Paediatric atypical teratoid/rhabdoid tumour of the pineal region mimicking a meningioma: a case report and literature review.

PURPOSE: Atypical teratoid/rhabdoid tumour (AT/RT) is a highly malignant central nervous system tumour of early childhood. According to the latest WHO classification, the diagnosis of AT/RTs needs to be confirmed by the absence of SMARCB1 (INI1) or SMARCA4 (BRG1) protein expression. AT/RT in the pineal region is infrequent and most have not been proven genetically. Here, we report a case of AT/RT in the pineal region, preoperatively misdiagnosed as a meningioma. Immunohistochemistry revealed the absence of INI1 protein expression. METHOD: A 29-month-old boy was admitted to the hospital after 14 days of emotional apathy and a 2-day vomiting history. AT/RT was not considered during the initial diagnosis because this tumour is rare in this region and is often accompanied by cystic degeneration and necrosis on imaging. Subsequently, the patient underwent surgery and the tumour was completely excised. RESULT: The pathological diagnosis was AT/RT. After discharge, the patient continued chemotherapy in other hospitals but died five months after surgery because of disease progression. CONCLUSION: To our knowledge, this is the fifth case of paediatric pineal AT/RT confirmed genetically. Although in children AT/RT in the pineal gland is rare, a differential diagnosis of AT/RT should be considered when new pineal masses appear in children. For this highly malignant disease with poor prognosis, it is very important to detect and recognize the disease as soon as possible, and to adopt surgery plus multiple treatment management.

Effects of combined acupuncture and medication on hyperarousal state and serum copeptin in patients with chronic insomnia / 针灸推拿医学（英文版）

Objective:To observe the effect of combined acupuncture and medication on hyperarousal state and serum copeptin(CPT)in patients with chronic insomnia(CI),and to explore its possible mechanism of action.Methods:A total of 70 CI patients meeting the inclusion criteria were divided into an observation group and a control group by the random number table method,with 35 cases in each group.The control group was given estazolam tablets before bedtime,1 mg/time,once a day.The observation group was treated with additional Yi Nao An Shen acupuncture therapy(acupuncture for benefiting the brain and tranquillization)on the basis of the medication treatment,4 times a week.After 4 weeks of treatment,the Pittsburgh sleep quality index(PSQI)score,insomnia severity index(ISI)score,pre-sleep arousal scale(PSAS)score,hyperarousal scale(HAS)score,and the change in serum CPT level were compared between the two groups.Results:During the study,there were 2 dropout cases in the observation group and 1 dropout case in the control group.After treatment,the PSQI,ISI,PSAS,and HAS scores and the serum CPT level in both groups decreased compared with the same group before treatment,and the intra-group differences were statistically significant(P<0.05).After treatment,changes in each above scale score and the serum CPT level in the observation group were much more significant and were statistically different from those in the control group(P<0.05).Conclusion:Acupuncture plus medication can improve sleep quality,reduce the degree of insomnia,and regulate hyperarousal state in patients with CI,and its mechanism of action may be related to the down-regulation of serum CPT level.

Role of activation of VGLUT2 neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice / 中华麻醉学杂志

