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Introduction: Diabetic peripheral neuropathy (DN) is the most common complication of type 2 diabetes mellitus (T2DM). Objective: This study aimed to explore the role of fibrinogen (FIB) in T2DM neuropathy and its preliminary mechanism. Methods: Ten male Sprague–Dawley rats were divided into a normal control group (NC group) and a T2DM neuropathy model group (DN group). The DN group was given a high-energy diet and streptozotocin, while the NC group was given a normal diet and a citric acid buffer. The expression levels of related proteins were analysed. Results: Electrophysiology: Compared with the NC group, the conduction latency of the somatosensory-evoked potential and nerve conduction velocity was prolonged in the DN group, while the motor nerve action potential was decreased. As seen under a light microscope, the peripheral nerve fibres in the DN group were swollen, and the nerve fibres in the posterior funiculus of the spinal cord were loose or missing. Moreover, as seen under an electron microscope, the peripheral nerve demyelination of the DN group was severe, with microvascular blood coagulation, luminal stenosis, and collapse. Compared with the NC group, in the DN group, the expression of FIB was positively correlated with the expression of both ionised calcium-binding adaptor molecule-1 and glial fibrillary acidic protein. Compared with the NC group, in the DN group, the expression of platelet/endothelial cell adhesion molecule-1 and B-cell lymphoma 2 was negatively correlated. Conclusion: The increased concentration of FIB may be the cause of neuropathy, and its mechanism may be related to its promotion of inflammatory response, blood coagulation, and vascular stenosis.

BackgroundCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the standard treatment for patients with peritoneal cancer (PC). Following CRS-HIPEC, patients may also face risks caused by whole body hyperthermia. This study analyzed the incidence of temperature increases following CRS-HIPEC and identified the attendant risk factors.MethodsA retrospective analysis was carried out among 458 patients who received CRS-HIPEC at the Fourth Hospital of Hebei Medical University between August 2018 and January 2021. The patients were divided into two groups according to post-HIPEC axillary temperature (≥38°C), with the demographics and the laboratory test results subsequently analyzed and compared, and the risk factors pertaining to temperature increases analyzed using univariate and multivariate logistic regression.ResultsDuring CRS-HIPEC, 32.5% (149/458) of the patients with a temperature increase had an axillary temperature of not lower than 38°C, and 8.5% (39/458) of the patients with hyperpyrexia had an axillary temperature of not lower than 39°C. Female gender, gynecological malignancies, type of chemotherapy drug, increased postoperative neutrophil percentage, and a sharp drop in postoperative prealbumin were associated with the incidence of a temperature increase and axillary temperatures of >38°C. Among these factors, the type of chemotherapy drug was identified as an independent risk factor for a temperature increase during CRS-HIPEC.ConclusionBy determining the risk factors pertaining to temperature increases during CRS-HIPEC, medical staff can identify the attendant risks among the patients and thus take preventive measures in a timely manner to maintain the patient’s body temperature at a stable level. This suggests that further clinical research should be conducted to build a risk-prediction model for temperature increases following CRS-HIPEC.

Low-gluten rice is part of a special diet for chronic kidney disease patients, but its digestive mechanism in the gastrointestinal tract is unclear. In this study, low-gluten rice (LGR), common rice (CR), and rice starch (RS) were used as experimental samples, and their digestion and bacterial fermentation were simulated using an in vitro gastrointestinal reactor to investigate the mechanism of the effect of LGR on human health. The starch digestibility of CR was higher than that of LGR, with statistically significant differences. LGR has growth-promoting and metabolic effects on Akkermansia muciniphila. Among the beneficial metabolites, the concentration of short-chain fatty acids (SCFAs) from LGR reached 104.85 mmol/L, an increase of 44.94% (versus RS) and 25.33% (versus CR). Moreover, the concentration of lactic acid reached 18.19 mmol/L, an increase of 60.55% (versus RS) and 25.28% (versus CR). Among the harmful metabolites, the concentration of branched-chain fatty acids (BCFAs) in LGR was 0.29 mmol/L and the concentration of ammonia was 2.60 mmol/L, which was 79.31% and 16.15% lower than CR, respectively. A significant increase in the concentration of the beneficial intestinal bacteria Bacteroides and Bifidobacterium occurred from LGR. The 16s rDNA sequencing showed that the abundance of the Bacteroidetes and Firmicutes increased and the abundance of the Proteobacteria and Fusobacteria decreased. Thus, LGR has positive effects on digestion and gut microbiota structure and metabolism in humans.

