Hepatocellular carcinoma (HCC) is a serious threat for human health, the incidence of HCC in China accounts for more than 50% worldwide. There is an urgent need to develop novel anticancer agents for the treatment of HCC patients. Here we characterized the inhibitory effect and the molecular mechanism of protopine on HCC cancer cells. The results of a CCK-8 assay indicated that protopine displays anticancer activities on HCC cells. Flow cytometry and JC-1 staining confirmed that treatment with protopine decreased the mitochondrial membrane potential and induced apoptosis in HCC cells. Western blot analysis showed that protopine was able to increase protein expression in the mitochondrial apoptotic pathway; the level of cytochrome C, apoptotic protease activating factor-1 (Apaf-1), Bax, cleaved-poly ADP-ribose polymerase (cleaved-PARP), cleaved-caspase-3, and cleaved-caspase-9 were increased while the expression of Bcl-2 was suppressed significantly. An in vivo study revealed that protopine significantly suppressed the growth of tumors in nude mice bearing HepG2 cells. Administration of protopine intraperitoneally at a concentration of 50 mg·kg^-1 inhibited tumor growth by 72.46%. Animal experiments were carried out according to the Regulation of the Animal Ethics Committee of Southwest Medical University. This study provides preliminary evidence that there is potential to develop protopine as a lead compound for the treatment of HCC.

Totally, 125 elderly inpatients with aspiration pneumonia (AP) were enrolled from departments of respiratory medicine and neurology at Zhongnan Hospital, Wuhan during June 2005 to October 2009 for analysis. Results showed that listlessness was manifested in 70 cases (56%), primary neurological illness in 80 cases (64%), 57 of them (46%) complicated with respiratory failure and 26 died with case-fatality of 21%. Main pathogen for them was Gram-negative bacillus, accounting for 57% of the total. Two kinds or more of antibiotics had ever been administered in 98 cases (78%), with an average length of antibiotics use for 28 days, ranging from one day to 128 days. Nasal feeding was instituted for those with choking over their feeding and coughing, and their inspired feeding was aspirated from the trachea or bronchi and lavished with bronchoscopy, with 38 cases by tracheal intubation, 26 by tracheotomy and 42 with artificial ventilation. Their average duration of hospital stay spanned 28 days with an average cost of 25 000 RMB yuan per capita, significantly higher than that for those with common pneumonia. In conclusion, clinical features of these elderly patients with AP were not so typical, most of them manifest severe, with lots of medical cost and bad prognosis.

Objective To observe the effects of endobronchial decimeter wave therapy on ventilation func-tion of patients with the constrictive endobronehial tuberculosis (EBTB). Methods Forty-four EBTB patients weredivided into an experiment group and a control group. All the patients of the two groups were treated with generalchemotherapy, the patients of experiment group accepted endobronehial decimeter wave therapy at the same time. Thepurulent secretion or caseous necrosis of the diseased region was drawn-off from the bronchi lumina by bronchoseope,then the antenna of the decimeter wave irradiator was inserted into the diseased region through the biopsy pore to per-form the radiation. The vital capacity, forced expiratory volume in the 1st second and maximal voluntary ventilationwere tested before and 60 days after the operation. Results Endobronehial decimeter wave therapy significantly re-duced the constriction of bronchi, improved the lung ventilation function, and relieved the anhelation symptom of pa-tients in the experiment group to a significantly larger extent than those in the controls group (P< 0. 01 ). Moreover,the therapeutic effects of endobronchial decimeter wave therapy were more significant for the endomembrane tuberculo-sis with pulmonary closure due to ulcerous necrosis or granulation hyperplasy ( P < 0. 05 ) , but ineffective for the atro-phy due to fibrous constriction. Conclusion Endobronchial decimeter wave therapy could reduce the incidence oflung closure in endomembrane tuberculosis and improve lung function.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Disease Outbreaks ; Female ; Herbicides ; poisoning ; toxicity ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Paraquat ; poisoning ; toxicity ; Risk Factors ; Time Factors ; Young Adult

