Although benzyl isothiocyanate (BITC), a major compound found in cruciferous vegetables, has been reported to exert antitumor effects in various cancers, its apoptotic mechanism remains unclear. This study aimed to elucidate the apoptotic mechanism of BITC by investigating its role in inhibiting Warburg effect in hepatocellular carcinoma (HCC) cells. BITC suppressed cell proliferation, increased the sub-G1 population, Annexin V/PI and reduced the expression of pro-poly (ADP-ribose) polymerase (pro-PARP), pro-caspase-3, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc, signal transducer and activator of transcription 3 (STAT3), and phosphorylated Janus kinase 1 (p-JAK1) in SK-Hep1 and Huh7 HCC cell lines. Notably, knockdown of STAT3 or its upstream regulator CNOT2 further enhanced BITC-induced apoptosis, as evidenced by decreased pro-PARP and pro-caspase-3 expression in SK-Hep1 cells. Additionally, BITC attenuated the expression of hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH) along with reduced LDH production and glucose in SK-Hep1 and Huh7 cells. However, treatment of pyruvate or overexpression of CNOT2 or c-Myc reversed the capacity of BITC to reduce the expression of HK2, pro-caspase-3, and pro-PARP in SK-Hep1 cells. Immunoprecipitation assays further revealed that BITC disrupted the interactions between CNOT2 and STAT3 or c-Myc. Collectively, these findings suggest that the CNOT2/c-Myc/STAT3 signaling axis plays a critical role in glycolysis mediated apoptosis of BITC in HCC cells.

Though Ginsenoside F2 (GF2), a protopanaxadiol saponin from Panax ginseng, is known to have an anticancer effect, its underlying mechanism still remains unclear. In our model, the anti-glycolytic mechanism of GF2 was investigated in human cervical cancer cells in association with miR193a-5p and the β-catenin/c-Myc/Hexokinase 2 (HK2) signaling axis. Here, GF2 exerted significant cytotoxicity and antiproliferation activity, increased sub-G1, and attenuated the expression of pro-Poly (ADPribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (procaspase3) in HeLa and SiHa cells. Consistently, GF2 attenuated the expression of Wnt, β-catenin, and c-Myc and their downstream target genes such as HK2, pyruvate kinase isozymes M2 (PKM2), and lactate dehydrogenase A (LDHA), along with a decreased production of glucose and lactate in HeLa and SiHa cells. Moreover, GF2 suppressed β-catenin and c-Myc stability in the presence and absence of cycloheximide in HeLa cells, respectively. Additionally, the depletion of β-catenin reduced the expression of c-Myc and HK2 in HeLa cells, while pyruvate treatment reversed the ability of GF2 to inhibit β-catenin, c-Myc, and PKM2 in GF2-treated HeLa cells. Notably, GF2 upregulated the expression of microRNA139a-5p (miR139a-5p) in HeLa cells. Consistently, the miR139a-5p mimic enhanced the suppression of β-catenin, c-Myc, and HK2, while the miR193a-5p inhibitor reversed the ability of GF2 to attenuate the expression of β-catenin, c-Myc, and HK2 in HeLa cells. Overall, these findings suggest that GF2 induces apoptosis via the activation of miR193a-5p and the inhibition of β-catenin/c-Myc/HK signaling in cervical cancer cells.

The current standard for the pharmacological management of lumbar disk herniation (LDH), involving non-steroidal anti-inflammatory drugs, muscle relaxants, and opioid analgesics, often carries a risk of adverse events. The search for alternative therapeutic options remains a vital objective, given the high prevalence of LDH and the critical impact on the quality of life. Shinbaro 2 is a clinically effective herbal acupuncture against inflammation and various musculoskeletal disorders. Therefore, we explored whether Shinbaro 2 exerts protective effects in an LDH rat model. The results showed that Shinbaro 2 suppressed pro-inflammatory cytokines, interleukin-1 beta, tumor necrosis factor-alpha, disk degeneration-related factors, matrix metalloproteinase-1,−3,−9, and ADAMTS-5 in LDH rats. Shinbaro 2 administration reinstated a behavioral activity to a normal level in the windmill test. The results indicated that Shinbaro 2 administration restored spinal cord morphology and functions in the LDH model. Therefore, Shinbaro 2 exerted a protective effect in LDH via actions on inflammatory responses and disk degeneration, indicating that future research is warranted to assess the action mechanisms further and validate its effects.

