Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study.

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. RESULTS: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. CONCLUSIONS: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052122).

Analysis of the Relationship Between the Changes of Serum SAA, LP-PLA2, sCD40L and Carotid Atherosclerosis Plaque in Patients with Acute Cerebral Infarction.

Objective: To explore the relationship between Serum amyloid protein A(SAA), lipoprotein-associated Phospholipase A2 (Lp-PLA2) and soluble CD40 ligand (sCD40L) in detecting the stability of carotid Atherosclerosis plaque. Methods: We examined 90 patients admitted to our hospital with acute cerebral infarction from July 2020 to December 2022. Carotid artery ultrasounds were performed for all of them. These patients were then divided into two groups: the stable plaque group (45 cases) and the unstable plaque group (45 cases), based on the ultrasound results. Additionally, we included a control group of 30 healthy individuals from our hospital. We collected fasting blood samples from the patients upon admission and used enzyme-linked immunosorbent assays to measure the mass concentrations of sCD40L, Lp-PLA2, and SAA in their serum. The results of these biomarkers were compared and analyzed to assess potential associations with plaque stability in patients with cerebral infarction. Results: Comparison of general clinical data and laboratory data: except for High-density lipoprotein, there was a statistical difference between the control group and the cerebral infarction group (P < .05), there was no statistical difference in gender, smoking history, drinking history and age (P > .05). Compared with the control group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in patients with stable and unstable plaques increased significantly (P < .05); Compared with the stable plaque group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in unstable plaque patients increased with statistical significance (P < .05). Correlation analysis shows that the mass concentrations of sCD40L, Lp-PLA2, and SAA are positively correlated with the stability of carotid artery plaques. SCD40L, Lp-PLA2 and SAA have certain diagnostic significance in the subject's working characteristic curve (Receiver operating characteristic) as a marker molecule for the diagnosis of unstable plaque. sCD40L (AUC=0.883) has more diagnostic value than SAA (AUC=0.756) and Lp-PLA2 (AUC=0.826). A binary logistic regression analysis was conducted using the stability of carotid artery plaques as the dependent variable and sCD40L, Lp-PLA2, and SAA as independent variables. The results showed that elevated serum sCD40L, Lp-PLA2, and SAA were independent risk factors for unstable carotid artery plaques (P < .05). Conclusion: The concentrations of sCD40L, Lp-PLA2 and SAA are closely related to the formation and type of carotid Atherosclerosis plaque in patients with acute cerebral infarction. This has potentially important clinical implications for the management and prevention of cardiovascular disease.

Microglial TLR4-induced TAK1 phosphorylation and NLRP3 activation mediates neuroinflammation and contributes to chronic morphine-induced antinociceptive tolerance.

BACKGROUND AND PURPOSE: The aim of this work was to investigate the role and signal transduction of toll-like receptor 4 (TLR4), TGF-ß-activated kinase 1 (TAK1) and nod-like receptor protein 3 (NLRP3) in microglial in the development of morphine-induced antinociceptive tolerance. METHODS: TLR4 and NLRP3 knockout mice and 5Z-7-oxozeaeno (a selective inhibitor against TAK1 activity) were used to observe their effect on the development of morphine tolerance. Intrathecal injections of morphine (0.75 mg/kg once daily for 7 days) were used to establish anti-nociceptive tolerance, which was measured by the tail-flick test. Spinal TLR4, TAK1, and NLRP3 expression levels and phosphorylation of TAK1 were evaluated by Western blotting and immunofluorescence. RESULTS: Repeated treatment with morphine increased total expression of spinal TLR4, TAK1, and NLRP3 and phosphorylation of TAK1 in wild-type mice. TLR4 knockout attenuated morphine-induced tolerance and inhibited the chronic morphine-induced increase in NLRP3 and phosphorylation of TAK1. Compared with controls, mice that received 5Z-7-oxozeaenol showed decreased development of morphine tolerance and inhibition on repeated morphine-induced increase of NLRP3 but not TLR4. NLRP3 knockout mice showed resistance to morphine-induced analgesic tolerance with no effect on chronic morphine-induced expression of TLR4 and TAK1. TLR4, TAK1, and NLRP3 were collectively co-localized together and with the microglia marker Iba1. CONCLUSIONS: Microglial TLR4 regulates TAK1 expression and phosphorylation and results in NLRP3 activation contributes to the development of morphine tolerance through regulating neuroinflammation. Targeting TLR4-TAK1-NLRP3 signaling to regulate neuro-inflammation will be alternative therapeutics and strategies for chronic morphine-induced antinociceptive tolerance.

