Mechanisms of complex regional pain syndrome.

Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial triggering event, accompanied by autonomic, sensory, motor, and sudomotor disturbances. The primary pathology of both types of CRPS (Type I, also known as reflex sympathetic dystrophy, RSD; Type II, also known as causalgia) is featured by allodynia, edema, changes in skin color and temperature, and dystrophy, predominantly affecting extremities. Recent studies started to unravel the complex pathogenic mechanisms of CRPS, particularly from an autoimmune and neuroimmune interaction perspective. CRPS is now recognized as a systemic disease that stems from a complex interplay of inflammatory, immunologic, neurogenic, genetic, and psychologic factors. The relative contributions of these factors may vary among patients and even within a single patient over time. Key mechanisms underlying clinical manifestations include peripheral and central sensitization, sympathetic dysregulation, and alterations in somatosensory processing. Enhanced understanding of the mechanisms of CRPS is crucial for the development of effective therapeutic interventions. While our mechanistic understanding of CRPS remains incomplete, this article updates recent research advancements and sheds light on the etiology, pathogenesis, and molecular underpinnings of CRPS.

Characterization of the interactions between Fulvic acid and Trypsin with Spectroscopic and Molecular Docking technology.

The interaction mechanism between trypsin and fulvic acid was analyzed by multispectral method and molecular docking simulation. The fluorescence spectra showed that fulvic acid induced static quenching of trypsin. The validity of this conclusion was further substantiated through the computation of the binding constants. The thermodynamic parameters show that the reaction is mainly controlled by van der Waals force and hydrogen bond force, and the reaction is spontaneous. In addition, based on the obtained binding distance, there may be a non-radiative energy transfer between the two. The ultraviolet spectrum showed that fulvic acid could shift the absorption peak of trypsin, indicating that fulvic acid had an effect on the secondary structure of trypsin. According to the synchronous fluorescence spectrum results, fulvic acid primarily interacts with tryptophan residues in trypsin and induces alterations in their microenvironment. Three-dimensional fluorescence spectrum and circular dichroism further proves this conclusion. The molecular docking simulation reveals that the interaction between the two groups primarily arises from hydrogen bonding and van der Waals forces. The findings suggest that FA has the ability to induce conformational changes in trypsin's secondary structure.

Effect of Chloramphenicol as Antibiotic on the Structure and Function of Pepsin and Its Mechanism of Action.

The interaction between chloramphenicol (CHL) and pepsin (PEP), as well as the impact of CHL on PEP conformation, were investigated using spectroscopic techniques and molecular docking simulations in this study. The experimental results demonstrate that CHL exhibits a static quenching effect on PEP. The thermodynamic parameters indicate that the reaction between CHL and PEP is spontaneous, primarily driven by hydrogen bonding and van der Waals forces. Moreover, the binding distance of r<7 nm suggests the occurrence of Förster's non-radiative energy transfer between these two molecules. In the synchronous fluorescence spectrum, the maximum fluorescence intensity of PEP produced a redshift phenomenon, indicating that CHL was bound to tryptophan residues of PEP. The addition of CHL induces changes in the secondary structure of PEP, as confirmed by the observed alterations in peak values in three-dimensional fluorescence spectra. The UV spectra reveal a redshift of 3 nm in the maximum absorption peak, indicating a conformational change in the secondary structure of PEP upon addition of CHL. Circular dichroism analysis demonstrates significant alterations in the α-helix, ß-sheet, ß-turn, and random coil contents of PEP before and after CHL incorporation, further confirming its ability to modulate the secondary structure of PEP.

Preparation and Molecular Structural Characterization of Fulvic Acid Extracted from Different Types of Peat.