A systematic review was conducted to evaluate the effectiveness of herbal medicine for neck pain. English, Chinese, Japanese, and Korean databases were searched for randomized controlled trials (RCTs) on the subject. The included literature was analyzed according to study design, and only studies in which herbal medicine was administered as the sole intervention or add-on treatment to standard care were included. Sixteen studies were identified; of these, 7 studies investigated herbal medicine as the sole intervention. The Visual Analogue Scale (VAS) of pain in these studies did not differ significantly from that of standard care. The mean difference (MD) was -0.52 (95 % confidence interval (CI) -1.28, -0.25). The level of evidence was evaluated as very low. Nine RCTs investigated herbal medicine as an add-on to standard treatment. The VAS of pain in these studies decreased significantly compared to standard care alone, yielding an MD of -1.23 (95 % CI -1.65, -0.80). One study reported Neck Disability Index (NDI) scores, and herbal medicine significantly improved function by an MD of -8.00 (95 % CI -8.82, -7.18) as an add-on treatment. The level of evidence was evaluated as low. Herbal medicine as an add-on treatment was found to achieve significantly better outcomes in neck pain patients compared to standard care alone, although the level of evidence was low. The possibility of herbal medicine use as a safe and effective method of pain management was indicated, but future large-scale clinical trials on herbal medicine treatment for neck pain are needed to explore this possibility.

[This retracts the article DOI: 10.1155/2018/4514329.].

Objective: This retrospective propensity score–matched cohort study aimed to examine the frequency of acromioplasty among patients with shoulder disorders receiving and not receiving acupuncture, based on Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) data. Methods: We included cases of high-frequency shoulder disorders—adhesive capsulitis, rotator cuff syndrome, shoulder impingement syndrome, and sprain and strain of the shoulder joint—stratified from the Korea NHIS-NSC database between 2002 and 2013; cases were classified into two groups based on a history of acupuncture treatment performed at least twice within 6 weeks (acupuncture group: n = 111,561; control group: n = 71,340). We examined propensity scores and hazard ratios (HRs) for the frequency of acromioplasty, within 2 years of the first treatment or first examination in the acupuncture and control groups, respectively; cumulative survival rates were estimated using Kaplan–Meier survival analysis. Results: Following propensity score matching, no differences were observed between the acupuncture and control groups for variables including sex, age, income and the Charlson comorbidity index. In addition, the incidence rates of acromioplasty within 2 years were lower in the acupuncture group than in the control group (HR 0.264; 95% confidence interval 0.224–0.311). Based on differences in sensitivity analyses for the numbers of acupuncture sessions and treatment duration, the frequency of acromioplasty within 2 years was lower in the acupuncture group than in the control group. Conclusion: This study found that the frequency of acromioplasty was reduced in patients with shoulder disorders who had been treated with acupuncture. Although the findings need to be verified by prospective randomized clinical trials, these results imply that acupuncture may be effective at reducing the incidence rate of shoulder surgery.

Objectives: The present study was undertaken to investigate the relationship between acupuncture therapy and surgery rate. Design: Matched, retrospective cohort study. Materials and Methods: From nationwide health insurance data (2002-2013 cohort data published by the National Health Insurance Service of Korea), patients with new cases of knee osteoarthritis that occurred between January 1, 2004 and December 31, 2010 were analyzed. Patients were divided into an acupuncture group (AG) and a control group (CG), based on records of acupuncture therapy. Propensity scores were calculated by using gender, age, income level, and Charlson comorbidity index (CCI), with the groups matched at a ratio of 1:3 (AG:CG). The final analysis period was 2 years after the first acupuncture therapy for AG and 2 years after initial diagnosis for CG; surgery rates were compared between the two groups. Stratified analyses were performed based on age, gender, and income level; sensitivity analyses were performed based on the frequency and duration of acupuncture therapy. Results: Propensity score-matched AG and CG included 8,605 and 25,815 subjects, respectively. Post-matching surgery rates were 0.26 and 0.93% in AG and CG, respectively. For all age groups, AG showed a lower surgery rate than CG. In the analysis based on gender, the female group showed a significantly lower hazard ratio of 0.225. In analysis based on income level, the results of the entire group were significant, with the lower income group showing the lowest hazard ratio. In sensitivity analyses, AG tended to show a lower surgery rate than CG. Conclusions: The present study demonstrated that acupuncture therapy is associated with a low rate of surgery for knee osteoarthritis. Additional studies are needed to support this conclusion.