US-Guided Transforaminal Cervical Nerve Root Block: A Novel Lateral in-Plane Approach.

OBJECTIVE: The aim of the present study was to investigate the effectiveness and safety of a novel lateral in-plane approach for ultrasound-guided transforaminal cervical nerve root block (US-guided TF-CNRB) in the treatment of cervical radiculopathic pain. DESIGN: The design of the present study consisted of an institutional, retrospective case series. SETTING: The present study was conducted at a university hospital. SUBJECTS: Thirty-two patients with cervical radiculopathy who were resistant to conservative therapies and regular US-guided CNRB were included as participants. METHODS: The included patients were treated with US-guided TF-CNRB. During the treatments, using real-time fluoroscopy, we monitored the spreading patterns of a contrast medium and double confirmed the positions of needle tips. Pain numeric rating scales (NRS) and symptom relief grades were determined via telephone interviews at one, four, and 12 weeks after the procedures. RESULTS: US-guided TF-CNRB was performed at the C5 level in six patients, the C6 level in 18 patients, and the C7 level in eight patients. Compared with NRS at baseline, pain scores decreased throughout the observation period. Symptom relief rates of US-guided TF-CNRB at one, four, and 12 weeks were 72%, 69%, and 63%, respectively. Venous blood was aspirated during the procedures in two patients, and the needle tips were corrected. No intravascular injections or neurologic injuries were observed. CONCLUSION: US-guided TF-CNRB produced circumferential spreading around the involved cervical nerve root and showed significant clinical effectiveness in patients resistant to regular US-guided CNRB.

Recombinant Human Growth Hormone Ameliorates Cognitive Impairment in Stroke Patients.

OBJECTIVE: We aimed to determine the effects of recombinant human growth hormone (rhGH) replacement on cognitive function in subjects with poststroke cognitive impairment using resting-state functional magnetic resonance imaging. METHODS: We included 60 patients with a first-ever stroke for 3 months and a diagnosis of cognitive impairment who were randomized 1:1 to receive either rhGH subcutaneously or placebo injection for 6 months. All subjects were required to receive the same rehabilitative therapy program. Both groups were subjected to pretreatment and posttreatment neuropsychological assessment using the Montreal Cognitive Assessment, serum neurotrophic factors, biomarkers of glucose and lipid metabolism, and functional magnetic resonance imaging during 6 months of the study period. The pattern of brain activity was determined by examining the functional connectivity and amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. RESULTS: Forty-three (82.7%) completed the study. Treatment with rhGH reduced levels of triglycerides and low-density lipoprotein cholesterol but did not significantly altered plasma concentrations of glucose and glycated hemoglobin. We found a significant increase in serum insulin-like growth factor 1 levels (32.6%; P < 0.001) in the rhGH-treated group compared with that in the controls. After 6 months of rhGH treatment, mean Montreal Cognitive Assessment score improved from 16.31 (5.32) to 21.19 (6.54) (P < 0.001). The rhGH group showed significant increased area of activation with increased ALFF values in the regions of the frontal lobe, putamen, temporal lobe, and thalamus (P < 0.05), relative to the baseline conditions. The correlation analysis revealed that the ALFF and functional connectivity of default mode network was positively correlated with the ΔMoCA score and ΔIGF-1 levels; that is, the more the scale score increased, the higher the functional connection strength. No undesirable adverse effects were observed. CONCLUSIONS: The rhGH replacement has a significant impact on global and domain cognitive functions in poststroke cognitive impairment.

