Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits / 神经科学通报·英文版

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Cardiovascular complications in malaria: a review / 中国中药杂志

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.

Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target / 中国中药杂志

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Neglect and associated factors among children aged 3-6 years in families with non only children in Beijing-Tianjin-Hebei Region / 中国学校卫生

Objective@#To analyze the neglect status of children aged 3-6 years old from non-only-child families in Beijing-Tianjin-Hebei region and influencing factors, so as to provide assistance for the healthy growth of preschool children from non-only-child families.@*Methods@#From April to June 2022, 2 882 parents of preschool children from 15 kindergartens were selected in urban areas of Beijing-Tianjin-Hebei by randomized cluster sampling method, and were investigated with general information and neglect experiences. The χ 2 test, t-test and ANOVA were used to compare the neglect status of different categories of preschool children, and the binary Logistic regression method was used to analyze the influencing factors of the neglect of preschool children who were not only children.@*Results@#The detection rate of neglect among children aged 3-6 years from non-only-child families in the Beijing-Tianjin-Hebei region was 33.47%, the detection rate of neglect among children from only-child families was 9.24%, and the difference was statistically significant ( χ 2=261.94, P <0.01). The neglect score for children aged 3-6 years in non-only-child families was (42.35±7.52), the neglect score for onechild families was (38.16±6.56), and the difference was also statistically significant ( t=15.95, P <0.01). Binary Logistic regression analysis showed that family income <4 000 yuan/month ( OR= 2.75, 95%CI =1.18-6.32), grandparents or other relatives as the primary guardian ( OR=2.18, 95%CI =1.35-3.52), and poor parental relationship ( OR=2.64, 95%CI =1.42-3.87), average ( OR=2.31, 95%CI =1.32-4.01) non-only-child preschoolers had a higher risk of neglect ( P <0.05).@*Conclusion@#Neglect is prevalent among 3-to 6-year-old children from non-only-child families in the Beijing-Tianjin-Hebei region. Targeted intervention measures based on influencing factors should be taken to reduce neglect among preschool children.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Role of NRF2 signaling pathway in trichloromethane-induced oxidative stress in L02 cells / 中国职业医学

@#Objective - （ ） To investigate the effects of nuclear factor erythroid 2 related factor 2 NRF2 on the oxidative stress （ ） Methods ） ，， induced by trichloromethane TCM in human normal hepatocyte L02 cells. i L02 cells were stimulated with 1 2 ， ， ， （ ）， 4 8 12 16 and 20 mmol/L TCM solution dissolved in dimethyl sulfoxide and the control group and blank group were set ， - ， up. After culturing for 24 hours the cell viability was detected by CCK 8 colorimetric method and the concentration of TCM ） -， - stimulation was screened. ii L02 cells in logarithmic growth phase were randomly divided into control group and low medium - ， ， ， and high dose groups. After 24 hours of exposure to 0 4 8 and 12 mmol/L TCM the cells were collected. The activity of （ ）， （ ）， （ - ） （ ） superoxide dismutase SOD catalase CAT glutathione peroxidase GSH Px and the level of malondialdehyde MDA NRF2， - （HO-1）， were detected by colorimetric analysis. The mRNA expression levels of heme oxygenase 1 glutamate cysteine （GCLC） （） （NQO1） - ligase catalytic subunit and NAD P H quinone dehydrogenase 1 were detected by real time fluorescence ， - ， polymerase chain reaction. The protein levels of NRF2 HO 1 GCLC and NQO1 were detected by Western blotting.Results ） ， ， ， ， i When the concentration of TCM was 4 8 12 16 and 20 mmol/L the survival rate of L02 cells decreased （ P ） ， ， significantly compared with the control group all <0.05 . The concentration of 0 4 8 and 12 mmol/L were selected as the ） ， - stimulation doses for subsequent experiments. ii Compared with the control group the activities of SOD and GSH Px in L02 （ P ） （ P ）， - cells in the three doses groups decreased all <0.05 and the levels of MAD increased all <0.05 with a dose effect - （P ）， relationship. The CAT activity of L02 cells in the medium dose group was lower than that in the control group <0.05 and the - （ P ） CAT activity of L02 cells in the high dose group was lower than that in the others three groups all <0.05 . Compared with the ， NRF2 - （P ），NRF2 control group the relative expression levels of mRNA in L02 cells in the low dose group decreased <0.05 - （P ）， NRF2 mRNA in L02 cells in the medium dose group increased <0.05 mRNA and NRF2 protein expression in L02 cells in （ P ） HO-1，GCLC， NQO1 ， the highdose group increased both <0.05 . The relative expression level of mRNA and GCLC NQO1 （ P ） protein expression in L02 cells in the three doses groups increased compared with the control group all <0.05 . The relative NRF2 - - - expression level of mRNA in L02 cells in the high dose group was higher than that in the low and medium dose groups （ P ）， - （P ）， both <0.05 and the relative expression of NRF2 protein was higher than that in the low dose group <0.05 but the HO-1 GCLC - - （ relative expression levels of and mRNA and HO 1 protein level were lower than those in the medium dose group all P ）Conclusion - <0.05 . TCM exposure can inhibit the proliferation of L02 cells by inducing oxidative stress with a dose effect ， relationship. In this process the antioxidant mechanism mediated by NRF2 was activated. The expression of antioxidant defense ， - ， and detoxification related target genes downstream of NRF2 signaling pathway was activated and the expression of HO 1 - GCLC and NQO1 was up regulated to alleviate the oxidative damage caused by TCM.