To compare the clinical effectiveness of different mesh fixation techniques in Lichtenstein tension-free repair using network meta-analysis.Cochrane Library, Medline, EMBASE, and Web of Science databases were searched until 1 December 2020, and randomized controlled trials (RCTs) comparing outcomes between different mesh fixation techniques were included. The primary endpoints were chronic postoperative inguinal pain (CPIP) and hernia recurrence. The second endpoint was seroma and infection. Data were processed using Stata MP16.0, and R x64 3.6.1.The results demonstrated that 32 RCTs (n = 6362) were eligible for pooling. Six types of mesh fixation techniques were used: non-absorbable suture, absorbable suture, chemical glue, fibrin glue, self-gripping mesh, and staple fixation. Network meta-analysis indicated that the incidence of CPIP with fibrin glue was lower than that with non-absorbable sutures (relative risk [RR] = 0.23, 95% credibility interval [95%CrI] [0.09, 0.50]), absorbable sutures (RR = 0.24, 95%CrI [0.08, 0.60]), chemical glue (RR = 0.36, 95%CrI [0.13, 0.87]), and self-gripping mesh (RR = 0.27 95%CrI [0.09, 0.62]). Self-gripping mesh was superior to non-absorbable sutures (RR = 0.44, 95%CrI [0.23, 0.74]) in reducing postoperative infection.This network meta-analysis suggests that fibrin glue might be best for reducing CPIP and recurrence. However, a large-scale RCT is warranted to confirm the results.

Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases with chronic, progressive, and irreversible characteristics, affecting nearly 50 million older adults worldwide. The pathogenesis of AD includes the formation of senile plaques, the abnormal aggregation of tau protein and the gradual degeneration and death of cerebral cortical cells. The main symptoms are memory loss, cognitive decline and behavioral disorders. Studies indicate that cannabidiol (CBD) possesses various pharmacological activities, including anti-inflammatory, anti-oxidation and neuroprotective activities. It has been suggested as a potential multi-target medicine for the treatment of AD. In this review, we aim to summarize the underlying mechanisms and protective effects of CBD on signaling pathways and central receptors involved in the pathogenesis of AD, including the endocannabinoid system (eCBs), the Transient receptor potential vanilloid type 1(TRPV1) receptor, and the Peroxisome proliferator-activated receptor (PPAR) receptor.

Background The present study aimed to compare and evaluate the efficacy of antidepressants in remission of esophageal reflux symptoms. Methods A comprehensive literature review was performed including sources published on MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials (Cochrane), Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese VIP Information Databases (VIP), Chinese Biology Medicine disc (CBM), and Wan-Fang databases for randomized controlled trials, published up to and including March 31, 2020. We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy in relieving esophageal reflux symptoms ADDIS 1.16.8 was used to perform the network meta-analysis. Furthermore, we performed a split analysis to test inconsistency, and rank probability was complemented for comparison among antidepressants. Results A total of 10 randomized controlled trials (RCTs) examining the effects of antidepressants, selective 5-HT reabsorption inhibitor (SSRI), 5-HT 1A receptor agonist (5-HT1AA), tricyclic antidepressants (TCAs), and the complex of flupentixol-melitracen (FM) were included. Flupentixol-melitracen and SSRIs exhibited a significantly higher rate of remission than placebo. However, there was no statistically significant difference among different antidepressants compared. Rank probability showed that FM exhibited the highest probability of rank 1 compared with other antidepressants and placebo. Conclusion This network meta-analysis of RCTs supported the use of FM and SSRIs as a potentially effective regimen for symptom remission of gastroesophageal reflux. Furthermore, according to our analysis, FM represents the most efficient antidepressant with highest probability of symptom remission.

Background Some significant differences exist between the outcomes of left‐ and right‐sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left‐ and right‐sided colon cancer patients to determine the influence of this factor on prognosis. Methods Our data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi‐square test to analyze the clinicopathological characteristics. The X‐tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan–Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C‐index and calibration plots were used to validate the nomograms. Results The study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right‐sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C‐index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right‐sided colon patients. Conclusions The influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients., The effect of lymph node status on predicting prognosis differed significantly between left‐sided and right‐sided colon cancer patients. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.

Health Qigong Baduanjin is China’s traditional fitness method, which has taken this method as one of the methods to treat lumbar disc herniation in China. However, its effectiveness and safety in the treatment of lumbar disc herniation are still controversial, and this study will use a systematic evaluation method to resolve this controversy.

