Mixed Lineage Kinase Domain-like Protein MLKL Breaks Down Myelin following Nerve Injury.

Successful regeneration of severed peripheral nerves requires the breakdown and subsequent clearance of myelin, tightly packed membrane sheaths of Schwann cells that protect nerve fibers and harbor nerve growth-inhibitory proteins. How Schwann cells initiate myelin breakdown in response to injury is still largely unknown. Here we report that, following sciatic nerve injury, MLKL, a pseudokinase known to rupture cell membranes during necroptotic cell death, is induced and targets the myelin sheath membrane of Schwann cells to promote myelin breakdown. The function of MLKL in disrupting myelin sheaths requires injury-induced phosphorylation of serine 441, an activation signal distinct from the necroptosis-inducing phosphorylation by RIP3 kinase. Mice with Mlkl specifically knocked out in Schwann cells showed delayed myelin sheath breakdown. Lack of MLKL reduced nerve regeneration following injury, whereas overexpression of MLKL accelerated myelin breakdown and promoted the regeneration of axons.

Clinical characteristics, treatment outcomes, and prognosis in patients with MKIs-associated hand-foot skin reaction: a retrospective study.

BACKGROUND: Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR. OBJECTIVE: To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR. METHODS: We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy. RESULTS: The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR. CONCLUSION: This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR.

Electric Field Enhanced Ammoxidation of Aldehydes Using Supported Fe Clusters Under Ambient Oxygen Pressure.

Heterogeneous catalytic ammoxidation provides an eco-friendly route for the cyanide-free synthesis of nitrile compounds, which are important precursors for synthetic chemistry and pharmaceutical applications. However, in general such a process requires high pressures of molecular oxygen at elevated temperatures to accelerate the oxygen reduction and imine dehydrogenation steps, which is highly risky in practical applications. Here, we report an electric field enhanced ammoxidation system using a supported Fe clusters catalyst (Fe/NC), which enables efficient synthesis of nitriles from the corresponding aldehydes under ambient air pressure at room temperature (RT). A synergistic effect between the external electric field and the Fe/NC catalyst promotes the ammonia activation and the dehydrogenation of the generated imine intermediates and avoids the unwanted backwards reaction to aldehydes. This electric field enhanced ammoxidation system presents high efficiency and selectivity for the conversion of a series of aldehydes under mild conditions with high durability, rendering it an attractive process for the green synthesis of nitriles with fragile functional groups.

TBC1D21 is an essential factor for sperm mitochondrial sheath assembly and male fertility‡.

During spermiogenesis, the formation of the mitochondrial sheath is critical for male fertility. The molecular processes that govern the development of the mitochondrial sheath remain unknown. Whether TBC1D21 serves as a GTPase-activating protein (GAP) for GTP hydrolysis in the testis is unclear, despite recent findings indicating that it collaborates with numerous proteins to regulate the formation of the mitochondrial sheath. To thoroughly examine the property of TBC1D21 in spermiogenesis, we applied the CRISPR/Cas9 technology to generate the Tbc1d21-/- mice, Tbc1d21D125A R128K mice with mutation in the GAP catalytic residues (IxxDxxR), and Tbc1d21-3xFlag mice. Male Tbc1d21-/- mice were infertile due to the curved spermatozoa flagella. In vitro fertilization is ineffective for Tbc1d21-/- sperm, although healthy offspring were obtained by intracytoplasmic sperm injection. Electron microscopy revealed aberrant ultrastructural changes in the mitochondrial sheath. Thirty-four Rab vectors were constructed followed by co-immunoprecipitation, which identified RAB13 as a novel TBC1D21 binding protein. Interestingly, infertility was not observed in Tbc1d21D125A R128K mice harboring the catalytic residue, suggesting that TBC1D21 is not a typical GAP for Rab-GTP hydrolysis. Moreover, TBC1D21 was expressed in the sperm mitochondrial sheath in Tbc1d21-3xFlag mice. Immunoprecipitation-mass spectrometry demonstrated the interactions of TBC1D21 with ACTB, TPM3, SPATA19, and VDAC3 to regulate the architecture of the sperm midpiece. The collective findings suggest that TBC1D21 is a scaffold protein required for the organization and stabilization of the mitochondrial sheath morphology.

Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: A SEER population-based study.

Background: Combined small cell lung cancer (C-SCLC) is a rare type of small cell lung cancer (SCLC), and it is controversial whether to choose the same treatment regimen as SCLC due to its multiple histologic components. Study methods and results: Records of patients with small cell lung cancer diagnosed between 2010 and 2020 were extracted using the SEER database. The OS of patients with different histological types under the same staging and treatment regimen was analyzed. It was found that early-stage (stage IA-IIA) surgical treatment, systemic chemotherapy alone, and chemoradiotherapy were more efficacious than C-SCLC and P-SCLC in patients with limited-stage (P = 0.054, P = 0.001, P = 0.019). In patients with extensive staging, the OS of patients with systemic chemotherapy regimens differed (P = 0.045) and was better in C-SCLC than in P-SCLC. We further explored the treatment strategy for patients with C-SCLC, which was shown by a COX regression model based on prognostic factors screened by Random Forest and LASSO regression models. Surgery, radiotherapy, and chemotherapy would be beneficial for survival. In a subgroup analysis based on stage and treatment regimen, it was shown that patients with early staging (stage IA-IIA) had a better prognosis with surgery (P < 0.001); in patients with extensive staging, chemoradiotherapy was favorable to the patient's prognosis (P = 0.022). Conclusion: Both limited-stage and extensive-stage C-SCLC patients are more sensitive to chemotherapy than P-SCLC patients. Patients with C-SCLC who have access to surgery should undergo surgery as early as possible, while chemoradiotherapy is recommended for patients with extensive staging. Patient age, gender, tumor size, surgery, chemotherapy, radiotherapy, and metastasis may individually affect patient prognosis.

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report.

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

The Efficacy and Safety of the Shouzu Ning Decoction Treatment Versus Halometasone Plus Celecoxib Treatment in Patients With Grade 2 HFSR: A Randomized Clinical Trial.

OBJECTIVES: To compare the effects of the Shouzu Ning Decoction (SND) and Halometasone plus Celecoxib (Hal/Cxb) as therapy in patients with grade 2 hand-foot skin reaction (HFSR). MATERIALS AND METHODS: Fifty patients with grade 2 HFSR participated in a randomized, single-center, open-label study. Patients were randomly assigned in a 1:1 ratio to receive the SND or Hal/Cxb treatment, twice daily for 4 weeks, followed by 4 weeks of post-treatment follow-up. The primary endpoint was clinical remission of HFSR at the end of the fourth week (W4). The secondary endpoints were recurrence rate, quality of life (QoL), pain intensity, and safety. RESULTS: In this study, 46 patients successfully completed the study, and 4 patients were excluded. There was no statistically significant difference between the 2 groups on demographic and baseline clinical characteristics. In the SND group, 56.52% of patients showed clinical remission at W4, which was significantly superior to that achieved in the Hal/Cxb group (26.09%, P = .036). In addition, the HF-QoL score was statistically lower in the SND group compared to the Hal/Cxb group at W2 (P = .007), W3 (P = .005), and W4 (P = .005), respectively. In line with this, the inter-group difference in NRS score was statistically significant (P = .004). CONCLUSION: In the present study, SND treatment has been observed to be effective and well tolerated for patients with grade 2 HFSR. Thus, SND treatment could be considered a suitable option for HFSR patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027518. Registered on 17 Nov 2019.

Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients.

Aim: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. Method: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. Results: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO2 before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO2 (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). Conclusion: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO2 were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.

The value of convolutional neural networks-based deep learning model in differential diagnosis of space-occupying brain diseases.

