ICG-Dimeric Her2-Specific Affibody Conjugates for Tumor Imaging and Photothermal Therapy for Her2-Positive Tumors.

Human epidermal growth factor receptor 2 (Her2) is abundantly expressed in various solid tumors. The Her2-specific Affibody (ZHer2:2891) has been clinically tested in patients with Her2-positive breast cancer and is regarded as an ideal drug carrier for tumor diagnosis and targeted treatment. Indocyanine green (ICG) can be used as a photosensitizer for photothermal therapy (PTT), in addition to fluorescent dyes for tumor imaging. In this study, a dimeric Her2-specific Affibody (ZHer2) based on ZHer2:2891 was prepared using the E. coli expression system and then coupled to ICG through an N-hydroxysuccinimide (NHS) ester reactive group to construct a novel bifunctional protein drug (named ICG-ZHer2) for tumor diagnosis and PTT. In vitro, ICG-ZHer2-mediated PTT selectively and efficiently killed Her2-positive BT-474 and SKOV-3 tumor cells rather than Her2-negative HeLa tumor cells. In vivo, ICG-ZHer2 specifically accumulated in Her2-positive SKOV-3 tumor grafts rather than Her2-negative HeLa tumor grafts; high-contrast tumor optical images were obtained. However, Her2-negative HeLa tumor grafts were not detected. More importantly, ICG-ZHer2-mediated PTT exhibited a significantly enhanced antitumor effect in mice bearing SKOV-3 tumor grafts owing to the good photothermal properties of ICG-ZHer2. Of note, ICG-ZHer2 did not exhibit acute toxicity in mice during short-term treatment. Overall, our findings indicate that ICG-ZHer2 is a promising bifunctional drug for Her2-positive tumor diagnosis and PTT.

Self-compassion and family cohesion moderate the association between suicide ideation and suicide attempts in Chinese adolescents.

BACKGROUND: In recent years, many studies have examined risks factors that facilitated the transition from suicide ideation to suicide attempts. Few studies, however, have examined protective factors against this transition. The current study thus assessed two protective factors, self-compassion and family cohesion, in buffering the transition from suicide ideation to suicide attempts. METHOD: A number of 520 Chinese adolescents (43.46% females, mean age = 12.96 years) completed questionnaires assessing self-compassion, family cohesion, suicide ideation, and suicide attempts two times with a 12-month interval. RESULTS: Self-compassion significantly moderated the association between Wave 1 SI and later SA. The positive dimension of self-compassion thwarted the transition from SI and SA, and the negative dimension of self-compassion strengthened the associations. In addition, family cohesion also significantly moderated the transition from SI to SA. CONCLUSION: Increasing the levels of self-compassion and family cohesion may be the targets for treating adolescents with suicide ideation to prevent them from attempting suicide.

Combined bone marrow stromal cells and oxiracetam treatments ameliorates acute cerebral ischemia/reperfusion injury through TRPC6.

Ischemic stroke has become one of the leading causes of deaths and disabilities all over the world. In this study, we investigated the therapeutic effects of combined bone marrow stromal cells (BMSCs) and oxiracetam treatments on acute cerebral ischemia/reperfusion (I/R) injury. A rat model of middle cerebral artery occlusion (MCAO) followed by complete reperfusion, as well as a cortex neuron oxygen-glucose deprivation (OGD) model was established. When compared with BMSCs or oxiracetam monotherapy, combination therapy significantly improved functional restoration with decreased infarct volume in observed ischemic brain. We propose that it may occur through the transient receptor potential canonical (TRPC)6 neuron survival pathway. The increased expression of TRPC6 along with the reduction of neuronal cell death in the OGD cortex neurons and combination therapy group indicated that the TRPC6 neuron survival pathway plays an important role in the combined BMSCs and oxiracetam treatments. We further tested the activity of the calpain proteolytic system, and the results suggested that oxiracetam could protect the integrity of TRPC6 neuron survival pathway by inhibiting TRPC6 degradation. The protein levels of phospho-cAMP response element binding protein (p-CREB) were tested. It was found that BMSCs play a role in the activation of the TRPC6 pathway. Our study suggests that the TRPC6 neuron survival pathway plays a significant role in the protective effect of combined BMSCs and oxiracetam treatments on acute cerebral I/R injury. Combined therapy could inhibit the abnormal degradation of TRPC6 via decreasing the activity of calpain and increasing the activation of TRPC6 neuron survival pathway.

