Neurotoxicity study of ethyl acetate extract of Zanthoxylum armatum DC. on SH-SY5Y based on ROS mediated mitochondrial apoptosis pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum armatum DC. (ZADC) is a traditional medicinal plant with various pharmacological activities and is widely used in China, Japan, India, and other regions. Previous studies have revealed that the methanol extract of ZADC can cause neurotoxicity symptoms in rats, such as drooling, decreased appetite, decreased movement, and increased respiratory rate. However, the basis of these toxic substances and the mechanism of neurotoxicity remain unclear. AIM OF THE STUDY: To evaluate the effects of ZADC on nerve cells and their damage mechanisms and discuss the possible toxic substance basis. MATERIALS AND METHODS: The ethyl acetate extract of ZADC is obtained by extracting the methanol extract of ZADC with ethyl acetate. The Q-Orbitrap LC-MS/MS method was employed to analyze the chemical composition of the EA extract of ZADC. SH-SY5Y cells were incubated with different concentrations of the ethyl acetate extract of ZADC. The cytotoxicity of the extract was evaluated using CCK-8, LDH, and ROS assays, and the oxidative stress status of cells was assessed using MDA, GSH, and SOD. Cell apoptosis was detected using flow cytometry. Damage to mitochondrial function was evaluated by labeling mitochondria, ATP, and MMP with fluorescence. Cyto-C, Caspase-3, Caspase-9, Apaf-1, Bax, and reduced Bcl2 expression were measured to evaluate the activation of the mitochondrial apoptosis pathway. Finally, NAC intervention was used to detect changes in the relevant indicators. The activation of mitochondrial apoptosis pathway was evaluated by measuring Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and Bcl2 expression. Finally, NAC intervention was utilized to detect changes in the relevant indicators. RESULTS: After treating SY-SY5Y cells with EA extract from ZADC, cell viability decreased significantly, and the intracellular ROS level increased in a dose-dependent manner. Meanwhile, ZADC can cause cellular oxidative stress and increase MDA and SOD concentrations while decreasing GSH concentrations. It can also shorten the mitochondrial cristae and decrease the number of mitochondria. In contrast, it can reduce ATP synthesis in the mitochondria and mitochondrial membrane potential (MMP). Furthermore, it increased the apoptosis rate and the expression of Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and reduced Bcl2 expression. NAC intervention alleviated the reduction in SH-SY5Y cell survival and the accumulation of reactive oxygen species induced by the EA extract in ZADC. It also inhibits signaling pathways dominated by proteins, such as Cyto-C, reducing cell apoptosis and cytotoxicity. A total of 46 compounds were identified in the extracts. CONCLUSIONS: The results suggest that EA extract of ZADC can induce the mitochondrial apoptotic pathway by accumulating ROS in cells, leading to apoptosis. Antioxidants had a good inhibitory and protective effect against cell damage caused by the EA extract of ZADC. The neurotoxic components of ZADC may be organic acids and compounds containing amino groups.

Progress of immunotherapy strategies for uveal melanoma / 肿瘤研究与临床

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recently, great progresses have been made in the diagnosis, treatment and prognosis of UM, however, nearly 50% of patients still develop liver metastases, which severely affects on the survival of UM patients. Whether UM patients will benefit from the immune checkpoint blockade similarly as the cutaneous melanoma (CM)? Whether the specific gene mutations targeting UM could improve the anti-tumor efficacy? Whether chimeric antigen receptor T cell or T cell receptor T cell immunotherapy is effective to UM patients with liver metastases? How about the combinational therapies in UM and the clinical effects? This review summarizes the anti-tumor research and novel treatment options of UM, analyzes the current achievements and problems.