Objectives: It is still a challenge to differentiate space-occupying brain lesions such as tumefactive demyelinating lesions (TDLs), tumefactive primary angiitis of the central nervous system (TPACNS), primary central nervous system lymphoma (PCNSL), and brain gliomas. Convolutional neural networks (CNNs) have been used to analyze complex medical data and have proven transformative for image-based applications. It can quickly acquire diseases' radiographic features and correct doctors' diagnostic bias to improve diagnostic efficiency and accuracy. The study aimed to assess the value of CNN-based deep learning model in the differential diagnosis of space-occupying brain diseases on MRI. Methods: We retrospectively analyzed clinical and MRI data from 480 patients with TDLs (n = 116), TPACNS (n = 64), PCNSL (n = 150), and brain gliomas (n = 150). The patients were randomly assigned to training (n = 240), testing (n = 73), calibration (n = 96), and validation (n = 71) groups. And a CNN-implemented deep learning model guided by clinical experts was developed to identify the contrast-enhanced T1-weighted sequence lesions of these four diseases. We utilized accuracy, sensitivity, specificity, and area under the curve (AUC) to evaluate the performance of the CNN model. The model's performance was then compared to the neuroradiologists' diagnosis. Results: The CNN model had a total accuracy of 87% which was higher than senior neuroradiologists (74%), and the AUC of TDLs, PCNSL, TPACNS and gliomas were 0.92, 0.92, 0.89 and 0.88, respectively. Conclusion: The CNN model can accurately identify specific radiographic features of TDLs, TPACNS, PCNSL, and gliomas. It has the potential to be an effective auxiliary diagnostic tool in the clinic, assisting inexperienced clinicians in reducing diagnostic bias and improving diagnostic efficiency.

Microneedle-enabled therapeutics delivery and biosensing in clinical trials.

Microneedles (MNs) are micron-sized protrusions attached to a range of devices that are used in therapeutic delivery and diagnosis. Because MNs can be self-applied, are painless, and can carry multiple therapeutic agents, they have received extensive attention, and have been widely investigated, for local and systemic therapy. Many researchers are currently working to extend the use of MNs to clinical applications. In this review, we provide an update and analysis on MN-based clinical trials since their inception in 2007. The MNs in clinical trials are classified into five types based on their appearance and properties, including: hollow MNs, MN patches, radiofrequency MNs, MN rollers, and other MNs. The various aspects of MN trials are summarized, such as MN types, clinical trial time, and trial regions. This review aims to present an overview of MN development and provide insights for future research in this field. To our knowledge, this is the first review focused on MN clinical trials which showcases the latest applications of this advanced technology in medicine.

Prognostic nomograms for predicting overall survival and cancer-specific survival in patients with angiosarcoma, a SEER population-based study.

Angiosarcoma (AS) is a kind of highly aggressive cancer with high occurrence and mortality rates. This study aimed to establish a comprehensive and validated prognostic nomogram with various clinical indicators in non-metastatic AS patients after surgery. Data of non-metastatic AS patients diagnosed after surgery between 2010 and 2015 was retrieved from the surveillance epidemiology and end results database. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent prognostic factors associated with survival to construct the predictive nomogram of 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Concordance-index (C-index), calibration plots and receiver operating characteristic (ROC) curves were applied to evaluate the predictive ability of the nomograms. 251 patients in total were divided into the training group (N = 177) and the validation group (N = 74). After the multivariate Cox regression analysis, gender, AJCC stage group 7th ed, T, N stage 7th ed, histologic grade and primary site were statistically identified as independent factors with OS and CSS (P < 0.05). We incorporated the significant factors above and age into nomograms. The C-index of the nomograms for OS and CCS in the training cohort was 0.757 (95%CI 0.697-0.817) and 0.762 (95%CI 0.702-0.822), meanwhile, the C-index of those in the validation cohort was 0.749 (95%CI 0.668-0.830) and 0.756 (95%CI 0.676-0.836) respectively. The results of calibration plots and ROC curve showed the nomograms qualified to measure the risk and prognosis. Our study has developed novel and practical nomograms for predicting prognosis in patients with non-metastatic AS after surgery contributing to cancer management.

Capecitabine-induced enterocolitis: a case report and pharmacogenetic profile.