A longitudinal study testing the role of psychache in the association between emotional abuse and suicidal ideation.

OBJECTIVE: Research suggests that emotional abuse is associated with adolescent suicidal ideation. But how they are related is still unclear. The present study tested the temporal relationship between emotional abuse and suicidal ideation, with psychache as the potential mediator. We also examined the reciprocal relationship between psychache and suicidal ideation. METHOD: A number of 2,259 Chinese high school students (53.8% females, mean age = 15.11, SD = 1.57) in Hong Kong completed questionnaires assessing emotional abuse, psychache, and suicidal ideation three times at 6-month intervals. RESULTS: The results supported the mediating effect of psychache in the path from emotional abuse to suicidal ideation. In addition, psychache and suicidal ideation were related reciprocally over time. CONCLUSION: The findings of this study may help researchers and practitioners understand the pathways by which emotional abuse impacts adolescent suicidal ideation. Implications for preventions and interventions of suicidal ideation were discussed.

A rare presentation of acute-onset chronic inflammatory demyelinating polyneuropathy with the detection of anti-GM3 and anti-sulfatides antibodies: a case report.

Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy defined by clinical progression for more than 2 months. 16-20% of CIDP patients may present with rapidly progressive weakness that resembles GBS, known as acute-onset CIDP (A-CIDP). However, it is challenging to distinguish from GBS-TRF because of their similar clinical symptom and features. In this case review, we report a patient with A-CIDP with the detection of anti-GM3 and anti-sulfatides antibodies, which rarely have been in A-CIDP and may account for her progressive and recurrent symptoms. Methods: We analyzed existing medical literature and described a clinical case of A-CIDP with antibodies positive. Results: We reported a 56-year-old female presented with bilateral lower extremity weakness and distal numbness. She experienced similar symptoms four times and responded well to the IVIg therapy. Lumbar puncture demonstrated albumin-cytologic dissociation and EDX examination revealed multiple peripheral nerve damage. After ruling out other demyelination diseases, a diagnosis of A-CIDP was made. Discussion: The antiganglioside and anti-sulfatide antibodies are involved in CIDP pathogenesis and can help to distinguish A-CIDP and other variants. To prevent secondary damage, it is important to monitor relapse and remission symptoms along the treatment line. A rare case of A-CIDP is discussed concerning the detection of anti-GM3 and anti-sulfatides antibodies, thus making a retrospective comparison of antibodies in some literature to understand A-CIDP better.

Different Acupuncture Therapies for Postherpetic Neuralgia: An Overview of Systematic Reviews and Meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).

Electroacupuncture and carbamazepine for patients with trigeminal neuralgia: a randomized, controlled, 2 × 2 factorial trial.

