The efficacy of silver needle therapy for treating low back pain: a protocol for meta-analysis of randomized controlled trials.

Background: As population aging and unhealthy living habits may exacerbate the prevalence and burden of low back pain (LBP), effective treatment and improvement of patient quality of life are particularly critical. Silver needle therapy (SNT), having evolved from traditional acupuncture, involves placing silver needles into muscles, tendons, and fascia for treatment. However, it still lacks robust clinical evidence to substantiate its effectiveness. Therefore, it is necessary to conduct more emphasis on meta-analysis to evaluate the clinical efficacy of SNT for treating LBP. Methods: We will search PubMed, Medline, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Databases up until December 2023 to identify randomized controlled trials of SNT treatment in adult patients with LBP. The primary outcome will be the intensity of pain after pain management. Secondary outcomes will include the Oswestry Disability Index, Japanese Orthopedic Association Back Pain Evaluation Questionnaire, requirement for analgesic drugs, and treatment-related adverse reactions. Two investigators conducted the literature search, selected studies that might meet the inclusion criteria based on the title and abstract, and extracted data from the eligible literature independently and will independently assess the risk of bias using the Revised Cochrane Risk-of-Bias (RoB2) tool. Multivariate analyses (including subgroup analysis, trial sequential analysis (TSA), sensitivity analysis, etc.) will be conducted to improve the quality of evidence. Clinical trial registration: Registration: PROSPERO Registration Number: CRD42023466207, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023466207.

High-voltage pulsed radiofrequency improves ultrastructure of DRG and enhances spinal microglial autophagy to ameliorate neuropathic pain induced by SNI.

Neuropathic pain (NeP) is intractable for which many therapies are ineffective. High-voltage pulsed radiofrequency (HVPRF) on dorsal root ganglion (DRG) is considered an effective treatment for NeP. The aim of this study is to explore the therapeutic voltage for the optimal efficacy of PRF and the underlying mechanisms. The radiofrequency electrode was placed close to the L5 DRG of rats with spared nerve injury (SNI) and emitted current by the corresponding voltage in different groups. Four different voltages (45 V, 65 V, 85 V, and 100 V) of PRF on DRG significantly alleviated the SNI-induced NeP, reduced the levels of activating transcription factor 3 (ATF3) in DRG, improved the ultrastructure of DRG, and promoted autophagy in spinal microglia to varying degrees and partially reversed the increased expression of TNF-α and the reduced expression of IL-10 in spinal cord dorsal horn (SCDH). The beneficial effect of 85V-PRF was superior to those of other three PRF treatments. The underlying mechanisms may be related to repairing the DRG damage and improving the DRG ultrastructure while regulating spinal microglial autophagy and thereby alleviating neuroinflammation.

Pulsed radiofrequency on DRG inhibits hippocampal neuroinflammation by regulating spinal GRK2/p38 expression and enhances spinal autophagy to reduce pain and depression in male rats with spared nerve injury.

Evidence indicates that microglial G protein-coupled receptor kinase 2 (GRK2) is a key regulator of the transition from acute to chronic pain mediated by microglial products via the p38 mitogen-activated protein kinase (MAPK) pathway in the spinal cord dorsal horn (SCDH). Increasing studies have shown that autophagic dysfunction in the SCDH and neuroinflammation in the hippocampus underlie NeP. However, whether GRK2/p38MAPK and autophagic flux in the SCDH and hippocampal neuroinflammation are involved in NeP and depression comorbidity has not been determined. Here, we explored the effects of high-voltage pulsed radiofrequency (PRF) (85 V-PRF; HV-PRF) to the dorsal root ganglion (DRG) on pain phenotypes in Wistar male rats with spared nerve injury (SNI) and the underlying mechanisms. The exacerbation of pain phenotypes was markedly relieved by PRF-DRG. The SNI-induced reduction in GRK2 expression, elevation of p-p38 MAPK levels in the SCDH, and increase in IL-1ß and TNF-α levels in the hippocampus were reversed by PRF, which was accompanied by an increase in autophagic flux in spinal microglia. The beneficial effect of 85 V-PRF was superior to that of 45 V-PRF. In addition, the improvements elicited by 85 V-PRF were reversed by intrathecal injection of GRK2 antisense oligonucleotide, and these changes were accompanied by GRK2 downregulation and p-p38 upregulation in the SCDH, increased pro-inflammatory factor levels in the hippocampus, and excessive autophagy in spinal microglia. In conclusion, our data indicate that the application of HV-PRF to the DRG could serve as an excellent therapeutic technique for regulating neuroimmunity and neuroinflammation to relieve pain phenotypes.