Humic acid is a type of polymeric, organic weak acid mixture with a core aromatic structure and main-component oxygen-containing functional group. Fulvic acid is a type of humic substance that can be dissolved in acid, alkali, or water. This study discusses the influence of different peptides on the molecular structure of fulvic acid, which was extracted from herbaceous, woody, and mossy peats using alkaline dissolution and acid precipitation methods. Analyses using infrared, UV-Vis, 13C-NMR, and X-ray photoelectron spectroscopies, as well as X-ray diffraction (XRD), were conducted to compare the effects of different peat types on the content and molecular structure of fulvic acid. The woody peat fulvic acid content was the highest among all peat fulvic acids (0.38%). However, the yield of fulvic acid from herbaceous peat was the highest (2.53%). Herbaceous peat fulvic acid contains significant quantities of carbonyl, amino, methylene, carboxyl, and phenolic hydroxyl groups and ether bonds. Woody peat fulvic acid contains carbonyl and methoxy groups, benzenes, aromatic carbons, aromatic ethers, and phenols. The degree of aromatization of woody peat fulvic acid was the highest. Mossy peat fulvic acid contains high levels of hydroxy, methyl, methylene, and phenol groups and aromatic ethers. The structural differences in fulvic acids in the different types of peat were primarily manifested in the content of functional groups, with little influence from the types of functional groups. XRD analysis of the different peats revealed that their structures all comprised benzene rings. However, mossy peat contained more C=O and -COOH groups, whereas herbaceous peat contained more C-O groups.

Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats.

Cancer chemotherapy-induced neuropathic pain is a devastating pain syndrome without effective therapies. We previously reported that rats deficient in complement C3, the central component of complement activation cascade, showed a reduced degree of paclitaxel-induced mechanical allodynia (PIMA), suggesting that complement is integrally involved in the pathogenesis of this model. However, the underlying mechanism was unclear. Complement activation leads to the production of C3a, which mediates inflammation through its receptor C3aR1. In this article, we report that the administration of paclitaxel induced a significantly higher expression level of C3aR1 on dorsal root ganglion (DRG) macrophages and expansion of these macrophages in DRGs in wild-type (WT) compared with in C3aR1 knockout (KO) mice. We also found that paclitaxel induced less severe PIMA, along with a reduced DRG expression of transient receptor potential channels of the vanilloid subtype 4 (TRPV4), an essential mediator for PIMA, in C3aR1 KO than in WT mice. Treating WT mice or rats with a C3aR1 antagonist markedly attenuated PIMA in association with downregulated DRG TRPV4 expression, reduced DRG macrophages expansion, suppressed DRG neuron hyperexcitability, and alleviated peripheral intraepidermal nerve fiber loss. Administration of C3aR1 antagonist to TRPV4 KO mice further protected them from PIMA. These results suggest that complement regulates PIMA development through C3aR1 to upregulate TRPV4 on DRG neurons and promote DRG macrophage expansion. Targeting C3aR1 could be a novel therapeutic approach to alleviate this debilitating pain syndrome.

The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review.

Complex Regional Pain Syndrome (CRPS) is an excess and/or prolonged pain and inflammation condition that follows an injury to a limb. The pathogenesis of CRPS is multifaceted that remains incompletely understood. Neuroinflammation is an inflammatory response in the peripheral and central nervous systems. Dysregulated neuroinflammation plays a crucial role in the initiation and maintenance of pain and nociceptive neuronal sensitization, which may contribute to the transition from acute to chronic pain and the perpetuation of chronic pain in CRPS. The key features of neuroinflammation encompass infiltration and activation of inflammatory cells and the production of inflammatory mediators in both the central and peripheral nervous systems. This article reviews the role of neuroinflammation in the onset and progression of CRPS from six perspectives: neurogenic inflammation, neuropeptides, glial cells, immune cells, cytokines, and keratinocytes. The objective is to provide insights that can inform future research and development of therapeutic targets for CRPS.

Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating ß-catenin.

Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula polysaccharides (CPPs) have been widely used in traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis in vivo. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by ALP and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to osteogenesis and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of ß-catenin, the core protein of the Wnt/ß-catenin signaling pathway, in a concentration-dependent manner. Adding DKK1, a mature inhibitor of the Wnt/ß-catenin signaling pathway, partially suppressed CPP-stimulated ß-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats in vivo, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs in vitro. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.

Removal of Heavy Metal Ions from Aqueous Solution Using Biotransformed Lignite.