Abstract: Objective　To investigate the pollution of paralytic shellfish poisons (PSP) in shellfish sold in Hainan Province from 2018 to 2021. Methods　From 2018 to 2021, the content of 10 paralytic shellfish poisons including saxitoxin (STX), neosaxitoxin (neoSTX), gonyautoxins 1 (GTX1), gonyautoxins 2 (GTX2), gonyautoxins 3 (GTX3), gonyautoxins 4 (GTX4), gonyautoxins 5 (GTX5), decarbamoylsaxitoxin (dcSTX), decarbamoylgonyau toxins 2 (dcGTX2) and decarbamoylgonyau toxins 3 (dcGTX3) in 7 kinds of shellfish commonly sold in 13 cities and counties in Hainan province was analyzed. Results　The detection rate of PSP in 360 shellfish samples was 10.3%. Among them, the highest detection rate of STX was 5.83%, followed by GTX2 detection rate of 4.17%; the detection rate of neoSTX and GTX3 were both 1.67%; the detection rate of GTX1 was 1.39%. None of the five PSP, GTX4, GTX5, dcSTX, dcGTX2 and dcGTX3, were detected. Four types of PSP were detected in fanscallops, two were detected in oysters, mussels and Scapharca subcrenata, only one was detected in scallops, and no toxin contamination was detected in clams and razor clams. A single sample of fanscallops detected a maximum of 4 PSP, and a single sample of oysters, scallops, mussels and Scapharca subcrenata detected a maximum of 1 PSP. The equivalence of PSP in all samples was ND-155.6 μg/kg.The annual detection rate of PSP from high to low was: 20.0% in 2020, 15.6% in 2019, 5.3% in 2018, and 2.0% in 2021, and none of the samples tested exceeded the standard. Continuously detectable STX in 2018-2020, all PSP that could be detected in 2018 were STX. In 2019, in addition to STX detected in scallops and Scapharca subcrenata, neoSTX was also detected in oysters, mussels and Scapharca subcrenata. In 2020, PSP was only detected from scallops, and GTX2 could be detected in all positive specimens, while 5 STX, 5 GTX1 and 6 GTX3 were detected. Only GTX2 detected from scallops in 2021. STX was detected in shellfish sold in 12 cities and counties, GTX2 can be detected in 10 cities and counties, neoSTX can be detected in 5 cities and counties, GTX1 and GTX2 were detected in 4 cities and counties respectively. Shellfish sold in Wenchang and Lingshui markets can detect 5 types of PSP. Conclusion　Some types of shellfish on the market in Hainan are contaminated with some kind of PSP pollution risks, and it is necessary to strengthen the supervision of PSP in marketed shellfish.

BACKGROUND:Stroke is the leading cause of death and long-term disability. This study was undertaken to investigate the factors influencing daily activities of patients with cerebral infarction so as to take interventional measures earlier to improve their daily activities. METHODS:A total of 149 patients with first-episode cerebral infarction were recruited into this prospective study. They were admitted to the Encephalopathy Center, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical College in Zhejiang Province from August 2008 to December 2008. The baseline characteristics of the patients and cerebral infarction risk factors on the first day of admission were recorded. White blood cell (WBC) count, plasma glucose (PG), and many others of laboratory targets were col ected in the next morning. Barthel index (BI) was calculated at 2 weeks and 3 months respectively after onset of the disease at the outpatient clinic or by telephone cal . Lung infection, urinary tract infection and atrial fibrillation if any were recorded on admission. The National Institute of Health Stroke Scale (NIHSS) scores and the GCS scores were recorded within 24 hours on and after admission, at the second week, and at the third month after the onset of cerebral infarction respectively. RESULTS:The factors of BI at 2 weeks and 3 months after onset were the initial PG level, WBC count and initial NIHSS scores. Besides, urinary tract infection on admission was also the factor for BI at 3 months. CONCLUSION:Active measures should be taken to control these factors to improve the daily activities of patients with cerebral infarction.