Systematic identification of potential key microRNAs and circRNAs in the dorsal root ganglia of mice with sciatic nerve injury.

Background: Neuropathic pain (NeP) is a pathological condition arising from a lesion or disease affecting the somatosensory system. Accumulating evidence has shown that circular RNAs (circRNAs) exert critical functions in neurodegenerative diseases by sponging microRNAs (miRNAs). However, the functions and regulatory mechanisms of circRNAs as competitive endogenous RNAs (ceRNAs) in NeP remain to be determined. Methods: The sequencing dataset GSE96051 was obtained from the public Gene Expression Omnibus (GEO) database. First, we conducted a comparison of gene expression profiles in the L3/L4 dorsal root ganglion (DRG) of sciatic nerve transection (SNT) mice (n = 5) and uninjured mice (Control) (n = 4) to define the differentially expressed genes (DEGs). Then, critical hub genes were screened by exploring protein-protein interaction (PPI) networks with Cytoscape software, and the miRNAs bound to them were predicted and selected and then validated by qRT-PCR. Furthermore, key circRNAs were predicted and filtered, and the network of circRNA-miRNA-mRNA in NeP was constructed. Results: A total of 421 DEGs were identified, including 332 upregulated genes and 89 downregulated genes. Ten hub genes, including IL6, Jun, Cd44, Timp1, and Csf1, were identified. Two miRNAs, mmu-miR-181a-5p and mmu-miR-223-3p, were preliminarily verified as key regulators of NeP development. In addition, circARHGAP5 and circLPHN3 were identified as key circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these differentially expressed mRNAs and targeting miRNAs were involved in signal transduction, positive regulation of receptor-mediated endocytosis and regulation of neuronal synaptic plasticity. These findings have useful implications for the exploration of new mechanisms and therapeutic targets for NeP. Conclusion: These newly identified miRNAs and circRNAs in networks reveal potential diagnostic or therapeutic targets for NeP.

A ratiometric fluorescence probe for imaging endoplasmic reticulum (ER) hypochlorous acid in living cells undergoing excited state intramolecular proton transfer.

Hypochlorous acid (HOCl), one of the most important ROS in living organisms, appears to serve an important role in the immune system in vivo. Endoplasmic reticulum (ER), the largest organelle in cells, manages many biological processes connected to vital activities. To better obtain insight into the relationship of ER stress and HOCl level, a ratiometric fluorescent probe RHE, based on rhodamine combined with HBT and ER-targeting group, was designed and synthesized for HOCl detection in the ER. Probe RHE shows a large stokes shift about 155 nm, which is derived to ESIPT principle. In addition, probe RHE exhibited excellent properties such as fast response (<80 s), high sensitivity with a low detection limit (40 nM), high selectivity and anti-interference. Moreover, probe RHE displayed an excellent ER-targeting ability and had been successfully applied for detection of exogenous and endogenous HOCl in HepG2 cells.

Effects of High-Voltage Pulsed Radiofrequency on the Ultrastructure and Nav1.7 Level of the Dorsal Root Ganglion in Rats With Spared Nerve Injury.

