Piezo2 Contributes to Traumatic Brain Injury by Activating the RhoA/ROCK1 Pathways.

Traumatic brain injury (TBI) can lead to short-term and long-term physical and cognitive impairments, which have significant impacts on patients, families, and society. Currently, treatment outcomes for this disease are often unsatisfactory, due at least in part to the fact that the molecular mechanisms underlying the development of TBI are largely unknown. Here, we observed significant upregulation of Piezo2, a key mechanosensitive ion channel protein, in the injured brain tissue of a mouse model of TBI induced by controlled cortical impact. Pharmacological inhibition and genetic knockdown of Piezo2 after TBI attenuated neuronal death, brain edema, brain tissue necrosis, and deficits in neural function and cognitive function. Mechanistically, the increase in Piezo2 expression contributed to TBI-induced neuronal death and subsequent production of TNF-α and IL-1ß, likely through activation of the RhoA/ROCK1 pathways in the central nervous system. Our findings suggest that Piezo2 is a key player in and a potential therapeutic target for TBI.

Photo-crosslinked enhanced double-network hydrogels based on modified gelatin and oxidized sodium alginate for diabetic wound healing.

The diabetic wound is hard to repair due to bacterial infection, lasting inflammation, and so on. Therefore, it is vital to fabricate a multi-functional hydrogel dressing for the diabetic wound. In this study, a kind of dual-network hydrogel loaded with gentamicin sulfate (GS) based on sodium alginate oxide (OSA) and glycidyl methacrylate gelatin (GelGMA) was designed through the Schiff base bonding and photo-crosslinking to promote the diabetic wound healing. The hydrogels exhibited stable mechanical properties, high water absorbency, and good biocompatibility and biodegradability. Antibacterial results showed that gentamicin sulfate (GS) had a remarkable antibacterial effect on Staphylococcus aureus and Escherichia coli. In a diabetic full-thickness skin wound model, the GelGMA-OSA@GS hydrogel dressing dramatically decreases inflammation and accelerated re-epithelialization and granulation tissue formation, promising applications in promoting diabetic wound healing.

The use of multiple datasets to identify autophagy-related molecular mechanisms in intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a stroke syndrome with high mortality and disability rates, but autophagy's mechanism in ICH is still unclear. We identified key autophagy genes in ICH by bioinformatics methods and explored their mechanisms. Methods: We downloaded ICH patient chip data from the Gene Expression Omnibus (GEO) database. Based on the GENE database, differentially expressed genes (DEGs) for autophagy were identified. We identified key genes through protein-protein interaction (PPI) network analysis and analyzed their associated pathways in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene-motif rankings, miRWalk and ENCORI databases were used to analyze the key gene transcription factor (TF) regulatory network and ceRNA network. Finally, relevant target pathways were obtained by gene set enrichment analysis (GSEA). Results: Eleven autophagy-related DEGs in ICH were obtained, and IL-1B, STAT3, NLRP3 and NOD2 were identified as key genes with clinical predictive value by PPI and receiver operating characteristic (ROC) curve analysis. The candidate gene expression level was significantly correlated with the immune infiltration level, and most of the key genes were positively correlated with the immune cell infiltration level. The key genes are mainly related to cytokine and receptor interactions, immune responses and other pathways. The ceRNA network predicted 8,654 interaction pairs (24 miRNAs and 2,952 lncRNAs). Conclusion: We used multiple bioinformatics datasets to identify IL-1B, STAT3, NLRP3 and NOD2 as key genes that contribute to the development of ICH.

Clinical and immune response characteristics among vaccinated persons infected with SARS-CoV-2 delta variant: a retrospective study.

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS: Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.

Real-World Evidence for COVID-19 Delta Variant's Effects on the Digestive System and Protection of Inactivated Vaccines from a Medical Center in Yangzhou, China: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

The effects of Baduanjin and yoga exercise programs on physical and mental health in patients with Multiple Sclerosis: A randomized controlled trial.

