A study on the 10-year trend of surgeries performed for lumbar disc herniation and comparative analysis of prescribed opioid analgesics and hospitalization duration: 2010-2019 HIRA NPS Data.

BACKGROUND: This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010-2019) trends in various types of lumbar spine surgeries performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed. METHOD: This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010-2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery. RESULTS: Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days). CONCLUSION: This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010-2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.

Systemic Analgesic Effects of Electroacupuncture in Healthy Individuals: Thermal Threshhold, Acupuncture Sensation Intensity and De-qi on Quantitative Sensory Test.

Background: Electroacupuncture (EA) has been known to exert analgesic effects according to several reports, but studies investigating the analgesic effect of EA using the quantitative sensory test (QST) are rare. Primary Study Objective: To investigate the analgesic effects of electroacupuncture through changes in thermal thresholds measured using the QST. Design: Pilot, randomized, single-blind, parallel design. Setting: The study was conducted at Dongguk University Bundang Oriental Hospital (DUBOH) in South Korea. Participants: We included 40 healthy participants age 20 to 40 years. Intervention: The EA group received EA for 30 minutes at 6 acupuncture points (LI4, PC6, LI10, LI11, ST36, and SP6) and the control group just rested. Outcome measures: The primary outcome measure was 4 thermal thresholds including warm detection (WDT), cold detection (CDT), hot pain (HPT), and cold pain (CPT) measured using QST at baseline and after 15, 30 and 60 minutes. The secondary outcomes were the intensity of acupuncture sensation (visual analogue scale [VAS]) and De-qi (Massachusetts General Hospital Acupuncture Sensation Scale [MASS]). Results: The EA group showed significant changes in HPT (P < .001) and CPT (P = .049) compared with the control group, whereas WDT and CDT did not significantly differ. Furthermore, the changes in thermal thresholds were more pronounced in the higher intensity acupuncture sensation group (VAS ≥40) than in the lower intensity group (VAS < 40), although not significantly. The high De-qi group presented greater changes in WDT, CDT, HPT and CPT than the low De-qi group, as measured using MASS. It was especially statistically significant at HPT a feeling of "heaviness" and "dull pain" and at CDT of "tingling." We observed no adverse events related to the study. Conclusion: The change in thermal pain thresholds effected by EA supports the analgesic effect of EA reported in previous studies. The underlying mechanisms need to be holistically considered, and further studies are needed for definitive evidence.

Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by δ-Opioid and α2-Adrenergic Receptors in Osteoarthritic Rats.

Context • Pain from osteoarthritis is associated with peripheral nociception and central pain processing. Given the unmet need for innovative, effective, and well-tolerated therapies, many patients, after looking for more satisfactory alternatives, decide to use complementary and alternative modalities. The analgesic mechanism of subcutaneous injections of diluted bee venom into an acupoint is thought to be part of an anti-inflammatory effect and the central modulation of pain processing. Objectives • Using the rat model of collagenase-induced osteoarthritis (CIOA), the study intended to investigate the analgesic effects of bee venom acupuncture (BVA) as they are related to the acupuncture points and dosage used and to determine whether the analgesic mechanisms of BVA for pain were mediated by opioid or adrenergic receptors. Design • Male Sprague-Dawley rats were randomly assigned to one of 19 groups, with n = 10 for each group. Setting • The study was conducted at the East-West Bone and Joint Research Institute at Kyung Hee University (Seoul, South Korea). Intervention • All rats were intra-articularly injected with collagenase solution in the left knee, followed by a booster injection performed 4 d after the first injection. For the groups receiving BVA treatments, the treatment was administered into the ST-36 acupoint, except for 1 group that received the treatment into a nonacupoint. Three BVA intervention groups received no pretreatment with agonists or antagonists; 1 of them received a dose of 1 mg/kg of bee venom into acupoint ST-36, 1 received a dose of 2 mg/kg into acupoint ST-36, and 1 received a dose of 1 mg/kg into a nonacupoint location. For the intervention groups receiving pretreatments, the opioid-receptor or adrenergic-receptor agonists or antagonists were injected 20 min before the 1-mg/kg BVA treatments. Outcome Measures • Changes in the rats' pain thresholds were assessed by evaluation of pain-related behavior, using a tail flick latency unit. Results • The pain reached its maximum value after 4 wk of CIOA induction. The 1-mg/kg ST-36 BVA treatment resulted in a more significant analgesic effect than nonacupoint BVA. Pain-related behavior was more effectively improved by treatment with 1 mg/kg of BVA than with 2 mg/kg of BVA. The analgesic effects of the BVA were not synergistic with the agonist pretreatments with the µ-, δ-, or κ-opioid receptors or with the α1-, α2-, and ß-adrenergic receptors. The analgesic effects of the BVA were not decreased by the antagonist pretreatments for the µ- or κ-opioid receptors or for the α1- or ß-adrenergic receptors. The ST-36-BVA-induced analgesia was inhibited by the antagonist pretreatments for the δ-opioid receptor and the α2-adrenergic receptor. Conclusion • The ST-36 BVA treatment exerted an analgesic effect on CIOA-induced pain through the partial involvement of the δ-opioid and α2-adrenergic receptors.

