Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD.

Chronic inflammatory and immune responses play key roles in the development and progression of chronic obstructive pulmonary disease (COPD). PANoptosis, as a unique inflammatory cell death modality, is involved in the pathogenesis of many inflammatory diseases. We aim to identify critical PANoptosis-related biomarkers and explore their potential effects on respiratory tract diseases and immune infiltration landscapes in COPD. Total microarray data consisting of peripheral blood and lung tissue datasets associated with COPD were obtained from the GEO database. PANoptosis-associated genes in COPD were identified by intersecting differentially expressed genes (DEGs) with genes involved in pyroptosis, apoptosis, and necroptosis after normalizing and removing the batch effect. Furthermore, GO, KEGG, PPI network, WGCNA, LASSO-COX, and ROC curves analysis were conducted to screen and verify hub genes, and the correlation between PYCARD and infiltrated immune cells was analyzed. The effect of PYCARD on respiratory tract diseases and the potential small-molecule agents for the treatment of COPD were identified. PYCARD expression was verified in the lung tissue of CS/LPS-induced COPD mice. PYCARD was a critical PANoptosis-related gene in all COPD patients. PYCARD was positively related to NOD-like receptor signaling pathway and promoted immune cell infiltration. Moreover, PYCARD was significantly activated in COPD mice mainly by targeting PANoptosis. PANoptosis-related gene PYCARD is a potential biomarker for COPD diagnosis and treatment.

Pharmaceutical care for one case of levofloxacin-induced hypersensitivity reaction by the participation of clinical pharmacists and literature analysis / 中国药房

OBJECTIVE To analyze the characteristics of levofloxacin-induced hypersensitivity reaction. METHODS Clinical pharmacists participated in the treatment for a case of levofloxacin-induced hypersensitivity reaction， and adjudged the relationship of levofloxacin with hypersensitivity reaction according to relative standards. Retrieved from CNKI， VIP， Wanfang database， PubMed and Embase， relevant literature about levofloxacin-induced hypersensitivity reaction was collected and analyzed. RESULTS Clinical pharmacists suggested checking the patient’s previous medication and allergy history based on symptoms such as fever and systemic rash， and determined that the drug hypersensitivity was “likely” or “highly likely” to be associated with levofloxacin. Clinicians provided symptomatic treatment to the patient based on the judgment of clinical pharmacists， and the patient improved after treatment. Results of the literature analysis showed that among 31 involved patients， there were 23 males and 8 females； 18 patients aged 50 and above； the incubation period of 24 patients was within 4 days after medication. The main adverse drug reactions were drug hypersensitivity syndrome， fixed drug eruption， erythema multiforme， etc. Most patients were improved after withdrawal and symptomatic treatment. CONCLUSIONS Hypersensitivity reaction is the rare adverse drug reaction of levofloxacin， mostly occurring within 2.5 h to 4 days after administration， and it is more likely to occur in middle-aged and elderly patients. Before clinical use， patients should be asked about their drug allergy history in detail； when patients experience fever or rash without obvious causes， medication should be stopped promptly and symptomatic treatment should be taken to ensure the safety and effectiveness of the patients’ medication.

Exploring the protective mechanism of Tibetan medicine Potentilla anserine on cyclophosphamide-induced myelosuppression based on metabonomics technology / 药学学报

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Research progress of diabetic renal fibrosis / 中国药理学通报

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes mellitus. Diabetic renal fibrosis ( DRF) is a major pathological change in the development of DN. In recent years the incidence of renal fibrosis (RF) has remained high. For diabetic patients, RF may expose them to kidney transplantation or even death, which brings a great burden to themselves and their families. Therefore, learning the pathogenesis and the current treat ment status of DRF is crucial for the treatment of the disease and the development of new drugs. Here we review the general situa¬tion of DN, the general situation, molecular mechanism, and the treatment of DRF,looking forward to providing a reference for the research and treatment of DRF.

Analysis of the impact of health management measures for entry personnel on imported Dengue fever in Guangdong Province, 2020-2022 / 中华流行病学杂志

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.

