Thermal stability of neuraminidase in influenza vaccine / 中国生物制品学杂志

@#Abstract：Objective To analyze the stabilities of neuraminidase（NA）in influenza vaccine at different temperatures and provide a reference for further complete understanding of overall shelf life of vaccines. Methods Monovalent bulks of influenza H1N1，H3N2 and B vaccines were stored at 4（low temperature），25（room temperature）and 37 ℃（changed temperature）for 0. 5，2，7，24 and 48 h separately，using that at 100 ℃（extreme temperature）for 1 h as control，and determined for NA activity by enzyme⁃linked lectin method. Results The NA activities of influenza H1N1 vaccines stored at 25 and 37 ℃ decreased significantly with the increasing of time. No significant decreases were observed in H3N2 and B vaccines even after storage at two non⁃storage temperatures for 48 h. However，all the NA activities of three vaccines decreased at 100 ℃. Conclusion Both H3N2 and B vaccines showed high stability at abnormal storage temperatures not more than 37 ℃，while H1N1 vaccine was relatively sensitive to the temperature for storage.

CiteSpace knowledge map of research hotspots and frontiers of traditional Chinese medicine intervention in psoriasis in recent ten years / 中国中药杂志

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.@*METHODS@#Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.@*RESULTS@#Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).@*CONCLUSION@#KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience / 中华血液学杂志

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis / 中华烧伤杂志

Objective: To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis. Methods: The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score <2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test. Results: The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ2=14.57, P<0.01). Conclusions: Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission.

Tapping at acupoints along meridian combined with thunder-fire moxibustion for upper-limb hemiplegia after stroke / 中国针灸

OBJECTIVE@#To observe the effect of tapping at acupoints along meridian combined with thunder-fire moxibustion on upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke.@*METHODS@#A total of 140 patients with upper-limb hemiplegia after stroke were randomly divided into a combination group (35 cases, 2 cases dropped off), an acupoint-tapping group (35 cases), a moxibustion group (35 cases, 2 cases dropped off) and a routine group (35 cases). The patients in the routine group were only treated with routine treatment and nursing. On the basis of the treatment in the routine group, the patients in the acupoint-tapping group were treated with tapping along the large intestine meridian of hand @*RESULTS@#Compared before treatment, body mass indexs of shoulder abduction, elbow extension, wrist flexion as well as BI scores in the four groups were significantly increased after treatment (@*CONCLUSION@#Tapping at acupoints along meridian combined with thunder-fire moxibustion could effectively improve the upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke, and its effect is superior to simple tapping at acupoints along meridian or thunder-fire moxibustion.

Comparison of Murraya exotica and Murraya paniculata by fingerprint analysis coupled with chemometrics and network pharmacology methods / 中国天然药物

There are two source plants for the traditional Chinese medicine Murrayae Folium et Cacumen (MFC) in Chinese Pharmacopoeia, i.e. Murraya exotica L. and M. paniculata (L.) Jack. Herein, a chemical comparison of M. exotica and M. paniculata by high performance liquid chromatography (HPLC) fingerprint analysis coupled with chemometrics and network pharmacology was performed. The main peaks in the fingerprints were identified by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) and authenticated by references. The chemometrics results showed that the HPLC fingerprints of these two species were clearly divided into two categories using hierarchical cluster analysis (HCA) and principal component analysis (PCA), and a total of 13 significantly differentiated markers were screened out by orthogonal partial least squares-discriminant analysis (OPLS-DA). However, the following network pharmacology analysis showed that these discriminated markers were found to act via many common targets and metabolic pathways, indicating the possibly similar pharmacological effects and mechanisms for M. exotica and M. paniculata. The above results provide valuable evidence for the equivalent use of these two plants in clinical settings. Moreover, the chromatographic fingerprint analysis coupled with chemometrics and network pharmacology supplies an efficient approach for the comparative analysis of multi-source TCMs like MFC.