Hemiplegia is the most common dysfunction in stroke patients, especially the dysfunction of lower limb, which can obviously affect the life quality of patients, and how to improve balance and walking function has been the focus of research in the field of post-stroke rehabilitation. Mirror visual feedback therapy is currently used in the rehabilitation of upper limb in hemiplegia patients, and the study of the method for rehabilitation of lower limb in hemiplegia patients is less reported. In the absence of relevant authoritative guidelines and evidence-based medical evidence, it is very necessary to make a scientific and systematic evaluation of the effectiveness of mirror visual feedback therapy on the lower limb balance and motor function of stroke patients, so as to provide evidence to support the rehabilitation of mirror visual feedback therapy on lower limb balance and motor function in stroke patients.

Background The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. Methods Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. Results Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2 = 85.5%), specificity (I2 = 75.0%), PLR (I2 = 59.0%), NLR (I2 = 79.5%) and DOR (I2 = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). Conclusions Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

β-1,3-Glucan oligosaccharides produced by enzymatic hydrolysis of β-1,3-glucans are of great interest, because they possess biological functionalities such as regulating intestinal health, improving immunity and anti-tumor. A significant qualification for the industrial production of glucan oligosaccharides is β-1,3-glucanase with high catalytic ability. These enzymes are widely present in fungi, bacteria, plants and invertebrates, they are separated into glycoside hydrolase families 3, 5, 16, 17, 55, 64, 72, 81, 128 and 132. This report presents the research progress on the construction and expression of β-1,3-glucanases in Pichia pastoris and Escherichia coli from different microorganisms. Culture conditions and strategies to improve enzyme activity in these hosts are summarized. The application of β-1,3-glucanases in different β-1,3-glucans (curdlan, scleroglucan, laminarin, and schizophyllan) degradation and their hydrolysate analysis are reviewed. This review provides an important reference for further modification and utilization of microbial β-1,3-glucanases in large-scale production of multi-functional oligosaccharides.

Objective To evaluate the diagnostic efficacy of gastric juice-based genotypic methods for Helicobacter pylori detection and antibiotic resistance testing. Methods We used electronic databases including Medline, Embase, Web of Science and the Cochrane Central Register of Controlled Trial for literature survey using keywords such as "gastric juice", "Helicobacter pylori" and their synonyms. The quality of the studies was assessed using QUADAS-2. Summary performance measures (sensitivity, specificity, positive predictive values, negative predictive values, diagnostic odds ratio, and area under the summary receiver operating characteristic curve) and HSROC curves were produced. In addition, fagan plots were applied to illustrate the relationship among the prior test probability, PLR/NLR, and posterior test probability. Results Our study cohort comprised eight studies with 1235 participants (617 participants of H. pylori infection and 618 participants of non-H. pylori infection). Pooled sensitivity and specificity with a corresponding 95% confidence interval (CI) of gastric juice-based genotypic methods reflected values of 94% (95%CI, 86% - 98%) and 98% (95%CI, 85% - 100%), respectively. The global sensitivity and specificity of clarithromycin resistance were 92% (95%CI, 85% - 96%) and 90% (95%CI, 80% - 95%), respectively. Conclusion Gastric juice-based genotypic methods can be used for diagnostic prediction of H. pylori infection as well as clarithromycin resistance testing.

Retinitis pigmentosa (RP) is a heterogeneous group of retinal degenerative diseases in which the final pathological feature is photoreceptor cell apoptosis. Currently, the pathogenesis of RP remains poorly understood and therapeutics are ineffective. 17β-Oestradiol (βE2) is universally acknowledged as a neuroprotective factor in neurodegenerative diseases and has manifested neuroprotective effects in a light-induced retinal degeneration model. Recently, we identified N-myc downstream regulated gene 2 (NDRG2) suppression as a molecular marker of mouse retinal photoreceptor-specific cell death. βE2 has also been reported to regulate NDRG2 in salivary acinar cells. Therefore, in this study, we investigated whether βE2 plays a protective role in RP and regulates NDRG2 in photoreceptor cells. To this end, we generated RP models and observed that βE2 not only reduced the apoptosis of photoreceptor cells, but also restored the level of NDRG2 expression in RP models. Then, we showed that siNDRG2 inhibits the anti-apoptotic effect of βE2 on photoreceptor cells in a cellular RP model. Subsequently, we used a classic oestrogen receptor (ER) antagonist to attenuate the effects of βE2, suggesting that βE2 exerted its effects on RP models via the classic ERs. In addition, we performed a bioinformatics analysis, and the results indicated that the reported oestrogen response element (ERE) sequence is present in the promoter region of the mouse NDRG2 gene. Overall, our results suggest that βE2 attenuated the apoptosis of photoreceptor cells in RP models by maintaining NDRG2 expression via a classic ER-mediated mechanism.