Clinicopathological features and prognostic factors of patients with lung metastasis of stage Ⅰa~Ⅲb cervical cancer / 中华肿瘤杂志

Objective: To investigate the clinicopathological features and prognostic factors of lung metastasis in patients with cervical cancer after treatment. Methods: The clinicopathological data of 191 patients with lung metastasis of stage Ⅰa-Ⅲb cervical cancer (FIGO 2009 stage) treated in Sichuan Cancer Hospital from January 2007 to December 2020 were analyzed retrospectively. Kaplan Meier method and Log rank test were used for survival analysis, and Cox regression model was used for prognostic factors analysis. Results: Among 191 patients with lung metastasis of cervical cancer, pulmonary metastasis was found in 134 patients (70.2%) during follow-up examination, and 57 patients (29.8%) had clinical symptoms (cough, chest pain, shortness of breath, hemoptysis, and fever). The time from the initial treatment of cervical cancer to the discovery of lung metastasis was 1-144 months in the whole group, with a median time of 19 months. Univariate analysis of the prognosis of lung metastasis after treatment of cervical cancer showed that the diameter of cervical tumor, lymph node metastasis, positive surgical margin, disease-free interval after treatment of cervical cancer, whether it is accompanied by other metastasis, the number, location and maximum diameter of lung metastasis, and the treatment method after lung metastasis are related to the prognosis of patients with lung metastasis of cervical cancer. Multivariate analysis showed that the number of lung metastases and other site metastases in addition to lung metastases were independent factors affecting the prognosis of patients with lung metastases of cervical cancer (P<0.05). Conclusions: For patients with cervical cancer, attention should be paid to chest CT examination during follow-up to guard against the possibility of lung metastasis after treatment. Besides lung metastasis, other site metastasis and the number of lung metastasis are independent factors affecting the prognosis of patients with lung metastasis of cervical cancer. For patients with lung metastasis after treatment of cervical cancer, surgical treatment is an effective treatment. It is necessary to strictly grasp the surgical indications, and some patients can achieve long-term survival. For patients with lung metastasis of cervical cancer who are not suitable for resection of lung metastasis, the remedial treatment of chemotherapy with or without radiotherapy is still a recommended choice.

Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism.@*METHODS@#MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot.@*RESULTS@#RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.@*CONCLUSION@#RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

Effect of Inhibiting SIX1 Expression on Drug-resistance of Acute Myeloid Leukemia Cell Line HL-60/ADR Cells / 中国实验血液学杂志

OBJECTIVE@#To establish HL-60 cells and adriamycin resistant HL-60 cells (H-60/ADR) in which the expression of homologous box gene 1 (SIX1) was inhibited, and investigate the effect of inhibiting the expression of SIX1 on the drug resistance.@*METHODS@#Lentivirus was used to transfect HL-60 and HL-60/ADR cells, and the cell lines stably inhibiting the expression of SIX1 were screened by puromycin. CCK-8 assay was used to detect the proliferation ability of cells in each group, apoptosis kit was used to detect the cell apoptosis, and real-time quantitative PCR was used to detect the expression level of drug-resistant related genes.@*RESULTS@#HL-60 and HL-60/ADR stably transfected cell lines with down-regulation of SIX1 expression were successfully constructed. Compared with control group, the inhibition of SIX1 expression significantly inhibited the proliferation of HL-60 and HL-60/ADR cells (P <0.05), increased the apoptosis rate (P <0.05), and the sensitivity of cells to adriamycin increased after inhibition of SIX1 expression.@*CONCLUSION@#Inhibition of SIX1 expression can improve cell sensitivity to adriamycin, and its role in reversing drug resistance may be related to the promotion of apoptosis gene expression.

The Expression and Correlation of miR-195, miR-125 and Calreticulin in Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression and correlation of microRNA-195 (miR-195), miR-125 and calreticulin in diffuse large B-cell lymphoma (DLBCL).@*METHODS@#From April 2020 to April 2021, 80 DLBCL patients with complete data archived by the Pathology Department of Handan First Hospital and The Second Hospital of Hebei Medical University were selected as the study group, and 70 patients with reactive lymph node hyperplasia were selected as the control group. The expressions of miR-195 and miR-125 were detected by real-time fluorescence quantitative PCR, and the expression of calreticulin was detected by Western blot. Pearson correlation was used to analyze the correlation between miR-195, miR-125, calreticulin and DLBCL, and ROC curve was used to analyze the predictive value of miR-195, miR-125 and calreticulin for DLBCL.@*RESULTS@#Compared with the control group, the expression of miR-195 decreased but miR-125 and calreticulin increased in the study group (P<0.001). The expression levels of miR-195, miR-125 and calreticulin were not related to sex, age, primary site and B symptoms of patients with DLBCL, but related to immunophenotype, Ann Arbor stage, lactate dehydrogenase, IPI score, nodule involvement and Ki-67 index. The expression of miR-195 decreased and the expression of miR-125 and calreticulin increased in DLBCL paitents with non-germinal center source, Ann Arbor stage III-IV, lactate dehydrogenase > 245 U/L, IPI score 3-5, nodule involvement≥2 and Ki-67 index≥75% (P<0.05). Pearson correlation analysis showed that miR-195 and miR-125 were negatively correlated (r=-0.536, P=0.001), miR-195 and calreticulin were negatively correlated (r=-0.545, P=0.001), while miR-125 and calreticulin were positively correlated (r=0.523, P=0.001). ROC curve showed that compared with the single diagnosis of miR-195, miR-125 and calreticulin, the combination of the three items had higher predictive value for DLBCL (P<0.001).@*CONCLUSION@#The expression of miR-195 decreases and the expression of miR-125 and calreticulin increase in patients with DLBCL. Along with the increase of disease stage and IPI score, the decrease of miR-195 and the increase of miR-125 and calreticulin aggravate gradually. The three items may participate in the occurrence and progress of DLBCL.

