Multidisciplinary Guidelines for the Rational Use of Topical Non-Steroidal Anti-Inflammatory Drugs for Musculoskeletal Pain (2022).

(1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the primary drugs for treating musculoskeletal pain. However, there are currently no evidence-based recommendations about drug selection, drug administration, drug interactions, and use in special populations or other pharmacology-related content of such medications. To this end, the Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee developed multidisciplinary guidelines on using topical NSAIDs to treat musculoskeletal pain. (2) Methods: The guidelines development process followed the World Health Organization guideline development handbook, the GRADE methodology, and the statement of Reporting Items for Practice Guidelines in Healthcare. The guideline panel used the Delphi method to identify six clinical questions to be addressed in the guidelines. An independent systematic review team conducted a systematic search and integration of evidence. (3) Results: Based on the balance between the benefits and harms of an intervention, the quality of the evidence, patient preferences and values, and resource utilization, the guideline panel developed 11 recommendations and nine expert consensuses on using topical NSAIDs to treat acute and chronic musculoskeletal pain. (4) Conclusions: Based on the effectiveness and overall safety of topical NSAIDs, we recommend patients with musculoskeletal pain use topical NSAIDs and suggest high-risk patients use topical NSAIDs, such as those with other diseases or receiving other concurrent treatments. The evidenced-based guidelines on topical NSAIDs for musculoskeletal pain incorporated a pharmacist perspective. The guidelines have the potential to facilitate the rational use of topical NSAIDs. The guideline panel will monitor the relevant evidence and update the recommendations accordingly.

Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia.

Background and purpose: Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application. Materials and methods: The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level. Results: Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia. Conclusions: The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.

Ozone induces autophagy by activating PPARγ/mTOR in rat chondrocytes treated with IL-1ß.

BACKGROUND: Osteoarthritis (OA) is the main cause of older pain and disability. Intra-articular injections of ozone (O3) commonly have been found to have antioxidative and anti-inflammatory effects to reduce pain and improve function in knee osteoarthritis. It has been reported that reduced autophagy in chondrocytes plays an important role in the development of OA. This study aimed to probe the role of O3 on the autophagy in chondrocytes treated with IL-1ß. METHODS: Primary chondrocytes were isolated from Wistar rats cartilage within 3 days. The OA chondrocytes model was induced via treatment with IL-1ß for 24 h. Then the cells were treated with O3 and GW9662, the inhibitor of PPARγ. Cell viability was assessed by CCK-8. Further, the cells subjected to Western blot analysis, qRT-PCR and immunofluorescence assay. The numbers of autophagosomes were observed via transmission electron microscopy. RESULTS: 30 µg/ml O3 improved the viability of chondrocytes treated with IL-1ß. The decreased level of autophagy proteins and the numbers of autophagosomes improved in IL-1ß-treated chondrocytes with O3 via activating PPARγ/mTOR. In addition, the qRT-PCR results showed that O3 decreased the levels of IL-6, TNF-α and MMP-3, MMP-13 in chondrocytes treated with IL-1ß. CONCLUSIONS: 30 µg/ml O3 improved autophagy via activating PPARγ/mTOR signaling and suppressing inflammation in chondrocytes treated with IL-1ß.

Expert consensus of Chinese Association for the Study of Pain on the application of ozone therapy in pain medicine.

This consensus was compiled by first-line clinical experts in the field of pain medicine and was organized by the Chinese Association for the Study of Pain. To reach this consensus, we consulted a wide range of opinions and conducted in-depth discussions on the mechanism, indications, contraindications, operational specifications and adverse reactions of ozone iatrotechnique in the treatment of pain disorders. We also referred to related previous preclinical and clinical studies published in recent years worldwide. The purpose of this consensus is to standardize the rational application of ozone iatrotechnique in pain treatment, to improve its efficacy and safety and to reduce and prevent adverse reactions and complications in this process.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain.

Chronic musculoskeletal pain (CMP) is a common occurrence in clinical practice and there are a variety of options for the treatment of it. However, the pharmacological therapy is still considered to be a primary treatment. The recent years have witnessed the emergence of opioid crisis, yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly. The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics. The purpose of this consensus is to present the application of nonsteroidal anti-inflammatory drugs, serotonin norepinephrine reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, muscle relaxants, ion channel drugs and topical drugs in CMP.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch.