Objective: Surgical treatment of neck pain often entails high costs and adverse events. The present cohort study investigated whether utilisation of acupuncture in neck pain patients is associated with a reduced rate of cervical surgery. Methods: The Korean National Health Insurance Service National Sample Cohort (NHIS-NSC) database was retrospectively analysed to identify the 2 year incidence of cervical surgery in Korean patients suffering neck pain from 2004 to 2010. The incidence was calculated and compared between patients receiving and not receiving acupuncture treatment using Cox proportional hazards models. Cumulative survival rates were compared using Kaplan-Meier survival analysis. Results: The acupuncture and control groups included 50 171 and 128 556 neck pain patients, respectively. A total of 50 161 patients were selected in each group following propensity score matching with regard to sex, age, income and Charlson comorbidity index. The hazard ratio (HR) for surgery within 2 years was significantly lower in the acupuncture group compared with the control group (HR 0.397, 95% CI 0.299 to 0.527). In addition, subgroup analyses according to gender, age and income revealed consistent results for both men (HR 0.337, 95% CI 0.234 to 0.485) and women (HR 0.529, 95% CI 0.334 to 0.836); the results were consistently observed across all age and income strata. Sensitivity analysis with varying numbers of acupuncture treatments and treatment course duration also consistently indicated lower HRs for surgery within 2 years in the acupuncture group compared with the control group. Conclusions: A significantly lower HR for cervical surgery was observed in neck pain patients following acupuncture treatment. Acupuncture treatment may therefore be an effective method for managing neck pain, and has the potential to mitigate unnecessary surgery. These findings need to be confirmed by prospective studies.

Shinbaro3, a formulation derived from the hydrolysed roots ofHarpagophytum procumbens var. sublobatum (Engl.) Stapf, has been clinically used in the pharamacopuncture treatment of arthritis in Korea. In the present study, Shinbaro3 inhibited NO generation in LPS-induced RAW 264.7 cells in a dose-dependent manner. Shinbaro3 also downregulated the mRNA and protein expression of inflammatory mediators in a dose-dependent manner. Three mechanisms explaining the effects of Shinbaro3 in RAW 264.7 cells were identified as follows: (1) inhibition of the extracellular signal-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase (SAPK)/c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways; (2) suppression of IκB kinase-α/β (IKK-α/β) phosphorylation and nuclear factor-kappa B (NF-κB) subunits in the NF-κB pathway, which are involved in MyD88-dependent signalling; and (3) downregulation of IFN-β mRNA expression via inhibition of interferon regulatory factor 3 (IRF3) and Janus-activated kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) phosphorylation, which is involved in TRIF-dependent signalling. Shinbaro3 exerted anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophage cells through modulation of the TLR4/MyD88 pathways, suggesting that Shinbaro3 is a novel anti-inflammatory therapeutic candidate in the field of pharmacopuncture.

Introduction Low back pain (LBP) is a globally prevalent disorder with high social significance. Invasive surgical procedures are increasingly being used to treat LBP despite a lack of solid evidence supporting their long-term benefits. This nationwide retrospective cohort study investigated the association between acupuncture treatment and lumbar surgery rate in patients with LBP. Methods Using the National Health Insurance Service Sample Cohort Database for 2002-2013, we identified newly diagnosed LBP patients in Korea between 2004 and 2010 and divided them into an acupuncture group and control group according to whether or not they received acupuncture. Propensity scores based on age, sex, income, and Charlson Comorbidity Index were matched between the two study groups. The lumbar surgery rate in the two years following the first visit (control group) or the first acupuncture session (acupuncture group) was calculated. In addition to the overall analysis, stratified analyses were also conducted in different age, sex, and income strata. Sensitivity analyses were further performed using varying definitions of acupuncture treatment. Results After matching, 130,089 subjects were included in each study group. The lumbar surgery rate was significantly lower in the acupuncture group than in the control group (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.576-0.696). Decrease in HR was consistently observed in the acupuncture group for all age strata, except for patients in their 20s (HR 1.031, 95% CI 0.804-1.323). HR for lumbar surgery tended to be further reduced in the older age groups upon acupuncture treatment, with no apparent sex-related differences. Lowered HR in the acupuncture group was continuously observed across all income groups; the higher income group showed a tendency of greater decrease. Sensitivity analyses showed that the number of acupuncture sessions had no major impact on the likelihood of lumbar surgery, but also that more intensive acupuncture treatment was associated with further reduction in lumbar surgery rates. Conclusion The present results found that administration of acupuncture treatment is associated with lower lumbar surgery rates for LBP patients in Korea. Prospective studies are warranted in the future to further investigate the effect of acupuncture treatment on lumbar surgery incidence.