OBJECTIVE: To discuss whether Baduanjin and yoga exercise interventions improve motor function, posture control, and relieving fatigue and depression in MS patients. And to explore whether practicing Baduanjin benefits MS patients more than yoga. DESIGN: A prospective, randomized, controlled, three-arm trial comparing BDJ (n = 30), yoga (n = 30) and control group (n = 20). SETTING: Jiangsu Provincial Corps Hospital. INTERVENTION: Eligible participants were randomized to a 24-week Baduanjin or yoga intervention, or a usual activity control group. Balance, posture control and trunk movement were measured with the Berg Balance Scale (BBS) and Trunk Impairment Scale (TIS). Fatigue was measured using the Fatigue Severity Scale (FSS) and depressive symptoms via the Zung Self-Rating Depression Scale (SDS). RESULTS: For BBS and TIS, there were significant changes pre- to post- exercise in two exercise groups (P < 0.05), with greater increases in the Baduanjin exercise group (BDJ group). For the FSS, there were significant changes pre- to post- exercise in both the BDJ (P = 0.0292) and yoga groups (P = 0.0150). For the SDS, the pre- and post-exercise difference of the BDJ group was larger than the yoga group (P < 0.0001). On the other hand, we could not find any changes of the BBS, TIS, FSS, and SDS scores in the control group (p > 0.05). CONCLUSION: The results suggest that practicing Baduanjin was more effective than yoga and that it is suitable for the MS patients.

miR-223 ameliorates thalamus hemorrhage-induced central poststroke pain via targeting NLRP3 in a mouse model.

Central poststroke pain (CPSP) is a central neuropathic pain syndrome that occurs following a stroke and mainly manifests as pain and paresthesia in the body region corresponding to the brain injury area. At present, due to the lack of clinical attention given to CPSP, patients suffer from long-term pain that seriously affects their quality of life. Current literature indicates that microRNA (miR)-223 can impede inflammation and prevent collateral damage. The NLR family pyrin domain containing 3 (NLRP3) inflammasome induces IL-18 and IL-1ß secretion and maturation and participates in the inflammatory response. Previous evidence has confirmed that miR-223 can negatively regulate NLRP3 in the development of inflammatory responses. However, whether the miR-223 targeting of NLRP3 is involved in CPSP remains unclear. In the present study, the expression of miR-223 was detected by reverse transcription-quantitative PCR analysis. The expression levels of NLRP3, caspase-1, ASC, IL-18, IL-1ß, ERK1/2, p-ERK1/2 and GFAP were detected by western blot analysis. The results demonstrated that thalamic hemorrhagic stroke triggered by microinjection of collagenase Ⅳ (Coll IV) into the ventral posterior lateral (VPL) nucleus results in pain hypersensitivity. miR-223 expression level were significantly reduced in the CPSP model. The expression levels of NLRP3, caspase-1, ASC, IL-18 and IL-1ß were significantly increased in the CPSP model. The expression level of GFAP was detected to determine astrocyte activation. The results demonstrated that astrocyte activation induced by Coll IV produced a CPSP model. The p-ERK1/2 expression level was demonstrated to be significantly increased in the CPSP model. The introduction of an miR-223 agomir significantly attenuated thalamic pain and significantly decreased the levels of NLRP3, caspase-1, ASC and proinflammatory cytokines (IL-18 and IL-1ß). Furthermore, introducing a miR-223 antagomir into the VPL nucleus of naïve mice mimicked thalamic pain and significantly increased the levels of NLRP3, caspase-1, ASC and proinflammatory cytokine levels (IL-18 and IL-1ß). These results indicated that miR-223 inhibited NLRP3 inflammasome activity (caspase-1, NLRP3 and ASC), which ameliorated thalamus hemorrhage-induced CPSP in mice via NLRP3 downregulation. In conclusion, these results may determine the mechanisms underlying CPSP and facilitate development of targeted therapy for CPSP.

Design of an Ankle Exoskeleton That Recycles Energy to Assist Propulsion During Human Walking.