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Upregulation of antioxidant and autophagy pathways via NRF2 activation protects spinal cord neurons from ozone damage.

Ozone therapy can relieve multiple types of pain but exhibits potential neurotoxicity, the mechanism of which is unclear. The present study aimed to identify the role of nuclear factor (erythroid­derived­2)­related 2 (NRF2) in preventing spinal cord injury caused by ozone overdose. Primary neuronal cells were extracted from newborn Wistar rats and authenticated by immunofluorescence using anti­microtubule­associated protein 2 as a cell type­specific marker. Cell viability assay with different ozone concentrations (0, 10, 20, 30 and 40 µg/ml) was used to determine the concentration that caused primary neuron injury; 30 min of 40 µg/ml ozone therapy notably decreased cell viability to 71%. In order to test the effects of ozone, the cells were divided into five treatment groups [0­, 30­ and 40 µg/ml ozone, tert­butylhydroquinone (tBHQ) + 40 µg/ml ozone (T40) and tBHQ (T0)]. Cells in the T40 and T0 groups received 40 µmol/l tBHQ on the fifth day of SCN cultivation. Reverse transcription­quantitative PCR and western blotting showed that protein expression levels of heme oxygenase­1 (HO­1) and mRNA expression levels of HO­1 and NRF2 were decreased. NRF2, ubiquitin­binding protein p62 and microtubule­associated proteins 1A/1B light chain 3B expression levels were decreased following treatment with 40 µg/ml ozone. Immunofluorescence showed that NRF2 nuclear expression levels also decreased following 40 µg/ml ozone treatment. However, cells in the T40 group did not display decreased NRF2 nuclear expression levels. Normal/Apoptotic/Necrotic Cell Detection kit revealed that necrosis rate increased following treatment with 40 µg/ml ozone; however, the T40 group did not exhibit this increased necrosis. At 40 µg/ml, ozone increased spinal cord neuron (SCN) death in vitro. Moreover, treatment with 40 µg/ml ozone damaged SCNs. The p62/NRF2/antioxidant response element pathway prevented such injury. tBHQ activated this pathway, upregulated autophagy and increased local nuclear NRF2 concentration, thus enhancing the antioxidant system to protect SCNs from injury caused by high concentrations of ozone.

Bupivacaine inhibits a small conductance calcium-activated potassium type 2 channel in human embryonic kidney 293 cells.

BACKGROUND: Bupivacaine blocks many ion channels in the heart muscle, causing severe cardiotoxicity. Small-conductance calcium-activated potassium type 2 channels (SK2 channels) are widely distributed in the heart cells and are involved in relevant physiological functions. However, whether bupivacaine can inhibit SK2 channels is still unclear. This study investigated the effect of bupivacaine on SK2 channels. METHODS: The SK2 channel gene was transfected into human embryonic kidney 293 cells (HEK-293 cells) with Lipofectamine 2000. The whole-cell patch-clamp technique was used to examine the effect of bupivacaine on SK2 channels. The concentration-response relationship of bupivacaine for inhibiting SK2 currents (0 mV) was fitted to a Hill equation, and the half-maximal inhibitory concentration (IC50) value was determined. RESULTS: Bupivacaine inhibited the SK2 channels reversibly in a dose-dependent manner. The IC50 value of bupivacaine, ropivacaine, and lidocaine on SK2 currents was 16.5, 46.5, and 77.8µM, respectively. The degree of SK2 current inhibition by bupivacaine depended on the intracellular concentration of free calcium. CONCLUSIONS: The results of this study suggested the inhibitory effect of bupivacaine on SK2 channels. Future studies should explore the effects of SK2 on bupivacaine cardiotoxicity.

Intrathecal injection of ozone alleviates CCI­induced neuropathic pain via the GluR6­NF­κB/p65 signalling pathway in rats.

