Manual Therapy in Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.

Objective: This research aimed to assess the effectiveness of manual therapy in alleviating pain among women undergoing primary dysmenorrhea (PD). Methods: All randomized controlled trials (RCTs) regarding manual therapy for PD were searched from online databases, spanning from their inception to July 2023. The identified literature underwent a thorough screening process, and the data were meticulously extracted and analyzed using RevMan 5.3. Subsequently, the included studies underwent Cochrane's quality assessment and meta-analysis. The evidence obtained was then assessed using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. Results: 32 RCTs, involving 2566 women were finally included for analysis. The overall quality of the concluding evidence was generally rated as low or very low. Performance bias and blind bias were found to be the main risk of bias of the included studies. In comparison to no treatment, manual therapy demonstrated a significant increase in pain relief in short-term (n=191, MD=1.30, 95% CI: 0.24~2.37). The differences in the effects of manual therapy and the placebo on pain intensity may not be statistically significant (n=255, MD=0.10, 95% CI: -0.37~0.58). In contrast to NSAIDs, manual therapy exhibited superior pain alleviation (n=507, MD=3.01, 95% CI: 1.08~4.94) and a higher effective rate (n=1029, OR=4.87, 95% CI: 3.29~7.20). Importantly, no severe adverse events were reported across all studies, indicating a relatively safe profile for manual therapy. Conclusion: Manual therapy presented promise in effectively relieving menstrual pain with minimal adverse events in short term, outperforming both no treatment and NSAIDs. However, this conclusion is tempered by the low quality of the included RCTs, highlighting the necessity for more robust trials to validate it.

Exploring the association between Frailty Index and low back pain in middle-aged and older Chinese adults: a cross-sectional analysis of data from the China Health and Retirement Longitudinal Study (CHARLS).

OBJECTIVES: This study explored the association between the Frailty Index (FI) and low back pain (LBP) in middle-aged and older Chinese adults. We hypothesised that a higher FI correlates with increased LBP prevalence. DESIGN: Cross-sectional analysis. SETTING: The study used data from the China Health and Retirement Longitudinal Study (CHARLS) across various regions of China. PARTICIPANTS: The analysis included 6375 participants aged 45 and above with complete LBP and FI data from the CHARLS for 2011, 2013 and 2015. We excluded individuals under 45, those with incomplete LBP data, participants with fewer than 30 health deficit items and those missing covariate data. OUTCOME MEASURES: We constructed an FI consisting of 35 health deficits. Logistic multivariable regression examined the relationship between FI and LBP, using threshold analysis to identify inflection points. Sensitivity analyses were performed to ensure the robustness of the findings. RESULTS: Of the participants, 27.2% reported LBP. A U-shaped association was observed between FI and LBP, with the highest quartile (Q4, FI ≥0.23) showing more than a twofold increased risk of LBP (OR=2.90, 95% CI: 2.45-3.42, p<0.001). Stratified analysis showed a significant association in participants under 60, particularly in the lowest FI quartile (OR=1.43, 95% CI: 1.14 to 1.79). Sensitivity analysis upheld the robustness of the primary results. CONCLUSIONS: The findings suggest a complex relationship between frailty and LBP, highlighting the need for early screening and tailored interventions to manage LBP in this demographic. Further research is necessary to understand the mechanisms of this association and to validate the findings through longitudinal studies.

Exploring the association between dietary Inflammatory Index and chronic pain in US adults using NHANES 1999-2004.

Chronic pain, a substantial public health issue, may be influenced by dietary patterns through systemic inflammation. This cross-sectional study explored the association between Dietary Inflammatory Index (DII) and chronic pain among 2581 American adults from NHANES data. The DII, ranging from - 4.98 to 4.69, reflects the inflammatory potential of the diet, with higher scores indicating greater pro-inflammatory capacity. Our findings showed no significant association between the continuous DII score and chronic pain prevalence. However, a nonlinear relationship emerged. When the DII was categorized, a significant association between higher DII scores (DII ≥ 2.5) and chronic pain prevalence was observed. The analysis uncovered a U-shaped pattern, with an inflection point at a DII score of - 0.9, indicating an association between both low and high levels of dietary inflammation are associated with higher pain prevalence. This nuanced interaction between dietary inflammation and chronic pain indicates the possibility of incorporating dietary modification into pain management strategies and underscores the need for further research into the long-term effects of diet on chronic pain.