Research hotspots and frontiers of hospital scientific research management based on CiteSpace: a visualization analysis / 中华医学科研管理杂志

Objective:To analyze the research hotspots and frontiers of hospital research management research from 1981 to 2022.Methods:The relevant literature in the field of hospital scientific research management was retrieved from the CNKI database to explore the trends of publications in this research field. A scientific knowledge graph was drawn and a visualization analysis of the information of authors, issuing units, and research institutions were conducted by Cite Space.5.8.R3.Research hotspots were discussed based on keyword emergence, cluster analysis, and keyword time zone graph.Results:The publication trend in this field was generally policy-oriented, but the cooperation among authors and institutions was relatively loose, and the research hotspots were gradually shifting from scientific research funding management to discipline construction, talent training, translational medicine, and informatization. Cluster analysis found that the main content of hospital scientific research management was scientific research funding and clinical scientific research management and the main management objects were the medical and nursing staff.Conclusions:Hospital scientific research managers must adhere to the policy-oriented approach, strengthen the cooperation and exchanges in scientific research management, innovate the scientific research management mode around the research hotspots and development trends, and promote the quality and efficiency of scientific research management.

Analysis of RS1 gene variant in a Chinese pedigree affected with X-linked congenital retinal splitters / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with X-linked retinoschisis.@*METHODS@#Clinical data of the pedigree was collected. Following DNA extraction, PCR and Sanger sequencing were carried out to detect potential variant in the RS1 gene. The result was verified by using PCR and restriction fragment length polymorphism assay.@*RESULTS@#All male patients were found to harbor a c.458T>G (p.Val153Gly) variant of the RS1 gene, for which Their mothers were heterozygous carriers. The same variant was not detected among unaffected members of the pedigree as well as 100 healthy controls. Bioinformatic analysis suggested the variant to be pathogenic.@*CONCLUSION@#The c.458T>G (p.Val153Gly) variant of the RS1 gene probably underlay the X-linked retinoschisis in this pedigree.

Goals-activity-motor enrichment can improve the motor functioning of infants with a mild to moderate developmental disorder / 中华物理医学与康复杂志

Objective:To explore the effect of goals-activity-motor enrichment (GAME) intervention on the motor function of infants with a mild or moderate developmental disorder.Methods:Randomized, single-blind, controlled trials were applied. Totally 108 infants with mild-to-moderate developmental delay, aged 0 to 12 months, were randomly divided into an observation group and a control group, each of 54. Both groups were further divided into two subgroups, a less-than-6-month-old subgroup and a not-less-than-6-month-old subgroup. All of the children received 30 minutes of routine rehabilitation training five days a week and a 60-minute family intervention every day. In addition, the control group was given traditional neuro-developmental treatment (NDT) while the observation group was provided with an intervention based on the GAME program. Before and after 8 weeks of treatment, both groups were evaluated using the Alberta infant motor scale (AMIS).Results:After the intervention, both groups′ average total scores and average scores in the different positions were significantly better than before the intervention. The average AIMS scores of the observation group supine, prone and seated, as well as their average total score were significantly higher than those of the control group after the intervention. There were no significant differences in the AIMS score increases in the different positions between the two subgroups. However, the increase in average total AIMS score of the less-than-6-month-old subgroup was significantly greater than that of the older subgroup.Conclusion:The GAME protocol can improve the motor function of infants with mild to moderate developmental disorders more effectively than a traditional NDT program. The effect is greater with younger infants.

Preoperative short-course radiotherapy (5 × 5 Gy) with delayed surgery versus preoperative long-course radiotherapy for locally resectable rectal cancer: a meta-analysis.