OBJECTIVE: Active exoskeletons can handle different walking conditions, but require bulky components (e.g., motors) that need a significant source of power to do so. Purely passive exoskeletons are lightweight and energy-neutral, containing energy-recycling mechanisms that capture energy loss during negative power phases and return it as walking assistance. However, they are usually designed for stereotyped gaits (e.g., walking at fixed speed) and thus show poor adaptivity for variable conditions. This study is aimed to overcome these issues. METHODS: A quasi-passive ankle exoskeleton is designed to integrate the merits of both active and passive exoskeletons, which captures the heel-strike energy loss and recycles it into propulsion. A novel, lightweight, energy-saving clutch and a heel-strike energy-storage mechanism are developed. They are coupled by a series spring that assists user's calf muscles. Six healthy subjects walked with the device on level ground and inclined surfaces to validate its functionality. RESULTS: Level ground studies indicate that the energy-storage mechanism enhances the assistance by increasing the output torque of the exoskeleton. Reductions in metabolic cost (6.4 ± 1.3%, p < 0.05) were observed. During uphill walking, the assistance torque decreased compared with that on level ground, but it still reduced overall metabolic cost compared with baseline walking. During downhill walking, the assistance torque increased, but metabolic cost also slightly increased. CONCLUSION: These results demonstrate the functionality of the prototype on level ground and its limitations on inclined surfaces. SIGNIFICANCE: The proposed device highlights the possibility of widening the potential applications of exoskeletons.

Biocompatible sulfur nitrogen co-doped carbon quantum dots for highly sensitive and selective detection of dopamine.

In this work, sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) were prepared via one-pot hydrothermal treatment of EDTA disodium and sodium sulfide. The prepared S,N-CQDs were characterized by TEM, XRD, FT-IR, XPS, UV-vis absorption and fluorescence spectra to characterize their morphology, crystal structure, functional groups, elemental composition, and optical properties. It was found that S and N elements were successfully doped into the CQDs and the morphology was approximately spherical with an average particle size of 2.16 nm, in which the excitation/emission wavelengths were 350 and 420 nm, respectively. Compared with single element doped CQDs, double element doped CQDs have a higher quantum yield and excellent optical stability. Cell experiments showed that S,N-CQDs had good biocompatibility because they had no obvious toxicity on both normal cell lines and cancer cell lines. More importantly, based on the synergy of static quenching and dynamic quenching, the S,N-CQDs were used as effective fluorescent probes for sensitive detection of DA, with high anti-interference and low limit of detection. Based on the good biocompatibility of S,N-CQDs, the detection of dopamine in actual serum samples were carried out and the results showed an excellent recovery rate. Therefore, this work provides a dopamine sensor with a practical application prospect.

A simple "turn off-on" ratio fluorescent probe for sensitive detection of dopamine and lysine/arginine.

Herein, a novel and unique "off-on" single-excited dual-emissive ratio fluorescence sensor for highly selective and sensitive detection of dopamine and lysine/arginine has been developed via covalently connecting the yellowish-green fluorescent carbon dots (CDs) with the orange-red fluorescent AgInSe2@ZnS quantum dots (AISe QDs). This ratiometric fluorescence sensor provided with two-emission peaks at 495 and 575 nm under a single-excitation wavelength of 395 nm. The fluorescence of AISe QDs (F575) is effective quenched by dopamine and only efficientlyrecovered by lysine/arginine; meanwhile, the light of CDs (F495) remains unchanged. The fluorescence intensity ratio (F495/F575) showed a linear relationship with the concentration of DA in the range of 0-100 µM, and the detection limit as low as 0.21 nM. lysine and arginine with the detection limit of 0.36 nM and 26 µM, respectively. Furthermore, the fluorescence probe is successfully used to detect DA in human serum. Therefore, the as-synthesized probe shows excellent potential application for the determination of DA in real samples.

Positive Regulatory Domain I-binding Factor 1 Mediates Peripheral Nerve Injury-induced Nociception in Mice by Repressing Kv4.3 Channel Expression.

BACKGROUND: The transcriptional repressor positive regulatory domain I-binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury-induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression. METHODS: Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund's adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging. RESULTS: Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury-induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation. CONCLUSIONS: PRDM1 contributes to peripheral nerve injury-induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons.

Efficient detection doxorubicin hydrochloride using CuInSe2@ZnS quantum dots and Ag nanoparticles.