The Efficacy of Neuromodulation Interventions for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Purpose: To determine the efficacy and safety of a neuromodulation intervention regimen in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Patients and Methods: Systematic searches were conducted in seven English databases. Randomized controlled trials of all neuromodulation interventions (both invasive and non-invasive) for the treatment of CIPN were selected. Group comparisons of differences between interventions and controls were also made. We divided the outcomes into immediate-term effect (≤3 weeks), short-term effect (3 weeks to ≤3 months), and long-term effect (>3 months). Results: Sixteen studies and 946 patients with CIPN were included. Among immediate-term effects, neuromodulation interventions were superior to usual care for improving pain (SMD=-0.77, 95% CI -1.07~ 0.47), FACT-Ntx (MD = 5.35, 95% CI 2.84~ 7.87), and QOL (SMD = 0.44, 95% CI 0.09~ 0.79) (moderate certainty); neuromodulation loaded with usual care was superior to usual care for improving pain (SMD=-0.47, 95% CI -0.71 ~ -0.23), and QOL (SMD = 0.40, 95% CI 0.12 ~ 0.69) (moderate certainty). There were no statistically significant differences between the neuromodulation interventions regimen vs usual care in short- and long-term outcomes and neuromodulation vs sham stimulation from any outcome measure. There were mild adverse events such as pain at the site of stimulation and bruising, and no serious adverse events were reported. Conclusion: Neuromodulation interventions had significant immediate-term efficacy in CIPN but had not been shown to be superior to sham stimulation; short-term and long-term efficacy could not be determined because there were too few original RCTs. Moreover, there are no serious adverse effects of this therapy.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism.

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

Short-term and long-term effectiveness of acupuncture and Tuina on knee osteoarthritis: study protocol for a randomized controlled trial.

Background: The effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA. Methods/design: This parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined. Clinical trial registration: https://www.chictr.org.cn.

Development of CORE-CM core outcome domain sets for trials of Chinese medicine for lumbar spinal stenosis.

OBJECTIVES: Most Asian countries have employed Chinese medicine (CM) and Western medicine to treat lumbar spinal stenosis (LSS). Evidence synthesis and comparison of effectiveness are difficult since outcomes examined and presented through trials possess heterogeneity. This study aimed to solve the outcome problems for CM clinical trials in LSS by building a core outcome set (COS). METHODS: To achieve an agreement on a set of core outcome domains, a four-phase study was carried out. First, we identified candidate outcome domains by systematically reviewing trials. In addition, we identified outcome domains associated with patients by conducting semistructured interviews with patients. Next, outcome domains were processed through a national two-round Delphi survey, in which 18 patients and 21 experts were recruited. Finally, the above domains were converted as a core outcome domain set based on a consensus meeting, in which 24 stakeholders were recruited. RESULTS: Seventeen outcome subdomains were identified by the systematic review and interviews. The Delphi survey assigned a priority to four outcome domains in the first round and four outcomes additionally in the second round. The core outcome domains were determined through discussion and redefinition of outcomes in the consensus meeting: pain and discomfort, health-related quality of life, lumbar function, activities of daily living, measures of walking, patient global assessment, adverse events and CM-specific outcomes. CONCLUSION: COS-CM-LSS is likely to enhance the consistency of outcomes reported in clinical trials. In-depth research should be conducted for the exploration of the best methods to examine the above outcomes.