PURPOSE: Preoperative short-course radiotherapy (PSRT) and preoperative long-course radiotherapy (PLRT) are standard treatment regimens for locally advanced rectal cancer. However, whether the efficacy and safety of PSRT with delayed surgery (more than 4 weeks) are superior to those of PLRT remains unresolved and was explored in this meta-analysis. METHODS: Studies published in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were systematically searched. RevMan 5.3 was used to calculate pooled hazard ratios (HR) and relative risk (RR). RESULTS: Seven studies including 4973 patients were identified in the meta-analysis. Pooled statistics showed that there was no statistically significant difference in overall survival (HR = 1.30, 95% CI 0.58-2.89, P = 0.52) or disease-free survival (HR = 1.10, 95% CI 0.73-1.66, P = 0.64) between the preoperative short-course and long-course radiotherapy groups. Moreover, pathological complete remission, early postoperative complications, treatment-related grade 3/4 toxicity, local recurrence, and distant metastasis were similar between the two groups. Interestingly, a subgroup analysis revealed that preoperative short-course radiotherapy without adjuvant chemotherapy not only resulted in lower treatment-related grade 3/4 toxicity than the long-course radiotherapy group (RR = 0.19, 95% CI 0.08-0.48, P < 0.01) but also resulted in significantly lower overall survival and pathological complete remission (P = 0.02, P < 0.01, respectively). Disappointingly, pooled statistics observed few advantages over long-course radiotherapy in short-course radiotherapy with the adjuvant chemotherapy subgroup. CONCLUSIONS: PSRT with delayed surgery was as effective as PLRT for the management of locally resectable rectal cancer. However, not adding additional chemotherapy to PSRT not only significantly decreased grade 3/4 toxicity but also decreased pathological complete remission and overall survival. TRIAL REGISTRATION: The protocol for this meta-analysis was prospectively registered with PROSPERO (CRD42019133641).

Drooling in cerebral palsy and its relationship with dysphagia and gross motor functioning / 中华物理医学与康复杂志

Objective To analyze the incidence and severity of drooling in children with cerebral palsy and explore its correlation with oral dyskinesia,dysphagia and gross motor function.Methods A hundred children with cerebral palsy treated in Qingdao Women's and Children's Hospital between July 2013 and 2016 and 50 healthy children examined in the health examination center were assessed using the drooling severity scale,oral motor assessment,a dysphagia disorders survey (DDS) and the gross motor function classification system (GMFCS).The relationship between drooling severity,oral dyskinesia,dysphagia and their gross motor function was analyzed.Results Of the 100 children with cerebral palsy,32％ displayed drooling (at levels Ⅱ through Ⅴ),which was significantly higher than among the healthy controls.Another sixty-eight displayed level Ⅰ drooling.The severity of drooling was significantly different among children with different cerebral palsies.The drooling of children with spastic quadriplegia,dyskinesia or mixed-type cerebral palsy was the most severe,followed by those with ataxia and spastic diplegia whose drooling was often mild.No hemiplegic child drooled at level Ⅱ.Drooling severity was negatively correlated with the oral motor score,but positively correlated with the average DDS and GMFCS scores.Conclusions About one third of cerebral palsy children suffer from drooling.Their drooling severity is closely associated with the type of the cerebral palsy,oral dyskinesia,dysphagia and GMFCS levels.

[Clinical significance of CD44 and CD133 expression in oral potentially malignant disorder and oral squamous cell carcinoma].

OBJECTIVE: This study aims to investigate the expression and relationship of CD44 and CD133 in normal oral mucosa, oral potentially malignant disorder (OPMD), and oral squamous cell carcinoma (OSCC). This work also analyzes the relationship between such expression and clinical factors. This study intends to evaluate the clinical value of using CD44 and CD133 as indices to evaluate the carcinogenic potential of OPMD. METHODS: Clinical data from 60 patients with OPMD, 60 patients with OSCC, and 10 cases of normal oral mucosa were analyzed. Double immunohistochemical analysis was applied to investigate the expression of CD44 and CD133 in paraffin sections of normal oral mucosa, OPMD, and OSCC tissues. Subsequently, the relationships between such expression and clinical factors were analyzed. RESULTS: The positive rates of CD44 expression in the normal oral mucosa, OPMD, and OSCC tissues were 100.00%, 96.67%, and 71.67% (P<0.05), respectively. Meanwhile, the positive rates of CD133 expression in the normal oral mucosa, OPMD, and OSCC tissues were 0.00%, 35.00%, and 63.33% (P<0.05), respectively. The expression of CD44 and CD133 was found to be correlated (P<0.05). Such expression was related to the clinical stages and lymphatic metastasis of OSCC (P<0.05). CONCLUSIONS: CD44 and CD133 can be used individually as clinical indices to evaluate the carcinogenic potential of OPMD.
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Effects of environmental enrichment on learning and memory ability, and the expression of brain-derived neurotrophic factor and synaptophysin in hippocampus of neonatal rats with hypoxic-ischemic brain damage / 中华实用儿科临床杂志