Moxibustion for cancer-related fatigue: study protocol for a randomized controlled trial.

BACKGROUND: Cancer-related fatigue is one of the most common symptoms experienced by cancer patients, and it diminishes their quality of life. However, there is currently no confirmed standard treatment for cancer-related fatigue, and thus, many patients who suffer cancer-related fatigue seek complementary and alternative medicines such as moxibustion. Moxibustion is one of the most popular therapies in traditional Korean medicine used to manage fatigue. Recent studies have also demonstrated that moxibustion is effective for treating chronic fatigue. However, there is insufficient evidence supporting the effect of moxibustion against cancer-related fatigue. The aim of this study is to assess the efficacy and safety of moxibustion treatment for cancer-related fatigue. METHODS/DESIGN: A multi-center, three-armed parallel, randomized controlled trial will be conducted. Ninety-six patients with cancer-related fatigue will be recruited from three clinical research centers. They will be randomly allocated to one of three groups in a 1:1:1 ratio. The moxibustion group will receive moxibustion treatment at CV8, CV12, LI4 and ST36. The sham moxibustion group will receive sham moxibustion at non-acupoints. Both the moxibustion and sham moxibustion groups will receive 30-min treatments twice a week for 8 weeks. The usual care group will not receive moxibustion treatment. All participants will be educated via a brochure on how to manage cancer-related fatigue in daily life. The outcome measurements will be evaluated at baseline, week 5, week 9, and week 13 by assessors who are blinded to the group allocation. The primary outcome measure will be the mean change in the average scores of the Brief Fatigue Inventory before and after treatments between groups. The secondary outcome measures will be the mean difference in changes from baseline of the Brief Fatigue Inventory, functional assessments of cancer therapy-fatigue, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 scores, and Montreal Cognitive Assessment scores between groups. Safety will be assessed by monitoring adverse events at each visit. DISCUSSION: The results of this study will provide evidence to confirm whether moxibustion can be used as a therapeutic option for treating cancer-related fatigue. TRIAL REGISTRATION: Clinical Research Information Service KCT0002170 . Registered 16 December 2016.

The electroacupuncture-induced analgesic effect mediated by 5-HT1, 5-HT3 receptor and muscarinic cholinergic receptors in rat model of collagenase-induced osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is an degenerative disease characterized by chronic joint pain. Complementary and alternative treatment such as acupuncture have been utilized to alleviate pain. The objective of this study was to investigate the analgesic mechanisms of electroacupuncture (EA) in the collagenase-induced osteoarthritis (CIOA) rat model. METHODS: Four weeks after inducing CIOA by injecting collagenase solution into the left knee of 5-week-old male Sprague-Dawley rats, 2 Hz and 100 Hz EA on Zusanli (ST 36) was performed. The analgesic effect of EA was evaluated by the tail flick latency (TFL) and paw pressure threshold (PPT) tests. To investigate the analgesic mechanism, serotonergic and muscarinic cholinergic receptor agonists and antagonists were injected 20 min prior to EA and the resultant changes were evaluated by the TFL and PPT tests. RESULTS: EA on Zusanli (ST 36) demonstrated an analgesic effect in the CIOA rat model. The 2 Hz EA treatment showed a significantly greater analgesic effect than the 100 Hz treatment. The analgesic effect of 2 Hz EA was not strengthened by 5-HT1, 5-HT2, 5-HT3, and muscarinic cholinergic receptor agonist pretreatment, was blocked by 5-HT1, 5-HT3, and muscarinic cholinergic receptor antagonist pretreatment, but not blocked by 5-HT2 receptor antagonist pretreatment. CONCLUSIONS: In the CIOA rat model, EA on Zusanli (ST 36) exhibited analgesic effects, and 2 Hz EA resulted in a significantly greater analgesic effect than 100 Hz EA. The analgesic effect of 2 Hz EA was reduced by pretreatment of 5-HT1 receptor, 5-HT3 receptor and muscarinic cholinergic receptor antagonists.

Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1ß in mesenchymal stem cells from subchondral bone and targets multiple aspects of the Smad and SOX9 pathways.

Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1ß-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1ß (IL-1ß). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-ß, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y-box (SRY-box) containing gene 9 (SOX9), type 2α1 collagen (Col2α1), cartilage link protein, and aggrecan. In IL-1ß-stimulated MSCs, mangiferin significantly reversed the production of TGF-ß, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1ß-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.

Survey on the current usage of ultrasound-guided procedures in Korean Medicine Clinics and Hospitals.

Ultrasound-guidance is applied during the administration of Korean medicine (KM) interventions to improve the safety and effectiveness of the interventions. Although many case series and reports on the use of ultrasound-guided KM interventions have been reported, no study has investigated the current use of ultrasound-guidance in clinical practice by doctors of Korean medicine (KMDs). An online survey was conducted with questions examining the status of ultrasound-guidance usage among KMDs practicing in various KM clinical settings. Survey responses from 335 KMDs were collected. Ultrasound started to be widely used in the clinical practice of KM since 2022. The primary objective of using ultrasound-guidance was "To improve the accuracy and efficacy" by 54.6%. Ultrasound-guidance was most frequently applied for shoulder joint diseases, and pharmacopuncture was the most frequently used intervention (76.1% and 90.4%, respectively). The respondents reported that effectiveness could be enhanced the most in nerve entrapment syndromes and especially when used in shoulder joints. Over 90% of KMDs responded that the safety and efficacy of treatment, specialty, and patients' satisfaction were improved after adopting ultrasound-guidance. Moreover, 94.9% of KMDs agreed with the necessity for reimbursement of ultrasound-guidance in KM under national health insurance coverage. Most KMDs responded that they had positive perceptions regarding the clinical use of ultrasound-guidance in KM in terms of treatment effects, safety, and patient satisfaction, and the need for national health insurance coverage of the service. Our findings may provide practice-based evidence for conducting clinical studies.

Analgesic effect of electroacupuncture on inflammatory pain in collagen-induced arthritis rats: mediation by alpha2- and beta-adrenoceptors.

This study was designed to investigate whether alpha- and beta-adrenergic systems mediate the analgesic effect of electroacupucture (EA) on inflammatory pain in a rat model of collagen-induced arthritis (CIA). To induce CIA, male Sprague-Dawley rats were immunized with bovine type II collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later. After induction of arthritis, the inflammatory pain threshold by the tail flick latency decreased as time passed and reached the minimum value at 4th week. Four weeks after the first immunization, low-frequency EA stimulation (2 Hz, 0.07 mA, 0.3 ms) delivered to Zusanli (ST(36)) for 30 min showed the analgesic effect. And also, the analgesic effect of EA was blocked by pretreatment with yohimbine (alpha2-adrenoceptor antagonist, 2 mg/kg, i.p.), but not by pretreatment with prazosin (alpha1-adrenoceptor antagonist, 1 mg/kg, i.p.) and propranolol (non-selective beta-adrenoceptor antagonist, 10 mg/kg, i.p.). These results suggest that the low-frequency EA can relieve the inflammatory pain in CIA, and the analgesic effect of EA can be mediated by alpha2- and beta-adrenoceptor, but not by alpha1-adrenoceptor.

The analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagenase-induced arthritis: mediation by opioidergic receptors.

