could be a potential treatment option for CPP in women. However, as a pilot study, further studies are needed to explore the longer-term benefits and definite safety of this therapy in the future. REGISTRATION NUMBER: PROSPERO registration number CRD42021249421.

Primary Pleural Squamous Cell Carcinoma, Highly Positive PD-L1, Shows Marked Response to Camrelizumab: A Case Report.

Here, we reported the rare case of primary pleural squamous cell carcinoma (PPSCC) in a 71-year-old male patient. After chemo and targeted therapies, the patient showed continuous tumor progression and clinical deterioration. Fortunately, the patient had a high expression level of PD-L1 (80%) in the tumor tissues. Ultimately, the patient survived for additional 6 months with camrelizumab treatment. In summary, camrelizumab may be a good candidate for the treatment of PPSCC, especially in tumors with high PD-L1 expression.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

Hangeshashinto for preventing oral mucositis in patients receiving cancer treatment: protocol for a systematic review and meta-analysis.

INTRODUCTION: Hangeshashinto has been employed for oral mucositis prevention in patients receiving cancer treatment, but the evidence has not been sufficiently robust to guide clinical decision-making. This study will therefore be undertaken to assess the effectiveness of Hangeshashinto for preventing oral mucositis in patients with cancer who are receiving treatment. METHODS AND ANALYSIS: The databases will include PubMed, Embase, the Cochrane Library, Chinese databases and Japanese databases. The literature will be searched from the databases' inception until May 2021. Other sources, such as potential grey literature, reference lists from included studies and relevant systematic reviews and conference papers, will also be searched. The primary outcome is the incidence of mucositis of any severity, and the secondary outcomes are interruptions to cancer treatment, oral pain and nutritional status. The risk of bias of eligible studies will be assessed using the Cochrane Collaboration's 'risk of bias' tool. Both the Q test and I2 statistic will be performed to assess statistical heterogeneity. If I2 >50%, sensitivity and subgroup analysis will be conducted. The quality of evidence will be rated according to the Grading of Recommendations, Assessment, Development and Evaluation approach. Egger's test will be used to assess reporting bias. ETHICS AND DISSEMINATION: This systematic review will evaluate only published data; therefore, ethical approval is not required. PROSPERO REGISTRATION NUMBER: CRD42020216145.

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis.

INTRODUCTION: Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs). METHODS: RCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs). RESULTS: A total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes. CONCLUSIONS: In emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42020223000.

Nalbuphine Versus Ketorolac as an Adjuvant to Local Wound Infiltration Anesthesia in Open Colorectal Surgery: A Prospective Randomized Controlled Study.

INTRODUCTION: Adding adjuvants to local wound infiltration (LWI) provides long analgesic duration with fewer adverse effects. We aimed to compare the clinical effects of nalbuphine and ketorolac as an adjuvant to LWI in patients undergoing open colorectal cancer surgery. METHOD: A total of 126 ASA I-III patients aged ≥ 18 years who were scheduled for open colorectal cancer surgery were included. Patients were randomly assigned to receive LWI using 10 mL 0.75% ropivacaine, with 20 mL normal saline (group R), 10 mg nalbuphine in 1 mL (group RN), or 25 mg ketorolac in 0.8 mL (group RK). Analgesia duration was the primary outcome. The total 48-h postoperative morphine-equivalent consumption and additional rescue analgesia rates were recorded as key secondary outcomes. RESULTS: Among 126 patients randomized, 124 completed the trial. The duration until the first press of the analgesia pump was significantly shorter in group R (median: 320.0 min) compared with group RN (median: 829.5 min) and group RK (median: 820.0 min) (P < 0.001). The median difference in morphine consumption was 113.0 mg for group R vs. group RN (P < 0.001), and 115.5 mg for group R vs. group RK (P < 0.001). The proportion of patients using additional morphine within the first day after surgery in group R showed a higher relative risk (RR) compared with group RN (RR, 3.89; P = 0.001) and group RK (RR, 3.17; P = 0.001). There were no apparent differences between the RN and RK groups in any outcomes, whether in adjusted or unadjusted analysis. CONCLUSIONS: Among patients undergoing open colorectal cancer surgery, both nalbuphine and ketorolac infiltration achieved equally prolonged duration of analgesia and reduced morphine consumption compared with ropivacaine alone after surgery, suggesting that the equivalent analgesic dose of nalbuphine and ketorolac as local anesthetic adjuvants in LWI could have a similar analgesic effect. TRIAL REGISTRATION: ChiCTR1800019209.