Capecitabine is a widely-used antineoplastic drug, a prodrug to 5-fluorouracil which commonly induces gastrointestinal toxicity. Enterocolitis, as a rarely recognized gastrointestinal adverse effect (AE) of capecitabine, is potentially severe and usually results in antitumor treatment withdrawal. For the better management of severe AEs, pharmacogenetics is one promising field. Herein, we describe a case of capecitabine-induced enterocolitis presenting with severe diarrhea in order to improve recognition by clinicians. Moreover, we conduct a pharmacogenetic profile of the patient and review the current studies of gene polymorphisms of 5-fluorouracil-related diarrhea, hoping to offer a reference for further clinical pharmacogenetic practice in predicting capecitabine AEs showing diarrhea as the main symptom.

Cutaneous adverse events in patients treated with PD-1/PD-L1 checkpoint inhibitors and their association with survival: a systematic review and meta-analysis.

Immune-related cutaneous adverse events (irCAEs) in patients treated with programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors may be associated with better clinical outcomes. However, the extent to which these results can be extrapolated to all tumour types remains unclear. Herein, we conducted a meta-analysis of patients with cancer receiving anti-PD-1/PD-L1 immunotherapy, to determine the cumulative incidence of irCAEs and their association with survival. We systematically searched six databases (PubMed, Embase, Cochrane, CNKI, CSPD, and CQVIP database) for all cohort studies reporting the relationship between irCAEs and patient survival from the time of database construction to 1 November, 2020. The primary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), with complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) as secondary outcomes. Patients with irCAEs exhibited higher ORR, and were more likely to report CR and PR and less likely to develop PD than those who did not experience irCAEs. Moreover, the occurrence of irCAEs was significantly associated with both favourable PFS and OS. Therefore, patients with irCAEs have better survival benefit and a significantly lower risk of tumour progression or death. Hence, the occurrence of irCAEs may be a useful marker for predicting the clinical efficacy of anti-PD-1/PD-L1 immunotherapy.

Tongqiao Huoxue Decoction for the treatment of acute ischemic stroke: A Systematic Review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this study was to evaluate the efficacy and safety of Tongqiao Huoxue Decoction (TQHXT) in the treatment of acute ischemic stroke (AIS); Study Design: A total of 17 randomized controlled trials, involving 1489 AIS patients, were included for data analyses. MATERIALS AND METHODS: All randomized controlled trials (RCTs) of TQHXT in the treatment of acute ischemic stroke before September 2020 were retrieved from seven electronic databases, including PubMed, Web of Science, Central, CNKI, CBM, Wanfang, and VIP. Data were analyzed by RevMan 5.3 software, and quality was evaluated by GRADEpro; Results: Results showed that, while TQHXT demonstrated undeniable positive effects in clinical effective rate, neurological deficit scores, activities of daily living (ADL) scores, and hemorheology (including HCT; fibrinogen; plasma viscosity and platelet adherence rate), adverse events (AE) require further study; and Conclusions: This study provides evidence that TQHXT is an effective treatment for acute ischemic stroke. However, due to the limited quality of the included studies, the above conclusion needs to be further verified by stricter randomized controlled, double-blind, large-sample, high-quality trials.

Effectiveness of gastrodin for migraine: A meta-analysis.

Background: Gastrodia elata Blume (GEB), a traditional Chinese medicine, has been widely used to treat dizziness, numbness of limbs, and infantile convulsion, among other issues. Gastrodin is the main component of GEB. This meta-analysis aimed to evaluate the efficacy and safety of gastrodin in the treatment of migraine. Methods: Ten electronic databases, namely the Cochrane Library, Embase, EBSCO, PubMed, Web of Science, CENTRAL, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedicine Database), WanFang, and VIP (Chinese Scientific Journals Database), were searched for randomized controlled trials (RCTs) of gastrodin for migraine published before September 2021. The data were analyzed by RevMan 5.3 software and evaluated by GRADEpro. Results: A total of 1,332 subjects were included in 16 RCTs. The meta-analysis showed that gastrodin was significantly effective in treating migraine (RR = 1.21, 95%CI = [1.17, 1.27]), reducing the pain degree (MD = -1.65, 95% CI = [-2.28, -1.02]), reducing the frequency of migraine attack (SMD = -2.77, 95% CI = [-3.92, -1.62]), shortening the duration of migraine attack (SMD = -1.64, 95% CI = [-2.35, -0.93]), and slowing average arterial cerebral blood flow velocity (SMD = -3.19, 95% CI = [-5.21, -1.17]), as well as being safe. Conclusions: This systematic review revealed gastrodin is effective and safe in the treatment of migraine. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197094, identifier: CRD42020197094.