OBJECTIVES: To investigate the analgesic effect of high-voltage pulsed radiofrequency (HV-PRF) on the dorsal root ganglion (DRG) for neuropathic pain induced by spared nerve injury (SNI) in rats, especially the influence of this treatment on the DRG ultrastructure and voltage-gated sodium channel 1.7 (Nav1.7) level in the DRG. MATERIALS AND METHODS: One hundred fifty adult male Sprague-Dawley rats were randomly divided into five groups: Sham, SNI, Free-PRF, standard-voltage PRF (SV-PRF), and HV-PRF. The 45V-PRF and 85V-PRF procedures applied to the left L5 DRG were performed in SV-PRF group and the HV-PRF group, respectively, on day 7 after SNI, whereas no PRF was concurrently delivered in Free-PRF group. The paw mechanical withdrawal threshold (PMWT) was detected before SNI (baseline) and on days 1, 3, 7, 8, 10, 14, and 21. The changes of left L5 DRG ultrastructure were analyzed with transmission electron microscopy on days 14 and 21. The expression levels of Nav1.7 in left L5 DRG were detected by immunofluorescence and Western blot. RESULTS: Compared with the Free-PRF group, PMWT in the SV-PRF group and HV-PRF group were both significantly increased after PRF (all p < 0.05). Meanwhile, the PMWT was significantly higher in the HV-PRF group than that in the SV-PRF group on days 14 and 21 (all p < 0.05). There were statistically significant differences between the SV-PRF and Free-PRF groups (p < 0.05). Similarly, statistically significant difference was found between the HV-PRF and Free-PRF groups (p < 0.05). Especially, comparison of the SV-PRF group and the HV-PRF group revealed statistically significant difference (p < 0.05). The Nav1.7 levels were significantly downregulated in the SV-PRF group and HV-PRF groups compared to that in the Free-PRF group (all p < 0.01). A significantly lower Nav1.7 level was also found in the HV-PRF group compared to that in the SV-PRF group (p < 0.05). CONCLUSIONS: The HV-PRF produces a better analgesic effect than SV-PRF applied to the DRG in SNI rats. The underlying mechanisms may be associated with improving the histopathological prognosis and the downregulation of Nav1.7 levels in the DRG.

Microglial BDNF, PI3K, and p-ERK in the Spinal Cord Are Suppressed by Pulsed Radiofrequency on Dorsal Root Ganglion to Ease SNI-Induced Neuropathic Pain in Rats.

Background: Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) has been applied to alleviate neuropathic pain effectively, yet the mechanisms underlying pain reduction owing to this treatment are not clarified completely. The activated microglia, brain-derived neurotrophic factor (BDNF), phosphatidylinositol 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal cord were demonstrated to be involved in developing neuropathic pain. Also, it has been just known that PRF on DRG inhibits the microglial activation in nerve injury rats. Here, we aim to investigate whether PRF treatment could regulate the levels of BDNF, PI3K, and p-ERK in the spinal cord of rats with spared nerve injury (SNI) via suppressing the spinal microglia activation to ease neuropathic pain. Methods: The rats with SNI were intrathecally treated with minocycline (specific microglia inhibitor) or same volume of dimethyl sulfoxide once daily, beginning from 1 h before nerve transection to 7 days. PRF was applied adjacent to the L4-L5 DRG of rats with SNI at 45 V for 6 min on the seventh postoperative day, whereas the free-PRF rats were treated without PRF. The withdrawal thresholds were studied, and the spinal levels of ionized calcium-binding adapter molecule 1 (Iba1), BDNF, PI3K, and p-ERK were calculated by western blot analysis, reverse transcription-polymerase chain reaction, and immunofluorescence. Results: The paw withdrawal mechanical threshold and paw withdrawal thermal latency decreased in the ipsilateral hind paws after SNI, and the spinal levels of Iba1, BDNF, PI3K, and p-ERK increased on day 21 after SNI compared with baseline (P < 0.01). An intrathecal injection of minocycline led to the reversal of SNI-induced allodynia and increase in levels of Iba1, BDNF, PI3K, and p-ERK. Withdrawal thresholds recovered partially after a single PRF treatment for 14 days, and SNI-induced microglia hyperactivity, BDNF upregulation, and PI3K and ERK phosphorylation in the spinal cord reduced on D14 due to the PRF procedure. Conclusion: Microglial BDNF, PI3K, and p-ERK in the spinal cord are suppressed by the therapy of PRF on DRG to ease SNI-induced neuropathic pain in rats.