BACKGROUND: Trigeminal neuralgia (TN) is difficult to treat due to its severe pain intensity and recurring episodes, which significantly impact quality of life. OBJECTIVES: We aimed to assess the effectiveness of electroacupuncture (EA) in alleviating the pain intensity in TN, and to determine whether EA combined with low-dosage carbamazepine (CBZ) has a synergistic effect. METHODS: A multi-centre, randomized, 2 × 2 factorial trial was conducted. Participants who met the inclusion criteria received active EA or sham EA for 60 min, three times a week for four weeks; CBZ (300 mg per day) or placebo for four weeks. The primary outcome was the change in visual analog scale (VAS) score from baseline to weeks 2, 4, 16, and 28. Secondary outcomes included quality of life and adverse events. RESULTS: A total of 120 participants (75 females and 45 males; mean (SD) age, 58.5 (15.3) years) were included. The main effects of EA and CBZ were significant (P < 0.001), and there was a significant interaction was identified between the interventions (P = 0.041). Participants who received EA (mean difference [MD], -0.3 [95% CI, -0.40 to -0.20] at week 2; -1.6 [-1.70 to -1.50] at week 4; -1.1 [-1.31 to -0.89] at week 16; -0.8 [-1.01 to -0.59] at week 28), CBZ (MD, -0.6 [95% CI, -0.70 to -0.50] at week 2; -0.9 [-1.03 to -0.77] at week 4, -0.2 [-0.41 to 0.01] at week 16, 0.2 [-0.01 to 0.41] at week 28), and the combination of both (MD, -1.8 [95% CI, -1.90 to -1.70] at week 2; -3.7 [-3.83 to -3.57] at week 4, -3.4 [-3.61 to -3.19] at week 16, -2.9 [-3.11 to -2.69] at week 28) had a greater reduction in VAS score over the treatment phase than their respective control groups (sham EA, placebo, and sham EA plus placebo). EA-related adverse events (6/59, 10.17%) were lower than that of CBZ (15/59, 25.42%) during the whole phases. CONCLUSIONS: EA or CBZ alone are effective treatments for TN, while the combination of EA and low-dosage CBZ exerts a greater benefit. These findings in this trial demonstrate that the combination of EA and low-dosage CBZ may be clinically effective under certain circumstances. TRIAL REGISTRATION: NCT03580317.

Construction of Yeast One-Hybrid Library of Alternaria oxytropis and Screening of Transcription Factors Regulating swnK Gene Expression.

The indolizidine alkaloid-swainsonine (SW) is the main toxic component of locoweeds and the main cause of locoweed poisoning in grazing animals. The endophytic fungi, Alternaria Section Undifilum spp., are responsible for the biosynthesis of SW in locoweeds. The swnK gene is a multifunctional complex enzyme encoding gene in fungal SW biosynthesis, and its encoding product plays a key role in the multistep catalytic synthesis of SW by fungi using pipecolic acid as a precursor. However, the transcriptional regulation mechanism of the swnK gene is still unclear. To identify the transcriptional regulators involved in the swnK gene in endophytic fungi of locoweeds, we first analyzed the upstream non-coding region of the swnK gene in the A. oxytropis UA003 strain and predicted its high transcriptional activity region combined with dual-luciferase reporter assay. Then, a yeast one-hybrid library of A. oxytropis UA003 strain was constructed, and the transcriptional regulatory factors that may bind to the high-transcriptional activity region of the upstream non-coding region of the swnK gene were screened by this system. The results showed that the high transcriptional activity region was located at -656 bp and -392 bp of the upstream regulatory region of the swnK gene. A total of nine candidate transcriptional regulator molecules, including a C2H2 type transcription factor, seven annotated proteins, and an unannotated protein, were screened out through the Y1H system, which were bound to the upstream high transcriptional activity region of the swnK gene. This study provides new insight into the transcriptional regulation of the swnK gene and lays the foundation for further exploration of the regulatory mechanisms of SW biosynthesis in fungal endophytic locoweeds.

Polybrominated diphenyl ethers in water, suspended particulate matter, and sediment of reservoirs and their tributaries in Shenzhen, a mega city in South China.

Urban reservoirs serve many purposes including recreation and drinking water, and larger bodies of water can alter the surrounding air temperatures, making urban areas cooler in summer and warmer in winter. However, reservoirs may also be sinks for contaminants. One such group of contaminants, the polybrominated diphenyl ethers (PBDEs), are persistent organic pollutants known to accumulate in sediments and suspended particulate matter (SPM). Few studies have been conducted on PBDEs in water, SPM, and sediment from reservoirs of Shenzhen which is a mega city in South China. To this end, 12 PBDEs were measured in water, SPM, and sediment samples during the dry season (DS) and wet season (WS), to explain the spatiotemporal distribution, congener profiles, sources, and risks of pollutants in four reservoirs (A-D) and their tributaries in the study region. The concentration of ∑12PBDEs during the DS was found to be significantly higher than that during the WS. Source apportionment suggested that commercial penta-, octa-, and deca-BDEs are the major components of PBDEs, resulting mainly from atmospheric deposition, wastewater discharge, and external water-diversion projects. Further, attention should be paid to electronic equipment manufacturing factories in the study area. Risk assessment indicated risk of PBDEs (especially BDE-209) in sediment and SPM to be of concern. This study provides important data support for the control of PBDEs in natural drinking water sources.

