The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis.

Background: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP). Methods: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed. Results: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain. Conclusion: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.

Glycyrrhizic acid suppresses atopic dermatitis-like symptoms by regulating the immune balance.

BACKGROUND: Glycyrrhiza is one of the most widely used traditional Chinese medicines in China. Its main bioactive ingredient glycyrrhizic acid (GA) has the potential to be used as a treatment for atopic dermatitis (AD) because it has similar actions to steroids, but with relatively few side effects. AIMS: The objective of this study was to explore the potential mechanisms of GA on AD mice model. METHODS: Calcipotriol, a vitamin D3 analogue (MC903) was applied topically to establish AD mouse model. Mice were intraperitoneally administrated with 2 mg/kg dexamethasone (DEX), 25 or 50 mg/kg GA for 15 days. After mice were executed, skin tissues were collected and detected the expression levels of IL-4, IFN-γ, TNF-α and thymic stromal lymphopoietin (TSLP). The percentages of Th1, Th2, Th17, langerhans cells (LCs) in draining lymph nodes (dLNs) were measured by flow cytometry. RESULTS: Our data demonstrated that GA improved the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that GA treatment decreased the level of total IgE in serum, suppressed ear swelling, reduced the infiltration of mast cells in skin lesions and decreased expressions of IL-4, IFN-γ, TNF-α and TSLP in skin lesions. Furthermore, our experimental results demonstrated that GA suppressed the Th1/Th2/Th17-immune responses in the dLNs, inhibited the migration of LCs in dLNs. CONCLUSIONS: In conclusion, our findings suggested potential therapeutic effects of GA against MC903-induced AD-like skin lesions in mice.

Therapeutic effects of myricetin on atopic dermatitis in vivo and in vitro.

BACKGROUND: Myricetin (Myr) is a flavonoid compound that exist widely in many natural plants. Myr has been proven to have multiple biological functions, including immunomodulatory and anti-inflammatory effects. PURPOSE: In this study, we investigated the therapeutic effect of Myr on calcipotriol (MC903) induced atopic dermatitis (AD) mouse model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulated human immortal keratinocyte line (HaCaT) in vivo and in vitro. METHODS: MC903 was applied topically to the left ears of mice to establish AD mouse model. After the AD model established successfully, the cream base, dexamethasone (DEX) cream or Myr cream were applied on the lesions of mice for 8 days. Through measuring ear thickness and scoring dermatitis severity, we evaluated the therapeutic effect of Myr, the draining lymph nodes (DLNs) and ears of the mice were collected for mechanistic study. In addition, TNF-α and IFN-γ-activated HaCaT cells were used to investigate the underlying mechanism. RESULTS: Our data demonstrated that Myr alleviated the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that Myr treatment suppressed ear swelling and IgE level in the serum, reduced the infiltration of mast cells in skin lesions, decreased expressions of thymus and activation regulated chemokine (TARC), IL-4, IFN-γ and thymic stromal lymphopoietin (TSLP) in ear lesions, increased the expressions of filaggrin (FLG). Furthermore, our experimental results demonstrated that Myr down-regulated the mRNA expressions of T-bet and GATA-3 in DLNs. In vitro, Myr treatment decreased MDC and TARC expressions in IFN-γ and TNF-α-induced HaCaT cells by blocking the NF-κB and STAT1 signal pathway. CONCLUSION: The present study is the first to investigate the anti-atopic effects of Myr. Our findings suggested the therapeutic effects of Myr against MC903-induced AD-like skin lesions in mice. Therefore, Myr may be a potential therapeutic agent for AD.

Risk factors for pulmonary cement embolism associated with percutaneous vertebral augmentation: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cement embolism (PCE) was a rare but fatal complication for percutaneous vertebral augmentation (PVA). Thus we did a systematic review and meta-analysis of cohort studies to investigate the risk factors for PCE after PVA. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to September 2021. All eligible studies assessing the risk factors for PCE after PVA were incorporated. Dichotomous data was calculated by risk difference (RD) from Mantel-Haenszel method (M - H method); continuous data was analyzed by mean difference (MD) from Inverse-Variance method (I-V method). All variables were taken as measure of effect by fixed effect model. Heterogeneity, sensitivity, and publication bias analyses were also performed. RESULTS: This study totally included 13 studies. According to the Newcastle-Ottawa Scale (NOS), 7 studies were considered as low quality, with NOS< 6. The others were of relatively high quality, with NOS≥6. 144/6251 patients (2.3%) had PCE after PVA. percutaneous vertebroplasty (PVP) (RD = 0.02, 95%CI: [0.01, 0.04], Z = 3.70, P < 0.01), thoracic vertebra (RD = 0.03, 95%CI: [0.01, 0.05], Z = 3.53, P < 0.01), higher cement volume injected per level (MD = 0.23, 95%CI: [0.05, 0.42], Z = 2.44, P = 0.01), more than three vertebrae treated per session (MD = -0.05, 95%CI: [-0.08, -0.02], Z = 3.65, P < 0.01), venous cement leakage (RD = 0.07, 95%CI: [0.03, 0.11], Z = 3.79, P < 0.01) were more likely to cause PCE. CONCLUSION: This study showed that risk factors for PCE included PVP, thoracic vertebra, higher cement volume injected per level, more than three vertebrae treated per session, venous cement leakage. As a serious complication, PCE should be paid attention and avoided.