Ozone is widely used to relieve chronic pain clinically, but the precise mechanisms governing its action have yet to be elucidated. The present study aimed to investigate the mechanisms underlying the pain­alleviating effect of ozone in the chronic constriction injury (CCI) model of sciatic nerve in rats. Pain behaviours of rats were assessed by mechanical allodynia and thermal hyperalgesia. The expression of spinal glutamate receptor 6 (GluR6) and NF­κB/p65 was detected by western blotting and reverse transcription­quantitative PCR. Meanwhile, the expression of spinal IL­1ß, IL­6 and TNF­α was detected by ELISA. GluR6 short interfering (si)RNAs were used intrathecally immediately following CCI once per day. Ozone (10, 20 or 30 µg/ml) or oxygen was injected intrathecally on day 7 after CCI. The expression level of spinal GluR6 increased on day 3 and reached a peak on day 7 after CCI. The expression level of spinal IL­1ß, IL­6, TNF­α and NF­κB/p65 also increased on day 7 after CCI. In addition, pre­intrathecal injection of GluR6 siRNAs inhibited pain behaviours and suppressed the expression of spinal GluR6, IL­1ß, IL­6, TNF­α and NF­κB/p65 in CCI rats on day 7. Intrathecal injection of ozone was also observed to inhibit pain behaviours and suppress the expression of spinal GluR6, IL­1ß, IL­6, TNF­α and NF­κB/p65 in CCI rats on day 7. The present study suggested that GluR6 served a pivotal role in neuropathic pain and that intrathecal injection of ozone may alleviate neuropathic pain via the GluR6­NF­κB/p65 signalling pathway.

Efficacy of different interventions for the treatment of postherpetic neuralgia: a Bayesian network meta-analysis.

OBJECTIVE: We aimed to perform a network meta-analysis that combined both direct and indirect evidence to compare the relative efficacy of interventional therapies to treat patients with postherpetic neuralgia (PHN) and to determine the treatments' superiority and validity. METHOD: A conventional paired meta-analysis was performed. This was followed by a network meta-analysis using the Bayesian framework. RESULTS: Botulinum toxin type A and pulsed radiofrequency (PRF) were the two most effective individual interventions. For combination therapy, PRF + nerve block (NB) was the best choice, followed by subcutaneous injection or local infiltration (SC) + NB + ozone (O3). However, the combination of PRF + NB + SC showed reduced the efficacy compared with each treatment and was highly invasive for patients. After a long-term follow-up, PRF was shown to be the most effective therapy for treating patients with PHN. CONCLUSIONS: Regular anti-neuropathic drug administration that was accompanied by interventional therapies at an early stage is the best choice to treat patients with PHN. Appropriate combinations of different interventions show improved pain relief. Clinicians should manage therapeutic regimens on the basis of the patients specific condition and existing measures and strive to achieve personalized treatment.

Effect of stellate ganglion block on postoperative recovery of gastrointestinal function in patients undergoing surgery with general anaesthesia: a meta-analysis.

BACKGROUND: The return of gastrointestinal function is an important sign of postoperative recovery in patients undergoing surgery with general anaesthesia. We aimed to summarize the effects of stellate ganglion block on the recovery of gastrointestinal function as a means of exploring methods through which anaesthesiologists can contribute to postoperative patient recovery. METHODS: We performed a quantitative systematic review of randomized controlled trials published between January 1, 1988, and November 11, 2019, in PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information, and the Wanfang and SinoMed databases. Study quality was assessed by using the GRADE criteria and bias of included studies were assessed using the revised Cochrane risk-of-bias tool for randomized trials. The time to peristaltic sound resumption, flatus, postoperative eating and the incidence of abdominal bloating in the stellate ganglion block and control groups were compared. The control group consisted of either a stellate ganglion block with normal saline or no treatment. Meta-analysis was performed using Review Manager software. RESULTS: After searching for relevant articles, 281 studies were identified, and five articles with data on 274 patients were eligible. Regarding postoperative flatus time, stellate ganglion block resulted in a mean reduction of 15 h (P = 0.02); then a sensitivity analysis was performed, and the standard mean difference decreased to 6 h (P = 0.007). For gastrointestinal surgery, the mean reduction was 23.92 h (P = 0.0002). As for the evaluation of the recovery of peristaltic sounds, stellate ganglion block promoted the recovery of regular peristaltic bowel sounds an average of 14.67 h earlier than in the control (P = 0.0008). When it comes to nutrients, stellate ganglion block shortened the total parenteral nutrition time by more than 50 h in patients who had undergone gastrointestinal surgery (P<0.00001). Finally, stellate ganglion block prevented the occurrence of postoperative abdominal bloating (P = 0.001).) No complications related to stellate ganglion block were reported. CONCLUSION: Stellate ganglion block may promote postoperative gastrointestinal recovery in patients undergoing various surgeries under general anaesthesia. However, additional trials investigating the use of stellate ganglion block are necessary to confirm our finding. TRIAL REGISTRATION: This meta-analysis has been registered at the International Prospective Register of Systematic Reviews (registration number CRD42020157602).