Performance appraisal of the business operation of a public hospital based on entropy weighted TOPSIS method / 中华医院管理杂志

Objective:To evaluate the business performance of an urban public tertiary hospital in Jiangsu province since the comprehensive reform of urban public hospitals started from the end of 2015, for reference in developing relevant policies.Methods:Such level-1 indicators as risk management ability, asset operation ability, revenue and expenditure structure management, asset profitability and future development ability were selected based on literature review, along with 14 level-2 indicators, to build an operation performance appraisal indicator system for urban public hospitals. The entropy weight TOPSIS method was used to evaluate the business performance of an urban public hospital in Jiangsu province from 2015 to 2019.Results:The drugs proportion(a level-2 indicator) under the revenue and expenditure structure management, the growth rate of fixed assets(a level-2 indicator) under the future development ability, and the total return(a level-2 indicator) under the asset profitability, were important ones affecting the business performance of hospitals, with the weights of 0.099, 0.097 and 0.080 respectively. The business operation performance ranking as calculated by the relative closeness, was 2015(0.515), 2016(0.480), 2019(0.467), 2018(0.450) and 2017(0.356) respectively.Conclusions:The reform once resulted in fluctuations in the operation performance of this hospital, with constant declines from 2015 to 2017. With the deepening reform, its performance recovered after 2018 to some extent. It is suggested to improve the business operation performance of urban public hospitals by optimizing their income and expenditure structure, improving their asset operation ability, and matching rationally their asset liability structure, among other measures.

Efficacy of ultrasound-guided serratus plane block versus PecsⅡblock for perioperative analgesia in patients undergoing modified radical mastectomy for breast cancer under general anesthesia / 中华麻醉学杂志

Objective:To compare the perioperative analgesic efficacy of ultrasound-guided serratus plane block (SPB) with pectoral nerves Ⅱ (Pecs Ⅱ) block in patients undergoing modified radical mastectomy for breast cancer under general anesthesia.Methods:Sixty female patients, aged 20-60 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for modified radical mastectomy for breast cancer, were divided into 2 groups ( n=30 each) using a random number table method: SPB group (group S) and Pecs Ⅱ block group (group P). Both groups received ultrasound-guided nerve block with 0.5% ropivacaine 20 ml before induction of general anesthesia.The patients in both groups received patient-controlled intravenous analgesia.Tramadol 100 mg was intramuscularly injected as rescue analgesic.The block status of each segmental dermatome, comsumption of intraoperative remifentanil and analgesics (sufentanil in patient-controlled intravenous analgesia and rescue analgesics) within 24 h after operation, duration of nerve block, Horner syndrome, and complications such as respiratory depression, nausea and vomiting within 24 h after operation were also recorded. Results:Compared with group S, the block rate of T 5-T 7 dermatome and consumption of sufentanil after surgery were significantly decreased ( P<0.01), and no significant change was found in the consumption of remifentanil and duration of nerve block in group P ( P>0.05). No rescue analgesic was used and no nerve block-related complications and postoperative complications were found in either group. Conclusions:The ultrasound-guided Pecs Ⅱ block provides better efficacy than SPB in the patients undergoing modified radical mastectomy for breast cancer under general anesthesia.