A Data-Driven Hybrid Three-Stage Framework for Hospital Bed Allocation: A Case Study in a Large Tertiary Hospital in China.

Beds are key, scarce medical resources in hospitals. The bed occupancy rate (BOR) amongst different departments within large tertiary hospitals is very imbalanced, a situation which has led to problems between the supply of and the demand for bed resources. This study aims to balance the utilization of existing beds in a large tertiary hospital in China. We developed a data-driven hybrid three-stage framework incorporating data analysis, simulation, and mixed integer programming to minimize the gaps in BOR among different departments. The first stage is to calculate the length of stay (LOS) and BOR of each department and identify the departments that need to be allocated beds. In the second stage, we used a fitted arrival distribution and median LOS as the input to a generic simulation model. In the third stage, we built a mixed integer programming model using the results obtained in the first two stages to generate the optimal bed allocation strategy for different departments. The value of the objective function, Z, represents the severity of the imbalance in BOR. Our case study demonstrated the effectiveness of the proposed data-driven hybrid three-stage framework. The results show that Z decreases from 0.7344 to 0.0409 after re-allocation, which means that the internal imbalance has eased. Our framework provides hospital bed policy makers with a feasible solution for bed allocation.

Predicting Intracerebral Hemorrhage Patients' Length-of-Stay Probability Distribution Based on Demographic, Clinical, Admission Diagnosis, and Surgery Information.

The vast majority of patients with intracerebral hemorrhage (ICH) suffer from long and uncertain length of stay (LOS). The aim of our study was to provide decision support for discharge and admission plans by predicting ICH patients' LOS probability distribution. The demographics, clinical predictors, admission diagnosis, and surgery information from 3,600 ICH patients were used in this study. We used univariable Cox analysis, multivariable Cox analysis, Cox-variable of importance (Cox-VIMP) analysis, and an intersection analysis to select predictors and used random survival forests (RSF)-a method in survival analysis-to predict LOS probability distribution. The Cox-VIMP method constructed by us effectively selected significant correlation predictors. The Cox-VIMP RSF model can improve prediction performance and is significantly different from the other models. The Cox-VIMP can contribute to the screening of predictors, and the RSF model can be established through those predictors to predict the probability distribution of LOS in each patient.

Downregulated spinal IRF8 and BDNF in NAC are involved in neuropathic pain-induced depression relief via pulsed radiofrequency on dorsal root ganglion in rat SNI model.

Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG), which produces remarkable analgesia through high-frequency electromagnetic energy, has become a main therapy for chronic neuropathic pain. The chronic neuropathic pain in patients is frequently accompanied by depression. However, the underlying neurophysiological mechanisms of the treatment of PRF on DRG for the neuropathic pain-induced depression remain unclear. This study was designed to explore the effect of PRF on DRG on the neuropathic pain-induced depression in rats with spared nerve injury (SNI). Here, we found that PRF on DRG or intrathecal injection of the interferon regulatory factor 8 (IRF8) siRNA prevented the increase of mechanical allodynia and depression-like behaviors of rats after receiving SNI. Meanwhile, Western blot, immunohistochemistry, and RT-PCR revealed that PRF on DRG or intrathecal injection of IRF8 siRNA inhibited IRF8 overexpression in the spinal cord and brain-derived neurotrophic factor (BDNF) in NAc. These results suggest that neuropathic pain-induced depression could be attenuated by PRF applied to DRG in SNI rats. The suppressed overexpression of the spinal IRF8 and BDNF in NAc may play an important role and contribute considerably to effectiveness of the therapy by PRF on DRG.

Pulsed Radiofrequency on Dorsal Root Ganglion Relieved Neuropathic Pain Associated with Downregulation of the Spinal Interferon Regulatory Factor 8, Microglia, p38MAPK Expression in a CCI Rat Model.