Retropharyngeal lymph node dissection in head and neck cancers treated with transoral robotic surgery / 中华肿瘤杂志

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

The clinical value of oral robotic surgery in the treatment of oropharyngeal squamous cell carcinoma / 中华肿瘤杂志

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P<0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P<0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P>0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P<0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P=0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P<0.001). HPV status was an independent prognostic factor (P=0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.

Application of transoral robotic surgery in treatment of oropharyngeal squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the therapeutic and prognostic outcomes of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OSCC). Methods: A retrospective study of 99 OSCC patients treated with TORS in Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center between April 2017 and May 2021 was conducted. There were 84 males and 15 females, with an age range of 35-85 years. Patients' clinical characteristics, including clinical staging, HPV infection status, perioperative management and postoperative adjuvant treatment, were recorded. The overall survival (OS) and progression-free survival (PFS) were analyzed. The survival outcomes were analyzed with Kaplan-Meier method and Log-rank test. Results: The hospital stay of OSCC patients with TORS was (5.3±2.9) days and the average time of postoperative nasal feeding tube indwelling was (15.2±10.8) days. Among the 99 patients, 21 (21.2%) received tracheotomy and the average time of tracheotomy tube indwelling was (11.9±11.4) days. The two-year OS and PFS in patients with follow-up over two years were 94.0% and 87.7%, respectively and the three-year OS and PFS of patients with follow-up over three years were 94.0% and 78.9%, respectively. The two-year OS and PFS were respectively 97.4% and 88.9%, for patients with stages I-II and 86.8% and 88.9% for patients with stages III-IV. HPV-negative and HPV-positive patients had respectively two-year OS (100.0% vs. 91.5%) and PFS (88.9% vs. 87.2%). There was no significantly statistical difference in survival between patients with and without adjuvant radiotherapy after TORS (82.6% vs. 90.5%, HR=0.52, 95%CI: 0.12-2.23, P=0.400). Conclusions: TORS is more suitable for the treatment of patients with early (Ⅰ-Ⅱ) or HPV-positive oropharyngeal squamous cell carcinoma, and the recovery after TORS treatment is good.