Objective To compare non-pharmacological interventions in their ability to prevent delirium in critically ill patients, and find the optimal regimen for treatment. Methods Literature searches were conducted using PubMed, Embase, CINAHL, and Cochrane Library databases until the end of June 2019. We estimated the risk ratios (RRs) for the incidence of delirium and in-hospital mortality and found the mean difference (MD) for delirium duration and the length of ICU stay. The probabilities of interventions were ranked based on clinical outcomes. The study was registered on PROSPERO (CRD42020160757). Results Twenty-six eligible studies were included in the network meta-analysis. Studies were grouped into seven intervention types: physical environment intervention (PEI), sedation reducing (SR), family participation (FP), exercise program (EP), cerebral hemodynamics improving (CHI), multi-component studies (MLT) and usual care (UC). In term of reducing the incidence of delirium, the two most effective interventions were FP (risk ratio (RR) 0.19, 95% confidence interval (CI) 0.08 to 0.44; surface under the cumulative ranking curve (SUCRA) = 94%) and MLT (RR 0.43, 95% CI 0.30 to 0.57; SUCRA = 68%) compared with observation. Although all interventions demonstrated nonsignificant efficacy in regards to delirium duration and the length of the patient's stay in the ICU, MLT (SUCRA = 78.6% and 71.2%, respectively) was found to be the most effective intervention strategy. In addition, EP (SUCRA = 97.2%) facilitated a significant reduction in hospital mortality, followed in efficacy by MLT (SUCRA = 73.2%), CHI (SUCRA = 35.8%), PEI (SUCRA = 34.8%), and SR (SUCRA = 31.8%). Conclusions Multi-component strategies are overall the optimal intervention techniques for preventing delirium and reducing ICU length of stay in critically ill patients by way of utilizing several interventions simultaneously. Additionally, family participation as a method of patient-centered care resulted in better outcomes for reducing the incidence of delirium.

A simple and efficient protocol was developed for the preparation of challenging α-aryl primary amides. This metal-free coupling process was triggered by TfOH-promoted electrophilic activation of α-silyl nitrile to generate keteniminium ion species, followed by reaction with aryl sulfoxide through [3,3]-sigmatrophic rearrangement to provide the target product. To the best of our knowledge, α-silyl nitrile has been rarely used as a pro-electrophilic reagent. Computational investigations confirmed the transient existence of a highly electrophilic keteniminium intermediate.

DOI：10.3969/j.issn.1672⁃6731.2020.06.016

Introduction: Previous studies have found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was involved in the progression of pulmonary hypertension (PH), and TRAIL knocking (KO) has an inhibitory effect on PH, but its mechanism is not completely clear. Methods: The effects of TRAIL on the accumulation of extracelluar matrix (ECM), which is one of the most important processes of vascular remodeling, were observed in mice and isolated pulmonary artery smooth muscle cells (PASMCs). In vivo, mice were divided into four groups: Control group (n = 5), hypoxia-induced PH mice group (n = 8), anti-TRAIL antibody (TRAIL-Ab) treatment group (n = 8) and IgG antibody (IgG) group (n = 8). The effects of TRAIL-Ab on ECM expression in hypoxic induced PH were researched; in vivo, PASMCs were divided into three groups: Control group, hypoxia-induced group, TRAIL-Ab group. Expressions of p-Smad2/3 and p-Smad1/5/8 were compared among the three groups. Results: Hypoxia-induced PH mice had significant increases in right ventricle systolic pressure (RVSP) (P < 0.001), right ventricular hypertrophy (RVH) (P = 0.007), vascular stenosis (P < 0.001) compared with controls. Mice with anti-TRAIL antibody had lower levels in RVSP (P < 0.001), RVH (P < 0.001), vascular stenosis (P < 0.001) than PH mice. Besides, the TRAIL-Ab significantly inhibited the phosphorylation of Smad2/3 compared with hypoxia-induced group. Conclusion: TRAIL regulates the accumulation of ECM in pulmonary artery by activating pSmad2/3.