Tamoxifen attenuates reactive astrocyte-induced brain metastasis and drug resistance through the IL-6/STAT3 signaling pathway.

Brain metastasis affects approximately 20%-30% of patients with triple-negative breast cancers (TNBCs). Even small metastatic lesions in the brain can trigger severe neurological impairments and result in extremely short survival time. Recently, active astrocytes were reported to be associated with brain metastases. However, how activated astrocytes regulate the behaviors of disseminated breast cancer cells in the brain remains unknown. In this study, human primary astrocytes were stimulated with IL-1ß to form active astrocytes to study the cross-talk between stromal cells (astrocytes) and TNBC cells in brain metastases. Our results showed that active astrocytes significantly increase the malignancy of TNBC cells and prevent them from undergoing apoptosis caused by doxorubicin. We also found that the high level of IL-6 secreted by activated astrocytes was responsible for the drug resistance of breast cancer, which could be abolished by treatment of astrocytes with tamoxifen (TAM). The blockage of active astrocyte-derived IL-6 by a neutralizing antibody resulted in the attenuation of drug resistance, consequently enhancing the sensitivity of breast cancer cells to doxorubicin. Furthermore, the possible involved TAM-modulated drug resistance mechanism may be associated with a decrease in IL-6 expression in astrocytes and the downregulation of MAPK and JAK2/STAT3 signaling in cancer cells. Our data suggested that TAMs might reduce drug resistance through the IL-6/JAK2/STAT3 signaling pathway, providing a possible therapy to treat brain metastasis in TNBCs, as estrogen receptor inhibitors (TAMs, etc.) can cross the blood-brain barrier.

MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1 in glioma cells.

Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients' clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas - Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.

Clinical efficacy of individual extracorporeal shockwave treatment.

BACKGROUND: This retrospective study investigated the clinical efficacy of individual extracorporeal shockwave treatment (IESWT) for early stage osteonecrosis of the femoral head (ONFH). MATERIAL AND METHODS: The study included 56 patients (89 hips) with 28 patients (46 hips) in the IESWT group and 28 patients (43 hips) in the conventional ESWT (CESWT) group. The ONFH was caused by the use of steroids, trauma and alcohol consumption. The IESWT focal point was from the front of the femoral head and the exposed necrotic tissue in 3D environment was guided by simulation software. The CESWT focal point was the side of the femoral head and guided by MRI and X­ray imaging. The evaluation standards included VAS score, Harris hip score (HHS), necrosis volume and healing rate. RESULTS: For the healing rate the results were 66.67% were improved, 21.43% unimproved and 11.90% aggravated in the CESWT group and 77.78% improved, 17.78% unimproved and 4.45% aggravated in the IESWT group. Statistically significant differences were observed in the healing rate between the two groups (P < 0.05). This retrospective study demonstrated that the healing rate for IEWST was higher than for CEWST. There were no statistically significant differences in the VAS score and the HHS between the two groups (P > 0.05). The effects of pain relief and functional recovery were not obvious and according to our clinical experience this may be due to a short clinical observation time where a longer time might result in better clinical results. Statistically significant differences were observed in the necrosis volume after 18 months between the 2 groups (P < 0.05) and implied that IESWT can significantly reduce the volume of necrosis. The volume after 18 months in the IESWT group was significantly improved compared with baseline (P < 0.05). CONCLUSION: The use of IESWT can significantly reduce the necrosis volume. No complications were found.

TGF-ß/SMAD signaling inhibits intermittent cyclic mechanical tension-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/RUNX2 axis.

