Piplartine is an alkaloids/amide component of Piper species,having diverse pharmacological and biological activities.Recent studies have indicated that piplartine has inhibitory effects on several kinds of tumors and is a kind of potential antitumor drugs.It can inhibit the proliferation of tumor cells,cause cell cycle arrest and induce apoptosis.More investigations suggest that targeting the reactive oxygen species(ROS) stressresponse pathway is closely related to its antitumor activity.

AIM: To study the bioequivalence of domestic and imported Metoprolol Tartrate Tablets in Chinese healthy volunteers.METHODS: According to the rule published by SFDA,the serum concentration of 20 selected volunteers among 18 to 40 years old was determined by HPLC-fluorescence detection after giving domestic and imported Metoprolol Tartrate Tablets 0.1g,and the pharmacokinetic parameters were calculated by DAS software.RESULTS: The method of HPLC-fluorescence detection to study the pharmakokinetics of Metoprolol Tartrate was sensitive,reliable,accurate and reasonable.The main pharmakokinetics parameters of domestic and imported Metoprolol Tartrate Tablets were T_(max):(1.11)?(0.36 h) and(1.39)?(0.65 h) respectively;C_(max):(269.20)?(87.15)(?g?L~(-1)) and(262.03)?(75.52)(?g?L~(-1)) respectively;AUC_(0-12h):(1088.91)?(510.52)(?g?L~(-1)?h) and(1098.29)?5(55.14)(?g?L~(-1)?h) respectively.The relative bioavailability of domestic Metoprolol Tartrate Tablets was(100.09)%.CONCLUSION: The domestic and imported Metoprolol Tartrate Tablets was bioequivalents.

OBJECTlVE To estabIish a simpIe,sensitive and quick method for determination of B7011 in rat pIasma. METHODS The method of protein precipitation with methanoI was used for pre-treatment of pIasma sampIes determined by Iiquid chromatography mass spectrometer. The Iinear reIa-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stabiIity of the pIasma sampIes were vaIidated. The concentration of B7011 in pIasma was determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in pIasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectiveIy,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectiveIy. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectiveIy. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectiveIy. CONCLUSlON The estabIished method is sensitive, fast and simpIe and concentration of B7011 in pIasma is determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.

OBJECTIVETo detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation.

METHODSIn a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry.

RESULTSCompared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01).

CONCLUSIONTRPC1 may play a role in ozone-induced lung inflammation in mice.

Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Gene Expression ; Inflammation ; pathology ; Lung ; metabolism ; pathology ; Mice ; Ozone ; adverse effects ; Pneumonia ; metabolism ; pathology ; RNA, Messenger ; TRPC Cation Channels ; metabolism

Objective To detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation. Methods In a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry. Results Compared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01). Conclusion TRPC1 may play a role in ozone-induced lung inflammation in mice.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December,2019.Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving,and driven by adaptation to the new host and environments is still under debate.Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,and providing guidance for disease control and treatments.Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30,2021,we demonstrate with popula-tion genetic evidence that during the course of SARS-CoV-2 pandemic in humans,1)SARS-CoV-2 genomes are overall conserved under purifying selection,especially for the 14 genes related to viral RNA replication,transcription,and assembly;2)ongoing positive selection is actively driving the evolution of 6 genes(e.g.,S,ORF3a,and N)that play critical roles in molecular processes involving pathogen-host interactions,including viral invasion into and egress from host cells,and viral inhi-bition and evasion of host immune response,possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution.According to an established haplotype phylogenetic relation-ship of 138 viral clusters,a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters,of which multiple mutations potentially conferring alterations in viral transmis-sibility,pathogenicity,and virulence of SARS-CoV-2 are highlighted,warranting attention.

Objective To detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation. Methods In a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry. Results Compared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01). Conclusion TRPC1 may play a role in ozone-induced lung inflammation in mice.

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective To investigate the relationship between the risk perception and nursing working environment with the mental resilience in the emergency department nurses.Methods The convenience sam-pling method was adopted.A total of 577 emergency department nurses in 45 hospitals of Guangdong Province from October to November 2023 were selected as the respondents.The CD-RISC scale,nursing staff risk per-ception questionnaire and nursing work environment scale were used to conduct the survey.The multiple line-ar regression was adopted to analyze the influencing factors of mental resilience in the emergency department nurses.The Pearson correlation was adopted to analyze the correlation between the risk perception and nursing working environment with the mental resilience.Results The gender,age,specialist nurse or not,post,hospi-tal type and hospital level had the effect on the mental resilience in the emergency department nurses (P<0.05).The scores of mental resilience scale in 577 nurses were (86.07±15.95) points and the scoring rate was 68.86％;the scores of nursing staff risk perception questionnaire were (79.38±16.32) points and the scoring rate was 56.70％;the scores of the nursing work environment scale were (93.51±13.25) points and the scoring rate was 75.41％.The multiple linear regression analysis showed that the post was the influencing factor of mental resilience in the emergency department nurses.The results of Pearson correlation analysis showed that the nursing work environment was positively correlated with the mental resilience (r=0.476),and negatively correlated with the risk perception (r=-0.252).Conclusion The hospital nursing managers should pay attention to the influencing factors of mental resilience in the emergency department nurses and fo-cus on three major types of risks affecting physical function,time and occupational exposure of the emergency department nurses to improve the working environment of emergency nursing.

Objective:To explore the epidemiologic characteristics and the possible risk factors of microtia in China. Meanwhile, the significant variables related to severe cases are integrated into a predictive nomogram.Methods:A total of 593 patients with congenital microtia from July 2015 to July 2018 were included. Patients conforming to congenital microtia with or without associated malformations were enrolled in this study, and patients with clear chromosomal syndromes were excluded. Questionnaire surveys were conducted among the parents to collect the demographic information and risk factors for exposure during perinatal period. Using Chi-Square and Fisher’s tests to statistically analyze the frequencies of variables. Univariate and multivariate logistic regression analysis were used to select variables related to severe cases for constructing nomogram. Concordance index (C-index), calibration plot, Hosmer-Lemeshow test, and receiver operating characteristics (ROC) curve were used to assess the nomogram model.Results:Of the patients, 456 (76.9%) were male and 137 (23.1%) were female. Right side was involved in 329 cases (55.5%), left side in 217 cases (36.6%) and both sides in 47 cases (7.9%). Among them, 16 cases were familial and the rest were sporadic. Multiple deformations were in 392 cases (66.1%). Maternal illness in early pregnancy( OR=2.205, 95% CI: 1.020-4.020)and parternal drinking history( OR=2.221, 95% CI: 1.329-3.677)were independent risk factors for severe microtia. While mother aged from 26 to 35 years old ( OR=0.507, 95% CI: 0.281-0.913; OR=0.258, 95% CI: 0.125-0.531) and father living in plain area( OR=0.512, 95% CI: 0.288-0.913)may be protective factors. All the significant predictors were combined into a predictive nomogram. The C-index was 0.703(95% CI: 0.646-0.760). The calibration plotshowed good performance of the nomogram, and the model passed Hosmer-Lemeshow goodness-of-fit test ( χ2=4.512, P=0.808). ROC curve analysis revealed a high sensitivity and specificity. Conclusions:The majority of microtia patients are male, sporadic, occur on right side, and often associated with other malformations. This nomogram predicting severe microtia based on multiple parental risk factors was with good discrimination and accuracy, which could provide scientific guidance for individualized prevention in clinical practice.