BACKGROUND: Interferon regulatory factor 8 (IRF8), which is induced by peripheral nerve injury (PNI), plays a key role in activating spinal microglia to release inflammatory cytokines in a p38-dependent way, thereafter results in formation of central sensitization. Pulsed radiofrequency (PRF) on dorsal root ganglion (DRG) alleviates neuropathic pain and inhibits the microglial activation in chronic constriction injury (CCI) rats. However, the consequences of PRF on spinal IRF8 of CCI rats remains unknown. OBJECTIVE: We explore if PRF on DRG of rats with CCI could restrain IRF8, microglia, and p38 hyperactivity in the spinal cord to alleviate neuropathic pain. STUDY DESIGN: A randomized, controlled animal study. SETTING: Department of Pain Management, Fujian Provincial Hospital, Fujian Key Laboratory of Geriatrics, Provincial Clinic College of Fujian Medical University. METHODS: The changes in pain behaviors and the expressions of IRF8, Iba1 and p-p38 in the spinal cord of CCI rats which were administrated with antisense/ mismatch oligodeoxynucleotide of IRF8 were studied. Rats in CCI+AS ODN group, CCI+MM ODN group or CCI+NS group were intrathecally treated with antisense oligodeoxynucleotide of IRF8, mismatch oligodeoxynucleotide of IRF8 or same volume 0.9% NaCl once daily respectively, beginning from the day after nerve transection 12 hours and lasting for 7 days. The effects of PRF on L4-5 DRG of rats with CCI were investigated. PRF was applied adjacent to the L4-5 DRG at an intensity of 45 V for 6 minutes after CCI, whereas the control rats were treated without radiofrequency current. The withdrawal thresholds were studied and the spinal levels of IRF8, ionized calcium-binding adapter molecule 1 (Iba1, microglia characteristic marker) and p-p38 were calculated by ELISA, western blot, RT-PCR, and immunofluorescence. RESULTS: Intrathecal administration of antisense oligodeoxynucleotide of IRF8 led to the reversal of CCI-induced allodynia, lower activation of spinal microglia and p-p38. Withdrawal thresholds were partially recovered after a single PRF treatment for 14 days. CCI-induced IRF8 upregulation, microglia hyperactivity, and p38 phosphorylation in the spinal cord were reduced due to PRF treatment. However, PRF did not alter pain behaviors and pain signals in normal rats. LIMITATIONS: In our study, one time point was selected just to assess the levels of microglia, and p-p38. The changes of IRF8, microglia, p-p38 in the ipsilateral DRG were not investigated. A more detailed study on how PRF on the DRG could further relieve NP is needed. CONCLUSIONS: Restraining IRF8, microglia and p38 hyperactivity in the spinal cord of CCI rats involved in the contribution to the long-lasting analgesia of PRF. KEY WORDS: Neuropathic pain, pulsed radiofrequency, dorsal root ganglion, microglia, p38MAPK, Interferon regulatory factor 8, chronic constriction injury of sciatic nerve.

Comparison of aqueous ammonia and dilute acid pretreatment of bamboo fractions: Structure properties and enzymatic hydrolysis.

The effect of two pretreatments methods, aqueous ammonia (SAA) and dilute acid (DA), on the chemical compositions, cellulose crystallinity, morphologic change, and enzymatic hydrolysis of bamboo fractions (bamboo yellow, timber, green, and knot) was compared. Bamboo fractions with SAA pretreatment had better hydrolysability than those with DA pretreatment. High crystallinity index resulted in low hydrolysis yield in the conversion of SAA pretreated bamboo fractions, not DA pretreated fractions. The increase of cellulase loading had modestly positive effect in the hydrolysis of both SAA and DA pretreated bamboo fractions, while supplement of xylanase significantly increased the hydrolysis of the pretreated bamboo fractions, especially after SAA pretreatment. The results indicated that SAA pretreatment was more effective than DA pretreatment in conversion of bamboo fractions, and supplementation of xylanase was necessary in effective conversion of the SAA pretreated fractions into fermentable sugars.