Background: Breast cancer is the most common malignancy, and approximately 70% of breast cancers are estrogen receptor-α (ERα) positive. The anti-estrogen tamoxifen is a highly effective and commonly used treatment for patients with ER+ breast cancer. However, 30% of breast cancer patients fail adjuvant tamoxifen therapy and most of metastatic breast cancer patients develop tamoxifen resistance. Although increasing evidence suggests that microRNA (miRNA) dysregulation influences tamoxifen sensitivity, the mechanism of the cross-talk between miRNA and ERα signaling remains unclear. miR-575 has been reported to be involved in carcinogenesis and progression, however, the role of miR-575 in breast cancer remains limited. The aim of this study was to understand the mechanism of miR-575 in breast cancer tamoxifen resistance. Method: RT-qPCR was employed to assess miR-575 expression in breast cancer tissues and cell lines. The association of miR-575 expression with overall survival in patients with breast cancer was evaluated with KM plotter. Additionally, the effects of miR-575 on breast cancer proliferation and tamoxifen sensitivity were investigated both in vitro and in vivo. Bioinformatic analyses and luciferase reporter assays were performed to validate CDKN1B and BRCA1 as direct targets of miR-31-5p. The ERα binding sites in the miR-575 promoter region was validated with ChIP and luciferase assays. ERα interactions with CDKN1B, cyclin D1 or BRCA1 were determined by IP analysis, and protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Results: miR-575 levels were higher in ER+ breast cancer than in ER- breast cancer and patients with high miR-575 expression had a significantly poorer outcome than those with low miR-575 expression. ERα bound the miR-575 promoter to activate its transcription, and tamoxifen treatment downregulated miR-575 expression in ER+ breast cancer. Overexpression of miR-575 decreased tamoxifen sensitivity by targeting CDKN1B and BRCA1. CDKN1B and BRCA1 were both able to antagonize ERα activity by inhibiting ERα nuclear translocation and interaction with cyclin D1. Furthermore, miR-575 expression was found to be upregulated in ER+ breast cancer cell with acquired tamoxifen resistance, whereas depletion of miR-575 partially re-sensitized these cells to tamoxifen by regulation of CDKN1B. Conclusions: Our data reveal the ERα-miR-575-CDKN1B feedback loop in ER+ breast cancer, suggesting that miR-575 can be used as a prognostic biomarker in patients with ER+ breast cancer, as well as a predictor or a promising target for tamoxifen sensitivity.

Profiling intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. High-fat foods (HFF) can alter the gut microbiota and its metabolites, posing a potential health risk. However, little is known about the effects of HFF on intestinal gas distribution. Therefore, in this study, we used human fecal microorganisms as strains, an

Background Transcription factor forkhead box M1 (FOXM1) is a crucial regulator in colorectal cancer (CRC) progression. However, the regulatory mechanisms causing dysregulation of FOXM1 in CRC remain unclear. Methods Dual-luciferase reporter assay was conducted to determine FOXM1 as miR-6868-5p target. The function of miR-6868-5p and FOXM1 in CRC angiogenesis was verified in vitro. Intratumoral injection model was constructed to explore the effect of miR-6868-5p on angiogenesis in vivo. Chromatin immunoprecipitation assays were used to assess direct binding of H3K27me3 to the miR-6868 promoter. Results Through integrated analysis, we identified miR-6868-5p as the potent regulator of FOXM1. Overexpression of miR-6868-5p in CRC cells inhibited the angiogenic properties of co-cultured endothelial cells, whereas silencing of miR-6868-5p had opposite effects. In vivo delivery of miR-6868-5p blocked tumor angiogenesis in nude mice, resulting in tumor growth inhibition. Rescue of FOXM1 reversed the effect of miR-6868-5p on tumor angiogenesis. Further mechanistic study revealed that FOXM1 promoted the production of IL-8, which was responsible for the miR-6868-5p/FOXM1 axis-regulated angiogenesis. Reciprocally, FOXM1 inhibited miR-6868-5p expression through EZH2-mediated H3K27me3 on miR-6868-5p promoter, thus forming a feedback circuit. Clinically, the level of miR-6868-5p was downregulated in CRC tissues and inversely correlated with microvessel density as well as levels of FOXM1 and IL-8 in tumor specimens. Conclusions Together, these data identify miR-6868-5p as a novel determinant of FOXM1 expression and establish a miR-6868-5p/FOXM1 regulatory circuit for CRC angiogenesis, providing potential target for CRC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0970-5) contains supplementary material, which is available to authorized users.