Shinbaro3, a formulation derived from the hydrolysed roots of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, has been clinically used in the pharamacopuncture treatment of arthritis in Korea. In the present study, Shinbaro3 inhibited NO generation in LPS-induced RAW 264.7 cells in a dose-dependent manner. Shinbaro3 also downregulated the mRNA and protein expression of inflammatory mediators in a dose-dependent manner. Three mechanisms explaining the effects of Shinbaro3 in RAW 264.7 cells were identified as follows: (1) inhibition of the extracellular signal-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase (SAPK)/c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways; (2) suppression of IκB kinase-α/β (IKK-α/β) phosphorylation and nuclear factor-kappa B (NF-κB) subunits in the NF-κB pathway, which are involved in MyD88-dependent signalling; and (3) downregulation of IFN-β mRNA expression via inhibition of interferon regulatory factor 3 (IRF3) and Janus-activated kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) phosphorylation, which is involved in TRIF-dependent signalling. Shinbaro3 exerted anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophage cells through modulation of the TLR4/MyD88 pathways, suggesting that Shinbaro3 is a novel anti-inflammatory therapeutic candidate in the field of pharmacopuncture.

Objectives Low back disability, along with low back pain, places a significant social burden in terms of work loss and medical expenses. Motion-Style-Acupuncture-Treatment using Traction (T-MSAT) is employed as one of the conservative treatments to such conditions. In the present study, effectiveness of Korean Medical treatments, including T-MSAT, was investigated in inpatients with low back disability and low back pain. Methods Among the patients who were admitted between January 2018 to June 2018 with disabled low back function, ones that were treated with T-MSAT were identified. Pain and function were compared at the point of admission and discharge, using Numerical Rating Scale (NRS) and Oswestry Disability Index (ODI), respectively. Results Over the hospitalization period of 34.55 days, pain intensity significantly de-creased from NRS score of 6.14 to 3.26 and low back function also significantly improved from ODI score of 50.93 to 33.73 upon receiving Korean Medical treatments including T-MSAT. Conclusions Korean Medical treatments including T-MSAT were found to be effective in inpatients with low back disability with a statistical significance. To evaluate the sole effectiveness of T-MSAT, rigorous clinical trials are necessitated in future. (J Korean Med Rehabil 2018;28(4):51-57)

Introduction: The aim of this systematic review was to assess the evidence from randomized controlled trials (RCTs) on the effectiveness and safety of pharmacopuncture in cervical spondylosis patients. Methods: Seven databases were searched, including Chinese and Korean databases, through to January 2018. Eligible trials were those with intervention groups receiving pharmacopuncture for cervical spondylosis and control groups receiving other conventional treatments including acupuncture. Outcome measures included pain, disability, quality of life, and adverse events (AEs). For statistical pooling, the mean difference (MD) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Twenty RCTs were selected. Eight trials on pharmacopuncture as a single treatment reported significant pain decrease in patients with cervical spondylosis compared to acupuncture (MD -1.79, 95% CI -2.39, -1.19). Add-on pharmacopuncture treatment also showed significant effects in alleviating pain compared to the control (MD -1.79, 95% CI -2.24, -1.34). Add-on pharmacopuncture treatment significantly increased quality of life compared to the control, as shown with SF-36 scores (MD 18.31, 95% CI 13.33, 23.29). However, all analysis results were assessed to be low or very low quality evidence due to considerably high heterogeneity and high risk of bias. In addition, solid conclusions on safety could not be drawn as few studies reported on AEs related with pharmacopuncture. Conclusions: Pharmacopuncture, both as a sole intervention and as an add-on treatment, was found to decrease pain in patients with cervical spondylosis. These results, however, should be interpreted with caution as the quality of evidence was found to be low.