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

Danggui Sinitang Mitigates Gouty Arthritis in Rats by Regulating Autophagy via PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of Danggui Sinitang in mitigating gouty arthritis （GA） in rats by regulating autophagy via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodSixty male SD rats were randomly assigned into normal， model， colchicine （0.3 mg·kg-1）， and low-， medium-， and high-dose Danggui Sinitang （6.54， 13.08， and 26.16 g·kg-1） groups （n=10） and administrated with corresponding drugs by gavage. The rats in the normal group and model group were administrated with equal volume of normal saline by gavage for 7 days. One hour after administration on day 5， the GA model was established by injecting sodium urate suspension （50 g·L-1） into the right ankle joint of rats in other groups except the normal group， and the rats in the normal group were injected with sterile normal saline of the same volume. The swelling and pathological changes of the ankle joint were observed. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β were determined. Western blot was employed to determine the protein levels of PI3K， phosphorylated PI3K （p-PI3K）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， mTOR， phosphorylated mTOR （p-mTOR）， microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3Ⅱ/Ⅰ）， autophagy effector Beclin-1， and ubiquitin-binding protein p62 in the synovial tissue. Real-time fluorescent quantitative PCR （Real-time PCR） was employed to determine the mRNA levels of PI3K， Akt， mTOR， LC3， Beclin-1 and p62. ResultCompared with the normal control， the model group showed increased joint swelling index （P<0.01）， elevated serum levels of TNF-α， IL-6， and IL-1β， inflammatory cell infiltration， and fibrous tissue hyperplasia. In addition， the model group showed up-regulated protein levels of PI3K， p-PI3K， Akt， p-Akt， mTOR， p-mTOR， and p62 and mRNA levels of PI3K， Akt， mTOR， and p62 in the synovial tissue， while it showed down-regulated protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and mRNA levels of LC3 and Beclin-1 （P<0.01）. Compared with the model group， medium- and high-dose Danggui Sinitang alleviated the joint swelling （P<0.01）， lowered the serum levels of TNF-α， IL-6， and IL-1β （P<0.05）， and relieved the inflammatory cell infiltration in the synovial tissue of the ankle joint and the fibrous tissue hyperplasia. Moreover， they down-regulated the protein levels of PI3K， p-PI3K， Akt， p-Akt， mTOR， p-mTOR， and p62 and the mRNA levels of PI3K， Akt， mTOR， and p62 in the synovial tissue （P<0.05）， while they up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and the mRNA levels of LC3 and Beclin-1 （P<0.05）. ConclusionDanggui Sinitang， especially at a high dose， can inhibit PI3K/Akt/mTOR signaling pathway to improve autophagy in the synovial tissue， thereby mitigating GA.

Research progress on the self-injury behavior in children with autism spectrum disorder / 中华实用儿科临床杂志

Self-injury behavior (SIB) is a common problem behavior of children with autism spectrum disorder (ASD), which is characterized by a series of harmful reactions made by themselves causing tissue and physical damages.It seriously affects the physical and mental health in children.An early identification of SIB in children with ASD is helpful to relieve symptoms and improve the prognosis.Aiming to enrich the understanding of SIB in children with ASD and to promote early detection and intervention, this article reviews and summarizes the research on clinical characteristics, influencing factors, evaluation, detection and intervention methods of SIB in children with ASD in recent years.

Atlas-scale single-cell multi-sample multi-condition data integration using scMerge2

The recent emergence of multi-sample multi-condition single-cell multi-cohort studies allow researchers to investigate different cell states. The effective integration of multiple large-cohort studies promises biological insights into cells under different conditions that individual studies cannot provide. Here, we present scMerge2, a scalable algorithm that allows data integration of atlas-scale multi-sample multi-condition single-cell studies. We have generalised scMerge2 to enable the merging of millions of cells from single-cell studies generated by various single-cell technologies. Using a large COVID-19 data collection with over five million cells from 1000+ individuals, we demonstrate that scMerge2 enables multi-sample multi-condition scRNA-seq data integration from multiple cohorts and reveals signatures derived from cell-type expression that are more accurate in discriminating disease progression. Further, we demonstrate that scMerge2 can remove dataset variability in CyTOF, imaging mass cytometry and CITE-seq experiments, demonstrating its applicability to a broad spectrum of single-cell profiling technologies.

Covidscope: An atlas-scale COVID-19 resource for single-cell meta analysis at sample and cell levels

Recent advancements in the use of single-cell technologies in large cohort studies enable the investigation of cellular response and mechanisms associated with disease outcome, including COVID-19. Several efforts have been made using single-cell RNA-sequencing to better understand the immune response to COVID-19 virus infection. Nonetheless, it is often difficult to compare or integrate data from multiple data sets due to challenges in data normalisation, metadata harmonisation, and having a common interface to quickly query and access this vast amount of data. Here we present Covidscope (http://covidsc.d24h.hk/), a well-curated open web resource that currently contains single-cell gene expression data and associated metadata of almost 5 million blood and immune cells extracted from almost 1,000 COVID-19 patients across 20 studies around the world. Our collection contains the integrated data with harmonised metadata and multi-level cell type annotations. By combining NoSQL and optimised index, our Covidscope achieves rapid subsetting of high-dimensional gene expression data based on both data set level, donor-level (e.g., age and sex of patients) and cell-level (e.g., expression of specific gene markers) metadata, enabling multiple efficient downstream single-cell meta-analysis.