Doxorubicin hydrochloride (DOX) is an effective anthracycline anticancer drug. However, the exceeded taken up could induce several side-effects such as cardiotoxicity, alopecia. Therefore, the level of DOX needs to be closely monitored to avoid the occurrence of its side-effects. Herein, we report a novel core CuInSe2 - shell ZnS quantum dots (CuInSe2@ZnS, QDs) and Ag nanoparticles (NPs) fluorescence sensor based on the surface plasmon resonance effect (SPR) of Ag NPs. The CuInSe2@ZnS QDs were prepared by water phase reflux method with the 3-mercaptopropionic acid (MPA) as stabilizer and ligand. The fluorescence intensity of CuInSe2@ZnS QDs/Ag NPs significantly reduced by DOX, which is mainly based on the electrostatic interaction between the DOX and fluorescence sensors. The inhibition of photoluminescence (ln F0/F) was linearly relationship to the concentration of DOX in the range of 2-100 µM with the detection limit as low as 0.05 µM. The as-prepared sensor has a high selectivity and sensitivity to DOX. Furthermore, the new sensor has been successfully applied to the determination of DOX in human serum samples with satisfactory results. Our work provides a clue for developing a novel CuInSe2@ZnS QDs/Ag NPs based fluorescence sensor for DOX detection.

Study on a novel antibacterial light-cured resin composite containing nano-MgO.

A new type of photocurable resin composite containing nano-MgO was synthesized in order to reduce the occurrence of secondary caries. Different mass ratios (0 %, 1 %, 2 %, 4 %, 8 %) of nano-MgO were added into resin composites. The antibacterial properties of nano-MgO powder and modified resin composites against Streptococcus mutans (S. mutans) were detected by antibacterial ring test and film contact test, respectively. Compressive strength (CS) and wear resistance were determined by a universal testing machine and an abrasion test machine. The results indicated that antibacterial activity and wear resistance of resin composites containing nano-MgO were superior to the control group (p < 0.05). The antibacterial rate reached as high as 99.4 % when the mass ratio of nano-MgO was 8 %. However, the CS values tended to decline as the content of nano-MgO increase. Hence, the addition of nano-MgO showed excellent antibacterial property to resin composites and enhanced wear resistance, but was detrimental to their mechanical properties.

The impact of N-cadherin-ß-catenin signaling on the analgesic effects of glial cell-derived neurotrophic factor in neuropathic pain.

Long-term neuropathic pain can lead to anxiety, depression, and other issues, which seriously affect patients' quality of life. For this reason, it is important to find effective treatments. Studies have shown that glial cell-derived neurotrophic factor (GDNF) can relieve neuropathic pain. However, its mechanism of action is unknown. Our previous study of GDNF suggested that the N-cadherin-ß-catenin transmembrane signaling system might play a role in GDNF transmembrane signaling. Based on this, the current study aimed to produce a neuropathic pain model to confirm the activation of the N-cadherin-ß-catenin signaling system in the spinal dorsal horn under pain conditions and to study the impact of GDNF intrathecal injection on central sensitization of dorsal horn neurons. The results showed that N-cadherin expression, as well as the expression of membrane-associated ß-catenin, was reduced in the dorsal horn of the spinal cord in the chronic pain model. Intrathecal injection of GDNF could reactivate the N-cadherin-ß-catenin system, improve central sensitization, and relieve pain. Knockdown of N-cadherin or ß-catenin could significantly reduce the analgesic effect of GDNF. These results provide clear experimental evidence that the N-cadherin-ß-catenin signaling system participates in the analgesic effect of GDNF in neuropathic pain and help identify transmembrane and intracellular signal transduction mechanisms associated with GDNF's analgesic effects.

Propofol reduces acute lung injury by up-regulating gamma-aminobutyric acid type a receptors.