Parkinson's disease (PD) is a common neurodegenerative disease, and acupuncture has shown potential advantages in the treatment. By analyzing the experimental researches on acupuncture therapy of PD over the past 10 years, the authors find that acupuncture can play a therapeutic role by regulating multiple targets such as basal ganglia neurotransmitter disorder, oxidative stress, abnormal protein folding, immune inflammatory response, apoptosis, neural stem cells and calcium homeostasis. Although the mechanism of acupuncture in the treatment of PD is widely studied, there is still a lack of systematic, in-depth and high-quality research, and the mechanism of acupuncture therapy has not reached a consensus. In the future, the potential mechanisms including mitochondrial dysfunction and intestinal flora should be further studied.本文通过分析近10年针刺治疗帕金森疾病的实验研究，发现针刺可通过调节基底节神经递质紊乱、氧化应激、蛋白质异常折叠、免疫炎性反应、细胞凋亡、神经干细胞及钙稳态等多个靶点发挥治疗作用。针刺治疗帕金森病的机制研究广泛，且不断有新的研究方向(如肠道菌群)出现，但仍缺乏系统、深入及优质的研究。目前针刺治疗帕金森病的机制阐述尚未达成共识，未来应围绕线粒体功能障碍、肠道菌群等热点方向进一步研究其潜在机制。.

Limb hemiplegia is one of the common sequelae of stroke. Physical therapy-based rehabilitation training can rapidly improve limb functioning and muscle strength. This study investigated the effect of physical therapy on the recovery of upper limb motor function by employing a literature search and meta-analysis.We searched Embase, The Cochrane Central Register of Controlled Trials library, Wiley online library, PubMed, Ovid, and Clinicaltrials.org for randomized controlled trial (RCT) studies and performed an electronic search with the keyword combinations 'physical therapy/rehabilitation''stroke/post-stroke''upper extremity/upper limb'. After screening the literature for inclusion criteria and assessing the risk of bias, Revman 5.4 software was used for the analysis and to obtain forest and funnel plots.A total of 15 RCTs with 1,081 patients were included in the quantitative analysis for this study. The meta-analysis results showed that compared with conventional therapy, physical therapy improved the upper limb Fugl-Meyer Assessment for Upper Extremity (FMA) scores in convalescent stroke patients (MD =7.27, 95% CI: 4.23-10.32, Z=4.68, P0.00001), and increased the Functional Independence Measure (FIM) scores (MD =18.82, 95% CI: 6.34-31.30, Z=2.96, P=0.003), the Action Research Arm Test (ARAT) scores (MD =8.84, 95% CI: 6.53-11.15, Z=7.50, P0.00001), and the Box and Block Test (BBT) scores (MD =6.11, 95% CI: 1.18-11.04, Z=2.43, P=0.02) of patients during the rehabilitation period.The use of physical therapy-based rehabilitation training in the recovery period for stroke patients with hemiplegia can improve upper limb movement ability, increase muscle strength, reduce limb pain, and improve the quality of life.

Background:Rhodiola rosea L. has long been used as traditional medicines in Europe and Asia to treat a variety of common conditions and diseases including Alzheimer’s disease, cardiovascular disease, cognitive dysfunctions, cancer, and stroke. Previous studies reported that Rhodiola rosea L. and its components (RRC) improve ischemia stroke in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to evaluate the effects of RRC and the probable neuroprotective mechanisms in ischemic stroke.Methods: Studies of RRC on ischemic stroke animal models were searched in seven databases from inception to Oct 2021. The primary measured outcomes included the neural functional deficit score (NFS), infarct volume (IV), brain water content, cell viability, apoptotic cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, B-cell lymphoma-2 (Bcl-2) level and tumor necrosis factor-α (TNF-α) level. The secondary outcome measures were possible mechanisms of RRC for ischemic stroke. All the data were analyzed via RevMan version 5.3.Results: 15 studies involving 345 animals were identified. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The quality score of studies range from 1 to 7, and the median was 5.53. Pooled preclinical data showed that compared with the controls, RRC could improve NFS (Zea Longa (p < 0.01), modified neurological severity score (mNSS) (p < 0.01), rotarod tests (p < 0.01), IV (p < 0.01), as well as brain edema (p < 0.01). It also can increase cell viability (p < 0.01), Bcl-2 level (p < 0.01) and reduce TNF-α level (p < 0.01), TUNEL-positive cells (p < 0.01), apoptotic cells (p < 0.01).Conclusion: The findings suggested that RRC can improve ischemia stroke. The possible mechanisms of RRC are largely through antioxidant, anti-apoptosis activities, anti-inflammatory, repressing lipid peroxidation, antigliosis, and alleviating the pathological blood brain barrier damage.