Research progress of autism spectrum disorder comorbid with obsessive compulsive disorder / 中华实用儿科临床杂志

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, restricted and repetitive behaviors, interests and activities, and abnormal perception.Obsessive compulsive disorder (OCD) is one of the common comorbid mental diseases of ASD.Accurate identification of the obsessive-compulsive symptoms and OCD comorbidity of ASD and early intervention are essential for the prognosis of patients.However, there are few domestic studies on comorbid OCD in ASD.Based on previous studies abroad, the progress of research on the epidemiology, etiology and neural mechanism, clinical characteristics, evaluation, diagnosis, intervention and treatment of comorbid OCD in ASD was reviewed in this paper.It aims to identify the manifestations of OCD in ASD patients in the early stage and improve the prognosis of patients.

Relationship between thalamocortical glutamate and neuronal activity in mice with sleep disorders induced by neuropathic pain / 中华麻醉学杂志

Objective:To evaluate the relationship between thalamocortical glutamate and neuronal activity in mice with neuropathic pain-induced sleep disorders.Methods:SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 15-25 g, were divided into 2 groups ( n=14 each) using a random number table method: sham operation group (Sham group) and neuropathic pain group (CCI group). Neuropathic pain was induced by chronic constrictive injury (CCI). The animals were anesthetized with intraperitoneal 10% chloral hydrate 3 ml/kg.The right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.The mechanical paw withdrawal threshold and thermal paw withdrawal latency on the operated side were measured at 1 day before CCI (T 0) and 3, 5, 7, 14 and 21 days after CCI (T 1-5). Electroencephalogram recording electrodes were stereotaxically implanted in visual cortex at T 3, and electroencephalogram were monitored for 6 h, the percentages of non-rapid eye movement, rapid eye movement and wakefulness in the total time were calculated.Microwire electrodes were implanted epidurally over the ventral posterior (VP) nucleus of the thalamus and primary somatosensory cortex (S1) using a brain stereotaxic apparatus at T 3, and the data acquisition system was used to record field potentials at T 4, the percentage of power of each wave was calculated, and the coherence of the field potentials of VP and S1 was simultaneously evaluated.The mice were sacrificed at T 4, brain tissues were collected, and proton nuclear magnetic resonance spectroscopy was used to determine the level of neurotransmitter in the thalamus and cortex. Results:Compared with group Sham, the mechanical paw withdrawal threshold was significantly decreased and thermal paw withdrawal latency was shortened at T 1-5, the percentage of non-rapid eye movement time was decreased, the percentage of wakefulness time was increased, the percentage of δ wave power in the VP area was decreased, the percentage of δ wave power in the VP and S1 areas was increased, and the coherence of the field potentials of VP-S1 was increased in the frequency range of δ wave (1-4 Hz) and α wave (8-14 Hz), and the levels of glutamate, glutamine and glutamate-glutamine in the thalamus and cortex were increased in group CCI ( P<0.05). Conclusions:Neuropathic pain-induced sleep disturbance is related to increased thalamocortical glutamate levels, resulting in changes in the electrical activity of thalamocortical neurons of mice.

The changes in effective connectivity in the precentral gyrus after transcranial magnetic stimulation / 中华物理医学与康复杂志

Objective:To investigate any change in the effective connectivity between the bilateral anterior central gyruses after transcranial magnetic stimulation (TMS).Methods:Twenty-one healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI) before and after receiving continuous theta burst stimulation (cTBS). The brain atlas of the Institute of Automation of the Chinese Academy of Sciences was used for fine partitioning of the bilateral anterior central gyruses. Granger causality analysis was used to compare any changes in the effective connectivity between them.Results:After the cTBS inhibited the right M1 area, significant changes in effective connectivity among the sub-regions of the bilateral M1 area were observed. The effective connectivity of the right upper limb to the left upper limb and the left head to face were weakened, while that of the left upper limb to the right head, as well as of the face to the right upper limb was enhanced.Conclusion:For people whose right M1 area has been inhibited by cTBS, the effective connectivity changes in both upper limb functional areas of the M1 region reflect inter-hemispheric inhibition. Opposite changes were found in the trunk and upper limbs.