A mechanical stimulation plays a pivotal role in maintaining normal cartilage function. Our objective was to reveal the mechanism of action of the tension-sensitive molecule miR-455-5p in the degeneration of endplate chondrocytes and to identify whether the transforming growth factor beta (TGF-ß)/SMAD signaling pathway has a regulatory effect on it. The expression profiles of members of the TGF-ß/SMAD pathway, miR-455-5p, and RUNX2 were determined by microRNA microarray analysis, reverse transcription quantitative polymerase chain reaction, luciferase reporter assay, and Western blot analysis. Intermittent cyclic mechanical tension (ICMT) induced the degeneration of endplate chondrocytes without affecting their viability. The tension-sensitive molecule miR-455-5p specifically bound to RUNX2, a gene involved in the degeneration of endplate chondrocytes. Activation of the TGF-ß/SMAD signaling pathway upregulated miR-455-5p expression and thus inhibited RUNX2 levels. Therefore, the TGF-ß/SMAD signaling pathway inhibits the ICMT-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/RUNX2 axis.

P120-Catenin Mediates Intermittent Cyclic Mechanical Tension-Induced Inflammation in Chondrocytes.

To study the role of the nuclear factor (NF)-κB signaling pathway and P120-catenin in the inflammatory effects of intermittent cyclic mechanical tension (ICMT) on endplate chondrocytes. Inflammatory reactions of endplate chondrocyte were measured by real-time reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, a dual-luciferase reporter assay system, immunofluorescence, and Western blot analysis. ICMT loading led to inflammatory reactions of endplate chondrocytes in both the rabbit endplate cartilage model and rat endplate chondrocytes in vitro. Inhibition of NF-κB signaling significantly ameliorated the inflammation induced by ICMT in endplate chondrocytes. Moreover, the expression of P120-catenin was decreased by ICMT. However, over-expression of P120-catenin suppressed NF-κB signaling and reversed the inflammatory effects. P120-catenin prevents endplate chondrocytes from undergoing ICMT-mediated inflammation by suppressing the expression of NF-κB. J. Cell. Biochem. 118: 4508-4516, 2017. © 2017 Wiley Periodicals, Inc.

Anti-nociceptive roles of the glia-specific metabolic inhibitor fluorocitrate in paclitaxel-evoked neuropathic pain.

Paclitaxel (Taxol) is a powerful chemotherapy drug used in breast cancers, but it often causes neuropathic pain, leading to the early cessation of therapy and poor treatment outcomes. Approaches for the management of paclitaxel-induced neuropathic pain are urgently needed. The involvement of spinal astrocytes in the pathogenesis of paclitaxel-induced neuropathy has been reported, but little is known about the role of fluorocitrate (FC), a selective inhibitor of astrocyte activation, during neuropathic pain related to paclitaxel treatment. In this study, we investigated the effects of FC on paclitaxel-induced neuropathic pain. Glial fibrillary acidic protein (GFAP) expression was determined to assess astrocyte activation. To explore the mechanisms involved, the expression of glial glutamate transporter 1 (GLT-1) and the activation of mitogen-activated protein kinases in the spinal dorsal horn were analyzed. The results showed that paclitaxel decreased the mechanical nociceptive thresholds and increased GFAP expression, leading to spinal astrocyte activation. After paclitaxel treatment, GLT-1 was significantly down-regulated, and the phosphorylation of ERK1/2 and JNK were obviously up-regulated. However, paclitaxel treatment did not increase p38 phosphorylation. Additional studies showed that paclitaxel-evoked mechanical hypersensitivity was reduced by FC treatment. Moreover, FC treatment inhibited the activation of astrocytes and reversed the changes in GLT-1 expression and MAPK phosphorylation. Further study indicated that FC did not influence the antitumor effect of paclitaxel, suggesting that FC blocked paclitaxel-induced neuropathic pain without antagonizing its antitumor effect. Together, these results suggested that paclitaxel induced astrocyte-specific activation, which may contribute to mechanical allodynia and hyperalgesia, and that FC could be a potential therapeutic agent for paclitaxel-induced neuropathic pain.

Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.