Heavy metal pollution caused by industrial wastewater such as mining and metallurgical wastewater is a major global concern. Therefore, this study used modified lignite as a low-cost adsorbent for heavy metal ions. Pingzhuang lignite was dissolved and modified using Fusarium lignite B3 to prepare a biotransformed-lignite adsorbent (BLA). The O, H, and N contents of the BLA increased after transformation, and the specific surface area increased from 1.81 to 5.66 m2·g-1. Various adsorption properties were investigated using an aqueous solution of Cu(Ⅱ). The kinetic and isothermal data were well-fitted by pseudo-second-order and Langmuir models, respectively. The Langmuir model showed that the theoretical Cu(II) adsorption capacity was 71.47 mg·g-1. Moreover, large particles and a neutral pH were favorable for the adsorption of heavy metal ions. The adsorption capacities of raw lignite and BLA were compared for various ions. Microbial transformation greatly improved the adsorption capacity, and the BLA had good adsorption and passivation effects with Cu(II), Mn(II), Cd(II), and Hg(II). Investigation of the structural properties showed that the porosity and specific surface area increased after biotransformation, and there were more active groups such as -COOH, Ar-OH, and R-OH, which were involved in the adsorption performance.

Molecular cloning, prokaryotic expression and its application potential evaluation of interferon (IFN)-ω of forest musk deer.

Forest musk deer (Moschus berezovskii) are currently a threatened species under conservation, and the development of captive populations is restricted by health problems. To evaluate the application potential of interferon (IFN)-ω in the prevention and control of forest musk deer disease, 5 forest musk deer IFN-ω (fmdIFNω) gene sequences were successfully obtained by homologous cloning method for the first time. FmdIFNω5 was selected and recombinant fmdIFNω protein (rIFNω) was successfully expressed by pGEX-6P-1 plasmid and E. coli expression system. The obtained protein was used to stimulate forest musk deer lung fibroblasts cells FMD-C1 to determine its regulatory effect on interferon-stimulated genes (ISGs). In addition, an indirect ELISA method based on anti-rIFNω serum was established to detect endogenous IFN-ω levels in 8 forest musk deer. The results showed that there were 18 amino acid differences among the 5 fmdIFNω subtypes, all of which had the basic structure to exert the activity of type I IFN and were close to Cervus elaphus IFN-ω in the phylogenetic tree. The protein expressed was 48 kDa, and the transcription levels of all ISGs were increased in FMD-C1 cells stimulated by rIFNω, and the amount of transcription accumulation was time-dependent. Meanwhile, Anti-rIFNω serum of mice could react with both rIFNω and forest musk deer serum, and the OD450nm value of forest musk deer serum with the most obvious symptoms was the highest, suggesting that the level of natural IFN-ω in different forest musk deer could be monitored by the rIFNω-based ELISA method. These results indicate that fmdIFNω has the potential as an antiviral drug and an early indication of innate immunity, which is of great significance for the prevention and control of forest musk deer diseases.

Insulin-like Growth Factor-1 (IGF-1) Related Drugs in Pain Management.

Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, and the development of neuropathic pain. Methods. We conducted a search of the PUBMED/MEDLINE database, Scopus, and the Cochrane Library for all reports published in English on IGF-1 in pain management from origination through November 2022. The resulting 545 articles were screened, and 18 articles were found to be relevant after reading abstracts. After further examination of the full text of these articles, ten were included in the analysis and discussion. The levels of clinical evidence and implications for recommendations of all the included human studies were graded. Results. The search yielded 545 articles, of which 316 articles were deemed irrelevant by reading the titles. There were 18 articles deemed relevant after reading abstracts, of which 8 of the reports were excluded due to lack of IGF-1-related drug treatment after reviewing the full text of the articles. All ten articles were retrieved for analysis and discussion. We found that IGF-1 may have several positive effects on pain management, including promoting the resolution of hyperalgesia, preventing chemotherapy-induced neuropathy, reversing neuronal hyperactivity, and elevating the nociceptive threshold. On the other hand, IGF-1R inhibitors may alleviate pain in mice with injury of the sciatic nerve, bone cancer pain, and endometriosis-induced hyperalgesia. While one study showed marked improvement in thyroid-associated ophthalmopathy in humans treated with IGF-1R inhibitor, two other studies did not find any benefits from IGF-1 treatment. Conclusions. This review highlights the potential of IGF-1 and IGF-1R inhibitors in pain management, but further research is needed to fully understand their efficacy and potential side effects.