Low-Frequency Magnetic Stimulation of Shenmen Acupoint Reduces Blood Oxygen Levels in the Prefrontal Cortex of Healthy Subjects: A Near-Infrared Brain Functional Imaging Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of low-frequency magnetic stimulation at Shenmen (HT 7) acupoint on blood oxygen levels in the prefrontal cortex of healthy subjects.@*METHODS@#Functional near-infrared spectroscopy (fNIRS) technology was used to collect real-time data of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex of 16 healthy subjects at resting state and low-frequency magnetic stimulation of Shenmen. The mean and integral values of blood oxygen concentration were analyzed.@*RESULTS@#Compared with the resting state, the mean and integral values of blood oxygen concentration were decreased during the task period, recovery period, and the whole process in the magnetic stimulation of Shenmen acupoint (P<0.05). In particular, the difference was statistically significant in the recovery period (P<0.01).@*CONCLUSIONS@#The prefrontal cortex was widely activated and produced an immediate effect by reducing the local blood oxygen concentration at low-frequency magnetic stimulation of Shenmen acupoint, which verifies the sedative effect of Shenmen acupoint.

Role of P2X 7 receptor in microglia in medial prefrontal cortex in neuropathic pain in rats: relationship with autophagy / 中华麻醉学杂志

Objective:To evaluate the role of P2X 7 receptor in microglia in the medial prefrontal cortex (mPFC) in neuropathic pain (NP) and the relationship with autophagy in rats. Methods:Sixty-four healthy SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=16 each) using a random number table method: sham operation group (S group), NP group, sham operation+ P2X 7 receptor blocking group (SP group), and NP+ P2X 7 receptor blocking group (NP+ P group). The NP model was established by ligation of the sciatic nerve.Fourteen days later a cannula was placed in the mPFC with a brain stereotactic instrument, P2X 7 receptor blocker A-740003 0.5 μg/0.5 μl was injected into bilateral mPFC for 3 consecutive days starting from the 14th day in SP and NP+ P groups, and DMSO 0.5 μl was injected instead of A-740003 in S and NP groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 3, 7 and 10 days after establishing the model and 14, 15 and 16 days after administration.Then the rats were sacrificed, and the mPFC was removed for determination of the expression of P2X 7 receptor and mRNA and autophagy-related proteins Beclin1 and LC3Ⅱ/Ⅰ (by quantitative real-time polymerase chain reaction or by Western blot) and co-expression of P2X 7R and microglia (by immunofluorescence) and the number of autophagosomes in mPFC (with a transmission electron microscope). Results:Compared with group S, MWT was significantly decreased, and TWL was shortened at 3, 7 and 10 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was up-regulated at 30 min after administration on 16 days after establishing the model, and the number of cells co-expressing P2X 7 receptor and IBA-1 and the number of autophagosomes were increased in NP and NP+ P groups ( P<0.05), and no significant change was found in the indexes mentioned above in group SP ( P>0.05). Compared with group NP, MWT was significantly increased, and TWL was prolonged at 30 min after administration on 14, 15 and 16 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was down-regulated, and the number of cells co-expressing P2X 7 receptor and Iba-1 and the number of autophagosome were decreased in group NP+ P ( P<0.05). Conclusion:Up-regulation of P2X 7 receptor expression in microglia in mPFC is involved in the process of NP in rats, which is associated with the promotion of autophagy.

Effect of transcutaneous electrical acupoint stimulation on labor analgesia / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on labor pain.@*METHODS@#A total of 151 primiparas who were vaginal delivery were randomized into a TEAS group (76 cases) and a peridural group (75 cases). In the peridural group, peridural blockage was applied to analgesia. In the TEAS group, TEAS was applied at Hegu (LI 4)，Neiguan (PC 6), Jiaji T~L (EX-B 2) and Ciliao (BL 32), disperse-dense wave (2 Hz/100 Hz), 15-50 mA in current intensity. The analgesic time was from 3 cm to completely opening of cervix. The visual analogue scale (VAS) scores were observed before analgesia, after 30, 60, 120 min of analgesia in the two groups. The time of different stages of labor, usage rate of oxytocin, incidence rate of adverse reaction and amount of postpartum hemorrhage were recorded. The newborn's 1 and 5 min Apgar scores were evaluated.@*RESULTS@#The VAS scores showed a downward trend in the two groups after analgesia (0.05). The usage rate of oxytocin and incidence rate of adverse reaction in the TEAS group were 9.2% (7/76) and 2.6% (2/76), which were lower than 34.7% (26/75) and 18.7% (14/75) in the peridural group (0.05).@*CONCLUSION@#The analgesic effect of TEAS is inferior to peridural blockage, but TEAS could relieve labor pain to the tolerance, shorten the time of active phase on the first stage and second stage of labor and reduce the use of oxytocin, has mild adverse reaction.

Clinical observation on filiform fire-needling plus continuous passive motion therapy for frozen shoulder / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of filiform fire-needling plus continuous passive motion (CPM) therapy for frozen shoulder. Methods: A total of 72 patients were randomized into an observation group and a control group by the random number table method, with 36 cases in each group. Patients in the control group received celecoxib capsule plus CPM, while those in the observation group received filiform fire-needling plus CPM. The whole course of treatment lasted for 2 weeks in both groups. The visual analog scale (VAS), Constant-Murley score (CMS) and range of motion of shoulder joint were measured for therapeutic efficacy evaluation. Results: The total effective rate was 91.7％ in the observation group, higher than 72.2％ in the control group, and the between-group comparison showed statistical significance (P<0.05). After treatment, the VAS scores in the two groups dropped significantly, the CMS as well as the range of motion including abduction, forward flexion and extension were all increased significantly, and the intra-group comparisons showed statistical significance (all P<0.05). The betweengroup comparisons showed the improvements in these items in the observation group were more significant than those in the control group (all P<0.05). Conclusion: Filiform fire-needling plus CPM can produce more significant efficacy than celecoxib capsule plus CPM for frozen shoulder; it can alleviate pain, improve shoulder function and restore joint range of motion in such patients.

A comparative study of bibliometrics between Chinese and American research-oriented hospitals in the context of "Double First-Class" :Taking West China Hospital of Sichuan University and Mayo Clinic as an example / 中华医学科研管理杂志

Objective To conduct a comparative study on the papers between domestic research hospital and world-class hospital in order to find out the gap between them,and to provide countermeasures and reference basis for the discipline construction of research hospitals in China.Methods A comparative study of papers published from 2016 to 2018 in Web of Science core database between West China Hospital and Mayo Clinic was conducted by bibliometric methods.Chi-square tests and non-parametric tests were carried out to verify the consistency of paper distribution between these two institutions.Results The results showed that there was a big gap between West China Hospital and Mayo Clinic in quality of papers.The proportion of papers participating in other institutions and the proportion of papers in clinical medical category of West China Hospital are much lower than those of Mayo.Conclusions It is suggested that domestic research hospitals should focus on improving the quality of scientific research achievements by strengthening substantive scientific research cooperation,vigorously developing clinical research,establishing full-time scientific research teams,and improving the supporting system of clinical translation services.

Effect and mechanism of microRNA-155 on cell biological behavior of thyroid papillary carcinoma cells / 中华内分泌外科杂志

Objective:To study the role of miR-155 in the differentiation of papillary thyroid carcinoma (PTC) cells, and to explore the possible mechanism.Methods:Human miR-155 analogues were constructed and transfected into PTC BCPAP cells in vitro. CCK8 test and Transwell test were used to observe the changes of cell proliferation and invasiveness. The miR-155 was transfected into BCPAP cells in vitro and the protein background and phosphorylation expression of MAPK pathway were detected by Western blot. ERK pathway inhibitor U0126 was given to observe whether it could reverse the abnormal proliferation and invasion of thyroid cancer cells caused by over-expression of miR-155.Results:The proliferation of BCPAP cells was detected by CCK8 test 48 hours after overexpression of miR-155, and the invasiveness of thyroid cancer cells was significantly enhanced by Transwell test 48 hours after overexpression of miR-155 ( P<0.05) ; Western blot method found that the expression of JNK, ERK and p38 in MAPK signal pathway was significantly up-regulated ( P<0.05) . At the same time, the expression of p-ERK protein in the cells was increased significantly ( P<0.05) . The expression of p-ERK in the cells treated with ERK pathway inhibitor U0126 and miR-155 was significantly lower than that in the miR-155 group ( P<0.05) . By detecting the proliferation and invasion of cells in each group, we found that the U0126 could reverse the proliferation and invasion promoting effect caused by miR-155. Conclusion:miR-155 can promote the proliferation and invasion of PTC BCPAP cells by activating the ERK pathway of MAPK pathway, which provides a potential target for the treatment of thyroid cancer.

Accuracy of three intraoral scans for primary impressions of edentulous jaws / 北京大学学报(医学版)

OBJECTIVE@#To provide a reference for using intraoral scanners for making clinical diagnostic dentures of edentulous jaws by comparing the accuracy of three intraoral scanners for primary impression and jaw relation record of edentulous jaws.@*METHODS@#This study contained 6 primary impressions of the edentulous patients. Each of the impressions consisted of the maxillary primary impression, the mandibular primary impression and the jaw relation record. For each of them, a dental cast scanner (Dentscan Y500) was used to obtain stereolithography (STL) data as reference scan, and then three intraoral scanners including i500, Trios 3 and CEREC Primescan were used for three times to obtain STL data as experiment groups. In Geomagic Studio 2013 software, trueness was obtained by comparing experiment groups with the reference scan, and the precision was obtained from intragroup comparisons. Registered maxillary data of the intraoral scan with reference scan, the morphological error of jaw relation record was obtained by comparing jaw relation record of the intraoral scan with the reference scan. Registered mandibular data with jaw relation record of intraoral scan and the displacement of the jaw position were evaluated. Independent samples t test and Mann-Whitney U test in the SPSS 20.0 statistical software were used to statistically analyze the trueness, precision and morphological error of jaw relation record of three intraoral scanners. The Bland-Altman diagram was used to evaluate the consistency of the jaw relationship measured by the three intraoral scanners.@*RESULTS@#The trueness of i500, Trios 3 and CEREC Primescan scanners was (182.34±101.21) μm, (145.21±71.73) μm, and (78.34±34.79) μm for maxilla; (106.42±21.63) μm, and 95.08 (63.08) μm, (78.45±42.77) μm for mandible. There was no significant difference in trueness of the three scanners when scanning the maxilla and mandible(P>0.05). The precision of the three scanners was 147.65 (156.30) μm, (147.54±83.33) μm, and 40.30 (32.80) μm for maxilla; (90.96±30.77) μm, (53.73±23.56) μm, and 37.60 (93.93) μm for mandible. The precision of CEREC Primescan scanner was significantly better than that of the other two scanners for maxilla (P<0.05). Trios 3 and CEREC Primescan scanners were significantly better than i500 scanner for mandible (P<0.05). The precision of the i500 and Trios 3 scanners for mandible was superior to maxilla (P<0.05). The upper limit of 95% confidence intervals of trueness and precision of three scanners for both maxilla and mandible were within ±300 μm which was clinically accepted. The morphological error of jaw relation record of the three scanners was (337.68±128.54) μm, (342.89±195.41) μm, and (168.62±88.35) μm. The 95% confidence intervals of i500 and Trios 3 scanners were over 300 μm. CEREC Primescan scanner was significantly superior to i500 scanner(P<0.05).The displacement of the jaw position of the three scanners was (0.83±0.56) mm, (0.80±0.45) mm, and (0.91±0.75) mm for vertical dimension; (0.79±0.58) mm, (0.62±0.18) mm, and (0.53±0.53) mm for anterior and posterior directions; (0.95±0.59) mm, (0.69±0.45) mm, and (0.60±0.22) mm for left and right directions. The displacement of the jaw position of the three scanners in vertical dimension, anterior and posterior directions and the left and right directions were within the 95% consistency limit.@*CONCLUSION@#Three intraoral scanners showed good trueness and precision. The i500 and Trios 3 scanners had more errors in jaw relation record, but they were used as primary jaw relation record. It is suggested that three intraoral scanners can be used for obtaining digital data to make diagnostic dentures and individual trays, reducing possible deforming or crack when sending impressions from clinic to laboratory.

Combined detection of AFP-L3, GP73 and TIP30 enhances diagnostic accuracy for HBV-related cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To investigate the value of combined tests of serum Golgi protein-73, alpha-fetoprotein- L3 and Tat-interacting protein-30 in the diagnosis of hepatitis B virus related cirrhosis and hepatocellular carcinoma. METHODS: The cross-sectional study was conducted at Yuebei People's Hospital, Guangdong, China, from January to October 2017, and comprised hepatitis B patients and healthy controls. Serum Golgi protein-73, alpha-fetoprotein-L3 and Tat-interacting protein-30 levels in both groups were detected by enzyme-linked immunosorbent assay (ELISA). Alpha-fetoprotein-L3 was separated and quantified by electrochemiluminescence immunoas says and the percentage of alpha-fetoprotein-L3 to alphafetoprotein was calculated. RESULTS: Of the 721 subjects, 525(%) were patients and 196(%) were healthy controls. Among the patients, 271(%) had chronic hepatitis B, 161(%) had liver cirrhosis and 93(%) had hepatocellular carcinoma. Serum Golgi protein-73, alpha-fetoprotein-L3 and Tat-interacting protein-30 levels were significantly different in the hepatocellular carcinoma patients compared to controls, and those with chronic hepatitis and liver cirrhosis (p<0.01 each). The sensitivity and specificity of the combined detection of the three serum levels for diagnosing cirrhosis were 78.26% and 86.72%. The corresponding values for diagnosing hepatocellular carcinoma were 86.02% and 92.51%. CONCLUSIONS: Combined detection of Golgi protein-73, alpha fetoprotein-L3 and Tat-interacting protein was found to have the potential to improve diagnostic accuracy.

Analysis of Recruitment Pattern of Related Muscles in Two Types of Active Straight Leg Raise / 中国康复理论与实践

Objective:To compare the rate of recruitment in two types of active straight leg raise (ASLR) and to investigate the activation patterns of the related muscles. Methods:From June to October, 2018, eleven healthy subjects were recruited. Surface electromyography (sEMG) signals of unilateral rectus femoris, bilateral rectus abdominis, internal oblique abdominis, external oblique abdominis and multifidus were recorded in normal ASLR (Action A) and raising leg for ten seconds (Action B). %maximal voluntary isometric contraction (MVIC) of these muscles was processed and analyzed. Results:%MVIC of ipsilateral internal oblique muscle and external oblique muscle were greater than the opposite side (t > 2.549, P < 0.05) in Action A; %MVIC of ipsilateral internal oblique muscle, external oblique muscle and rectus abdominis muscle were greater than the opposite side (t > 2.240, P < 0.05) in Action B; compared with action B, Action A had higher %MVIC of bilateral internal oblique and rectus femoris (t > 3.549, P < 0.05). Conclusion:The activation mode of ipsilateral dominance was shown in both actions, and the different motion control strategies may be adopted by the neuromuscular system in different ASLR.

Regulatory perspective for chemistry manufacturing and controls considerations in chimeric antigen receptor-modified T cell therapy / 药学学报

As a living cell product, chimeric antigen receptor (CAR)-T cell therapy displays multiple characteristics including the diversity of raw materials, the complexity of manufacturing process and the complementarity of quality control set. Pharmaceutical research and evaluation of CAR-T cell therapy are fundamentally different from small molecule and macromolecular recombinant proteins. Chemistry manufacturing and controls (CMC) review of investigational new drug (IND) submission for CAR-T therapy should especially pay attention to above unique characteristics and focus on potential risks to ensure clinical safety. Based on questions and concerns from recent CMC review practice and workshop on CAR-T cell therapy IND application, the critical points to consider for CMC study is proposed, and questions related to supplementation are also discussed in this review to accelerate the clinic translation of CAR-T therapy.