Effects of menopause on depressive and anxiety symptoms in community women in Beijing / 中华妇产科杂志

Objective:To determine the effects of menopausal stage, age and other associated risk factors on symptoms of anxiety and depression among women in a community in Beijing.Methods:This study was a community-based prospective cohort. Participants who had transitioned through natural menopause, completed two or more depressive and anxiety symptoms evaluations, aged 35 to 64 years, and did not use hormone therapy were selected from the Peking Union Medical College Hospital aging longitudinal cohort of women in midlife to this analysis. The primary outcome variables were depressive and anxiety symptoms, assessed by hospital anxiety and depression scale (HADS). The generalized estimation equation was used in the statistical analysis.Results:Followed up from 2006 to 2014, 430 women and 2 533 HADS assessments were retained in the cohort. Depressive symptoms were more common than anxiety symptoms during all menopausal stages. The incidences of depressive and anxiety symptoms were 14.5% (19/191) and 3.1% (4/191) in the premenopausal -3 stage, respectively. The incidence increased in both menopausal transition and postmenopausal stage, with the highest incidence in the +1c stage [20.6% (155/751) and 8.8% (66/751), respectively]. However, these differences were not statistically significant (all P>0.05). Depressive symptoms were highest in the ≥60-<65 age group [20.8% (74/355)], and anxiety symptoms were highest in the ≥50-<55 age group [8.2% (62/754)]; but there were no statistical significances between different age groups and depressive and anxiety symptoms (all P>0.05). Multivariable analysis showed that high body mass index, low education status, and poor health status were independently associated with depressive symptoms (all P<0.05), and that poor health status, trouble falling asleep, and early awakening were independently associated with anxiety symptoms (all P<0.01). Conclusions:Depressive and anxiety symptoms are more common during menopausal transition and postmenopausal stage compared with reproductive stage. Depressive symptoms are more common than anxiety symptoms. To screen and assess depressive and anxiety symptoms in perimenopausal women is essential, especially for women with high risk factors.

Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes / 中华肝脏病杂志

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

The Treatment of Newly Diagnosed Primary Immune Thrombocytopenia by Recombinant Human Thrombopoietin Combined with Glucocorticoid / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP).@*METHODS@#Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed.@*RESULTS@#The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment.@*CONCLUSION@#RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.

Mechanism of Tibetan medicine Ershiwuwei Shanhu Pills on scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway / 中国中药杂志

This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice / 中国中药杂志

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.

Mechanism of Tibetan medicine Ershiwuwei Songshi Pills against liver injury induced by acetaminophen in mice based on Keap1/Nrf2 and TLR4/NF-κB p65 signaling pathways / 中国中药杂志

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.

Research progress on precious Tibetan medicine formula in prevention and treatment of central nervous system diseases / 中国中药杂志

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.

Application of imaging evaluation in endovascular recanalization of non-acute symptomatic intracranial large artery occlusion / 国际脑血管病杂志

Many studies have shown that endovascular recanalization is feasible for the treatment of non-acute symptomatic intracranial large artery occlusion. However, its incidence of perioperative complications is relatively high. Appropriate imaging evaluation can better observe the occluded segments of the vessels before procedure, thereby guiding the choice of clinical treatment.

Analysis on characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive after discharge in Guangdong Province / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive in anal and/or throat swabs after discharge during the domestic imported epidemic stage in Guangdong Province in early 2020. Methods: The COVID-19 confirmed cases with the onset time before March 1, 2020 in Guangdong Province were collected to analyze the demographic data, epidemiological characteristics, and specimen collection and testing data after discharge. Logistic regression model was used for influencing factors analysis of re-positive cases. Results: A total of 1 286 COVID-19 confirmed cases were included, the M(Q1,Q3) of age was 44(32,58)years, 617 cases were male, 224 cases were re-positive in anal and/or throat swabs with the re-positive rate 17.42%. The M(Q1,Q3) of age of re-positive cases was 35(23, 50) years, which was younger than that of re-negative cases age was those 46(33, 59) years (P<0.001). With the increase of age, re-positive rate decreased (χ2trend=52.73, P<0.001). 85.27% (191/224) of re-positive cases were found in 14 d after discharge, the duration time of re-positive status was 13(7, 24) d, and 81.69% (183/224) of re-positive cases were re-tested negative in 28 d after re-positive date. No fever and other symptoms had been observed among re-positive cases during the whole follow-up. No secondary infectious cases had been found among close contacts after 14 d of centralized isolation and sampling screening. Univariate logistic regression model analysis revealed that the influencing factors of the re-positive cases included age, occupation, clusters, clinical types, and admission time. Multivariate logistic regression model analysis revealed that age was an independent risk factor. Conclusions: SARS-CoV-2 viral nucleic acid re-positive is found in COVID-19 confirmed cases after discharge in Guangdong Province. Most re-positive cases are confirmed among 14 d after discharge and re-test to negative among 28 d after re-positive date. Age is an risk factor for re-positive cases after discharge.