Non-pharmaceutical Chinese medical therapies for degenerative lumbar spinal stenosis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of the study was to assess the effectiveness of utilizing Non-Pharmaceutical Chinese Medical (NPCM) therapy singularly or in combination for the treatment of Degenerative Lumbar Spinal Stenosis (DLSS). METHODS: The comprehensive search for all randomized controlled trials regarding NPCM therapies for the treatment of DLSS was performed through online databases searches, commencing from their inception to January 1st, 2023. The relevant literature underwent a thorough screening process, and the data was meticulously extracted and subjected to analysis through the implementation of RevMan 5.3 software. The Cochrane Risk of Bias tool was employed to assess the potential risk of bias. The synthesis of evidence was performed Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: The extensive search procedure produced 5674 records, including data from 37 studies of 38 comparisons (2965 participants). Moderate evidence was obtained demonstrating that the application of acupuncture for a duration of 6-8 weeks was significantly superior to sham acupuncture in terms of intermediate-term (6 months) alleviation of back pain (2 trials, n = 128; MD, -1.08; 95% CI, -1.81∼-0.34) and improvement in lumbar function (2 trials, n = 128; MD, -1.40; 95% CI, -2.93∼-0.13). The available low evidence suggested that, as compared to sham acupuncture, acupuncture was effective in reducing short-term (3 months) back pain and enhancing lumbar function but had no impact on leg pain. A trial with low risk of bias found that acupuncture was more effective than sham acupuncture in enhancing disability and walking capabilities. The other studies presented inconsistent evidence with regards to the efficacy of the various interventions employed. CONCLUSIONS: Evidence of low-to-moderate quality suggests that for DLSS patients, the implementation of acupuncture in comparison to sham acupuncture presents favorable outcomes in terms of short- and intermediate-term alleviation of back pain, improvement in lumbar function, enhancement of disability and walking capacity. The conclusion regarding the efficacy of other NPCM therapies was not obtained due to the insufficient quality of the available evidence. REGISTRATION: PROSPERO CRD42022307631.

A Protocol for a Single-Centered, Pragmatic, Randomized, Controlled, Parallel Trial Comparing Comprehensive Nonsurgical Therapy Options for Individuals with Lumbar Spinal Stenosis.

Aim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient's age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment. Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up. Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.

Similarities and Differences in Health-Related Quality-of-Life Concepts Between the East and the West: A Qualitative Analysis of the Content of Health-Related Quality-of-Life Measures.

OBJECTIVES: Most of the commonly used health-related quality of life (HRQoL) measures were developed in the West and have been introduced into other countries for use worldwide. Arguably, this adaptation process assumes that health, as a concept, has universal cultural equivalence. This study identified those Chinese-developed HRQoL measures and summarized their contents, with which the Western-developed HRQoL measures were compared, aiming to explore cultural differences in defining and measuring health between the East and the West. METHODS: A systematic literature search was conducted to identify Chinese-developed generic HRQoL measures. Two Western-developed HRQoL measures (EQ-5D, SF-36) and a cross-culturally developed measure (WHOQOL-100) were included for comparison. A qualitative content analysis was undertaken both deductively and inductively to categorize and summarize the content of the questionnaires in analyzing similarities and differences between Western and Chinese-developed HRQoL measures. RESULTS: Eight HRQoL measures that were designed in a Chinese cultural context were identified and compared with the 3 non-Chinese-developed HRQoL measures. Although there is an agreement between the East and the West regarding the domains and subdomains of HRQoL, health concepts including "emotion control," "weather adaption," "social adaption," "spirit," and "complexion" were exclusively introduced by the Chinese measures. CONCLUSIONS: The results demonstrate that health is a culturally grounded concept, and because of cultural differences, it cannot be taken for granted that a well-recognized Western HRQoL measure is always appropriate for use in other cultural contexts. This study implies the necessity of further examining the legitimacy of applying Western-developed HRQoL measures in other cultural settings.

Evidence-Based Study to Compare Daodi Traditional Chinese Medicinal Material and Non-Daodi Traditional Chinese Medicinal Material.