Clinical and radiological subsequent fractures after vertebral augmentation for treating osteoporotic vertebral compression fractures: a meta-analysis.

PURPOSE: This study aimed to identify all relevant randomized controlled trials (RCT) and prospective non-RCTs to further investigate whether percutaneous vertebral augmentation (PVA) was associated with clinical and radiological subsequent fractures on unoperated levels. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to January 2020. All eligible studies comparing subsequent fractures after PVA with those after conservative treatment (CT) were incorporated. The pooled risk ratio (RR) with its 95% confidence intervals (95% CIs) was used. Heterogeneity, sensitivity, and publication bias analyses were performed. RESULTS: In all, 32 studies were included in the study: 82/512 patients (16.02%) and 58/433 patients (13.39%) had clinical subsequent fractures in the PVA group and CT group, respectively. No significant differences were observed between the two groups [RR = 1.22, 95% CI 0.70-2.12, P = 0.49]. Further, 175/837 patients (20.91%) in the PVA group and 160/828 patients (19.32%) in the CT group had radiological subsequent fractures. No significant difference was observed between groups [RR = 0.91, 95% CI 0.71-2.12, P = 1.16]. Further, no statistical difference was observed on subgroup analysis between RCTs and non-RCTs or PVP and PKP. CONCLUSION: Our systematic review revealed that subsequent fractures on unoperated levels were not associated with PVA, regardless of whether they were clinical or radiological subsequent fractures.

Preliminary Study of Obese Patients with Chronic Obstructive Pulmonary Disease Suffering from Painful Osteoporotic Vertebral Compression Fracture Treated by Percutaneous Vertebroplasty in Improved Prone Position and Right Lateral Position.

OBJECTIVE: To assess outcomes in obese patients with chronic obstructive pulmonary disease (COPD) who sustained an osteoporotic vertebral compression fracture (OVCF) treated by percutaneous vertebroplasty (PVP) in the improved prone position and right lateral position. METHODS: Between January 2015 and May 2016, a total of 60 patients were enrolled in this randomized controlled study. Patients in group A were placed in the improved prone position for a bilateral transpedicular technique, and those in group B were placed in the right lateral position for a left transverse process-pedicle approach. Clinical and radiologic outcomes were assessed and compared between the 2 groups during the 12-month follow-up period. RESULTS: All operations were successfully completed without any serious sequelae. The operation time, fluoroscopic time, scores for respiratory condition during the operation, intravertebral cement volume, and incidence of cement leakage were significantly greater in group A compared with group B (P < 0.01). During the follow-up period, all patients in both groups experienced significant improvement in pain relief. Satisfactory functional improvement was obtained at 3 months postoperatively. CONCLUSIONS: Treatment of obese patients with COPD suffering from painful OVCF by PVP in both the improved prone position with a bilateral technique and the right lateral position with a unilateral technique was relatively safe and effective. However, unilateral PVP in the right lateral position was associated with a shorter operation time, limited fluoroscopic time, and minimal cement leakage.

[Eye-acupuncture intervention reduces cerebro-cortical apoptosis of neurovascular unit in cerebral ischemia-reperfusion injury rats].