The Significance of CD319 and CD269 in the Detection of Immunophenotyping and Minimal Residual Disease in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD319 and CD269 in plasma cells of patients with multiple myeloma (MM) and the feasibility of using CD319 instead of CD38 as a gating antigen in immunophenotyping and minimal residual disease (MRD) monitoring.@*METHODS@#The expression levels of CD319 and CD269 antigens in clonal bone marrow plasma cells of 387 patients were detected by CD38/CD138 gating strategy with 8-color flow cytometry, and the stability of antigens was also analyzed, and the sensitivity and correlation of two different gating strategies employing CD319/CD138 and CD38/CD138 were compared as well. The control group consisted of 53 cases with non-malignant blood disease matched by age and sex.@*RESULTS@#Monoclonal plasma cells were detected in 303 of 387 MM patients, among which 277 cases (91.42%) were positive for CD269, and all cases were positive for CD319 (100%). In newly diagnosed MM (NDMM) and recurrent refractory MM (RRMM) patients, the expression levels of CD269 were 97.53% (0-99.92%) and 94.96% (0.22%-99.99%), respectively, while levels of CD319 were 99.90% (87.77%-100%) and 99.78% (63.12%-100%), respectively. The expression levels of CD269 and CD319 in the control group were 97.00% (77.00%-100%) and 100% (89.00%-100%), respectively. There were no significant differences in the expression levels of CD269 and CD319 among NDMM, RRMM and the control group. Patients acquiring therapeutic effects were divided into complete remission (CR) group, very good partial response (VGPR) group and partial response (PR) group. Gating with CD38/CD138, median MRD values were 0.76% (0-1.88%), 0.77% (0-4.96%) and 1.75% (0.09%-10.90%) in the three groups, respectively, while gating with CD319/CD138, median MRD values were 0.57% (0.18%-1.96%), 1.07% (0.12%-4.85%) and 1.77% (0.08%-8.22%), respectively. There was no significant difference in MRD level by the two gating strategies, but a good correlation between the two (r=0.808, P<0.05). In addition, in 4 patients treated by CD38 monoclonal antibody (DARA), the expression level of CD38 was observed to be down-regulated or even negative after treatment. When the MRD level was very low, CD38/CD138 gating resulted in false MRD@*CONCLUSION@#CD319 and CD269 express stably and continuously in plasma cells of MM patients at different disease stages. CD319 can be used as an alternative of CD38 for immunophenotyping and MRD detection, especially for MRD detection after DARA treatment, while CD269 is suitable for detection before BCMA-CAR-T treatment.

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis based on network pharmacology and molecular docking analyses / 药学学报

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis (AS) were identified by network pharmacology and molecular docking analyses. The Traditional Chinese Medicine Database (TCMD) and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to identify the likely active components of Polygonati rhizoma. The potential targets set of Polygonati rhizoma were predicted with the PharmaDB database and the Swiss TargetPrediction database. The targets set for AS was retrieved by OMIM, DisGeNET and NCBI Gene database. We used the STRING platform to construct a protein-protein interaction network of the intersectional targets and performed visual analysis in Cytoscape. The key targets of Polygonati rhizoma in AS were searched by network topology and the resulting GO and KEGG enrichment was analyzed by Clue GO. In addition, the key targets were verified by molecular docking in Discovery Studio 4.0. A total of 45 active ingredients and 51 potential targets were obtained in the treatment of AS. The results of the topology analysis included five key targets: serum albumin, mitogen-activated protein kinase 3, mitogen-activated protein kinase 1, proto-oncogene tyrosine-protein kinase Src and matrix metalloproteinase-9. The 131 GO items showed that the biological process mainly involved the steroid receptor, cell response to steroid stimulation, the phosphatidylinositol-3 kinase signal pathway, and others. The KEGG pathway analysis included 37 pathways, which were closely related to peroxisome proliferation activated receptor signaling pathway, platelet activation pathway, vascular endothelial growth factor pathway, hypoxia inducible factor pathway and adhesion connection pathway. The results of molecular docking proved that the combined activity of the components with potential key targets is excellent. This study proposes mechanisms by which Polygonati rhizoma might act to reverse or minimize AS and provides a scientific basis for clinical research on Polygonati rhizoma.

Research progress of receptor protein FUNDC1 in mitophagy / 医学研究生学报

Mitochondria, which play an important role in cell metabolism, stress response and cell death, are the key organelles that regulate the energy balance of cells. Under the influence of internal and external environment, damaged or senescent mitochondria pose a serious threat to cell survival. Mitophagy refers to the selective elimination of dysfunctional mitochondria to maintain the homeostasis of the intracellular environment. FUN14 domain containing 1 (FUNDC1) is a newly discovered mitophagy receptor protein, which plays an important regulatory role in mediating mitophagy. This paper mainly reviews the recent research progress of FUNDC1 regulation mechanism and its pathophysiological significance in mitophagy.

Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomized controlled trial / 中华医学杂志(英文版)

Background@#At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The virus has since rapidly spread to all provinces and autonomous regions of China, and to countries outside of China. Patients who become infected with 2019-nCoV may initially develop mild upper respiratory tract symptoms. However, a significant fraction of these patients goes on to subsequently develop serious lower respiratory disease. The effectiveness of adjunctive glucocorticoid therapy uses in the management of 2019-nCoV infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*Methods@#The present study will be conducted as an open-labelled, randomised controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at 4 consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*Discussion@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in severe coronavirus disease 2019 (COVID-19) patients.@*Trial registration@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies / 中华医学杂志(英文版)

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Clinicopathological analysis of mucosa associated lymphoid tissue lymphoma secondary to Sjögren' s syndrome in salivary gland / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinicopathological characteristics of mucosa associated lymphoid tissue (MALT) lymphoma secondary to Sjögren' s syndrome (SS) (SS-MALT lymphoma) in salivary gland and to explore the value of the combined application of histopathological morphology, protein expression and molecular phenotype in pathological diagnosis and prognostic evaluation of SS-MALT lymphoma.@*METHODS@#Sixteen patients with SS-MALT lymphoma were collected from 260 patients who were diagnosed with SS in Peking University School and Hospital of Stomatology from January 1997 to December 2016. Twelve patients with non-MALT lymphoma secondary to SS (non-SS-MALT lymphoma) in salivary gland were selected as controls. The clinical data of the patients were retrospectively reviewed and analyzed. All the patients were followed up until December 20, 2019. Hematoxylin-eosin staining, immunohistochemistry, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were used to observe the histologic characteristics and to detect the manifestations of light chain restrictive expression, immunoglobulin (Ig) gene clonal rearrangement, chromosome translocation and gene abnormality, so as to evaluate their values in pathological diagnosis and prognostic evaluation.@*RESULTS@#The malignant transformation rate of SS to MALT lymphoma was about 6.15%, ranged from 3 to 240 months, during which 2 patients died due to high-level deterioration. Microscopically, the acini of the glandular tissue were atrophied and destroyed. The tumor cells dominated by central cell-like lymphocytes grew diffusely, destroying the epithelial islands. All SS-MALT lymphoma cases were positive in CD20 and Pax5. Half of them had the Ki-67 proliferation index of 10% or less, and half greater than 10%. 93.75% cases expressed AE1/AE3 protein, which showed the residual glandular epithelium. All the tumor cells were negative in CD3ε, and the plasma cells were detected by CD138 antigen. The light chain restrictive expression of κ and λ was 37.5% in SS-MALT lymphoma group. The positive detection rates of immunoglobulin heavy chain (IgH)-FR1, IgH-FR2, IgH-FR3, immunoglobulin kappa chain (IgK)-A, and IgK-B in SS-MALT lymphoma group were 33.3%, 53.3%, 33.3%, 20.0%, and 26.7%, respectively, and 93.3% when together used with IgH and IgK. The positive rates of the MALT1, IGH and BCL6 genes with dual color break-apart probes were 36.4%, 27.3% and 27.3%, and the detection rate of chromosome translocation and gene abnormality by applying the three probes was 72.7%.@*CONCLUSION@#There are no specific histological characteristics and protein phenotypes in the histologic diagnosis of SS-MALT lymphoma in salivary gland. The combined application of histopathological manifestations, immunohistochemistry, PCR and FISH techniques helps the accurate pathologic diagnosis of the disease. Although SS-MALT lymphoma is considered as an indolent lymphoma with a relatively favorable prognosis, the regular return visit and long-term follow-up should be conducted to detect the clues of recurrence and advanced deterioration.

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*METHODS@#The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*DISCUSSION@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

A comparative study on the mechanisms of two classical herbal formulae for rheumatoid arthritis applying cold and heat patterns based on target network / 药学学报

Wu-tou decoction (WTD) and Baihu-Guizhi decoction (BHGZD) as described in the Synopsis of the Golden Chamber have been used extensively for the treatment of rheumatoid arthritis (RA) with apparent therapeutic efficacy. However, characteristics of pharmacological effects and their underlying molecular mechanisms have not been fully elucidated due to a lack of appropriate scientific methodology. In the current study, we performed an integrative approach applying gene expression profiling and network analysis to examine the therapeutic effects and molecular mechanisms of WTD and BHGZD based on adjuvant-induced arthritis (AIA) animal model. Results demonstrated that both WTD and BHGZD could relieve the severity of arthritis in AIA rats, while the significant differences were observed in the changes of the withdrawal response scores and latency time of AIA rats treated with WTD and BHGZD. Mechanistically, our network pharmacology-based investigation demonstrated that the major candidate targets of WTD and BHGZD were significantly associated with several inflammation-immune regulatory pathways, such as Toll-like receptor signaling pathway, T cell receptor signaling pathway, cytokine-cytokine receptor interaction, chemokine signaling pathway, B cell receptor signaling pathway, antigen processing and presentation, Fc epsilon RI signaling pathway, natural killer cell mediated cytotoxicity, as well as leukocyte transendothelial migration. In particular, the major candidate targets of WTD were also involved in the regulation of hormone and energy metabolism, which might be imbalanced during RA progression. In conclusion, the current study revealed differences and similarities regarding the effects and network regulatory mechanisms of WTD and BHGZD. These findings may present a scientific basis for elucidation of mechanisms by which WTD and BHGZD alleviates RA.