The ZFP541-KCTD19 complex is essential for pachytene progression by activating meiotic genes during mouse spermatogenesis.

Meiosis is essential for fertility in sexually reproducing species and this sophisticated process has been extensively studied. Notwithstanding these efforts, key factors involved in meiosis have not been fully characterized. In this study, we investigate the regulatory roles of zinc finger protein 541 (ZFP541) and its interacting protein potassium channel tetramerization domain containing 19 (KCTD19) in spermatogenesis. ZFP541 is expressed from leptotene to the round spermatid stage, while the expression of KCTD19 is initiated in pachytene. Depletion of Zfp541 or Kctd19 leads to infertility in male mice and delays progression from early to mid/late pachynema. In addition, Zfp541-/- spermatocytes show abnormal programmed DNA double-strand break repair, impaired crossover formation and resolution, and asynapsis of the XY chromosomes. ZFP541 interacts with KCTD19, histone deacetylase 1/2 (HDAC1/2), and deoxynucleotidyl transferase terminal-interacting protein 1 (DNTTIP1). Moreover, ZFP541 binds to and activates the expression of genes involved in meiosis and post-meiosis including Kctd19; in turn, KCTD19 promotes the transcriptional activation activity of ZFP541. Taken together, our studies reveal that the ZFP541/KCTD19 signaling complex, acting as a key transcription regulator, plays an indispensable role in male fertility by regulating pachytene progression.

Aqueous extract of Taxus chinensis var. mairei targeting CD47 enhanced antitumor effects in non-small cell lung cancer.

Immunoglobulin protein CD47 is overexpressed in malignant tumor cells, allowing them to evade host immunity mainly by inhibiting macrophage-mediated phagocytosis. Taxus chinensis var. mairei (TC) exhibits high antitumor efficacy with low toxicity and notable cost-effectiveness. However, it is unknown whether aqueous extract of TC (AETC) is an immunomodulator that mediates antitumor efficacy. In this study, we aimed to elucidate the critical role of CD47 degradation in the treatment of AETC in non-small cell lung cancer (NSCLC) cells. A mouse Lewis lung carcinoma model was developed to determine whether the administration of AETC, as an anti-CD47 antibody, in combination with anti-PD-1 could synergistically inhibit tumor growth and promote a peripheral immune response. AETC treatment downregulated CD47 levels in NSCLC cells and Lewis tumor xenograft mice. Furthermore, treatment enhanced immunity against NSCLC by triggering CD47 ubiquitination and degradation, promoting macrophage-mediated tumor cell phagocytosis, and activating CD8+ T cells. The present study empirically demonstrated, for the first time, that AETC exerts antitumor properties as an immunomodulator. Our findings present AETC as a promising alternative or adjuvant treatment in lung cancer therapy.

The Efficacy and Safety of the Shouzu Ning Decoction Treatment for Multi-Kinase Inhibitors-Associated Severe Hand-Foot Skin Reaction.

