OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Reduced protein S activity is one of the high-risk factors for venous thromboembolism.Hereditary protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene.We reported a female patient with a mutation of c.292 G>T in exon 3 of the PROS1 gene,which was identified by sequencing.The genealogical analysis revealed that the mutation probably originated from the patient's mother.After searching against the PROS1 gene mutation database and the relevant literature,we confirmed that this mutation was reported for the first time internationally.
Humans ; Female ; Protein S/genetics* ; Protein S Deficiency/genetics* ; Pedigree ; Mutation

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

ObjectiveTo explore the effects and related mechanisms of modified Shuyuwan on the decline of learning and memory in Alzheimer's disease （AD） mice. MethodForty 5-month-old SPF APP/PS1 mice were randomly divided into model group， Donepezil group， modified Shuyuwan group， modified Shuyuwan+ chloroquine （CQ） group， 10 mice in each group， the same background wild type C57BL/6J ten mice were set as the normal group. Among them， the modified Shuyuwan group was given the modified Shuyuwan decoction （10 g·kg^-1）， the Donepezil group was given the Donepezil hydrochloride solution （0.45 mg·kg^-1）， the modified Shuyuwan + CQ group was CQ （10 mg·kg^-1） was injected intraperitoneally on the basis of the modified Shuyuwan group， and the normal group and the model group were given the same amount of normal saline intragastrically， once a day， for a total of 35 days. After the administration， Morris water maze experiment and new object recognition experiment to detect the spatial memory ability of mice. TdT-mediated dUTP Nick-End Labeling（TUNEL） staining to detect the apoptosis level of mouse hippocampal CA1 neurons， biochemical detection of reactive oxygen species （ROS） and superoxide in mouse hippocampal neurons dismutase （SOD） levels. transmission electron microscopy to observe the ultrastructure of neuronal mitochondria in the CA1 region of mouse hippocampus. Western blot to detect mouse hippocampal mitochondrial autophagy adaptor protein （p62） and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）， PTEN-induced kinase 1 （PINK1）， E3 Ubiquitin Ligase（Parkin）protein expression level. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） detection of mouse hippocampal mitochondrial forkhead transcription factor O1 （FoxO1）， PINK1， Parkin mRNA expression level. ResultCompared with the normal group， the escape latency of the model group mice increased significantly， the number of crossing platforms and the retention time in the target quadrant decreased significantly， the relative resolution index decreased significantly， and the ability to recognize new objects was weakened （P<0.05）， neurons in the hippocampus CA1 area decreased. The number of dead cells increased significantly （P<0.05）， the level of ROS was significantly increased （P<0.01）， and the level of SOD was significantly decreased （P<0.01）， the morphology of hippocampal mitochondria was severely damaged， the expression of p62 and LC3Ⅱ proteins increased （P<0.01）， Parkin protein expression decreased （P<0.05）， and PINK1 protein expression increased （P<0.05）， FoxO1， PINK1， Parkin mRNA expressions all decreased （P<0.05）. Compared with the model group， the mice's escape latency was significantly shortened after the intervention of the modified Shuyuwan， the number of crossing platforms and the proportion of residence time in the target quadrant increased significantly， the relative resolution index increased significantly， and the ability to identify new objects was enhanced （P<0.05）. Apoptotic cells were significantly reduced （P<0.05）. ROS levels were significantly reduced （P<0.01）， and SOD levels were significantly increased （P<0.05， P<0.01）， mitochondrial morphology and various structures were significantly improved， p62， LC3Ⅱ protein expression decrease （P<0.05，P<0.01）， PINK1， Parkin protein expression increased （P<0.01）. FoxO1， PINK1， Parkin mRNA expression increased （P<0.05， P<0.01）. Compared with the modified Shuyuwan group， the evasion latency of mice in the modified Shuyuwan + CQ group increased significantly， the number of crossing platforms and the proportion of residence time in the target quadrant decreased， and the relative resolution index decreased （P<0.05）， the SOD level was significantly reduced （P<0.01）. The damage of mitochondrial morphology and structure increased again， the expression of p62 and LC3Ⅱ protein increased （P<0.05， P<0.01）， and the expression of PINK1 and Parkin decreased significantly（P<0.05， P<0.01）. FoxO1， PINK1， and Parkin mRNA expression was significantly reduced （P<0.05， P<0.01）. ConclusionModified Shuyuwan can effectively improve the oxidative stress damage and learning and memory ability of AD mice. The mechanism may be related to up-regulating the expression of FoxO1， PINK1， and Parkin factors， promoting mitochondrial autophagy， reducing oxidative stress， and protecting neuronal damage.

China ; Deep Learning ; Emergency Service, Hospital/statistics & numerical data* ; Forecasting/methods* ; Humans ; Triage ; Weather

Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics* ; MicroRNAs/genetics* ; Netrin Receptors ; RNA, Long Noncoding/genetics*

Objective: To explore the relationship between plasma coagulation factor XIII (FXIII) and bleeding events. Methods: A total of 55 cases of acute leukemia (AL) at the myelosuppression phase after chemotherapy hospitalized in our hospital from August 2017 to March 2018 were enrolled, with 35 normal controls. The concentration of plasma coagulation factor XIII (FXIII) was detected by ELISA to determine the relationship between the plasma FXIII levels in AL patients at the myelosuppression phase after chemotherapy with bleeding events. Results: The level of FXIII in AL patients at the myelosuppression phase after chemotherapy was significantly lower than that in controls (P<0.001) . The level of FXIII was inversely related with the bleeding severity (the Spearman correlation coefficient -0.761) . Given the diagnosis cut-off point of FXIII concentration as 103.9 μg/L, the sensitivity of diagnosing bleeding in AL patients at the myelosuppression phase after chemotherapy was 0.939, and the specificity 0.909. Conclusion: AL patients at the myelosuppression phase after chemotherapy had low level of plasma FXIII, and patients with lower plasma FXIII associated with higher incidence and severity of bleeding. FXIII level was an independent influencing factor of bleeding in AL patients at the myelosuppression phase after chemotherapy.
Acute Disease ; Blood Coagulation Tests ; Factor XIII ; Factor XIII Deficiency ; Hemorrhage ; Humans ; Leukemia