Electroacupuncture (EA) is widely practiced for the treatment of osteoarthritic (OA) pain, but its therapeutic mechanisms have not yet been fully studied, especially in the experimental OA rat model. In order to induce collagenase-induced arthritis (CIA) in rats, male Sprague-Dawley rats were intra-articularly injected with 0.05 ml of 4 mg/ml collagenase solution in the left knee of the hind limb, followed by a booster injection 4 days later. Maximal gross, histopathological features and biomarker activity changes consistent with human OA characteristics were observed four weeks after the first collagenase injection. In the exploratory preliminary study of EA stimulation parameters, low-frequency train pulse EA stimulation (2 Hz, 0.07 mA, 0.3 ms) delivered to the Zusanli (ST36) acupoint exerted an antinociceptive effect with acupoint specificity in a rat model of CIA. The antinociceptive effect of Zusanli EA was blocked by intraperitoneal pretreatment with naloxone (µ-opioid receptor antagonist, 2 mg/kg) and naltrindole (δ-opioid receptor antagonist, 1 mg/kg), but not with norbinaltophimine (κ-opioid receptor antagonist, 20 mg/kg). The synergistic antinociceptive effects of Zusanli EA were achieved with statistical significance by i.p. pretreatment with DAMGO (µ-opioid receptor agonist, 1 mg/kg) and with [D-Ala2]-Deltorphin II (δ-opioid receptor agonist, 6 mg/kg), but not with (±)-U-50488 (κ-opioid receptor agonist, 3 mg/kg). These results suggest that the 2-Hz EA can attenuate the osteoarthritic pain in CIA, and the analgesic effects of EA can be mediated by µ-opioid and δ-opioid, but not by κ-opioid receptors.

Clinical effectiveness of bee venom acupuncture and physiotherapy in the treatment of adhesive capsulitis: a randomized controlled trial.

BACKGROUND: Bee venom acupuncture (BVA) has been used in the treatment of adhesive capsulitis (AC) in the clinical field. This study aimed to investigate whether the addition of BVA to physiotherapy (PT) would be more effective in the management of AC, and whether BVA would have a dose-dependent effect. MATERIALS AND METHODS: Sixty-eight patients diagnosed with AC were recruited into 3 groups; BV 1 (1:10,000 BVA plus PT), BV 2 (1:30,000 BVA plus PT), and group 3 (normal saline (NS) injection, as a control, plus PT). PT was composed of 15 minutes of transcutaneous electrical nerve stimulation (TENS), transcutaneous infrared thermotherapy (TDP), and manual PT. Treatments were given in 16 sessions within 2 months. Shoulder pain and disability index (SPADI), pain visual analogue scale (VAS), and 3) active/passive range of motion (ROM) were measured before treatment and at 2, 4, 8, and 12 weeks after the treatment. RESULTS: All 3 groups showed statistically significant improvements in SPADI, pain VAS scores, and active/passive ROM. The BV 1 group showed significantly better outcomes in SPADI at 8 and 12 weeks, in pain VAS (at rest) at 8 weeks, and in pain VAS (during exercise) at 12 weeks than the NS group. No significant differences were found in active/passive ROM among all the groups. CONCLUSION: BVA in combination with PT can be more effective in improving pain and function than PT alone in AC. However, the effectiveness of BVA was not shown in a dose-dependent manner.

Thermal stimulation with meridian points for enhanced recovery after spine surgery: A PRISMA-compliant protocol for network meta-analysis of randomized controlled trials.

BACKGROUND: Enhanced recovery after surgery programs are widely known as a far-reaching approach to help patients with surgeries recover rapidly by giving optimized care. However, especially in the spine medicinal domain, relevant studies are scarce. In order to manage proper recovery after surgery, practitioners need to take a comprehensive look at the suppression of pain, strategies for improving the results of surgery, improving the quality of life, and mental support of patients. To this end, a recovery-enhancing program through integrated medical technology which covers both conventional and Korean medicine is highly required. We want to develop an integrated medical program that covers a wide range of medicinal domains for the early recovery of patients after spinal surgery. The aim of the present study is to check out which thermal stimulation with meridian points are more effective than others to enhance recovery after spinal surgery. METHODS: The following online databases will be retrieved in the present study: PubMed; Scopus; the Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid EMBASE; Chinese Biomedical Literature Database; China National Knowledge Infrastructure; and Chinese Scientific Journal Database (VIP database). We will independently classify articles and will encapsulate characteristics of the study components. Primary outcomes will be categorized into visual analog scale, Tolerance to liquid and solid diet, postoperative hospitalization period, and quality of life. Secondary outcomes will be analyzed based on the study findings. RESULTS AND CONCLUSION: The results of this study will be submitted to a peer-reviewed journal for publication. Furthermore, the outcomes of this study would afford the documentation of whether thermal stimulation on meridian points can be effective for enhanced recovery after spine surgery.