The F-box protein OsEBF2 confers the resistance to the brown planthopper (Nilparvata lugens Stål).

The brown planthopper (BPH; Nilaparvata lugens) is a piercing-sucking insect pest specific to rice plants and may cause severe declines in rice yields. Therefore, it is of great theoretical significance and practical application value to elucidate the molecular mechanism of rice resistance to BPH. Previous studies have shown that an ethylene (ET) signaling pathway gene, OsEBF1, positively regulates BPH resistance in rice. OsEBF1 is an E3 ligase that mediates the degradation of another ET pathway gene, OsEIL1. OsEBF2 is the homologous gene of OsEBF1, and the sequence identity between the two genes is 78.5%. Our results indicated that OsEBF2 can directly interact with OsEIL1 and positively regulate rice resistance to BPH. More importantly, there were no obvious differences in agronomic traits between WT and OsEBF2OE transgenic lines. The resistance mechanism of the OsEBF2 gene may be to reduce the content of ET in rice by inhibiting the expression of ethylene response factor genes. This study revealed that OsEBF2 is an F-box protein that positively regulates the rice resistance to BPH and can be used as an effective target gene for rice BPH resistance breeding.

Research Trends of Acupuncture Therapy on Polycystic Ovary Syndrome: A Bibliometric Analysis.

Background: Acupuncture has been confirmed as a suitable therapy for treating polycystic ovary syndrome (PCOS). However, there is no bibliometric analysis of the global use of acupuncture for PCOS. Our study used CiteSpace (5.8.R3) to provide a profile of the current state and trends in this field. Methods: Articles regarding acupuncture therapy for treating PCOS were retrieved from the Web of Science Core Collection. CiteSpace was used to analyze the number of publications, countries, institutions, journals, authors, cited references, and keywords by using standard bibliometric indicators. Results: A total of 159 publications were considered for the final analysis. The number of publications has slowly increased with fluctuations between years, and the most active countries, institutions, journals, and authors concerning acupuncture therapy for PCOS were identified. Evidence-Based Complementary and Alternative Medicine was the most productive journal, and Fertil Steril was the most cited. China and Heilongjiang University of Chinese Medicine were considered the most prolific countries and institutions in this field, respectively. Elisabet Stener Victorin became the most influential author and most cited author. Jedel E. published the most cited article. "Polycystic ovary syndrome" was the most frequent keyword, and the top three frontiers mentioned were research method, intervention, and outcome. Conclusion: The current status and trends in clinical research of acupuncture therapy on PCOS patients are revealed according to the results of this bibliometric study, which may facilitate researchers to identify hot topics and new directions for future study in this field.

Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium.

Cerebrovascular effects of ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inactivation have not been systematically studied. In the present study we employed cultured human brain microvascular endothelial cells (BMECs), BACE1-knockout (BACE1-/-) mice and conditional (tamoxifen-induced) endothelium-specific BACE1-knockout (eBACE1-/-) mice to determine effect of BACE1 inhibition on expression and function of endothelial nitric oxide synthase (eNOS). Deletion of BACE1 caused upregulation of eNOS and glypican-1 (GPC1) in human BMECs treated with BACE1-siRNA, and cerebral microvessels of male BACE1-/- mice and male eBACE1-/- mice. In addition, BACE1siRNA treatment increased NO production in human BMECs. These effects appeared to be independent of amyloid ß-peptide production. Furthermore, adenoviral-mediated overexpression of BACE1 in human BMECs down-regulated GPC1 and eNOS. Treatment of human BMECs with GPC1siRNA suppressed mRNA and protein levels of eNOS. In basilar arteries of male eBACE1-/- mice, endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to NO donor, DEA-NONOate, were not affected, consistent with unchanged expression of eNOS and phosphorylation of eNOS at Ser1177 in large cerebral arteries. In aggregate, our findings suggest that under physiological conditions, inactivation of endothelial BACE1 increases expression of eNOS in cerebral microvessels but not in large brain arteries. This effect appears to be mediated by increased GPC1 expression.

