Baicalin Induces Ferroptosis in Gastric Cancer Cells via p53-mediated SLC7A11 Down-regulation / 中国实验方剂学杂志

ObjectiveTo explore the inhibitory effect of different concentration of baicalin （0， 100， 200， 400 μmol·L-1） on the proliferation of human gastric cancer SGC-7901 cells and the underlying mechanism. MethodSGC-7901 cells were treated with baicalin. Then methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibitory effect of baicalin on the cells. At the same time， ferrostatin-1 （Fer-1） was added to observe the viability of cells after baicalin treatment. The expression of ferroptosis-related genes was detected by Real-time polymerase chain reaction （Real-time PCR） and Western blot. The content of malondialdehyde （MDA） and the level of glutathione （GSH） were detected respectively by MTT assay and enzyme-linked immunosorbent assay. The role of tumor protein 53 （p53）/solute carrier family 7 member 11 （SLC7A11） pathway in the regulation of ferroptosis was investigated respectively via overexpression and small interfering RNA （siRNA） methods. ResultCompared with the blank group， baicalin decreased the viability of SGC-7901 （P<0.05， P<0.01） in a dose- and time-dependent manner. The intervention of Fer-1 significantly alleviated the decrease of SGC-7901 cell viability caused by baicalin （P<0.01）. In addition， compared with the baicalin group， Fer-1+baicalin group showed decrease in MDA content and the mRNA and protein levels of prostaglandin-endoperoxide synthase 2 （PTGS2） in the cells （P<0.01）， and increase in GSH activity and mRNA and protein levels of glutathione peroxidase 4 （GPX4） （P<0.01）. The protein level of SLC7A11 in the baicalin group was decreased compared with that in the blank group （P<0.05， P<0.01） in a dose-dependent manner. Compared with the baicalin group， the reactive oxygen species （ROS） level and MDA content in SLC7A11-overexpressing cells were significantly decreased after baicalin treatment （P<0.01）， and the GSH activity was significantly increased （P<0.01）. The fluorescence intensity of p53 in the cells of the baicalin group was increased compared with that of the blank group （P<0.01）. Compared with the baicalin group， the expression level of p53 protein in the cells transfected with p53 siRNA was significantly decreased after baicalin treatment （P<0.01）， and the expression level of SLC7A11 was significantly increased （P<0.01）. ConclusionBaicalin can effectively inhibit the proliferation of SGC-7901 cells by regulating p53/SLC7A11-mediated ferroptosis.

Comparative analysis of differentially expressed genes for biosynthesis of active ingredients in fruits of different cultivars of Lycium barbarum L. based on transcriptome sequencing / 生物工程学报

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.

Clinical characteristics and survival of patients with HIV/AIDS and pulmonary tuberculosis / 公共卫生与预防医学

Objective To analyze the clinical characteristics of patients with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) and pulmonary tuberculosis, and investigate their survival and influencing factors of survival. Methods A total of 107 patients with HIV/AIDS and pulmonary tuberculosis were selected. The relationships of clinical symptoms, CT findings and CD4 cell count with positive laboratory tests were analyzed. Th survival of patients was investigated, and independent risk factors for death were analyzed. Results Most the 107 patients had symptoms such as cough, chest pain and fatigue. CT findings mainly included patchy shadow (75.70%), tree-in-bud sign (46.73%), nodular shadow (35.51%) and pulmonary hilar or mediastinal lymph node enlargement (86.92%). The proportion of lesions ≥ 3 pulmonary fields (47.66%) was higher. The positive rates of purified protein derivative (PPD), acid-fast bacilli and Mycobacterium tuberculosis were significantly higher in the CD4 cell count > 200/µL group than in the ≤200/µL group (P<0.05). There were statistically significant differences in body mass index (BMI), baseline CD4 cell count, multidrug resistant tuberculosis (MDR-TB) and standard anti-tuberculosis treatment between the survival group and the death group (P<0.05). Baseline CD4 cell count ≤200/µL, MDR-TB, and no standard anti-tuberculosis treatment were independent risk factors for death of patients with HIV/AIDS and pulmonary tuberculosis (P<0.05). Conclusion The clinical symptoms and imaging manifestations of patients with HIV/AIDS and pulmonary tuberculosis are complex and diverse, but characteristic. Baseline CD4 cell count ≤200/µL, MDR-TB and no standard anti-tuberculosis treatment are main risk factors for death of the patients.