OBJECTIVE: To observe the effect of eye-acupuncture intervention on cerebro-cortical apoptosis of microvascular endothelial cells, neurons and astrocytes (main components of neurovascular unit) and the expression of Bad (an apoptosis promoter) and B-cell lymphoma-extra large(Bcl-xL) proteins in focal cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its mechanisms underlying improvement of CIRI. METHODS: SD rats were randomly divided into control, sham-operation, model 3 h, model 24 h, model 72 h, eye-acupuncture 3 h, eye-acupuncture 24 h and eye-acupuncture 72 h groups(n＝12 in each group). The CIRI model was established by middle cerebral artery occlusion/reperfusion (MCAO/R). Eye-acupuncture was applied to bilateral "Gan" (Liver) regions, "Shen" (Kidney) regions, "Shangjiao" (Upper-energizer) and "Xiajiao" (Lower-energizer) for 20 min, once 3 h and every 12 h after modeling. The expression levels of Bad and Bcl-xL in the ischemic cerebral cortex tissue were detected by Western blot. The apoptotic neurons, microvascular endothelial cells and astrocytes were assayed by immunofluorescence double labeling (Nestin/TUNEL, CD34/TUNEL and glial fibrillary acidic protein [GFAP]/TUNEL) separately. RESULTS: After modeling, the numbers of apoptotic neurons, microvascular endothelial cells and astrocytes in the ischemic cerebral cortex tissue were significantly increased in the model 72 h group than in the sham-operation group (P<0.01). Following the treatment, the numbers of the 3 types of apoptotic cells were markedly lower in the eye-acupuncture 72 h group than in the model 72 h group(P<0.01). The expression levels of Bad and Bcl-xL proteins were notably up-regulated in the model 3 h, model 24 h and model 72 h groups than in the sham operation group(P<0.01). Following eye-acupuncture intervention, modeling induced increase of the Bad expression were obviously reversed in eye-acupuncture 24 h and eye-acupuncture 72 h groups than those in the 2 model groups(P<0.05). And the increase of Bcl-xL expression levels were further increased in the eye-acupuncture groups in comparison with those in the 3 model groups (P<0.01). CONCLUSION: Eye-acupuncture can down-regulate the expression of Bad protein, and up-regulate the expression of Bcl-xL protein in the ischemic cerebral cortex in CIRI rats, which may contribute to its function in reducing apoptotic neurons, microvascular endothelial cells and astrocytes, suggesting a protective effect of eye-acupuncture intervention on neurovascular unit.

[Improved anatomical locking plate internal fixation through tarsal sinus incision in treating Sanders III-IV calcaneal fractures].

OBJECTIVE: To investigate clinical effects of improved anatomical locking plate internal fixation through tarsal sinus incision in treating Sanders III and IV calcaneal fractures. METHODS: From February 2015 to October 2016, 35 patients with Sanders III and IV calcaneal fractures treated by improved anatomical locking plate internal fixation through tarsal sinus incision were collected, including 22 males and 13 females aged from 22 to 68 years old with an average of (42.3±12.7) years old. According to Sanders classification, 23 patients were type III and 12 patients were type IV. Postoperative complications were observed, Bö hler angle and Gissane angle before and after operation were compared, and Maryland foot function scoring standard was evaluated at 12 months after operation. RESULTS: All patients were followed up from 12 to 20 months with an average of (14.5±2.0) months, the length of incision ranged from 4.0 to 5.5 cm with an average of (4.7±0.4) cm. Superficial infection occurred in 1 patient, delayed union in 2 patients, gastrocnemius nerve injury in 1 patient. No complications such as steel plate exposure and fracture reduction loss occurred. Wound healing time ranged from 14 to 28 days with an average of(15.4±4.7) days, the fracture healing time ranged from 8 to 14 weeks with an average of (9.8±1.9) weeks. Bö hler angle increased from preoperative (9.81±14.28)° to 3 days after operation (26.35±11.04)°, and (25.96±10.79)° at 12 months after operation(P<0.05). Gissane angle ranged from preoperative (122.54±16.79)° to 3 days after operation (120.85±11.88)°, and (120.62±11.44)° at 12 months after operation and had statistical meaning. Maryland score increased from 12.66±4.10 before operation to 92.20 ±7.82 at 12 months after operation, and 32 patients got excellent results, 2 good and 1 moderate. CONCLUSIONS: Improved anatomical locking plate internal fixation through tarsal sinus incision in treating Sanders III and IV calcaneal fractures, which has advantages of less incision, less soft tissue injury, better fracture reduction and fixation, could receive good reduction and fixation. It is an effective method for Sanders III and IV fracture of calcaneus fracture.

A potential material to cut down infection caused by application of artificial muscles.

Artificial muscles are so important that can be used to cure prosthetic limbs. A new kind of taurine Schiff base sodium was synthesized by a series of chemical reactions, which may be applied to strengthen antibacterial activity of artificial muscle. The bioactivity of this material was screened by cytotoxicity test, antibacterial test, and thermal gravity test and so on. All results told us that this material had low toxicity, high antibacterial activity and thermal stability. Combine our deep studies on pharmacological activity of the active material with our knowledge on artificial muscles; we want to know if we can put this material into the content of artificial muscle, in order to strengthen its antimicrobial activity, so that the pains of the patients who were applied artificial muscle would be relieved.

N'-(2-Chloro-benzyl-idene)-4-methyl-benzohydrazide.

In the title compound, C(15)H(13)ClN(2)O, the mol-ecule displays a trans conformation with respect to the C=N bond. The two aromatic rings form a dihedral angle of 12.0 (3)°. In the crystal, mol-ecules are connected via N-H⋯O hydrogen bonds into chains propagating along the c-axis direction.