BACKGROUND: Multi-kinase inhibitors (MKIs) treatment plays an important role in cancer therapy, but still suffers from a high incidence of hand-foot skin reaction (HFSR), leading to MKIs dose modification or termination. Thus, there is a high need for therapeutic strategy for HFSR. PATIENTS AND METHODS: This prospective analysis included twenty patients, who were continuously administered with MKIs treatment and presented with a grade 3 HFSR during January 2018 to December 2019. All the patients were treated with the Shouzu Ning Decoction (SND) twice a day, in addition to the MKIs treatment. Grading of HFSR was assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Pain intensity was evaluated using the numerical rating scale (NRS). Quality of life was assessed using the Hand-Foot Quality of Life Scale (HF-QoLS). RESULTS: The median time from MKIs initiation to onset of grade 3 HFSR was 26.2 days. Following the SND treatment, seventeen (17/20) patients displayed grade 2 HFSR with a median time of 5.1 days. Among whom, seven (7/17) finally transformed to grade 1 with a median time of 9.9 days. While all of the grade 1 patients (7/7) had local recurrence, and retreatment of the SND was effective. In addition, after the SND treatment, the score of NRS and HF-QoLS decreased to 1.60 ± 1.14 (P < 0.01) and 26.75 ± 11.76 (P < 0.01), respectively. CONCLUSION: The SND treatment could alleviate symptoms, relieve pain and improve quality of life in HFSR patients. The SND treatment was proved to be an effective and well-tolerated treatment for MKIs-associated grade 3 HFSR patients for the first time. Indeed, further randomized controlled trails with large-scale, multi-center are require to fully determine the clinical application of the SND in MKIs-associated HFSR.

Governor vessel acupuncture for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is the major type of stroke, which highly risks human health and life quality. Governor vessel acupuncture (GV Ac) is one specific acupoint selection treatment. This study aimed to systematically evaluate the clinical value of GV Ac in AIS patients. METHODS: Seven electronic databases were searched for all related randomized controlled trials before December 2020. The included studies should meet the following criteria: all target patients were diagnosed as AIS; the experimental group used GV Ac as the only intervention or combined with routine neurology therapy as conventional treatment; the control group received ordinary acupuncture, or the same conventional treatment as the experimental group, or both. Evaluated the quality of all included trials and performed a meta-analysis of the extracted data. RESULTS: A total of 18 trials were included, involving 1,543 AIS patients. The results showed compared to the conventional treatment, GV Ac combining with conventional therapy resulted in Barthel Index (BI) (MD =14.16, 95% CI: 7.34, 20.79) improvement, mRS (MD =-0.63, 95% CI: -0.95, -0.32, P<0.0001) decrease, better National Institute of Health Stroke Scale (NIHSS) scores (MD =-1.18, 95% CI: -1.52, -0.83), and lower China Stroke Score (CSS)/Modified Edinburgh-Scandinavia Stroke Scale (MESSS) scores (MD =-3.77, 95% CI: -4.98, -2.57). Furthermore, GV Ac could better improve activities of daily living (ADL) (MD =8.27, 95% CI: 4.29, 12.26) and neurological deficit scores (NIHSS: MD =-1.32, 95% CI: -2.18, -0.47; CSS/MESSS: MD =-4.63, 95% CI: -5.91, -3.35), when compared to the ordinary acupuncture. DISCUSSION: According to the current evidence, GV Ac for AIS's efficacy appears to be better than that of ordinary acupuncture. When combined with conventional treatment, GV Ac may increase the benefit. But limited by the methodological quality of the included studies, more strictly designed large-scale randomized controlled trials are needed. TRIAL REGISTRATION NUMBER: CRD42020203480.

Rational design of flexible capacitive sensors with highly linear response over a broad pressure sensing range.

Flexible capacitive pressure sensors have many important applications but usually exhibit a highly non-linear response as the sensitivity drops dramatically towards high pressure. Herein, we propose a novel strategy to achieve high linearity over a broad sensing range by using percolative composites as the dielectric layer. The linear response is attributed to the fast increase in dielectric constant that can compensate for the sensitivity drop caused by the decreased compressibility during compression. An analytical model is established to predict the linearity by coupling the percolation theory and Mooney-Rivlin equation. Based on the model, a capacitive pressure sensor using a spiky nickel/polydimethyl siloxane composite as the dielectric layer is fabricated as a demonstration and exhibits excellent linearity (R2 = 0.999) up to 1.7 MPa. In addition, owing to the nature of the polymer composite, its dispersion can be conformally coated on surfaces with complex shapes or be molded into films with surface microstructures to achieve a unique combination of high sensitivity and linear response over a wide pressure sensing range.