BACKGROUND/AIMS: Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. METHODS: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. RESULTS: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. CONCLUSION: Therefore, we suggest that microglial activation increases the synthesis of BDNF and that the release of BDNF can, in turn, activate microglia. A positive autocrine BDNF feedback loop from microglia may contribute to prolonged microglial activation.

Circulating microRNA expression profile: a novel potential predictor for chronic nervous lesions.

The mechanisms of chronic neuropathic pain are not clear. Serum microRNAs (miRNAs) might show a special feature for chronic nervous lesions. However, little is known about the changes in circulating miRNAs for the neuropathic pain. Therefore, changes in the circulating miRNAs expression profile for the neuropathic pain were investigated. Serum was collected from rats before and after spinal nerve ligation (SNL) surgery, and a microarray analysis was performed to determine the changes in miRNA expression profile. The expression of inflammatory cytokines in serum from the same individuals, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), was also measured. The results showed that the expression levels of IL-6, TNF-α, and MCP-1 were significantly elevated in SNL rats which were significantly correlated with pain levels. Nine miRNAs with significantly different expression levels before and after SNL surgery were identified by microarray analysis, which were further validated by quantitative real-time polymerase chain reaction analyses. Compared with naive rats without SNL surgery, the expression of five miRNAs (hsa-miR-221, hsa-miR-34c, hsa-miR-21, hsa-miR-30a-5p, and hsa-miR-206) in the serum of rats after SNL surgery was decreased and four miRNAs (hsa-miR-31-5p, hsa-miR-133b, hsa-miR-22, and hsa-miRPlus-A1087) were increased, suggesting that miRNA changes may involve in the regulation of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs, and the results showed that the transcripts with multiple predicted target sites belonged to neurologically important pathways. Bioinformatics analysis revealed that several target genes are related to the activation of cell signaling associated with nervous lesions. In this study, the changes to miRNA profiles in serum under neuropathic pain conditions were shown for the first time, suggesting that circulating miRNAs profile in serum is a potential predictor for neuropathic pain.

Characterizing and decoding the key odor-active compounds in fresh, pasteurized, and high pressure processing sea buckthorn (Hippophae rhamnoides L.) juice.

The non-thermal and thermal effects on aroma of sea buckthorn juice have rarely been investigated. In this study, 57 odor compounds were identified in fresh sea buckthorn juice (FSBJ), high pressure processing sea buckthorn juice (HSBJ), and pasteurized sea buckthorn juice (PSBJ), including 29 esters, 8 aldehydes, 1 ketone, 5 alcohols, 5 acids, 6 terpenoids, and 3 others. Ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl hexanoate, and ethyl 2-hydroxy-3-methylbutanoate with flavor dilution factors ranging from 729 to 59,049 contributed to the fruity odors of FSBJ and HSBJ. Besides, the formation of off-odor compounds including hexanal, nonanal, furfural, 3-methylbutanoic acid, and dimethyl disulfide with odor activity values ≥ 1, imparts fatty, roasted, sweaty, and cooked odor in PSBJ. The variations of vitamin C and reducing sugar are significantly associated with changes in odor-active compounds during pasteurized processing. These findings provide new insights that high pressure processing minimizes the adverse effects of pasteurization.

Improvement of antibacterial activity of polysaccharides via chemical modification: A review.

Antibiotic residue and bacterial resistance induced by antibiotic abuse have seriously threatened food safety and human healthiness. Thus, the development and application of safe, high-efficiency, and environmentally friendly antibiotic alternatives are urgently necessary. Apart from antitumor, antivirus, anti-inflammatory, gut microbiota regulation, immunity improvement, and growth promotion activities, polysaccharides also have antibacterial activity, but such activity is relatively low, which cannot satisfy the requirements of food preservation, clinical sterilization, livestock feeding, and agricultural cultivation. Chemical modification not only provides polysaccharides with better antibacterial activity, but also promotes easy operation and large-scale production. Herein, the enhancement of the antibacterial activity of polysaccharides via acetylation, sulfation, phosphorylation, carboxymethylation, selenation, amination, acid graft, and other chemical modifications is reviewed. Meanwhile, a new trend on the application of loading chemically modified polysaccharides into nanostructures is discussed. Furthermore, possible limitations and future recommendations for the development and application of chemically modified polysaccharides with better antibacterial activity are suggested.