Characterization of the Interactions between Minocycline Hydrochloride and Trypsin with Spectroscopic and Molecular Docking Technology.

In the current study, the interaction of minocycline hydrochloride (MC) and trypsin (TRP) was studied using fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, UV-Vis spectroscopy, and molecular docking simulation techniques. The results show that the fluorescence quenching of trypsin at different degrees can be caused by minocycline hydrochloride at different temperatures. According to the Stern-Volmer equation, the fluorescence quenching type was static quenching. By calculating critical distance, we concluded that there is a possibility of non-radiative energy transfer between minocycline hydrochloride and trypsin. The effect of minocycline hydrochloride on the secondary structure of trypsin was demonstrated using ultraviolet spectroscopy. Synchronous fluorescence spectroscopy showed that minocycline hydrochloride could bind to tryptophan residues in trypsin, resulting in corresponding changes in the secondary structure of trypsin. Three-dimensional fluorescence spectroscopy showed that minocycline hydrochloride had a particular effect on the microenvironment of trypsin that led to changes in the secondary structure of trypsin. The molecular docking technique demonstrated that the binding of minocycline hydrochloride and trypsin was stable. Circular dichroism showed that the secondary structure of trypsin could be changed by minocycline hydrochloride.

Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study.

BACKGROUND: Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions. OBJECTIVES: We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion. METHODS: In this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks. RESULTS: Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome. CONCLUSIONS: The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

MicroRNA let-7f-5p regulates PI3K/AKT/COX2 signaling pathway in bacteria-induced pulmonary fibrosis via targeting of PIK3CA in forest musk deer.

Background: Recent studies have characterized that microRNA (miRNA) is a suitable candidate for the study of bleomycin/LPS-induced pulmonary fibrosis, but the knowledge on miRNA in bacteria-induced pulmonary fibrosis (BIPF) is limited. Forest musk deer (Moschus berezovskii, FMD) is an important endangered species that has been seriously affected by BIPF. We sought to determine whether miRNA exist that modulates the pathogenesis of BIPF in FMD. Methods: High-throughput sequencing and RT-qPCR were used to determine the differentially expressed miRNAs (DEmiRNAs) in the blood of BIPF FMD. The DEmiRNAs were further detected in the blood and lung of BIPF model rat by RT-qPCR, and the targeting relationship between candidate miRNA and its potential target gene was verified by dual-luciferase reporter activity assay. Furthermore, the function of the candidate miRNA was verified in the FMD lung fibroblast cells (FMD-C1). Results: Here we found that five dead FMD were suffered from BIPF, and six circulating miRNAs (miR-30g, let-7f-5p, miR-27-3p, miR-25-3p, miR-9-5p and miR-652) were differentially expressed in the blood of the BIPF FMD. Of these, let-7f-5p showed reproducibly lower level in the blood and lung of the BIPF model rat, and the expression levels of PI3K/AKT/COX2 signaling pathway genes (PIK3CA, PDK1, Akt1, IKBKA, NF-κB1 and COX2) were increased in the lung of BIPF model rats, suggesting that there is a potential correlation between BIPF and the PI3K/AKT/COX2 signaling pathway. Notably, using bioinformatic prediction and experimental verification, we demonstrated that let-7f-5p is conserved across mammals, and the seed sequence of let-7f-5p displays perfect complementarity with the 3' UTR of PIK3CA gene and the expression of the PIK3CA gene was regulated by let-7f-5p. In order to determine the regulatory relationship between let-7f-5p and the PI3K/AKT/COX2 signaling pathway in FMD, we successfully cultured FMD-C1, and found that let-7f-5p could act as a negative regulator for the PI3K/Akt/COX2 signaling pathway in FMD-C1. Collectively, this study not only provided a study strategy for non-invasive research in pulmonary disease in rare animals, but also laid a foundation for further research in BIPF.