Rapid screening and identification of sesquiterpene lactones in Kudiezi injection based on high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry / 中国天然药物

Sesquiterpene lactones are considered as the major active compounds in Kudiezi injection in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of sesquiterpene lactones in Kudiezi injection using high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Second, based on extracted ion chromatography (EIC) data-mining method and characteristic fragmentation pathways analysis, sesquiterpene lactones in Kudiezi injection were rapidly screened and identified. Finally, an important parameter Clog P was adopted to discriminate the isomers of sesquiterpene lactones. As a result, 50 sesquiterpene lactones were characterized, including 9 sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively identified as new compounds. The results demonstrated that the established method would be a rapid, effective analytical tool for screening and identification of sesquiterpene lactones in the complex system of natural medicines.

Protective effect of Sestrin2 on apoptosis of dendritic cells induced by high mobility group box-1 protein / 解放军医学杂志

Objective To investigate the potential role of Sestrin2 (SESN2) in regulating the apoptosis of dendritic cells (DCs) induced by high mobility group box-1 protein (HMGB1).Methods DCs (the murine DC cell line DC2.4) were cultured with or without HMGB1 stimulation (cultured with 10ng/ml HMGB1 for 8,24 and 48 hours,or cultured with HMGB1 for 48 hours at different concentrations of 1,10 and 100ng/ml,respectively,n=4).The protein level of SESN2,cleaved-caspase-3 and Bcl-2 were analyzed with Western blotting.Localization of SESN2 in cells was observed under confocal laser microscope (LSCM).Cell apoptosis was analyzed with flow cytometry.In addition,DC2.4 cells were transfected with lentivirus containing SESN2 LV-RNA,SESN2 siRNA sequence expressing plasmids or blank vector (NC,NS,n=4).These cells were then stimulated with HMGB1 (100ng/ml)for 48 hours,and the apoptosis was accessed as mentioned above.Results Compared with the control group,the expression of SESN2 was obviously up-regulated after HMGB1 (10ng/ml) stimulation for 24 and 48 hours (P＜0.05).In a dose-dependent response,the expression of SESN2 was markedly enhanced in treatment with 1,10,100ng/ml HMGB1 for 48 hours (P＜0.05).Compared with the control group (7.35％ ± 1.33％),the percentage of apoptosis was significantly increased with 10,100ng/ml HMGB1 for 48 hours [(17.02％ ± 4.85％,17.48％ ± 4.04％,respectively,P＜0.05 or P＜0.01].After transfection,compared with blank vector group,the apoptosis of SESN2 siRNA group obviously elevated [(65.96％ ± 2.50％) vs.(50.01％ ± 2.07％),P＜0.05],and cleaved-caspase-3 expression significantly increased while Bcl-2 expression obviously decreased.In SESN2 LV-RNA group,the apoptosis significantly decreased [(35.57％ ± 1.69％) vs.(49.04％ ± 4.87％),P＜0.05],and cleaved-caspase-3 expression decreased and Bcl-2 expression obviously increased compared with blank vector group (P＜0.05).Conclusion SESN2 has a protective effect against HMGB 1 induced apoptosis of D C2.4 cells.

Role of the Ca-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes.</p><p><b>METHODS</b>We manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells. One-way analysis of variance and Student's t-test were performed to determine the statistical significance between the groups.</p><p><b>RESULTS</b>Overexpression of MFN2 enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 ± 10.130 vs. 266.940 ± 10.170, P = 0.000), calcineurin (0.513 ± 0.014 vs. 0.403 ± 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs) activation (1.040 ± 0.086 vs. 0.700 ± 0.115, P = 0.005), whereas depletion of MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+ (141.140 ± 14.670 vs. 267.060 ± 9.230, P = 0.000), calcineurin (0.054 ± 0.030 nmol/L vs. 0.404 ± 0.063 nmol/L, P = 0.000), and NFAT activation (0.500 ± 0.025 vs. 0.720 ± 0.061, P = 0.012). Furthermore, upregulated calcineurin partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity evidenced by elevations in T cell proliferation (1.120 ± 0.048 vs. 0.580 ± 0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 ± 24.100 vs. 175.330 ± 12.900 pg/ml, P = 0.000), and the interferon-γ/IL-4 ratio (3.080 ± 0.156 vs. 0.953 ± 0.093, P = 0.000). Meanwhile, calcineurin activity inhibitor depleted the positive effects of overexpressed MFN2 on T cells function.</p><p><b>CONCLUSIONS</b>Our findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.</p>