Objective To explore the effects of environmental enrichment (EE) on learning and memory ability and the expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods Forty Wistar neonatal male rats aged 7 days were randomly divided into EE intervention for 6 hours(6 h EE) group (n =10),EE intervention for 12 hours (12 h EE) group (n =10),model group (n =10) and sham group (n =10).The first 3 groups were performed with HIBD.The 6 h EE and 12 h EE group received EE stimuli for 6 h and 12 h respectively,once a day for 14 days.Learning and memory of the rats were tested by using Morris water maze.The expression levels of BDNF and synaptophysin in hippocampus were determined with Western blot.Results The escape latency of all groups gradually reduced with the increase of training days,but there was no significant difference in the escape latency among the 4 groups (F =0.237,P ＞ 0.05).The rats in the 6 h EE group,12 h EE group and model group spent less time in the target quadrant and showed a significant reduction of BDNF and synaptophysin(6 h EE group:0.529 ± 0.038,0.889 ± 0.027;12 h EE group:0.660 ± 0.034,1.114 ± 0.037;model group:0.225 ± 0.015,0.672 ± 0.057) in the hippocampus compared with the sham group (0.803 ± 0.026,1.347 ± 0.092) (all P ＜ 0.01).In the 6 h EE group and 12 h EE group,the rats significantly increased the time spent in target quadrant and aggrandized the expression of BDNF and synaptophysin in hippocampus compared with the model group.Moreover,the 12 h EE group had a better performance than the 6 h EE group in the space exploration and the expression of BDNF and synaptophysin.Conclusion EE is helpful for improving learning and memory ability in neonatal rats with HIBD,which may be associated with up-regulating the expression of BDNF and synaptophysin in hippocampus.

Effect of Acupuncture Combined with Low Frequency Electrical Stimulation on Cerebral Palsy Salivation / 中国康复理论与实践

Objective To explore the effect of oral sensorimotor therapy (OSMT), acupuncture, and low frequency electrical stimulation on salivation in patients with cerebral palsy. Methods From September, 2014 to October, 2015, 80 cerebral palsy patients with salivation were recruited. They were randomly divided into four treatment groups:group A was treated with OSMT, group B was treated with acupunc-ture, group C was treated with frequency electrical stimulation, and group D was treated with acupuncture and low frequency electrical stim-ulation, for eight weeks. Meanwhile, 20 cerebral palsy patients with salivation from outpatients were chosen as control group. Results There was no improvement in the root mean square (RMS) value of surface electromyography (sEMG) after treatment in both the control group and group A (t0.05), and the RMS value significantly improved in the groups B, C and D (t>8.983, P0.05), and they was better in the groups B, C and D than in the control group and group A (W>226.0, t>8.534, P306.0, t>3.663, P<0.05). Conclusion Acupuncture and low frequency electrical stimulation could effectively improve salivation in children with cerebral palsy, and their combination was superior to either ones, while OSMT did not show obvious benefit.