BACKGROUND: We used a two-hit lung injury rat model that involves mechanical ventilation (MV) following lipopolysaccharide exposure to investigate the effects of propofol on the expression of GABAA receptors (GABAAR) and cytokine responses, and we then determined the specific effects of GABA on cytokine responses in vitro in alveolar epithelial cells (AECs). METHODS: Forty-eight adult male Wister rats were equally and randomly divided into the following 4 groups (n = 12) using a random number table: sham group, sham+propofol group, lipopolysaccharide (LPS) + VILI group, and LPS + VILI + propofol group. All animals were anesthetized, and the animals received a 3.75 mg/kg intratracheal instillation of endotoxins or phosphate-buffered saline (PBS) as the control, as described previously. After 30 min, rats were ventilated for 5 h in a volume-controlled ventilation mode. In the LPS + VILI group, animals were ventilated with a tidal volume (Vt) of 22 ml/kg and zero positive end-expiratory pressure (PEEP) at a respiratory rate of 16-18 breaths/min, whereas control (sham) rats were ventilated with a Vt of 6 ml/kg and PEEP of 5 cmH2O at a rate of 45-55 breaths/min. The FiO2 remained constant as 0.4, propofol was administered intravenously in the LPS + VILI + propofol and sham + propofol groups at a rate of 10 mg·kg-1·h-1 while normal saline at the same rate was intravenously administered in the LPS + VILI and sham groups during the entire mechanical ventilation period. Five hours after mechanical ventilation, the rats were killed. Survival rates, histopathology, concentrations of inflammatory mediators in bronchoalveolar lavage fluid (BALF), wet weight/dry weight (W/D) ratio of the lung, myeloperoxidase (MPO) activity in lung tissues, and expression of GAD and GABAAR by immunohistochemical detection and Western blotting were assessed. Then, human type II-like alveolar epithelial cells (A549 cells) were cultured to full confluence and incubated with GABA (100 nM) alone, picrotoxin alone, a GABAAR antagonist (PTX, 50 nM), or GABA + PTX for 10 min, followed by stimulation with LPS (control) at 100 ng/ml for 4 h. The concentrations of IL-1ß, IL-2, IL-8, and IL-10 were then measured. RESULTS: Administration of propofol in a two-hit lung injury rat model can increase survival rates and the expression of GAD and GABAAR (P < .05). The administration of propofol can attenuate the release of pro-inflammatory cytokines both in vivo and in vitro, and the administration of propofol can attenuate histopathological changes, the W/D ratio, and MPO activity (P < .05). CONCLUSIONS: In this study, we found that the administration of propofol improved lung function, alleviated lung injury, and up-regulated the GAD and GABAAR expressions in a two-hit model of acute lung injury (ALI) characterized by intratracheal instillation of an endotoxin and prolonged MV. Therefore, the protective effects of propofol may be associated with the up-regulation of GABAA receptors in AECs.

Comparison of single- and triple-injection methods for ultrasound-guided interscalene brachial plexus blockade.

Ultrasound-guided interscalene brachial plexus blockade (IBPB) has a relatively high success rate in shoulder surgery; however, whether multiple injections are superior to a single injection (SI) is currently unknown. In the present study, ultrasound-guided SI and triple-injection (TI) IBPBs were compared in a prospective randomized trial. A total of 111 patients undergoing arthroscopic shoulder surgery and presenting with an American Society of Anesthesiologists physical status grading of I-II were randomly allocated to receive IBPB with 15 ml of 1% ropivacaine as a SI or TI. Performance time, procedure-related pain scores, success rate and prevalence of complications were recorded. The distribution of sensory and motor block onset in the radial, median, ulnar and axillary nerves were assessed every 5 min until 30 min post-local anesthetic injection. The duration of sensory and motor blocks were also assessed. A significantly longer performance time was recorded in the TI group (P<0.001). No significant difference was observed in success rate (91% in TI vs. 88% in SI) 30 min post-injection, and the prevalence of complications and procedure-related pain were similar between the two groups. Sensory and motor blocks of the ulnar nerve in the TI group were significantly faster and more successful compared with the SI group at all time points (P<0.041). It was also observed that sensory and motor blocks in the TI group were prolonged compared with the SI group (P<0.041). In conclusion, the TI method exhibited a faster time of onset and resulted in a more successful blockade of the ulnar nerve. TI method may be a more effective approach for IBPB in a clinical setting.

Involvement of integrin ß1/FAK signaling in the analgesic effects induced by glial cell line-derived neurotrophic factor in neuropathic pain.