BACKGROUND: Daodi medicinal material is widely used in Chinese herb medication. However, there is a lack of systematic methodology for identifying characteristics associated with good quality and reliable efficacy of Daodi med-material. PURPOSE: The purpose of this study is to provide some evidence to further substantiate the use of Daodi medicinal materials. METHODS: Seven relevant databases were searched before July 2014. Two evaluators were responsible for screening and categorizing the results. The data was analyzed with Microsoft Excel 2007 and SPSS 21.0 statistical software. RESULTS: Overall, 107 articles were systematically analyzed. Of these studies, 55.1% (59/107) focused on the methodology to assess Daodi med-material, and 38.3% (41/107) were interested in med-material ingredients, soil physical and chemical properties, and the geological background system (GBS). Only 6.5% (7/107) of studies were mainly conducted as clinical trials and animal experiments. CONCLUSION: Comparisons between Daodi and non-Daodi materials have been studied mainly in terms of the ingredients or composition of medical materials, soil physics and chemistry, and the GBS, and some identifying methodologies have been created to identify Daodi attributes. Until now, there is still no consensus of comparison criteria between Daodi and non-Daodi medicinal material. Only a few studies were conducted through animal experiments and clinical trials to determine Daodi superiority.

Multistage analysis method for detection of effective herb prescription from clinical data.

Determining effective traditional Chinese medicine (TCM) treatments for specific disease conditions or particular patient groups is a difficult issue that necessitates investigation because of the complicated personalized manifestations in real-world patients and the individualized combination therapies prescribed in clinical settings. In this study, a multistage analysis method that integrates propensity case matching, complex network analysis, and herb set enrichment analysis was proposed to identify effective herb prescriptions for particular diseases (e.g., insomnia). First, propensity case matching was applied to match clinical cases. Then, core network extraction and herb set enrichment were combined to detect core effective herb prescriptions. Effectiveness-based mutual information was used to detect strong herb-symptom relationships. This method was applied on a TCM clinical data set with 955 patients collected from well-designed observational studies. Results revealed that groups of herb prescriptions with higher effectiveness rates (76.9% vs. 42.8% for matched samples; 94.2% vs. 84.9% for all samples) compared with the original prescriptions were found. Particular patient groups with symptom manifestations were also identified to help investigate the indications of the effective herb prescriptions.

Effectiveness of acupuncture for angina pectoris: a systematic review of randomized controlled trials.

BACKGROUND: The purpose of this systematic review is to assess the effectiveness of acupuncture for angina pectoris. METHODS: Eleven electronic databases were searched until January 2013. The study included randomized controlled trials that the effectiveness of acupuncture alone was compared to anti-angina medicines (in addition to conventional treatment) and the effectiveness of a combination of acupuncture plus anti-angina medicines was compared to anti-angina medicines alone. The trial selection, data extraction, quality assessment and data analytic procedures outlined in the 2011 Cochrane Handbook were involved. RESULTS: The study included 25 randomized controlled trials (involving 2,058 patients) that met our inclusion criteria. The pooled results showed that the number of patients with ineffectiveness of angina relief was less in the combined acupuncture-anti-angina treatment group than in the anti-angina medicines alone group (RR 0.33, 95% CI 0.23-0.47, p < 0.00001, I2 = 0%). Similarly, compared to the anti-angina medicines alone group, fewer patients in the combined treatment group showed no ECG improvement (RR 0.50, 95% CI 0.40-0.62, p < 0.00001, I2 = 0%). However, no differences were observed between acupuncture treatment alone and anti-angina medicines alone for both outcome measures. Only four trials mentioned adverse effects. One trial found no significant difference between acupuncture and Chinese medicine, and three reported no adverse events. The quality of the trials was found to be low. CONCLUSIONS: The findings showed very low evidence to support the use of acupuncture for improving angina symptoms and ECG of angina patients. However, the quality of the trials included in this study was low. Large and rigorously designed trials are needed to confirm the potential benefit and adverse events of acupuncture.

Lung fibrosis: drug screening and disease biomarker identification with a lung slice culture model and subtracted cDNA Library.