Objectives This study examined National Health Insurance claims data to investigate the epidemiology of shoulder disorders in Korea. Detailed information on medical services and related costs was assessed by major shoulder disorder category. Design and setting The 2014 National Patient Sample dataset provided by the Health Insurance Review and Assessment Service was analysed. Among shoulderrelated diagnosis codes, adhesive capsulitis of the shoulder (ACS), rotator cuff syndrome (RCS) and shoulder impingement syndrome (SIS) categories were of highest prevalence. Sociodemographic characteristics and medical service use, frequency and medical costs regarding common shoulder disorders were evaluated. Results The majority of patients with shoulder disorder received ambulatory care (97%). Total and per-patient expenses were highest in patients with RCS. The number of inpatients with RCS was more than twice that of the other two groups, and patients with RCS were more likely to receive surgical management compared with patients with ACS and SIS. Prevalence of shoulder disorders was highest among subjects in their 50s for all three groups. Primary care physicians treated 75.80% of patients with ACS, 56.99% of patients with RCS and 48.06% of patients with SIS, respectively, outlining the difference in medical institution usage patterns. In all three groups, the highest proportion of patients visited orthopaedic surgeons out of medical departments. In the ACS and SIS groups, cost of visits (consultations) took up the largest part of total expenses at 32.30% and 18.88%, respectively, while cost of procedure/surgery constituted the largest portion in patients with RCS (37.77%). The usage proportion of subcutaneous or intramuscular and intra-articular injections ranged between 20% and 30% for outpatients in all three groups. Conclusions Medical service use, frequency and cost distributions relating to major shoulder disorders in Korea were assessed using nationwide claims data. These findings are expected to aid policy-makers as well as researchers and practitioners as basic healthcare data.

Wonil Koh, Jinho Lee, In-Hyuk Ha, Hwa-Jin Chung, In-Hee Lee, Jae-Woong Lee, Eun Jee Kim, Byeong-Gu Gang, Se Hwan Jeon, Yongkyu Cho, and Min-Jeong Kim. J Korean Med Rehabil 2017;27:29-38. https://doi.org/10.18325/jkmr.2017.27.2.29

Background: GCSB-5, an herbal drug composition with an anti-inflammatory effect, is prepared by boiling, which is the most common herbal extraction method in traditional Korean medicine. Several parameters are involved in the process, i.e., extractant type, herb-to-extractant ratio, extraction temperature and pressure, and total boiling time. Objectives: The aim of this study was to examine the influence of boiling time on index compound amount and the antioxidative and anti-inflammatory activities of GCSB-5. Materials and Methods: Different samples of GCSB-5 were obtained by decocting for 30, 60, 90, 120, 150, and 240 min. Each sample was tested for hydrogen ion concentration (pH), total soluble solid content (TSSC), marker compound profiles, and antioxidative and anti-inflammatory activity. Results: pH was found to decrease while TSSC increased with extended decoction. Marker compound contents for GCSB-5 (acanthoside D for Acanthopanax sessiliflorus Seem, 20-hydroxyecdysone for Achyranthes japonica Nakai, and pinoresinol diglucoside for Eucommia ulmoides Oliver) remained relatively constant regardless of the length of boiling. Total D-glucose amount increased with longer boiling. The antioxidative and anti-inflammatory potentials of GCSB-5 were not substantially affected by decoction duration. Conclusion: Biological characteristics and marker compound content of GCSB-5 were not altered significantly in prolonged boiling. Abbreviations used: CAM: Complementary and alternative medicine; KIOM: Korea Institute of Oriental Medicine; KMD: Korean medicine doctor; TSSC: Total soluble solid content; pH: Hydrogen ion concentration; HPLC: High-performance liquid chromatography; NO: Nitric oxide; NO2: Nitric dioxide; LPS: Lipopolysaccharide; DMSO: Dimethyl sulfoxide.