Relationship between iron metabolism and gestational diabetes mellitus: A systemic review and meta analysis.

BACKGROUND AND OBJECTIVES: To investigate the relationship between serum iron metabolism indexes and gestational diabetes mellitus (GDM) using a meta-analysis. METHODS AND STUDY DESIGN: Databases including PubMed, Web of Science, Embase, and Cochrane Library were searched. Prospective cohort or case-control studies evaluating the relationships between serum iron metabolism indexes and GDM were retrieved from these data-bases. The outcome indicators, such as mean ± standard deviation, relative risk (RR), or odds ratio (OR) were extracted. The RR or OR, standard mean difference (SMD), and 95% confidence interval (CI) were used to calculate the combined effect sizes. RESULTS: A total of 32 studies on the relationships between serum iron metabolic indexes and GDM were included. The serum iron [SMD=0.40 mg/dL, 95% CI (0.16, 0.64), p=0.001], ferritin [SMD=0.58 ng/mL, 95% CI (0.35, 0.81), p˂0.001], hemoglobin [SMD=0.48 g/dL, 95% CI (0.28, 0.67), p˂0.001], transferrin saturation [SMD=0.83%, 95% CI (0.15, 1.52), p=0.000], and hepcidin [SMD=0.63 ng/mL, 95% CI (0.09, 1.18), p=0.023] levels were higher in the GDM group than in the non-GDM group, whereas total iron binding ability [SMD = -0.53 µg/dL, 95% CI (-1.05, -0.02), p=0.001] was lower in the GDM group than in the non-GDM group. High serum ferritin [OR=1.92, 95% CI (1.59, 2.32), p˂0.001] and hemoglobin levels [OR=1.30, 95% CI (1.04,1.63), p=0.023] were associated with GDM risk. CONCLUSIONS: Serum iron, ferritin, transferrin saturation, hepcidin, and hemoglobin levels were higher and total iron binding ability was lower in GDM patients than in those without GDM. High serum ferritin and hemoglobin levels were associated with GDM risk.

Association Between the Risk of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

Objective: To explore the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1168 patients with T2DM were divided into the non-CKD and CKD groups, and the difference in the prevalence of NAFLD was compared. The differences in serum creatinine (SCr) and urine albumin-to-creatinine ratio (UACR) levels were compared between the non-NAFLD and NAFLD groups. Patients with T2DM were divided into three groups according to their UACR levels (UACR < 30 mg/g [U1 group]; UACR ≤ 30 mg/g to < 300 mg/g [U2 group]; and UACR ≥ 300 mg/g [U3 group]) or estimated glomerular filtration rate (eGFR) levels (≥ 90 mL/min [G1 group]; eGFR ≤ 60 mL/min to < 90 mL/min [G2 group]; and eGFR < 60 mL/min (G3 group]). The difference in the prevalence and risks of NAFLD in the different UACR or eGFR level groups was analyzed. Results: The prevalence of NAFLD in the CKD group was higher than that in the non-CKD group (63.5% vs 50.5%, p < 0.001). The SCr and UACR levels in the NAFLD group were higher than those in the non-NAFLD group (both p<0.05). The prevalence of NAFLD in the U3 group (75.6%) was higher than that in the U1 (50.5%, p < 0.05) and U2 (60.1%, p < 0.05) groups, and the prevalence of NAFLD in the U2 group (60.1%) was higher than that in the U1 group (50.5%, p < 0.05). The risk of NAFLD in the U3 group was higher than that in the U2 group (odds ratio [OR] = 3.032 and 1.473). Despite adjusting the parameters further, the NAFLD risk in the U3 group remained higher than that in the U2 group (OR = 1.660 and 2.342). Conclusion: The risk of NAFLD in patients with T2DM is closely related to CKD.

Advances in Interventional Therapies for Painful Diabetic Neuropathy: A Systematic Review.

BACKGROUND: Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice. METHODS: We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN. RESULTS: We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+). CONCLUSIONS: Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.