Determination and effect of five alkaloids from extracts of Piper longum on rats with experimental myocardial ischemia induced by injection of pituitrin / 药学实践与服务

Objective To determine the content of five alkaloids from extracts of Piper longum and test the pharmacodynamic effect of them on rats with experimental myocardial ischemia induced by injection of pituitrin. Methods The content of five alkaloids was determined simultaneously by HPLC. The experimental myocardial ischemia in rats was induced by injection of pituitrin, and the absolute value of T wave change and change of heart rate before and after model establishment were chosen to be the observation index. The effects of large, medium and small dose groups were evaluated. Results Three batches of samples were analyzed, with the contents of piperine for 56.1%, 49.7%, 51.6%; N-isobutyl-(2E,4E)-octadecatrienamide for 4.5%, 4.2%, 4.3%; guineensine for 0.46%, 0.38%, 0.40%; piplartine for 1.73%, 1.67%, 1.70% and piperamide for 0.55%, 0.46%, 0.49%, respectively. All dose groups from extracts of piper longum had significantly reduced the absolute value of T wave and almost have no effect on the change of heart rate, except the high dose group showed the effect of reducing heart rate at some time . Conclusion The HPLC method was suitable for the simultaneous determination of five alkaloids from extracts of Piper longum. It was shown that extracts of Piper longum had good bioactivity in anti-myocardial ischemia.

Diagnosis and treatment procedures and health management for patients with hereditary angioedema / 中华预防医学杂志

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Incidence and related factors of antiviral drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019 / 中华预防医学杂志

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4+T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Preliminary insights into the practice of hypoallergenic home visiting program / 中华预防医学杂志

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

Diagnosis and treatment procedures and health management for patients with hereditary angioedema / 中华预防医学杂志

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Incidence and related factors of antiviral drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019 / 中华预防医学杂志

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4+T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Preliminary insights into the practice of hypoallergenic home visiting program / 中华预防医学杂志

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives / 中西医结合学报

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

Voltage-gated potassium channel-complex antibodies associated clinical syndromes with myasthenia gravis complicated with thymoma: analysis of 2 cases and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

Effects of salidroside on cerebral vascular endothelial cells in MCAO rats / 中国药理学通报

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100

Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway / 中国中药杂志

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 μmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 μmol·L~(-1)), low-concentration(10 μmol·L~(-1)) saikosaponin D, and high-concentration(16 μmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Application of TARP luciferase reporter system in function identification of CAR-T cells / 细胞与分子免疫学杂志

Objective To investigate a convenient and quantitative solution to activation levels and functional characterization of CAR-T cells by inserting T cell activity-responsive promoter (TARP) nanoluciferase reporter gene system into a lentiviral plasmid containing the gene encoding the chimeric antigen receptor (CAR). Methods The recombinant plasmid was constructed by using whole gene synthesis and molecular cloning techniques. The lentivirus was packaged and was infected with human primary T lymphocytes. Flow cytometry was used to detected the positive rate of lentivirus-infected T cells. The functional characterization of CAR-T cells was identified by luciferase reporter gene system, Western blot, flow cytometry, and small animal live imaging techniques. Results The results of enzyme digestion identification and the plasmid sequencing showed that the recombinant plasmids were constructed, and flow cytometry displayed the normal preparation of CAR-T cells. This system could dynamically respond to the activation of CAR-T cells by luciferase reporter gene system. The functional assay in vitro confirmed that the system could reflect the exhaustion of CAR-T cells, and the small animal live imaging results demonstrated that the system can be used as a tracer of CAR-T cells in mice. Conclusion TARP nanoluciferase reporter gene system provides a more convenient, sensitive and quantitative method for evaluating CAR-T cells activation level, exhaustion phenotype and tracing.

Clinical, neuroimaging and gene mutation characteristics of McLeod syndrome and literature review / 中华神经科杂志

Objective:To study the characteristics of clinical, laboratory, imaging, genetic and differential diagnosis of McLeod syndrome.Methods:The clinical characteristics of 2 cases of McLeod syndrome confirmed by gene detection in Qilu Hospital (Qingdao) on June 27, 2018 and in Qilu Hospital of Shandong University on September 11, 2019 were analyzed retrospectively. And the characteristics of patients of McLeod syndrome reported in China were analyzed in combination with literature review.Results:Both of the 2 patients were adult male, aged 57 and 61 years, respectively, with a slowly progressive course, beginning with gradually involuntary movement of trunk and extremities, involving involuntary biting of the tongue and dysphagia. Two patients had mild cognitive impairment; one patient had emotional agitation. Imaging study showed atrophy of caput nuclei caudate. Neuroelectrophysiological examination of case 1 showed sensory axon neuropathy in both upper limbs with severe damage to the left ulnar nerve. Creatine kinase (CK) was mildly elevated in 2 patients. The peripheral blood smear of 1 patient showed increased acanthocytes, accounting for 13%, the other patient showed no increased acanthocyte. McLeod syndrome related gene was tested in the 2 patients, case 1 with deletion mutation of exon 2 of XK gene, and case 2 with hemizygotic mutation of XK gene c.898delC p.L300 *. Conclusions:The clinical manifestations of McLeod syndrome are various and the differential diagnosis is crucial. For elderly male with cephalic facial chorea, elevated CK level and neuromuscular diseases, the possibility of McLeod syndrome should be screened.

Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.