Objective To find out the prevalence of bullying behaviors among urban middle school students in China. Methods An anonymous questionnaire survey was conducted among middle school students selected by multiply stage cluster random sampling in 18 provinces in China. 187 328 self- administration questionnaires were finished by students from grade 7 to 12 in urban middle school(male,86 472; female, 91 106), in which 177 578 were valid. Results Bullying was common in urban middle school students in China. Multiple bullying behavior also existed. About 66.1% of boys and 48.8% of girls suffered from one or more kinds of bullying; 8.1% of boys and 2.9% of girls suffered from four or more kinds of bullying. Boys were more likely to be bullied than girls. Malicious teasing was the most common bullying behavior(43.2%), followed by sexual bullying behavior(27.0%). In addition to malicious teasing and sexual bullying, the prevalence of other types of bullying declined when the grade was increasing. Residential students were more likely to be maliciously teased, excluded or isolated and sexual bullied than non-residential students. Students from single-parent or recomposed-families were more likely to be bullied than other students. Male and ordinary school students, students living with single or step-parents were more likely to suffer multiple bullying behaviors at the same time. Conclusion The suggesting among students was associated with personal, familiar and social factors, mobilize more social forces and comprehensive actions to be taken to prevent bullying among students.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective To investigate the variation of procalcitonin(PCT)level and the significance of PCT for the diagnosis of infection during perioperative period of valve replacement for rheumatic heart disease.Methods Routine blood testing and procalcitonin(PCT)level were measured in the perioperative period of 56 patients with rheumatic heart disease receiving valve replacement.Prophylactic antibiotics management was given based on the serum procalcitonin level especialy that 3 days after operation or later.The postoperative infective complications and the duration of prophylactic antibiotics management were recorded and assessed.Results The duration of prophylactic antibiotics for all patients were 4.6 ± 2.0 days.Six patients were suffered from poor incision healing and one was suffered from pulmonary infection.There were no severe postoperative infective complications.The PCT of the patients without postoperative infection rise to peak level on the 1st day after operation and return to normal on the 3rd day.There was no significant difference in the PCT levels between the two groups.The duration for PCT descending to 0.25 mg/L was 3.7 ± 2.5 days.The PCT level of the patients suffered from pulmonary infection went up again after infection on the 5th day and return to normal on the 9th day.No severe postoperative infective complications happened after withdrawn of prophylactic antibiotics if PCT had descended tobelow 0.25 mg/L after operation.Conclusions The serum PCT level may be a good parameter for the prediction or diagnosis of infective complication in the perioperative period of patients undergoing valve replacement for rheumatic heart disease.It can be a useful marker to guide the use of prophylactic antibiotics.

Objective To investigate the dynamic expressions of exchange protein directly activated by cyclic adenosine monophosphate (cAMP) (Epac) in rat model of hepatic fibrosis(HF).Methods Forty-two male SD rats were divided into control group (n = 6) and model group (n = 36)which was divided into six subgroups of day 4, week 1, week 2, week 4,week 6 and week 8 with six rats in each subgroup. The rat model of HF was established by intraperitoneal injection of dimethylnitrosamine (DMN). The pathological changes of liver were observed by Hematoxylin-Eosin and Masson staining. Reverse transcription-polymerase chain reaction (RT-PCR),immunohistochemistry and Western blot were employed to detect the mRNA and protein expressions of Epac1, Epac2 and transforming gronth factor (TGF)β1 during the process of modeling and localization in the liver. The statistical analysis was done using one-factor ANOVA, LSD-t test,Dunnett T3 test and Pearson linear correlation analysis. Results Rat model of liver fibrosis was established successfully. In control group, Epac1 (0. 031 28±0. 008 96) and Epac2 protein (0.034 43±0. 002 45) mainly expressed in the cytoplasm of hepatocytes. In model group, the level of Epac1 decreased at day 4 (0. 023 97±0. 003 81) and week 1 (0. 015 81±0. 002 48) ,then began to increase at week 2 of modeling and peaked at week 6 (0. 039 54±0. 001 43), which had statistical significance compared to the control group (t= 5.47,11.58 and - 6.18, respectively; all P＜0.05). Epac2 protein expression declined after modeling, reached the lowest level at week 4 (0. 011 21 ±0. 001 32), which had statistical significance compared to the control group (t= 24. 50, P＜0. 05). TGFβ1 protein expression increased after modeling and peaked at week 4 (0. 011 30±0.001 03) which had statistical significance (t= -23. 36, P＜0. 05) compared to the control group (0. 002 08 ±0. 000 18). The expressions of Epac1, Epac2 and TGFβ1 mRNA were consistent with the trend of protein levels.Correlation analysis showed that Epac1 protein was positively correlated with the course of HF (r =0. 703, P＜0.01 ), while Epac2 protein was negatively correlated (r = - 0. 409, P＜0.05). Conclusions During the progression of HF, Epac1 expression tends to decrease firstly and increase afterwards,while Epac2 expression declines continually. Epac may be involved in the pathogenesis of HF.