Efficacy of Electroacupuncture for the Treatment of Postherpetic Neuralgia: Study Protocol for a Multicenter Randomized Controlled Trial.

Introduction: Postherpetic neuralgia (PHN) is a severe complication of herpes zoster (HZ), representing an important burden of disease in the elderly. Electroacupuncture (EA) has become growingly appreciated as a therapy of PHN with the situation that effectiveness of conventional therapy of PHN is less than ideal. Owing to its low price, no side effects, high safety and high patients acceptance, EA has been used in treating PHN more frequently. Therefore, the randomized controlled trial which is to evaluate the effectiveness and safety of EA in patients with PHN and whether EA could be an alternative therapy of medication is needed. Patients and Methods: A total of 88 patients with PHN will be recruited from 2 hospitals and randomized assigned to EA group or Medication group in a 1:1 ratio, utilizing a central randomization system. The trial will involve a 4-week treatment period, and a 4-week follow-up period. All variables will be evaluated at week 0 (baseline), week 2 (treatment), week 4 (treatment), week 8 (follow-up) and week 16 (follow-up). Primary outcomes will be pain intensity. Secondary outcomes will contain quality of life, mood state and sleep quality. All adverse effects will be assessed during the trial. Conclusion: This study will provide significant evidence that whether EA therapy is effective and safe for patients with PHN and whether EA could be an alternative therapy of medication. Ethics and Dissemination: Ethics approval has been obtained from the Ethics Committee of the Hangzhou Third People's Hospital (No. 2021KAO43). Informed consent will be signed before enrolment. Results of this trial will be presented to international journals for publication and be reported in relevant international conferences. Trial Registration Number: This protocol has been registered in the Chinese Clinical Trial registry with the identification code ChiCTR2100054592.

Research Trends of Moxibustion Therapy for Pain Treatment Over the Past Decade: A Bibliometric Analysis.

Background: Accumulate evidence indicated that moxibustion has a positive effect on pain treatment. However, the bibliometric analysis of moxibustion on pain remains uncertain. Herein, this study aimed to explore the current hotspots and the research trends over the past decade to bring a great panorama in this field. Methods: Publications were retrieved from the database Web of Science Core Collection (WoSCC) related to moxibustion therapy for pain treatment from January 1, 2012, to December 31, 2021. CiteSpace and Excel were applied to analyze the volume of publications, journals, cited journals, dual-map analysis, countries, institutes, authors, references, and keywords with citation bursts. Results: A total of 360 publications were retrieved from 2012 to 2021. The annual number of publications increased steadily with some fluctuations over the past 10 years. "The Evid Based Complement Alternat Med" and "the Gut" were the top-cited journals in frequency and centrality. China and Shanghai University of Traditional Chinese Medicine were the most prolific country and institutions, respectively. Among authors, Huangan Wu was the most active author with the highest cited frequency. Jun Xiong, Fanrong Liang and Guixing Xu held the articles with higher centrality. In the ranking of frequency and centrality in cited references, the top one was the article published by Shamseer L and Deng HY, respectively. "Acupuncture" was the keyword with the highest frequency. Pain disease (including rheumatoid arthritis, knee osteoarthritis, herpes zoster), research method (including randomized controlled trial), and risk (including quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field. Conclusion: This bibliometric study reveals the current status and research trend in the treatment of pain with moxibustion. The formulation with bibliometric analysis further elicits hot spots and frontier issues in this field.

Identification of pyroptosis-related immune signature and drugs for ischemic stroke.