Peripheral nerve adjustment for postherpetic neuralgia: a randomized, controlled clinical study.

OBJECTIVE: To observe the therapeutic effect of peripheral nerve adjustment for the treatment of postherpetic neuralgia (PHN). METHODS: One hundred and two patients with PHN were randomly assigned to three groups; the control group (A), the experimental group (B), which was subjected to peripheral nerve adjustment, and patients who received a sham peripheral nerve adjustment, thus serving as a positive control group (C). The patients' Visual Analogue Scale (VAS) and total oral rescue dosage for pain management were recorded at days 1, 3, 7, 14, and 28 following treatment. Quality of life (QOL), 36-Item Short-Form Health Survey (SF-36), and side effects were recorded following treatment. RESULTS: We observed that the average VAS score was significantly lower in the treatment group (B) than in the control groups A and C following treatment (P < 0.05). In addition, the QOL and SF-36 scores for group B improved substantially following treatment compared to groups A and C, and this effect was maintained up to 180 days after treatment (P < 0.05). The average dosage of pain medication was also lower in group B, compared to groups A and C, following treatment (P < 0.05). CONCLUSIONS: We conclude that peripheral nerve adjustment can relieve PHN pain and improve patients' quality of life. The possible mechanisms involved may include the reduction of both peripheral and central sensitization, the modulation of nerve plasticity, and an increase in endogenous analgesic molecules.

L6 spinal nerve ligation produces prolonged development of mechanical allodynia and gradual increase of GFAP on ipsilateral dorsal horn.

BACKGROUND: L5/6 spinal nerve ligation (SNL), one of the most widely used approaches rat models for neuropathic pain, results in the rapid development of mechanical allodynia within 24-72 h. However, the result of a single L6 SNL remains unclear. METHODS: The first series of experiments were performed to examine the pain behavior of rats with different nerve ligations. Thirty-six rats were randomly assigned to four groups as follows: group I, controls (n = 6); group II, L5/6 nerve ligation (n = 6); group III, single L6 nerve ligation (n = 18); and group IV, the sham operation group (n = 6). The mechanical allodynia of rats was assessed using a 50 % paw withdrawal threshold (PWT), and tail antinociception was determined using the percentage of the maximal possible antinociceptive effect (% MPE). The second series of experiments were performed using Western blots to evaluate dorsal horn GFAP expression in different groups at different time points (D1, D7, D14, and D28). For this series of experiments, fifty-four rats were randomly divided into three groups: group I, controls (n = 6); group II, L5/6 nerve ligation (n = 24); and group III, L6 nerve ligation (n = 24). RESULTS: In this study, a single L6 SNL induced prolonged development (1-14 days) of mechanical allodynia and gradually increased expression of glial fibrillary acidic protein (GFAP) in the ipsilateral dorsal horn. Notably, once mechanical allodynia developed, both the severity of mechanical allodynia and the alteration of GFAP expression were similar regardless of the identity of the ligated nerve (L5/6 or L6 only). CONCLUSIONS: Single L6 SNL might be used as an effective model for researching the development period of neuropathic pain and is thus worth further investigation.

Spatial and temporal variations of net ecosystem productivity in Xinjiang Autonomous Region, China based on remote sensing.