Effect of Electromyographic Biofeedback on Pointed Foot in Children with Spastic Cerebral Palsy / 中国康复理论与实践

Objective To explore the clinical curative effect of electromyographic biofeedback on pointed foot in children with spastic cerebral palsy. Methods From June, 2014 to December, 2015, 80 children with spastic cerebral palsy and pointed foot were divided into con-ventional group (n=40) and electromyographic biofeedback group (n=40). The conventional group received exercise and massage, while the electromyographic biofeedback group received electromyographic biofeedback in addition. The passive range of motion (PROM) of ankle, the surface electromyographic results and the selective control results were compared before and eight weeks after treatment. Results After treatment, the PROM significantly decreased in both groups (t>9.142, P3.456, Z>3.178, P3.737, Z=-2.748, P<0.01). Conclusion Electromyographic biofeedback can further improve the foot dor-sal flexure and pointed foot gait of spastic cerebral palsy children.

Effect of Phosphorylation Cyclic Adenosine Monophosphate Response Element Binding Protein on Expression of Apoptotic Regulated Genes in Hippocampus after Status Convulsivus / 中国康复理论与实践

Objective To explore the effect of the exogenous phosphorylation cyclic adenosine monophosphate response element bind-ing protein (pCREB) antibody on the expression of apoptotic regulated genes (Bcl-2 and c-Jun) in hippocampus after status convulsivus (SC), to elucidate the role and regulation mechanism of pCREB in convulsive brain injury. Methods Seizures were induced in 24 adult Wi-star rats with lithium-pilocarpine intraperitoneal injection (SC group), another 24 rats were as the normal controls (NC group). Each group was divided into no injection subgroup, normal saline injection subgroup and anti pCREB subgroup according to the injection contents of lat-eral ventricle, with 8 cases in each group. They were sacrificed 6 hours after injection. Both the protein and mRNA expression of Bcl-2 and c-Jun in bilateral hippocampus were detected by immunohistochemistry and in situ hybridization, respectively. Results There was no signifi-cant difference in Bcl-2 protein/mRNA expression among 3 subgroups in the NC group (P>0.05). In the SC group, the expression of Bcl-2 protein/mRNA were lower in the anti pCREB subgroup than in the no injection subgroup and normal saline injection subgroup (P<0.05). There was significant difference in c-Jun protein/mRNA expression among 3 subgroups in both NC group and SC group (P<0.001). The ex-pression of c-Jun protein/mRNA was higher in the normal saline injection subgroup and the anti pCREB subgroup than in the no injection group (P<0.05), especially in the anti pCREB subgroup (P<0.05). Conclusion Exogenous anti-pCREB antibody can down-regulate the ex-pression of Bcl-2 and up-regulate the expression of c-Jun in hippocampal cells after SC.

Progress in establishment and application of feline calicivirus reverse genetics operating system / 病毒学报

Feline calicivirus (FCV) is an important and highly prevalent pathogen of cats that causes feline respiratory disease. The reverse genetic systems for FCV have been established in national and international laboratories since 1995. This technique has been used widely in FCV basic research and good progress has consequently been made to determine the relationship between viral genome structures and the function of their proteins, the expression of foreign proteins, virus-host interactions, and viral pathogenic mechanisms. In this article,we review the state of progress with regards to the establishment and application of the FCV reverse genetic operating system,which will provide a useful reference tool for future related research.

Assessment Report of Methodological Quality of Systematic Literature Reviews onTong-Xin-Luo’s Efifcacy and Safety Using the AMSTAR Statement / 世界科学技术-中医药现代化

This study was aimed to assess the methodological quality of systematic literature reviews on the efficacy and safety ofTong-Xin-Luo(TXL) using the AMSTAR statement. The literatures were searched from major domestic and international databases include the CJFD Database, VIP Database, CNKI database, CBM Database Online, WanFang Data and TCM Database, Medline, Pubmed, ISI Web of knowledge, Web of science, from the database was built to 20th December, 2014. And 5 evaluators screened the literatures independently according to the inclusion and exclusion criteria. Then, all systematic reviews were assessed using the list of AMSTAR statement. The results showed that 22 literatures were finally included, which contained 17 systematic reviews and 5 meta-analysis. In the included literatures, there were different degrees of impairments on the methodological and reporting quality, which were mainly focused on program and registration, retrieving and collecting literatures, inclusion and exclusion criteria, authentic assessment, data processing, funds, and etc. The average reporting rate of AMSTAR statement was 57.02% in all included literatures. It was concluded that the methodological quality of systematic literature reviews on the efficacy and safety of TXL was relatively low from the current level of average reported rate, which affected the quality of the article. It indicated that there were different degrees of impairments in all links of test reports in current systematic reviews, which will be bound to affect the reliability of clinical evidence and the determination of clinical decision. It showed that the methodological quality of writing of such articles should be in compliance with entries of AMSTAR statement to improve its quality.