Spinal cord stimulation for chronic intractable trunk or limb pain: study protocol for a Chinese multicenter randomized withdrawal trial (CITRIP study).

BACKGROUND: Although effective results of many studies support the use of spinal cord stimulation in chronic pain patients, no randomized controlled trial has been undertaken in China to date. CITRIP is a multicenter, prospective, randomized, withdrawal study designed to evaluate the clinical effectiveness and safety of spinal cord stimulation plus remote programming management in patients with intractable trunk or limb pain. METHOD: Participants will be recruited in approximately 10 centers across China. Eligible participants with intractable trunk or limb and an average visual analog scale (VAS) score ≥ 5 will undergo a spinal cord stimulation test. Participants with VAS score reduction ≥ 50% could move forward to receive implantation of an implanted pulse generator. In the withdrawal period at 3-month follow-up visit, participants randomized to the experimental group (EG) will undergo continuous stimulation while ceasing the stimulation in the control group (CG). The outcome assessment will occur at baseline and at 1, 3 (pre- and post-randomization), and 6 months. The primary outcome is the difference of maximal VAS score between EG and CG in the withdrawal period compared with baseline before the withdrawal period. Additional outcomes include VAS score change at 1-, 3-, and 6-month follow-ups; responder rate (VAS score improving by 50%); achievement rate of a desirable pain state (VAS score ≤ 4); awake times during sleep; Beck Depression Inventory for depression evaluation; short-form 36 for quality of life evaluation; drug usage; and satisfaction rating of the device. Adverse events will be collected. The primary analysis will follow the intention-to-treat principle. DISCUSSION: The CITRIP study seeks to evaluate the effectiveness and safety of a randomized withdrawal trial of spinal cord stimulation for patients with intractable trunk or limb pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT03858790 . Registered on March 1, 2019, retrospectively registered.

The effect of medical ozone treatment on cartilage chondrocyte autophagy in a rat model of osteoarthritis.

Many studies have shown that ozone (O3) can inhibit inflammation in osteoarthritis (OA) and regulate the metabolic balance of articular cartilage, but the mechanisms of this process are not well understood. Our study investigated the therapeutic mechanism of O3 in OA. OA models were established, and the MWT and PWL were measured. HE staining and safranin O-fast green staining were used to observe cartilage degeneration. The levels of MMP-13, collagen-2, LC3II and P62 were measured by immunohistochemistry, and the levels of TNF-α and IL-6 were measured by ELISA. The results showed that intra-articular injection of O3 can effectively alleviate pain and inhibit cartilage degeneration in OA rats. O3 can also reduce the concentrations of TNF-α and IL-6, inhibit the expression of MMP-13 and the degradation of collagen-2, upregulate the autophagy-related protein LC3II and inhibit P62. This effect is associated with the upregulation of chondrocyte autophagy in OA.

Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons.