Net ecosystem productivity (NEP), which plays a key role in the carbon cycle, is an important indicator of the ecosystem's carbon budget. In this paper, the spatial and temporal variations of NEP over Xinjiang Autonomous Region, China from 2001 to 2020 were studied based on remote sensing and climate re-analysis data. The modified Carnegie Ames Stanford Approach (CASA) model was employed to estimate net primary productivity (NPP), and the soil heterotrophic respiration model was used to calculate soil heterotrophic respiration. Then NEP was obtained by calculating the difference between NPP and heterotrophic respiration. The annual mean NEP of the study area was high in the east and low in the west, high in the north and low in the south. The 20-year mean vegetation NEP of the study area is 128.54 gC·m-2, indicating that the study area is a carbon sink on the whole. From 2001 to 2020, the annual mean vegetation NEP ranged between 93.12 and 158.05 gC·m-2, and exhibited an increasing trend in general. 71.46% of the vegetation area showed increasing trends of NEP. NEP exhibited a positive relationship with precipitation and a negative relationship with air temperature, and the correlation with air temperature was more significant. The work reveals the spatio-temporal dynamics of NEP in Xinjiang Autonomous Region and can provide a valuable reference for assessing regional carbon sequestration capacity.

lA multiple PAHs-degrading Shinella sp. strain and its potential bioremediation in wastewater.

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic derivatives are organic pollutants which threaten ecosystems and human beings. In this study, a new strain, Shinella sp. FLN 14, was isolated and characterized. It can utilize fluorene as its sole carbon source and effectively co-metabolize multiple PAHs and heterocyclic derivatives, including phenanthrene, acenaphthene, and fluoranthene. Two possible metabolic pathways are proposed (i.e., salicylic acid pathway and phthalic acid pathway). Whole-genome sequencing revealed that strain FLN14 possesses a chromosome and four plasmids. However, when combined with ensemble genetic information, novel fluorene-degrading functional gene clusters were not located within the genome of FLN 14, except for some new dioxygenases and electron transport chains, which typically initiate the oxidation of aromatic compounds. In wastewater bioremediation, strain FLN14 removed nearly 95 % of PAHs within 5 days and maintained high degrading activity during the 18-day reaction compared to the control. Overall, our study provides a promising candidate to achieve bioremediation of PAHs-contaminated environments.

Prediction of the Efficacy of Lumbar Sympathetic Block in Patients with Lower Extremity Complex Regional Pain Syndrome Type 1 Based on the Sympathetic Skin Response.

INTRODUCTION: Complex regional pain syndrome type 1 (CRPS-1) is prevalent after trauma, with intractable pain being the most prominent clinical symptom. The impact of sympathetic block on CRPS is unclear. The goal of this study was to explore the characteristics that predict successful symptom relief with lumbar sympathetic block (LSB) in patients with lower extremity CRPS-1. METHODS: The study was designed as a prospective cohort study. Ninety-eight patients diagnosed with lower extremity CRPS-1 between March 2021 and March 2022 were enrolled as participants. All of the patients received two LSB treatments within a month. Sympthetic skin response (SSR) and numeric rating scale (NRS) were recorded before and after LSB treatment. The procedure was judged as a clinically positive response if the patients a 50% or greater reduction in NRS scores. Patients were divided into positive response and negative response groups after LSB treatment: LSB (+) and LSB (-), and the different characteristics and examination findings of the two groups of patients were compared. Furthermore, a multivariable logistic regression model was utilized to evaluate the predictors of successful symptom relief following LSB treatment. RESULTS: A total of 43.9% (43/98) of patients experienced successful symptom relief, while 56.1% (55/98) had unsuccessful symptom relief. After LSB treatment of all subjects, the overall NRS score decreased, the SSR amplitude increased, and the SSR latency shortened in the affected extremity (P < 0.05). There was a significant difference in the change in SSR amplitude between the LSB (-) and LSB (+) groups (P = 0.000). A 12-month disease duration had an OR (odds ratio) of 4.477 (P = 0.009), and a 510-µV baseline SSR amplitude of the affected extremity had an OR of 7.508 (P = 0.000) in the multivariable analysis that included these explanatory variables. CONCLUSIONS: Patients with lower extremity CRPS-1 can experience significant pain relief after LSB treatment. The predictors of successful symptom relief after LSB treatment were a baseline SSR amplitude of the affected extremity < 510 µV and a disease duration < 12 months. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000037755, date of registration: September 4, 2020).