Effect of panlong needling at Jiaji (EX-B 2) on motor dysfunction in patients with Parkinson's disease of liver and kidney deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the curative effect of panlong needling at Jiaji (EX-B 2) combined with western medication and western medication alone on motor dysfunction in patients with Parkinson's disease (PD) of liver and kidney deficiency.@*METHODS@#A total of 98 patients with PD were randomly divided into an acupuncture and medication group (49 cases, 1 case dropped off) and a western medication group (49 cases,1 case was removed). The patients in the western medication group were given oral of levodopa and benserazide hydrochloride tablets, 125 mg each time, three times a day in the 1st week, and the dose was increased according to the needs of the patients' condition from the 2nd week until 250 mg each time, three times a day, for 16 consecutive weeks. On the basis of the same western medication treatment as the western medication group, panlong needling was applied at Jiaji (EX-B 2) from C2 to L5 in the acupuncture and medication group, once a day, 20 times as a course of treatment, for 4 consecutive courses. The scores of unified Parkinson's disease rating scale (UPDRS-Ⅲ, UPDRS-Ⅳ), TCM symptoms score, and 39-item Parkinson's disease questionnaire (PDQ-39) score were evaluated before treatment, after treatment and during follow-up of 1 month after treatment, respectively. The safety of the two groups was compared.@*RESULTS@#After treatment and during follow-up, except the PDQ-39 score of the western medication group, the scores of UPDRS-Ⅲ, UPDRS-Ⅳ, TCM syndrome and PDQ-39 were lower than those before treatment in the two groups (P<0.05), and the scores of above indexes in the acupuncture and medication group were lower than those of the western medication group (P<0.05). The total incidence of adverse reactions in the acupuncture and medication group was 10.4% (5/48), which was lower than 29.2% (14/48) in the western medication group (P<0.05).@*CONCLUSION@#Panlong needling at Jiaji (EX-B 2) combined with western medication could significantly improve the motor dysfunction and clinical symptoms, improve the quality of life and has high safety, and the efficacy is superior to western medication alone.

Effect Analysis of Artemisiae Annuae Herba and Chuanxiong Rhizoma in Treatment of Cerebral Malaria Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio^® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.

Effect and Mechanism of Shenlian Formula in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases / 中国实验血液学杂志

OBJECTIVE@#To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level.@*METHODS@#IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR.@*RESULTS@#CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing.@*CONCLUSION@#Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.

Determination of β-nicotinamide mononucleotide and nicotinamide adenine dinucleotide in Dendrobium officinale and congeneric species by UPLC-MS/MS / 中国中药杂志

As anti-aging ingredients, β-nicotinamide mononucleotide(NMN) and nicotinamide adenine dinucleotide(NAD~+) have attracted worldwide attention in recent years. After oral administration, NMN can be converted into NAD~+ in vivo and the latter is the actual ingredient which exerts anti-aging effect. In order to explore the "rejuvenating and anti-aging" effect of Dendrobium officinale, which was firstly recorded in Shennong's Herbal Classic of Materia Medica, this study established the quantitative method of UPLC-MS/MS for simultaneous determination of NMN and NAD~+ in D. officinale and the congeneric species for the first time, and 34 batches of samples were detected. UPLC conditions are as follows: ACQUITY UPLC HSS T3 column(2.1 mm × 100 mm, 1.8 μm), gradient elution with acetonitrile-0.1% formic acid in water at the flow rate of 0.3 mL·min~(-1), and column temperature of 40 ℃. MS conditions were scanned electrospray ionization source and multiple reaction monitoring mode. The method was verified by systematic methodology. The mean recoveries of NMN and NAD~+ were 77.58% and 80.70%, respectively, with RSD of 3.6% and 4.3%, separately. All results showed that the content of NMN was higher in D. officinale than in the other congeneric species. Particularly, the content in fresh D. officinale stems was as high as 0.931 9 μg·g~(-1). NAD~+ was only found in D. officinale and the content was three times higher than that of NMN. This may be the reason that D. officinale topped the "nine famous anti-aging herbs". In addition, processing method influences the content of NMN and NAD~+ in Dendrobium. Specifically, the content of NMN and NAD~+ was in the order of fresh Dendrobium stems > dried Dendrobium stem segments > spiral or spring-like dried Dendrobium stems.