Treatment of neuropathic pain (NP) continues to be a clinical challenge and the underlying mechanisms of NP remain elusive. More evidence suggests that glial cell line-derived neurotrophic factor (GDNF) has potent anti-nociceptive effects on NP, but the underlying mechanisms are still largely unknown. Recent data have shown that integrin ß1 plays an important part in NP induction, and that the activity of integrin ß1 signaling is associated with the phosphorylation of the conserved threonines in the cytoplasmic domain and recruitment of focal adhesion kinase (FAK) to the integrin ß1 tail and phosphorylation. We assessed the effect of GDNF on integrinß1/FAK signaling in NP states. Immunostaining results showed that integrin ß1 was mainly observed in the superficial dorsal horn in the spinal cord of rats, and was mostly expressed in intrinsic neurons. Expression of p-integrin ß1 and the phosphorylation of integrin ß1-associated FAK, but not integrin ß1 itself, was up-regulated after chronic constriction injury (CCI), which could be reversed by GDNF, and the effect of GDNF on integrin ß1/FAK signaling was inhibited by pre-treatment with RET function-blocking antibody (RET Ab). Moreover, pre-treatment with RET Ab could antagonize the effect of GDNF on inhibiting the NP induced by CCI. These data suggest that GDNF can regulate integrin ß1 activity via a RET-related mechanism.

Efficacy of perineural dexamethasone with ropivacaine in adductor canal block for post-operative analgesia in patients undergoing total knee arthroplasty: A randomized controlled trial.

Adductor canal block (ACB) is an effective analgesic alternative to femoral nerve block after total knee arthroplasty (TKA). The aim of the present study was to investigate whether addition of dexamethasone to ropivacaine for ACB is able to prolong analgesia and reduce pain. Study participants were randomized into groups receiving ACB with either 0.5% ropivacaine + normal saline (control group; n=93) or 0.5% ropivacaine + 8 mg dexamethasone (dexamethasone group; n=93). All patients were subjected to identical peri-operative management. Patients were assessed for the duration of analgesia by the return of pinprick sensation. A numerical rating scale, ranging from 0 to 10, was used to assess post-operative pain at 6, 12, 18, 24 and 48 h. Opioid use was recorded. Serum C-reactive protein and interleukin-6 levels were measured at 3, 6, 12, 24 and 48 h after surgery. The results revealed that the duration of sensory block was significantly longer in the dexamethasone group (23.42±3.35 vs. 14.67±2.96 h in control group, P<0.05). The dexamethasone group also had significantly lower pain scores at 6, 12, 18 and 24 h after surgery (all P<0.001), and at 48 h, pain was comparable in the two groups. Reduction in post-operative pain was associated with a decrease in serum C-reactive protein. Morphine use in the first 24 h after surgery was also lower in the dexamethasone group (4.23±1.80 vs. 8.42±2.44 mg in control group, P<0.05). In conclusion, addition of dexamethasone to ropivacaine for ACB was able to prolong the duration of analgesia and decreased early post-operative pain following TKA.

Preconditioning of physiological cyclic stretch attenuated HMGB1 expression in pathologically mechanical stretch-activated A549 cells and ventilator-induced lung injury rats through inhibition of IL-6/STAT3/SOCS3.

Previous studies have shown that physiologically cyclic stretch (5% CS) attenuated both oxidative- and LPS-induced increases in HMGB1 expression via STAT3. However, little information exists about the effect of precondition of physiological cyclic stretch (CS) on the expression of HMGB 1, which play a crucial role in ventilator-induced lung injury (VILI). We found that 5% CS-preconditioning significantly inhibited HMGB 1 expression, but not HMGB 1 receptors. 5% CS-preconditioning inhibits the IL-6/STAT3 pathway, and the inhibitory effect on the expression of HMGB 1 induced by 5% CS-preconditioning is abolished by additional treatment of rmIL-6. 5% CS-preconditioning also induces SOCS3 upregulation, and 5% CS-preconditioning fails to inhibit the IL-6/STAT3 pathway in cells transfected with SOCS3 siRNA. Moreover, low tidal volume ventilation preconditioning also decreases the severity of VILI evidenced by the markedly improved pulmonary alveolar-capillary barrier dysfunction, wet/dry weight ratio, and histological analysis. These results suggest that preconditioning of physiological 5% CS can reduce the expression of HMGB 1 induced by pathologically mechanical stretch through IL-6/STAT3 pathway associated with up-regulated SOCS3 expression.