Impact of different nutritional approaches on sarcopenia: a protocol for systematic review and network meta-analysis.

Although it is known that proper nutrition is effective in managing sarcopenia, the most powerful nutrients have not yet been determined. This study is designed to investigate the effects of various nutritional approaches on muscle mass, muscle strength, and sarcopenia prevention in systematic reviews. In study design, network and pairwise meta-analyses of randomized clinical trials were considered. Clinical studies regarding the nutritional effects associated with the physiological activity of skeletal muscle and management of sarcopenia will be covered. The main outcomes will cover the following five elements: anti-fatigue impact with skeletal muscle, muscle atrophy prevention, differentiation level with skeletal muscular cell, anti-inflammatory effect, and muscle injury prevention. Authors will conduct the study selection, extracting data process, and methodological quality investigation.Systematic review registrationOSF registry (ethical approval number: https://osf.io/ye4q7 ).

Efficacy, Safety and Cost-Effectiveness of Thread-Embedding Acupuncture for Adhesive Capsulitis (Frozen Shoulder): A Study Protocol for a Multicenter, Randomized, Patient-Assessor Blinded, Controlled Trial.

Background: The aim of the present study is to confirm the efficacy, safety, and cost-effectiveness of thread-embedding acupuncture (TEA) in the treatment of adhesive capsulitis (AC). Methods: This is a randomized, sham-controlled, patient-assessor blinded trial with two parallel arms in a 1:1 ratio. A total of 160 participants with AC, also known as frozen shoulder, will be recruited and screened according to the eligibility criteria. Those who meet the eligibility criteria will be randomly allocated to a TEA group or a sham TEA (STEA) group. Both groups will receive either real TEA or thread-removed STEA treatment on nine acupoints once a week for 8 weeks while being blinded to the intervention. The shoulder pain and disability index will be evaluated as a primary outcome measure. In addition, a 100-mm pain visual analogue scale, rotator cuff quality of life scale, European Quality of Life 5-dimension 5-level scale, treatment satisfaction, safety assessment, and economic evaluation will be assessed as secondary outcome measures. Outcome assessments will be conducted for a total of 24 weeks, including a treatment period of 8 weeks and follow-up of 16 weeks, according to the schedule. Discussion: The results of this trial will provide a clinical basis for the efficacy, safety and cost-effectiveness of TEA in the treatment of patients with AC. Trial Registration Number: KCT0005920 (Clinical Research Information Service of the Republic of Korea). Registered on 22 February 2021.

Oriental medicine as collaborating treatments with conventional treatments for knee osteoarthritis: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: We aimed to evaluate the effectiveness and safety of oriental medicine (OM) treatments as monotherapy and add-on therapy compared to conventional treatments for knee osteoarthritis and assess the quality of evidence for these results. OM treatment included acupuncture, herbal medicine, pharmacoacupuncture, and moxibustion. METHODS: PubMed, Embase, Cochrane, Google Scholar, 4 Korean medical databases (KoreaMed, Korean Studies Information Service System, Research Information Service System, and Oriental Medicine Advanced Searching Integrated System), and one Chinese database (China National Knowledge Infrastructure) were searched for articles published between January 1, 2000, and January 1, 2021. Randomized controlled trials (RCTs) investigating the effect of OM interventions, single or combined with conventional treatments, on knee osteoarthritis were searched. The risk of bias and quality of evidence of the included studies were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation methods, respectively. RESULTS: A total of 3911 relevant studies were retrieved and only 23 studies were included for systematic review. Most of the studies showed a significant effect on knee osteoarthritis. 21 studies comparing single OM treatment with conventional treatment were included in the meta-analysis. The effect size of standardized mean difference (SMD) was analyzed as a "small effect" with 0.48 (95% CI -0.80 to -0.16, Z = 2.98, P = .003). In addition, a meta-analysis of 4 studies comparing integrative treatment with conventional treatment showed a "very large effect" with 1.52 (95% CI -2.09 to -0.95, Z = 5.19, P < .001). CONCLUSION: Our results suggest that single OM treatment and integrative treatment significantly reduce pain in patients with knee osteoarthritis. However, there is a limited number of RCTs considering integrative treatment which implies more related RCTs should be conducted in the future.

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03-1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04-1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.