Systematic Review on Vertigo Treatment with Tian-Ma Gou-Teng Decoction and Its Modifications / 世界科学技术-中医药现代化

This study was aimed to make a systematic and comprehensive evaluation on clinical efficacy and safety of vertigo treatment with Tian-Ma Gou-Teng (TMGT) Decoction. Articles had been searched in the Chinese Journal Full-text Database, Chongqing VIP Chinese Scientific Journals Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database Online, Wanfang Data and Chinese Medicine Journal Literature Database for randomized controlled trials (RCT) on vertigo treatment with TMGT Decoction. The data retrieval time was from the establishment time of the database until present. Two investigators screened literatures, extracted data and assessed quality according to inclusion and exclusion criteria independently. RevMan5.0.2 was used in the meta-analysis. The results showed that a total of 33 trials were involved, which covered 2922 vertigo cases. The meta-analysis showed that from the aspect of clinical effectiveness, the comparison between Chinese medicine treatment group and modern medicine treatment group (OR = 3.67, 95% CI [2.66~5.07]), comparison between integrative medicine treatment group and modern medicine treatment group (OR = 3.28, 95% CI [2.33~4.62]), the comparison between Chinese medicine combined with other method (such as acupuncture, Tuina) treatment group and other Chinese medicine treatment group (OR = 2.29, 95% CI [1.34~3.91]), therapeutic effect in the experimental group was better than the control group. For the aspect of relapse rate, TMGT Decoction in the treatment of vertigo was better than the control group (OR = 0.27, 95% CI [0.12~0.65]). In the aspect of adverse reactions, TMGT Decoction in the treatment of vertigo was better than the control group (OR = 0.40, 95% CI [0.13~1.24]). For aspects of other indicators such as quality of life, no further analysis was conducted since there was no complete reported literature. It was concluded that the system evaluation results showed that compared with other methods, TMGT Decoction has better clinical efficacy and low recurrence rate, but safety needs to be further eualuated. However, due to the quality of included studies was not high, current evidences cannot be determined to be fully applicable in the clinical practice. But its efficacy advantages are worthy of further research. It especially requires high quality multi-center, large sample, double-blind, RCTs to verify.

Myeloid-derived suppressor cells and tumor immune escape / 中国肿瘤生物治疗杂志

Myeloid-derived suppressor cells(MDSCs) are heterogeneous cells derived from myeloid progenitor cells and immature myeloid cells(IMCs) in bone marrow;they are the progenitors of dendritic cells(DCs),macrophages and granulocytes.MDSCs proliferate in the blood,spleen,and tumor tissues in tumor-bearing mice and in the peripheral blood and tumor tissues in patients with cancer.MDSCs prevent tumors from attacks by body immunosurveillance and promote tumors progression through inhibiting both innate and adaptive antitumor immunity by a variety of pathways;they are recruited to the peripheral tissues from bone marrow and exert their inhibitory effects on antitumor immunity after activation in peripheral tissues.Chronic inflammation-related cytokines produced by tumors play crucial roles in the recruitment and activation of MDSCs.Progress has been made in antitumor therapies targeting MDSCs.But it has only been 10 years since the discovery of MDSCs,and many questions remain to be answered through experimental and clinical investigations.This review focuses on progress in MDSCs and its subsets,the recruitment and activation of MDSCs,the mechanisms of MDSCs-mediated immunosurveillance and antitumor treatment targeting MDSCs.