According to studies at home and abroad, hypertension is an important disease that endangers human life and health. How to early warn the increase in blood pressure in time has become a hot research issue. To solve this problem, a long-short-term memory network (LSTM)-convolutional neural network (CNN) combined prediction model based on ensemble empirical mode decomposition is proposed. Firstly, the blood pressure data is decomposed into several intrinsic mode functions (IMF), and then LSTM and CNN are used to extract the time features and image features respectively, and predict the blood pressure change trend in the next time period. Finally, the prediction results of all IMF components are superimposed and combined to obtain the prediction results. The experiment uses root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and R2 to evaluate it, and this prediction method is combined with a single LSTM model, CNN model and LSTM-CNN combination model. Model comparison shows that our method has the smallest error and the highest prediction accuracy, which verifies the effectiveness and scalability of our model.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. In this article, we show that expression of abnormal spindle‐like microcephaly‐associated protein (ASPM) is up‐regulated in liver cancer samples, and this up‐regulation is significantly associated with tumor aggressiveness and reduced survival times of patients. Down‐regulation of ASPM expression inhibits the proliferation, invasion, migration and epithelial‐to‐mesenchymal transition of HCC cells in vitro and inhibits tumor formation in nude mice. ASPM interacts with disheveled‐2 (Dvl2) and antagonizes autophagy‐mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule‐associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β‐catenin signaling activation in HCC cells. Thus, our results define ASPM as a novel oncoprotein in HCC and indicate that disruption of the Wnt–ASPM–Dvl2–β‐catenin signaling axis might have potential clinical value., The abnormal spindle‐like microcephaly‐associated protein (ASPM) promotes hepatocellular carcinoma progression by activating Wnt/β‐catenin signaling. ASPM interacts with disheveled‐2 (Dvl2) and antagonizes autophagy‐mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule‐associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β‐catenin signaling activation in HCC cells.

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment., Graphical Abstract

Seven new guanacastane-type diterpenoids, namely dahlianes E-K (1–7), and three known ones (8–10) were isolated from the cultures of the fungus Verticillium dahliae. Their structures were established by extensive spectroscopic data analysis along with Rh2(OCOCF3)4- and Mo2(OAc)4-induced electronic circular dichroism (ECD) experiment. Dahliane G showed an 80-fold potentiation effect on the sensitization of doxorubicin at the concentration of 15 μM when screening the reversal activity on doxorubicin-resistant human breast cancer cells (MCF-7/DOX).

Seven undescribed phenylspirodrimane derivatives, stachybochartins A–G (1–7), and four known analogues (8–11) were isolated from the endophytic fungus Stachybotrys chartarum obtained from Pinellia ternata. Stachybochartins A–D are four rare C–C-coupled dimeric derivatives and stachybochartin G features a seco-bisabosqual skeleton. Their structures and configurations were elucidated via spectroscopic analysis, electronic circular dichroism (ECD) calculations, the ECD exciton chirality method and the modified Mosher's method. Stachybochartins A–D and G displayed cytotoxic activities against MDA-MB-231 breast cancer cells and U-2OS osteosarcoma cells, with IC50 values ranging from 4.5 to 21.7 μM. Stachybochartins C and G exerted strong anti-proliferative activities against U-2OS cells in concentration- and time-dependent manners and induced apoptosis.

Objective: To study the correlation of blood uric acid level with the degree of anxiety as well as the neurotransmitter and cytokine secretion in young and middle-aged patients with anxiety disorder. Methods: The young and middle-aged patients diagnosed with generalized anxiety disorder in our hospital between March 2015 and February 2018 were selected as the anxiety group, and the healthy subjects receiving physical examination during the same period were selected as the control group. Peripheral blood was collected to determine the contents of uric acid, neurotransmitters and cytokines, and Hamilton Anxiety Scale (HAMA) was adopted to judge the degree of anxiety. Results: The blood uric acid level of anxiety group was obviously higher than that of control group and the higher the HAMA scores, the more significant the rising of blood uric acid levels; serum 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), interleukin-1α (IL-1α), IL-17 and interferon-γ (IFN-γ) contents of anxiety group were significantly higher than those of control group whereas neuropeptide Y (NPY), IL-4 and transforming growth factor-β (TGF-β) contents were significantly lower than those of control group; blood uric acid level of the anxiety group was positively correlated with 5-HT, NE, DA, IL-1α, IL-17 and IFN-γ contents, and negatively correlated with NPY, IL-4 and TGF-β contents. Conclusion: The rise of blood uric acid level in young and middleaged patients with anxiety disorder is related to the aggravation of anxiety degree as well as the abnormal secretion of neurotransmitters and cytokines.