Efficacy and Safety of SIKD1977 in Combination with Standard Treatment for Postherpetic Neuralgia: Study Protocol for a Double Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Clinical Trial.

Purpose: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, associated with poor quality of life and increased patient and healthcare resource expenditure. This randomized controlled trial aims to evaluate the efficacy and safety of SIKD1977 (Sogeonjungtang) in combination with standard treatment and estimate an effective dose for treating PHN. Patients and Methods: This is a protocol for a randomized, placebo-controlled, double-blind, multicenter trial. A total of 90 eligible participants with PHN will be recruited from three hospitals and randomly allocated to high-dose group, low-dose group, or placebo group in a 1:1:1 ratio. The trial will involve a 6-week oral administration of SIKD1977/placebo, and a 1-week follow-up period. The primary outcome will be the weekly average change in average daily pain score (ADPS) from baseline to the end of treatment. The secondary outcomes will include the weekly average changes in ADPS from baseline to week 2, 4, and 7, differences in Short-Form McGill Pain Questionnaire, Visual analogue scale, 5-level EuroQol-5 dimensions, Patient Global Impression of Change, and consumption of rescue drugs. All adverse events will be assessed during the trial. Conclusion: This study will provide evidence for the efficacy and safety of SIKD1977, and an effective dose for PHN. Trial Registration: This protocol has been registered in the Clinical Research Information Service with the identification code KCT0007939.

Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial.

BACKGROUND: Electroacupuncture (EA) may reduce the severity of acute pancreatitis (AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented. OBJECTIVE: This study was undertaken to compare the pain-relieving effects of EA and conventional treatment in patients with AP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted using a randomized, controlled, three-arm, parallel-group and multi-center design. Patients diagnosed with AP were randomly and equally assigned to EA1, EA2 or control groups. All participants received conventional standard-of-care therapy for AP. Local EA alone was administered in EA1, and local plus distal EA was given in EA2. Local EA included two abdominal acupoints, while distal EA included twelve peripheral acupoints. EA groups underwent one session of EA daily for 4 days (days 1-4), or until pain was resolved or discharged. MAIN OUTCOME MEASURES: The primary outcome measure was the change in the visual analogue scale (VAS; 0-100) pain score between baseline and day 5. RESULTS: Eighty-nine participants were randomized into EA1, EA2 and control groups, and 88 (EA1, 30; EA2, 29; control, 29) were included in the full-analysis set. VAS score change (median [interquartile range]) on day 5 was (12.3 ± 22.5) in the EA1 group, (10.3 ± 21.5) in the EA2 group, and (8.9 ± 15.2) in the control group. There were not significant differences in the change in VAS score among treatments (P = 0.983). However, time to food intake was significantly shorter in the EA group (EA1 + EA2) than in the control group (median 2.0 days vs 3.0 days), with a hazard ratio of 0.581 (P = 0.022; 95% CI, 0.366-0.924). No significant adverse events occurred. CONCLUSION: EA treatment did not significantly reduce pain after 4 days of treatment in patients with AP-associated abdominal pain but significantly reduced time to first food intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03173222. Please cite this article as: Jang DK, Lee JK, Jung CY, Kim KH, Kang HR, Lee YS, Yoon JH, Joo KR, Chae MK, Baek YH, Seo BK, Lee SH, Lim C. Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial. J Integr Med. 2023; 21(6): 537-542.

Standardized butanol fraction of WIN-34B suppresses cartilage destruction via inhibited production of matrix metalloproteinase and inflammatory mediator in osteoarthritis human cartilage explants culture and chondrocytes.