Background and Objective: Ozone therapy has shown therapeutic efficacy in different disorders particularly low back pain (LBP). However, ozone therapy has been associated with toxic effects on the respiratory, endocrine, cardiovascular systems as well as nervous system because of its strong oxidizing capacity. Recent studies have reported possible associations between ozone exposure and metabolic disorders, but the findings are controversial and little is known on the mechanisms of action. This study aims to investigate the cytotoxic effects of ozone exposure and possible mechanism of action in the animal model. Methods: Wistar neonate rats with the age of 24 h after birth were sacrificed by cervical dislocation under general anesthesia, then immersed in 75% alcohol and iodophor for 5 min, respectively. The spinal cord was isolated and cut to samples of ~1 mm3 and prepared for further experiments. The spinal cord neurons (SCNs) were exposed to ozone at different concentrations and then cultured in 96-well plates with glass bottom for 7 days. The cell viability, ATP levels and the NAD+ concentration were determined and compared between the different experimental groups and the control group. Results: Analyses of the data by non-targeted liquid chromatography-mass spectrometry (LC-MS) analysis determined the metabolic disorder in SCNs following the ozone exposure. Moreover, our assessments showed that ozone exposure resulted in DNA damage, poly (ADP)-ribose polymerase-1 (PARP1) excessive activation, nicotinamide adenine dinucleotide (NAD+) depletion and decrease of ATP level in SCNs. The PARP1 inhibitor can inhibit the cytotoxic effect of ozone to SCNs without inhibiting the activation of AMP-activated protein kinase (AMPK). Our findings revealed that the cytotoxic effects of ozone to SCNs might be mediated by excessive PARP1 activation and subsequent NAD+ depletion. Moreover, using PARP1 inhibitor can protect SCNs from cytotoxic effects of ozone by preventing NAD+ depletion during ozone exposure. Conclusion: Ozone exposure seems to induce metabolic disorders and NAD+ depletion through excessive PARP1 activation in SCNs.

Effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain in vitro.

The combination of morphine and ketamine is considered safe and efficacious in many patients. However, a considerable number of immunomodulatory effects have been reported to be produced by both morphine and ketamine. The aim of the present study was to assess the direct effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain in vitro. Venous blood was obtained from patients with refractory cancer pain and peripheral blood mononuclear cells were isolated using the Ficoll-Hypaque density gradient method. Anti-CD3 beads were used to isolate T cells by positive selection. Subsequently, the T cells were treated with vehicle, 200 ng/ml of morphine or 200 ng/ml of morphine + 100 ng/ml ketamine for 24 h, following which the cells were stimulated with anti-CD3 and anti-CD28. Flow cytometric analysis of CD3+ T cells, and interleukin (IL)-2 and interferon (IFN)-γ in the supernatant, reverse transcription-quantitative PCR analysis for the detection of IL-2 and IFN-γ and western blotting for the detection of p65 nuclear factor (NF)-κB were performed. In vitro, the CD4+ and CD8+ T cell counts, CD4+/CD8+ ratio, secretion of IL-2 and IFN-γ in the supernatant, mRNA expression levels of IL-2 and IFN-γ and expression of p65 NF-κB were significantly decreased following treatment with morphine and morphine + ketamine, compared with results in the control group (all P<0.05). However, there was no significant difference between treatment with morphine and that with morphine + ketamine. Treatment with morphine + ketamine in vitro decreased the immune functions of patients with refractory cancer pain, although the effect of treatment with morphine and a low dose of ketamine did not differ significantly from that with morphine treatment alone.

The Chinese Association for the Study of Pain (CASP): Consensus on the Assessment and Management of Chronic Nonspecific Low Back Pain.

Chronic nonspecific low back pain (CNLBP) is defined as pain or discomfort originating from the waist, which lasts for at least 12 weeks, but no radiculopathy or specific spinal diseases. CNLBP is a complicated medical problem and places a huge burden on healthcare systems. Clinical manifestation of CNLBP includes discogenic LBP, zygapophyseal joint pain, sacroiliac joint pain, and lumbar muscle strain. Further evaluation should be completed to confirm the diagnosis including auxiliary examination, functional assessment, and clinical assessment. The principle of the management is to relieve pain, restore function, and avoid recurrence. Treatment includes conservative treatment, minimally invasive treatment, and rehabilitation. Pharmacologic therapy is the first-line treatment of nonspecific LBP, and it is most widely used in clinical practice. Interventional therapy should be considered only after failure of medication and physical therapy. Multidisciplinary rehabilitation can improve physical function and alleviate short-term and long-term pain. The emphasis should be put on the prevention of NLBP and reducing relevant risk factors.

Retrospective study of the interlaminar approach for percutaneous endoscopic lumbar discectomy with the guidance of pre-operative magnetic resonance neurography.