The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review.

BACKGROUND CONTEXT: There are limited treatments for discogenic low back pain. Intradiscal injections of biologic agents such as platelet-rich plasma (PRP) or stem cells (SC) are theorized to have regenerative properties and have gained increasing interest as a possible treatment, but the evidence supporting their use in clinical practice is not yet well-defined. PURPOSE: Determine the effectiveness of intradiscal biologics for treating discogenic low back pain. STUDY DESIGN: PRISMA-compliant systematic review. PATIENT SAMPLE: Patients with discogenic low back pain confirmed by provocation discography or clinical and imaging findings consistent with discogenic pain. OUTCOME MEASURES: The primary outcome was the proportion of individuals with ≥50% pain relief after intradiscal biologic injection at 6 months. Secondary outcomes included ≥2-point pain score reduction on NRS; patient satisfaction; functional improvement; decreased use of other health care, including analgesics and surgery; and structural disc changes on MRI. METHODS: Comprehensive literature search performed in 2018 and updated in 2020. Interventions included were biologic therapies including mesenchymal stem cells, platelet rich plasma, microfragmented fat, amniotic membrane-based injectates, and autologous conditioned serum. Any other treatment (sham or active) was considered for comparative studies. Studies were independently reviewed. RESULTS: The literature search yielded 3,063 results, 37 studies were identified for full-text review, and 12 met established inclusion criteria for review. The quality of evidence on effectiveness of intradiscal biologics was very low. A single randomized controlled trial evaluating platelet-rich plasma reported positive outcomes but had significant methodological flaws. A single trial that evaluated mesenchymal stem cells was negative. Success rates for platelet-rich plasma injectate in aggregate were 54.8% (95% Confidence Interval: 40%-70%). For mesenchymal stem cells, the aggregate success rate at six months was 53.5% (95% Confidence Interval: 38.6%-68.4%), though using worst-case analysis this decreased to 40.7% (95% Confidence Interval: 28.1%-53.2%). Similarly, ≥30% functional improvement was achieved in 74.3% (95% Confidence Interval: 59.8%-88.7%) at six months but using worst-case analysis, this decreased to 44.1% (95% Confidence Interval: 28.1%-53.2%). CONCLUSION: Limited observational data support the use of intradiscal biologic agents for the treatment of discogenic low back pain. According to the Grades of Recommendation, Assessment, Development and Evaluation System, the evidence supporting use of intradiscal mesenchymal stem cells and platelet-rich plasma is very low quality.

Reference gene screening for analyzing gene expression in the heart, liver, spleen, lung and kidney of forest musk deer.

The screening of reference genes for real-time quantitative PCR (qPCR) in forest musk deer (FMD) tissue is of great significance to the basic research on FMD. However, there are few reports on the stability analysis of FMD reference genes so far. In this study, We used qPCR to detect the expression levels of 11 reference gene candidates (18S rRNA, beta-actin [ACTB], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], TATA box-binding protein [TBP], hypoxanthine phosphoribosyltransferase 1 [HPRT1], tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta polypeptide [YWHAZ], hydroxymethylbilane synthase [HMBS], eukaryotic translation elongation factor 1 alpha 1 [EEF1A1], succinate dehydrogenase complex flavoprotein subunit A [SDHA], peptidylprolyl isomerase B [PPIB], and ubiquitin C [UBC]) in heart, liver, spleen, lung and kidney of FMD. After removing 18S rRNA on account of its high expression level, geNorm, NormFinder, BestKeeper and ΔCt algorithms were used to evaluate the expression stability of the remaining genes in the five organs, and further comprehensive ranking was calculated by RefFinder. According to the results, the selected reference genes with the most stable expression in the heart of FMD are SDHA and YWHAZ, while in the liver are ACTB and SDHA; in the spleen and lung are YWHAZ and HPRT1; in the kidney are YWHAZ and PPIB. The use of common reference genes in all five organs is not recommended. The analyses showed that tissue is an important variability factor in genes expression stability. Meanwhile, the result can be used as a reference for the selection of reference genes for qPCR in further study.