Ethnopharmocological relevance: Cortex Eucommiae (CE), the bark of Eucommia ulmoides Oliv., has been traditionally used for its kidney-tonifying and bone- and tendon-enhancing properties in Korea, China, and Japan. CE has been historically prescribed for inflammatory conditions such as arthritis of the knee and ankle. Aim of the study: Although CE has recently been shown to suppress inflammation in scientific studies, whether this effect involves modulation of the toll-like receptor 4 (TLR-4) pathway is currently unknown.Materials and methods: The modulatory effect of CE on the TLR-4 pathway, both myeloid differentiation primary response gene 88 (Myd88)-dependent and independent, was investigated through real-time reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, and a reporter gene assay in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages.Results: CE dose-dependently inhibited nitric oxide production without significant cytotoxicity with an IC50 of 356.23 mu g/mL. In addition, CE down-regulated both LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (INF-alpha), and interleultin-1 beta (IL-1 beta) in a dose-dependent manner. CE suppressed LPS-induced activation of nuclear factor-kappa B (NF-kappa B) and the mitogen-activated protein kinase (MAPK) pathways, which together comprise the Myd88-dependent TLR-4 pathway. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also down-regulated by CE in a dose-dependent manner. CE additionally suppressed LPS-induced activation of interferon-beta (IFN-beta) and signal transducer and activator of transcription (STAT) pathway, which is associated with the Myd88-independent TLR-4 pathway.Conclusions: CE down-regulated both Myd88-dependent and independent TLR-4 pathways, thus exerting anti-inflammatory effects. These results suggest that CE may be used as a potential therapeutic agent against chronic inflammatory diseases.

Background Osteoarthritis (OA) and meniscal and ligament injuries of the knee are the two most common knee disorders in Korea. The aim of this study was to analyze the demographic characteristics, medical service use and related costs for these disorders, and the results are expected to help inform practitioners, researchers, and policy-makers. Methods The present study aimed to evaluate incidence and patient characteristics, and to assess current medical service use, usual care, and medical expenses of knee disorders by analyzing 2014 national patient sample data from the Korean Health Insurance Review and Assessment Service. Data was extracted using 3% stratified sampling from all Korea national health insurance claims submitted in 2014, and analyzed. Usual care for M17 knee osteoarthritis and S83 knee meniscal and ligament injury codes of the International Classification of Diseases, 10th revision (ICD-10) were determined by investigating total number of patients, sociodemographic characteristics, days in care, number of visits, and expenses. Results Knee OA showed the highest incidence in females aged ≥60 years, whereas meniscal and ligament injuries of the knee were most prevalent among patients aged <20 years and young adults. Total inpatient care expenses exceeded the cost of ambulatory care for both disorders. Ambulatory care was mainly provided at primary care clinics, with 90% of these visits made to orthopedic specialists. Medical expenses for knee OA and meniscal and ligament injuries were largely due to procedures/surgeries and injections, and procedures/surgeries and hospitalizations, respectively. Total replacement arthroplasty was the most commonly performed surgery for knee OA, while meniscectomy and cruciate ligament reconstruction were the most often performed surgeries for meniscal and ligament injuries. Intra-articular injection rates were 55% in knee OA patients and 3% in meniscal and ligament injury patients. Aceclofenac, diclofenac, and tramadol were the most frequently prescribed analgesics. Conclusions The current findings may be used as basic data for establishing medical policies and can benefit researchers and clinicians in recognizing trends and patterns of treatment for knee disorders.

BACKGROUND:Bee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action. METHODS:The anti-inflammatory potential of eBV was assessed in vivo using a carrageenan-induced paw edema model. To further investigate the mechanism by which eBV exerts anti-allergic and anti-inflammatory effects, compound 48/80-stimulated RBL-2H3 cells and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were studied in vitro. RESULTS:Release of β-hexosaminidase and histamine was increased by eBV in a dose-dependent manner, but these levels were lower in eBV compared to original BV at the same concentration. In addition, eBV suppressed compound 48/80-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RBL-2H3 cells. eBV was also shown to suppress nitric oxide (NO) production by down-regulating mRNA expression and subsequent protein expression of inflammatory mediators in LPS-induced RAW 264.7 cells. Phosphorylation of activators and signal transducers of transcription 1/interferon regulatory factor 3 (STAT1/IRF3) was attenuated by eBV treatment. eBV significantly inhibited carrageenan-induced acute edema in vivo. Serum levels of prostaglandin E2 (PGE2), TNF-α, and IL-1β were also down-regulated by eBV. CONCLUSIONS:These results demonstrate that eBV inhibits allergic and inflammatory response by reducing inflammatory mediator production via regulation of the STAT1/IRF3 signaling pathway, suggesting that eBV is a feasible candidate for regulation of allergic-inflammatory response in complementary and alternative medicine.