Rapid discovery of tyrosinase inhibitors from Sophora flavescens:significance for comprehensive utilization of its non-medicinal resources / 中国中药杂志

Sophorae Flavescentis Radix,derived from the root of Sophora flavescens in the Leguminosae family,has been widely used in the medicine,agriculture,animal husbandry,and daily chemical industry. A pharmacophore model-based method for rapid discovery of tyrosinase inhibitors( TIs) from S. flavescens was established by molecular docking under Lipinski rules,and verified by enzyme assays. Briefly,the chemical constituent database of S. flavescens( CDSF) was established based on the previous papers. Theoptimal pharmacophore model( OPM) was constructed by DS 2019 on the basis of known active TIs. Eighty-three hits predominated by flavonoids having higher fitting scores with OPM than the positive control were screened out,and subjected to molecular docking based on the three-dimensional structure of tyrosinase crystal protein. The potential TIs such as kurarinone and nor-kurarinone were rapidly discovered from the compounds with higher docking scores than the positive control under the Lipinski rules. The results were verified by the in vitro enzyme assays. The inhibition activities of tyrosinase from non-medicinal parts of S. flavescens were also tested to explore the relationship between the inhibition activity and chemical compositions. This study is expected to provide data support for the comprehensive application and development of S. flavescens and also a new method for the rapid discovery of active substances or functional constituents in the complex systems.

Predictive diagnostic value of serum 25-hydroxyvitamin D3 in eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

Transoral robotic surgery for parapharyngeal space neoplasm: a report of 7 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the safety, efficacy and feasibility of transoral robotic surgery (TORS) for parapharyngeal space (PPS) neoplasms. Methods: We collected data from 7 patients with PPS neoplasm who received TORS in Sun Yat-sen University Cancer Center between May 2017 and November 2020, and patients' clinical and pathological characteristics were analysed. There were 2 men and 5 women with age ranged from 35 to 76 years. Among them, 2 patients underwent secondary surgery, 2 patients required combined transcervical approach to complete surgery, and 1 patient was suspected of ipsilateral cervical lymph node metastasis and scheduled for diagnostic TORS. The preoperative tumor size, operation time, intraoperative blood loss, postoperative bleeding, dyspnea, neurological impairment, feeding time and postoperative hospital stay were analyzed. SPSS 24.0 was used to analyze the data. Results: TORS was performed successfully with complete removal of tumors in all 7 cases. Among 6 patients with curative TORS, 5 patients received TORS with postoperative diagnoses of neurogenic tumors and 1 patient underwent TORS combined transcervical approach with postoperative disgnosis of recurrent pleomorphic adenoma; no intraoperative tumor rupture occurred; the intraoperative blood loss was 20-200 ml with a median of 40 ml; the operation time was 65.0-238.0 min with a median of 77.5 min; the oral feeding time was 3-6 days with a median of 3 days; and the postoperative hospital stay was 4.2±1.6 days. One patient presented with neck swelling 3 days after surgery, but this symptom relieved 3 days later after treatments with antibiotic, hemostasis and detumescence. One patient received diagnostic TORS, as intraoperative pathology indicating a recurrent pleomorphic adenoma, then the neoplasm got completely resected through transcervical-transparotid approach. None of 7 patients manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All patients were followed for 2 to 44 months, no local recurrence or distant metastasis was found. Conclusions: TORS is a safe, effective and feasible treatment for selected PPS neoplasms, with less cosmetic impact, less trauma and blood loss, few postoperative complications, enhanced postoperative recovery and short hospital stay.