Turbulent agglomeration is a simple and economical method to improve the agglomeration of fine particles from coal combustion, which is beneficial to the particle removal efficiency of conventional equipment. However, the agglomeration efficiency for fine particles is low by single turbulent agglomeration because of the weak adhesion forces between particles, which leads to plenty of ineffective collisions. In this study, a novel technique was presented to improve the effect of fine particles agglomeration in turbulent agglomeration by adding chemical spray. The influence of single turbulent agglomeration and chemical-turbulent agglomeration on fine particle concentrations, particle size distributions, ESP performance, particle removal efficiencies in different stages and total dust concentrations after ESP were investigated respectively. The results showed the chemical-turbulent agglomeration had better effects on the agglomeration and removal of fine particles than single turbulent agglomeration. After chemical-turbulent agglomeration, the PM10 number concentration decreased about 34.1% than single turbulent agglomeration, and particle number concentration dropped at each stage under 10 µm, especially at 0.1 µm. Meanwhile, the application of chemical-turbulent agglomeration led to the number removal efficiency of PM10 increasing from 82.6% to 89.9%, the mass removal efficiency increasing from 84.5% to 91.8%, and the total dust concentrations after ESP reducing about 638 mg·m−3 than single turbulent agglomeration, respectively. Furthermore, the enhancement mechanism of chemical-turbulent agglomeration was explored by analyzing adhesion forces between particles and calculating the turbulent agglomeration kernel. In this study, the capillary and solid-bridge forces between particles and the increasing value of KTS after chemical spray were considered as the main reasons for better effects of chemical-turbulent agglomeration.

A nanoflower-like nickel foam supported Co3O4 (Co-NF) monolithic catalyst was synthesized via a green and facile electro-deposition strategy. The optimized Co-NF presents much higher catalytic activity per Co3O4 loading, ca. 6.7 × 10−4 mol/(gCo3O4·s) at 220 °C and exhibits a lower activation energy of 46 kJ/mol compared with powder Co3O4. It also exhibited good stability (e.g. >80% propane conversion) for 40 h at 350 °C and a GHSV of 30,000 mL/(gcat·h) without any notable decrease. The 3D hierarchical microstructures with interconnected pore channels, the high Co2+ content and the weak Co O bond strength of Co-NF-300 s were considered key factors responsible for the good activity and stability in the propane catalytic total oxidation.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target., Graphical abstract, Dysregulated alternative splicing is closely associated with oncological processes. Our study revealed that splicing factor PHF5A was associated with poor prognosis of CRC patients and promoted CRC progression by inducing aberrant splicing of TEAD2 to activate YAP signaling. Splicing modulators targeting PHF5A had potent antitumor activity.

RNA binding proteins (RBPs) have been proved to play pivotal roles in a variety types of tumors. However, there is no convincible evidence disclosing the functions of RBPs in thyroid cancer (THCA) thoroughly and systematically. Integrated analysis of the functional and prognostic effect of RBPs help better understanding tumorigenesis and development in thyroid and may provide a novel therapeutic method for THCA. In this study, we obtained a list of human RBPs from Gerstberger database, which covered 1,542 genes encoding RBPs. Gene expression data of THCA was downloaded from The Cancer Genome Atlas (TCGA, n = 567), from which we extracted 1,491 RBPs’ gene expression data. We analyzed differentially expressed RBPs using R package “limma”. Based on differentially expressed RBPs, we constructed protein-protein interaction network and the GO and KEGG pathway enrichment analyses were carried out. We found six RBPs (AZGP1, IGF2BP2, MEX3A, NUDT16, NUP153, USB1) independently associated with prognosis of patients with thyroid cancer according to univariate and multivariate Cox proportional hazards regression models. The survival analysis and risk score analysis achieved good performances from this six-gene prognostic model. Nomogram was constructed to guide clinical decision in practice. Finally, biological experiments disclosed that NUP153 and USB1 can significantly impact cancer cell proliferation and migration. In conclusion, our research provided a new insight of thyroid tumorigenesis and development based on analyses of RBPs. More importantly, the six-gene model may play an important role in clinical practice in the future.

Additional file 1: Figure S1. ROC curve analysis used to determine the cutoff value of pretreatment EBV DNA levels.

HDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg

Curcumin (CUR) is a low-solubility polyphenolic compound with many physiological functions. Cyclic β-1,2-glucans (cyclosophoraoses [Cys]), which contain rings of different sizes with degrees of polymerization ranging from 17 to 23, were obtained from Rhizobium radiobacter ATCC 1333, a soil microorganism. The complexation ability and solubility enhancement of cyclic β-1,2-glucans with insoluble curcumin were investigated. Phase-solubility analysis revealed that the stoichiometric ratio of the inclusion complexes was 1:1. The stability constant of Cys was 930 M