Background: Ischemic stroke (IS) is a common and serious neurological disease, and multiple pathways of cell apoptosis are implicated in its pathogenesis. Recently, extensive studies have indicated that pyroptosis is involved in various diseases, especially cerebrovascular diseases. However, the exact mechanism of interaction between pyroptosis and IS is scarcely understood. Thus, we aimed to investigate the impact of pyroptosis on IS-mediated systemic inflammation. Methods: First, the RNA regulation patterns mediated by 33 pyroptosis-related genes identified in 20 IS samples and 20 matched-control samples were systematically evaluated. Second, a series of bioinformatics algorithms were used to investigate the contribution of PRGs to IS pathogenesis. We determined three composition classifiers of PRGs which potentially distinguished healthy samples from IS samples according to the risk score using single-variable logistic regression, LASSO-Cox regression, and multivariable logistic regression analyses. Third, 20 IS patients were classified by unsupervised consistent cluster analysis in relation to pyroptosis. The association between pyroptosis and systemic inflammation characteristics was explored, which was inclusive of immune reaction gene sets, infiltrating immunocytes and human leukocyte antigen genes. Results: We identified that AIM2, SCAF11, and TNF can regulate immuno-inflammatory responses after strokes via the production of inflammatory factors and activation of the immune cells. Meanwhile, we identified distinct expression patterns mediated by pyroptosis and revealed their immune characteristics, differentially expressed genes, signaling pathways, and target drugs. Conclusion: Our findings lay a foundation for further research on pyroptosis and IS systemic inflammation, to improve IS prognosis and its responses to immunotherapy.

Identification of Adipocytokine Pathway-Related Genes in Epilepsy and Its Effect on the Peripheral Immune Landscape.

Epilepsy is a multifactorial neurological disorder with recurrent epileptic seizures. Current research stresses both inflammatory and autoimmune conditions as enablers in the pathophysiological process of epilepsy. In view of the growing concern about the role of adipocytokines in antiepileptic and modulating immune responses, we aimed to investigate the relevance of the adipocytokine signaling pathway in the pathological process of epilepsy and its impacts on peripheral immune characteristics. In this study, expression profiles of 142 peripheral blood samples were downloaded from the Gene Expression Omnibus (GEO) database. Adipocytokine pathway-related genes were screened out by feature selection using machine-learning algorithms. A nomogram was then constructed and estimated for the efficacy of diagnosis. Cluster analysis was employed for the recognization of two distinct epilepsy subtypes, followed by an estimation of the immune cell infiltration levels using single-sample gene-set enrichment analysis (ssGSEA). The biological characteristics were analyzed by functional enrichment analysis. The aberrant regulation of adipocytokine signaling pathway was found in the peripheral blood of patients with epilepsy. Twenty-one differently expressed adipocytokine pathway-related genes were identified and five (RELA, PRKAB1, TNFRSF1A, CAMKK2, and CPT1B) were selected to construct a nomogram. Subsequent validations of its forecasting ability revealed that this model has satisfactory predictive value. The immune cell infiltration degrees, such as those of innate immune cells and lymphocytes, were found to significantly correlate to the levels of adipocytokine pathway-related genes. Additionally, 239 differentially expressed genes (DEGs) were identified and their biological functions were mainly enriched in the regulation of the immune response. In conclusion, our results confirmed the predictive value of adipocytokine pathway-related genes for epilepsy and explored their effects on immune infiltration, thereby improving our understanding of the pathogenesis of epilepsy and providing assistance in the diagnosis and treatment of epilepsy.