Pulmonary fibrosis is a progressive and irreversible disorder with no appropriate cure. A practical and effective experimental model that recapitulates the disease will greatly benefit the research community and, ultimately, patients. In this study, we tested the lung slice culture (LSC) system for its potential use in drug screening and disease biomarker identification. Fibrosis was induced by treating rat lung slices with 1ng/ml TGF-ß1 and 2.5µM CdCl2, quantified by measuring the content of hydroxyproline, and confirmed by detecting the expression of collagen type III alpha 1 (Col3α1) and connective tissue growth factor (CTGF) genes. The anti-fibrotic effects of pirfenidone, spironolactone and eplerenone were assessed by their capability to reduce hydroxyproline content. A subtractive hybridisation technique was used to create two cDNA libraries (subtracted and unsubtracted) from lung slices. The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed to assess the subtraction efficiency of the subtracted cDNA library. Clones from the two libraries were sequenced and the genes were identified by performing a BLAST search on the NCBI GenBank database. Furthermore, the relevance of the genes to fibrosis formation was verified. The results presented here show that fibrosis was effectively induced in cultured lung slices, which exhibited significantly elevated levels of hydroxyproline and Col3α1/CTGF gene expression. Several inhibitors have demonstrated their anti-fibrotic effects by significantly reducing hydroxyproline content. The subtracted cDNA library, which was enriched for differentially expressed genes, was used to successfully identify genes associated with fibrosis. Collectively, the results indicate that our LSC system is an effective model for the screening of drug candidates and for disease biomarker identification.

EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts.

Long-term, low-dose macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis and cystic fibrosis, although the mechanisms by which it does so remain unknown. To elucidate the molecular mechanisms of the anti-inflammatory effects of macrolides, the authors examined the effects of erythromycin (EM-A) and new derivative EM703 on transforming growth factor (TGF)-beta /Smad signaling fibroblasts. EM-A and EM703 each inhibited fibroblast proliferation and the collagen production in human lung fibroblasts induced by TGF-beta. EM-A and EM703 inhibited the augmentation of Smad3 mRNA induced by TGF-beta. Smad7 mRNA was inhibited by TGF-beta, but augmented by coincubation with EM-A or EM703. EM-A and EM703 each inhibited p-Smad2/3 proteins induced by TGF-beta. Smad7 protein inhibited by TGF-beta restored beyond basal level by EM-A and EM703. These findings suggest that EM-A and EM703 inhibit TGF-beta signaling in human lung fibroblasts via inhibition of p-Smad2/3 through recovery of Smad7 level.

Effects of gefitinib on radiation-induced lung injury in mice.

Clinical studies have demonstrated that gefitinib, an epidermal growth factor receptor inhibitor, is an effective treatment for some patients with advanced non-small cell lung cancer and is generally well-tolerated. However, several reports have also suggested that gefitinib is associated with acute lung injury and subsequent fibrosis. One hypothesis is that gefitinib exacerbates lung injury induced by radiation therapy. It is important to confirm the safety of gefitinib in radiotherapy for patients with lung cancer. In this preclinical study we aimed to clarify the effect of gefitinib on thoracic radiotherapy. Six-week-old female C57BL/6 mice were immobilized in a plastic frame, and the thorax was irradiated once with a dose of 12 Gy on day 0. Gefitinib (20, 90 and 200 mg/kg/day) was administered on days 0 to 5 (acute phase) or days 14 to 19 (late phase) postirradiation. Thoracic irradiation induced lung injury and subsequent fibrosis 5 months later. Gefitinib, administered in the acute phase, had no effect on lung fibrosis or collagen levels induced by irradiation. A high dose of gefitinib (200 mg/kg/day) administered during the late phase significantly reduced fibrosis scores and collagen levels. These results suggest that gefitinib does not exacerbate radiation-induced lung injury and fibrosis in this strain of mice. Therefore, thoracic irradiation is unlikely to be a risk factor for lung injury associated with gefitinib treatment.