BACKGROUND: WIN-34B is a novel Oriental medicine, which represents the n-butanol fraction prepared from dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE. The component herb of WIN-34B is used for arthritis treatment in East Asian countries. The aim of this study was to determine the cartilage-protective effects and mechanisms of WIN-34B and its major phenolic compounds, chlorogenic acid and mangiferin, in osteoarthritis (OA) human cartilage explants culture and chondrocytes. METHODS: The investigation focused on whether WIN-34B and its standard compounds protected cartilage in interleukin (IL)-1ß-stimulated cartilage explants culture and chondrocytes derived from OA patients. Also, the mechanisms of WIN-34B on matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinases (TIMPs), inflammatory mediators, and mitogen-activated protein kinases (MAPKs) pathways were assessed. RESULTS: WIN-34B was not cytotoxic to cultured cartilage explants or chondrocytes. WIN-34B dose-dependently inhibited the release of glycosaminoglycan and type II collagen, increased the mRNA expression of aggrecan and type II collagen, and recovered the intensity of proteoglycan and collagen by histological analysis in IL-1ß-stimulated human cartilage explants culture. The cartilage protective effect of WIN-34B was similar to or better than that of chlorogenic acid and mangiferin. Compared to chlorogenic acid and mangiferin, WIN-34B displayed equal or greater decreases in the levels of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, and markedly up-regulated TIMP-1 and TIMP-3. WIN-34B inhibited inflammatory mediators involved in cartilage destruction, such as prostaglandin E2, nitric oxide, tumor necrosis factor-alpha, and IL-1ß. The phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38 was significantly reduced by WIN-34B treatment, while phosphorylation of JNK was only inhibited by chlorogenic acid or mangiferin in IL-1ß-stimulated chondrocytes. CONCLUSIONS: WIN-34B is potentially valuable as a treatment for OA by virtue of its suppression of MMPs, ADAMTSs, and inflammatory mediators, and it's up-regulation of TIMP-1 and TIMP-3 involved in the MAPK pathway.

Spadework for Establishing Integrative Enhanced Recovery Program After Spine Surgery: Web-Based Survey Assessing Korean Medical Doctors' Perspectives.

Introduction: Efforts are necessary to promote postoperative patient management to reduce complications or side effects, particularly those adapted to spinal surgery. Considering compatible medical system in Korea, the study objective is to report the opinions of Korean medical doctors regarding integrative enhanced recovery after spine surgery. Methods: From December 2020 to January 2021, members of the Korean Medical Association were asked to complete an online questionnaire regarding an integrative enhanced recovery program after spine surgery. A total of 726 participants responded to the survey. Results: Approximately half of the respondents had more than 10 years of medical experience in the Korean health-care system, and 58.29% were affiliated with primary Korean medical clinics. The majority of respondents were not aware of the ERAS program (N = 412, 79.08%) but said that patient management would be advanced from the establishment of a postoperative medical program that reflected an integrated medical perspective (N = 505, 96.92%). Furthermore, Korean medical professionals believe that Korean medical interventions should play a major role in the pain management and digestive improvement sections of the upcoming postoperative program. Moreover, respondents claimed that Korean traditional medical modalities such as acupuncture, moxibustion, cupping, and herbal decoction should be included in the program. Discussion/Conclusion: Responses collected from the present study can be used as a spadework for future studies. A study on the development of a comprehensive postoperative program that reflects the perspectives of patients and conventional medical doctors is needed.

The effectiveness and safety of Simiao Xiaobi decoction on rheumatoid arthritis: A study protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disease that contributes to progressive disability, systemic complications, higher mortality, and societal burden. Typical symptoms of RA include symmetrical pain and swelling in multiple joints, morning stiffness, and elevated levels of erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor. The representative treatment for RA is medication, including disease-modifying antirheumatic drugs, glucocorticoids, and nonsteroidal anti-inflammatory drugs. However, these medications are not yet curative nor preventative and are associated with several adverse effects, leading to their discontinuation. Recent articles reported that Simiao Xiaobi decoction (SXD) could relieve the symptoms of RA by clinical trial and experimental study, but an evidence-based review on the effectiveness and safety of SXD on RA has not yet been provided. METHODS: Searching for randomized controlled trials on the use of SXD for RA will be performed by using multiple electronic databases, manual search, and contacting the authors by e-mail if needed. Studies will be selected according to the predefined criteria and the data collected on study participants, interventions, control groups, outcome measurements, their results, adverse events, and risk of bias will be summarized. The primary outcome will be the disease activity score (including effective rate, swollen joint count, tender joint count, and morning stiffness), and the secondary outcomes will be blood tests (including erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. We will use Review Manager software to perform a meta-analysis, the Cochrane Collaboration "risk of bias" tool for assessing the risk of bias, and grades of recommendation, assessment, development and evaluation for the determination of the quality of evidence. TRIAL REGISTRATION NUMBER: https://inplasy.com; INPLASY202230026. RESULTS: We are going to investigate the effectiveness and safety of SXD for RA. CONCLUSION: This study will provide reliable evidence on whether SXD is effective on RA.