Acupuncture therapies for postherpetic neuralgia: a protocol for a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common sequela of herpes zoster, and it is often refractory to guideline-recommended treatments. Acupuncture therapy, a wildly applied complementary-alternative treatment, may help in the management of PHN. Diverse types of acupuncture therapy for PHN have been proposed, however, their comparative efficacies remain unclear. This study protocol plans to compare the efficacy and safety of different acupuncture therapies for PHN. METHODS AND ANALYSIS: Databases including MEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register and OpenGrey will be searched from their inception to January 2022. Randomised controlled trials (RCTs) assessing the effectiveness of acupuncture therapy on the management of PHN will be selected. The primary outcome is pain intensity. Secondary outcomes include negative emotions, sleep condition, quality of life and adverse events. Reviewers will conduct study selection, data extraction and risk of bias assessment procedures. Then, standard pair-wised meta-analysis and Bayesian network meta-analysis will be performed (if applicable). The Confidence in Network Meta-Analysis application will be used to assess the confidence in the evidence for the primary outcome. ETHICS AND DISSEMINATION: All data used for this study will be extracted from published RCTs, thus, no ethical approval will be required. The results of this systematic review will be disseminated through peer-reviewed journal and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020219576.

Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme.

Background: Ankyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted to explore its function in prognosis and immune microenvironment. Method: In this study, mRNA expression data were downloaded from TCGA and GTEx database. Next generation sequencing data from 14 glioblastoma multiforme (GBM) samples by neurosurgical resection were used as validation dataset. Multiple bioinformatics methods (ssGSEA, Kaplan-Meier, Cox regression analysis, GSEA and online tools) were applied to explore ASB3 expression, gene activity, prognosis of patients in various cancers, and its correlation with clinical information, immune microenvironment and pertinent signal pathways in GBM. The biological function of ASB3 in tumor-infiltrating lymphocytes (TILs) was verified using an animal model. Results: We found that ASB3 was aberrant expressed in a variety of tumors, especially in GBM, and significantly correlated with the prognosis of cancer patients. The level of ASB3 was related to the TMB, MSI and immune cell infiltration in some cancer types. ASB3 had a negative association with immune infiltration and TME, including regulatory T cells (Tregs), cancer-associated fibroblasts, immunosuppressors and related signaling pathways in GBM. ASB3 overexpression reduced the proportion of Tregs in TILs. GSEA and PPI analysis also showed negative correlation between ASB3 expression and oncogenetic signaling pathways in GBM. Conclusion: A comprehensive pan-cancer analysis of ASB3 showed its potential function as a biomarker of cancer prognosis and effective prediction of immunotherapy response. This study not only enriches the understanding of the biological function of ASB3 in pan-cancer, especially in GBM immunity, but also provides a new reference for the personalized immunotherapy of GBM.

Her3-specific affibody mediated tumor targeting delivery of ICG enhanced the photothermal therapy against Her3-positive tumors.

Photothermal therapy (PTT), mediated by tumor-targeted drug delivery of indocyanine green (ICG), is a promising strategy for cancer therapy. Human epidermal growth factor receptor 3 (Her3) is highly expressed in several solid tumors and is an ideal target for tumor diagnosis and therapy. This study prepared a Her3-specific dimeric affibody (ZHer3) using an Escherichia coli expression system. The affibody could bind explicitly to Her3-positive MCF7 and LS174T cells, rather than to Her3-negative SKOV-3 cells in vitro. ICG was coupled with the ZHer3 affibody (ICG-ZHer3) through an N-hydroxysuccinimide (NHS) ester reactive group for tumor-targeted delivery. As expected, Her3-positive cells were selectively and efficiently killed by ICG-ZHer3-mediated PTT in vitro. In vivo, ICG-ZHer3 preferentially accumulated in Her3-positive LS174T tumor grafts because of the tumor-targeting ability of the ZHer3 affibody. As a result of the local generation of cytotoxic reactive oxygen species and hyperthermia, the growth rates of LS174T tumor grafts were significantly inhibited by ICG-ZHer3-mediated PTT, and ICG-ZHer3 showed good safety performance during short-term treatment. In conclusion, these results demonstrated that ICG-ZHer3 is a promising photosensitizer for PTT against Her3-positive tumors.

Development of a 3 RNA Binding Protein Signature for Predicting Prognosis and Treatment Response for Glioblastoma Multiforme.

Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction. Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients' survival rates. Moreover, western blot was for the detection of the proteins. Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells. Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients.