Vasculitic neuropathies / 中华神经科杂志

Vasculitic neuropathies occur when inflammatory cells infiltrate the vessels of peripheral nerves. Patients with vasculitic neuropathies typically present with multiple mononeuropathies (also known as multifocal neuropathy), characterized by the acute-to-subacute onset of painful sensory and motor deficits. Vasculitic neuropathies could develop in the setting of systemic vasculitis. It also could present as a non-systemic vasculitis without other organs involvement. Peripheral nerve biopsy has an important role in the diagnosis of vasculitic neuropathies. In this review, the classification, clinical and electrophysiological manifestations, diagnosis, treatment, and prognosis of vasculitic neuropathies are summarized, with a focus on recent progresses in these areas.

Detection of IgG protein in human urine based on vertical flow paper microfluidic chip / 生物工程学报

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.

The research of relationship between medical students' time engagement outside classes and general self-efficacy / 中华医学教育探索杂志

Objective:To analyze the relationship between the clinical medical college students' time investment (including study, activities, entertainment and exercise) and general self-efficacy (GSE) in a medical university in Liaoning province, China.Methods:The first-year medical students were asked to participate the survey. Their GSE was measured by using general self-efficacy scale (GSES) in 2018. One year later, the independent variable table was used to investigate the extracurricular activity time, and 683 valid questionnaires were collected. Ordered logistic regression method was used to analyze the correlation between students' extracurricular activities and GSE.Results:Medical students' GSE was positively associated with their time in extracurricular study ( OR = 1.94, 95%CI = 1.49-2.54), volunteer activities ( OR=1.36, 95%CI = 1.01-1.83), and physical activities ( OR = 1.37, 95%CI = 1.01-1.85). However, there was no significant correlation with the time in activities organized by students ( OR = 1.09, 95%CI = 0.79-1.50) or activities organized by school ( OR = 1.15, 95%CI = 0.84-1.59). Furthermore, compared with clinical students of "5+3" year program, the 5-year program clinical students had a stronger correlation between medical students' GSE and the input of extracurricular study time. Conclusion:There is a positive correlation between medical students' GSE and their extracurricular time investment, which indicates that increasing medical students' GSE could be an effective method to improve their extracurricular time investment and eventually improve their comprehensive quality.

Transferrin receptor is another receptor for SARS-CoV-2 entry

Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

Susceptibility of tree shrew to SARS-CoV-2 infection

Since SARS-CoV-2 became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and COVID-19 were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39{degrees} C) particular in female animals during infection. Low levels of virus shedding and replication in tissues occurred in all three age groups, each of which showed his own characteristics. Histopathological examine revealed that pulmonary abnormalities were mild but the main changes although slight lesions were also observed in other tissues. In summary, tree shrew is not susceptible to SARS-CoV-2 infection and may not be a suitable animal for COVID-19 related researches.

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence SummaryM. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.

Analysis of first-line NSCLC chemotherapy in the phaseⅣpatients with distant metastasis and first diagnosis after postop-erative adjuvant chemotherapy / 实用肿瘤学杂志

Objective In patients with non -small cell lung cancer(NSCLC)undergoing radical surgery,there were still many inevitable recurrences and distant metastases,even after systemic postoperative adjuvant chemotherapy.At the same time,many patients were in the stage Ⅳ at the time of initial treatment.The aims of this study were to investigate and compare the first-line chemotherapy(First-line Chemotherapy at Recurrence Post-adjuvant Chemotherapy,FCRPC)in NSCLC patients with distant metas-tasis after adjuvant chemotherapy with initial treatment at the phase Ⅳ of NSCLC patients with first-line chemotherapy(Initial First-line Chemotherapy,IFC).Methods A total of 603 patients with distant metastatic NSCLC were collected in this study.Among them,73 of them were FCRPC and 530 of them for IFC.Statistical methods for propensity score matching were used to balance the clinical features between FCRPC and IFC groups.Chi-square test was used to compare the short-term efficacy between FCRPC and IFC groups.Survival analysis was performed using regression analysis and Kaplan-Meier analysis.Results There was no significant difference in objective response rate(ORR)and disease control rate(DCR)between FCRPC and IFC groups in NSCLC patients with dis-tant metastases(ORR rate:27.46% in the FCRPC group,24.7% in the PFC group,P=0.851 and DCR rate:78.1% in the FCRPC group,65.6% in the PFC group,P=0.140).There was also no significant difference in the median progression-free survival(9.8 months in the FCRPC group and 8.5 months in the PFC group,P=0.337)and median overall survival(20.0 months in the FCRPC group and 14.4 months in the PFC group,P=0.087).Conclusion There is no significant difference in the prognosis of first-line chemotherapy between NSCLC patients with distant metastases and with initial treatment at the stageⅣafter adjuvant chemotherapy.

Expression and purification of rabies virus glycoprotein and analysis of its specific binding capacity to memory B cells / 生物工程学报

We aimed to express and purify three rabies virus glycoproteins with different tags and sizes. After analyzing their binding function, we wish to obtain a rabies virus glycoprotein with higher affinity and ability to specifically bind memory B cells. Experiments were carried out to express full length, as well as the ectodomain RVG by gene engineering method. Combined with the antibody of CD19 and CD27, the candidate protein labeling with fluorescence was used to analyze its binding function. Flow cytometry was used to detect the anti-rabies virus specific memory B cells in PBMCs, and confirm the binding ability between the candidate proteins and anti-rabies virus-specific memory B cells. We successfully constructed three expression vectors pGEX-5X-1-RVG, pET28a-RVG and pET30a-G. Three glycoproteins GST-RVG, His-RVG and His-G were obtained by optimized expression and purification conditions. The antigen specificity of purified GST-RVG, His-RVG and His-G were identified by Western blotting and ELISA. The affinity of these three purified glycoproteins to anti-rabies virus antibody were detected by competitive ELISA. Anti-rabies virus specific memory B cells in positive PBMCs gained from people who had ever been injected with the vaccine can be detected by flow cytometry. Thus, we got a recombinant rabies virus glycoprotein that had high-affinity and could sort antigen specific memory B cells.

MicroRNA-939 regulating CD2 -associated protein expression by targeting promoter / 中华实用儿科临床杂志

Objective To verify the targeting regulatory relationship between microRNA -939 (miR -939) and CD2 -associated protein (CD2AP).Methods The online RegRNA software was used to predict the human CD2AP promoter for potential binding sites complementary to miR -939.HEK -293T cells were cotransfected with hu-man CD2AP promoter plasmid pGL3 -2K and microRNA negative control (miR -NC)or miR -939 mimics,and the relative luciferase activity(RLA)was detected at 24 h post -transfection.HEK -293T cells were transfected with miR -NC or miR -939 mimics for 48 h,and the CD2AP mRNA expression level was detected by adopting reverse tran-script and real -time fluorescence quantification -PCR,while the CD2AP protein expression level was detected by using Western blot.Results (1 )There were 2 miR -939 binding sites at CD2AP promoter region,located at -468 to -491 and -654 to -677 upstream of initiation codon ATG (marked as +1 )relatively.(2)At 30 nmol/L,50 nmol/L,the RLA in miR -NC group and miR -939 group were 6.81 ±0.88 vs 6.07 ±2.24,5.88 ±1 .44 vs 3.94 ± 0.79 relatively,and there were no significant differences between the 2 groups (t =3.04,2.06,all P >0.05),while the RLA between the 2 groups were 5.58 ±0.58 vs 3.29 ±0.64 at 1 00 nmol/L,and the difference was significant between the 2 groups(t =4.07,P <0.05).(3)At 30 nmol/L,50 nmol/L and 100 nmol/L,the relative CD2AP mRNA expression in miR -NC group and miR -939 group were 1 .00 ±0.01 vs 0.80 ±0.08,1 .00 ±0.00 vs 0.80 ±0.1 3 and 1 .00 ± 0.00 vs 0.72 ±0.07 relatively,while the CD2AP mRNA expression was decreased by 20% -30% at each concentration level,and there were significant differences between the 2 groups (t =4.44,2.93,6.84,all P <0.05).(4)At 50 nmol/L, the relative CD2AP protein expression in miR -NC group and miR -939 group were 0.48 ±0.09 vs 0.19 ±0.12,and the CD2AP protein expression was decreased,and the difference was significant (t =3.36,P <0.05).Conclusions CD2AP is the target gene of miR -939,and miR -939 can down -regulate the expression of CD2AP both in mRNA and protein levels by targeting its promoter region,which indicates that miR -939 may mediate the podocyte injury.

Clinical Efficacy of Ginkgo biloba Extract Combined with Olmesartan Medoxomil in the Treatment of Essen-tial Hypertension and Its Effect on the Expression of Serum Protein / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Ginkgo biloba extract combined with olmesartan me-doxomil in the treatment of essential hypertension,and to discuss its effect on the expression of serum protein. METHODS:98 pa-tients with essential hypertension were selected and randomly divided into observation group A and observation group B,with 49 cases in each group;40 healthy volunteers were included in control group. Observation group A was given Olmesartan medoxomil tablet 20-40 mg,po,qd;observation group B was given Olmesartan medoxomil tablet 20-40 mg,po,qd+ Extract of G. biloba leaves tablet 40-80 mg,po,bid. Treatment course lasted for 4 weeks. Blood pressure(SBP and DBP),TCM symptom score,the repeti-tiveness and resolution ratio of 2-DE spectrum,protein differentiation expression point,related information of differentiation expres-sion protein in 3 groups and ADR of observation group were observed. RESULTS:After treatment,SBP,DBP and TCM symptom score of observation group were significantly lower than before;those indexes after 4 weeks of treatment were significantly lower than those after 2 weeks after treatment;the observation group B was significantly lower than the observation group A,with statisti-cal significance(P0.05). CONCLUSIONS:G. biloba extract combined with olmesartan medoxomil greatly influences the expression of serum pro-tein in patients with essential hypertension and shows good antihypertensive and pressure-control effects with good safety.

Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy

BACKGROUND AND PURPOSE: The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). METHODS: Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. RESULTS: Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. CONCLUSIONS: Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis.

Comparing the effects of transcuataneous electrical nerve stimulation and fluoxetine on central pain in patients with spinal cord injury / 中华物理医学与康复杂志

Objective To compare the effects of fluoxetine and transcuataneous electrical nerve stimulation (TENS) on central pain after spinal cord injury (SCI) using a sham-controlled crossover method.Methods Ele-ven patients with central pain after SCI were randomly divided into two groups which were then subject to 2 phases of treatment.Patients in group 1 were treated by oral intake of fluoexetine for 4 weeks followed by TENS treatment for 4 weeks.Those in group 2 were treated in the reverse sequence.A fifteen day washout period was arranged between the two phases of treatment.The short-form McGill pain questionnaire (SF-MPQ) and the Beck depression inventory (BDI) were used to assess all patients pre-and post-treatment.Results SF-MPQ scores were reduced significantly after either fluoexetine or TENS treatment.After each phase of treatment there was no significant difference between the two groups.Significant improvement in terms of BDI scores was found with fluoxetin treatment in both phases of the trial,but not with TENS treatment.Conclusions Both fluoxetine and TENS can alleviate central pain after SCI,and fluoxetine can relief patients' depression at the same time.

Suppression of invasion and migration by 7-hydroxystaurosporine(UCN-01),a new anti-tumor agent / 中国临床药理学与治疗学

Aim and Methods To investigate the effect of UCN-01(7-hydroxystaurosporine) on cell migration and invasion ability of DU-145, an invasive human prostate cancer cell line.Results It was found that UCN-01 at non-cytotoxic doses (100 nmol· L-1) significantly inhibited prostate cancer DU-145 cell invasion and migration behaviors.Moreover, this anti-invasion and migration activity of UCN-01 was associated with an up-regulation of cell adhesion molecule E-cadherin. Conclusion These results indicate for first time that UCN-01 inhibits the invasion and migration of human prostate cancer cells.Thus, clinical application of UCN-01 may contribute to the potential benefit for suppression of prostate cancer invasion and metastasis.