BACKGROUND: To measure the direct effects of pre-operative magnetic resonance neurography (MRN), and analyze the procedure and clinical outcomes of the percutaneous endoscopic interlaminar discectomy, in order to demonstrate the feasibility and safety of the interlaminar approach. METHODS: In this study, 127 patients who underwent percutaneous endoscopic lumbar discectomy (PELD) and were followed up by more than 12 months, were retrospectively evaluated. The pre-operative demographic data were collected. In addition, the coronal scan and the reconstruction of the lumbosacral plexus were examined to measure the distance between the nerve root and the dural sac at the coronal plane. Furthermore, the post-operative and pre-operative visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were compared. RESULTS: The mean and minimum values of distance T between the nerve root and dural sac of L5/S1 to L2/3 on the operation side of the MRN images were all larger than 7.3 mm which is the diameter of the working canal. During the follow-up, VAS and ODI data improved significantly compared with their corresponding pre-operative scores (P<0.01). Regarding the post-operative complications, there were 2 (1.57%) cases of hypesthesia and 3 (2.36%) cases of neuropathic pain, which were transient and alleviated in 3 months. In addition, there was 1 (0.79%) case of intervertebral space infection and 1 (0.79%) dural tear. No relapse of disc herniation and iatrogenic instability occurred by the end of the last follow-up. CONCLUSIONS: The MRN indicates that the incidence of herniated disc impingement increases over the distance between the nerve root and the dural sac, thus making the interlaminar approach more suitable for the treatment of herniation. The procedures and clinical outcomes of the IL-PELD demonstrate the safety and advantages of the interlaminar approach.

Underreporting, crash severity and fault assignment of minor crashes in China - a study based on self-reported surveys.

Unreported minor crashes have importance as a surrogate for more serious crashes that require infrastructure, education, and enforcement strategies; and they still inflict damages. To study factors that influence underreporting, cause, and severity of minor crashes; a survey was performed in Kunming and Beijing to collect self-reported personal characteristics and crash history data of the three major urban road users in China: automobile drivers, bicycle riders and electric bike (e-bike) riders. Underreporting rates of automobile to automobile, automobile to non-motorized vehicle, and non-motorized vehicle to non-motorized vehicle crashes are 56%, 77% and 94%, respectively. Minor crashes with higher reported injury severity levels are more likely to be reported. E-bike riders without a driver's license are more likely to cause crashes. Licensing and education could be an effective way to reduce their crashes. The party that is not at fault in a crash is more likely to sustain high level of injury.

Ozone induces autophagy in rat chondrocytes stimulated with IL-1ß through the AMPK/mTOR signaling pathway.

BACKGROUND: Ozone injection is generally used for the management of pain in diseases such as osteoarthritis (OA). Recent studies have shown that reduced autophagy in chondrocytes plays an important role in the development of OA. The purpose of this study was to determine whether ozone treats OA by inducing autophagy in OA chondrocytes. MATERIALS AND METHODS: In this study, primary chondrocytes were stimulated with IL-1ß for 24 hours to simulate an OA chondrocyte model, followed by treatment with ozone (30 µg/ mL) or pretreatment with 3-methyladenine or compound C before ozone treatment. Then, cell viability was detected by a CCK-8 kit, and the AMPK/mTOR signaling pathway and autophagy were detected by Western blotting and immunofluorescence. The mRNA expression levels of IL-6, TNF-α, MMP-13 and TIMP-1 were measured by quantitative real-time PCR. Finally, autophagosomes in chondrocytes were observed by transmission electron microscopy. RESULTS: Ozone improved cell viability in chondrocytes stimulated by IL-1ß. The decreased level of autophagy in IL-1ß-stimulated chondrocytes improved with ozone treatment through activation of the AMPK/mTOR signaling pathway. In addition, the mRNA expression levels of IL-6 and TNF-α were suppressed by ozone treatment in chondrocytes stimulated with IL-1ß. Ozone increased the mRNA level of TIMP-1 and decreased the mRNA level of MMP-13 in chondrocytes stimulated with IL-1ß. CONCLUSION: These results suggested that ozone improved the decreased level of autophagy in chondrocytes stimulated with IL-1ß through activation of the AMPK/mTOR signaling pathway. Moreover, ozone treatment suppressed inflammation and helped maintain metabolic balance in chondrocytes stimulated with IL-1ß.