BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.

Objective To investigate the knowledge-attitude-practice(KAP)of drug application among university students in Karamay,to analyze potential risk factors of medication risk.Methods Using the convenience sampling method,the basic information,current status of the KAP of medication of university students in Karamay were collected through online and offline questionnaire.Multiple linear regression was performed to analyze the influence of different characteristics of the research objects on KAP concerning medication risk.Results A total of 948 valid questionnaires were retrieved,the interviewees were mostly aged between 18 and 20 years old(55.06％),females(63.92％)were more than males(36.08％).The mean scores of knowledge,behavior,education and attitude towards medication among university students were(36.17±11.82),(31.04±9.17),(11.66±4.66)and(11.50±3.53)respectively.Most university students had good drug use habits and considered it necessary to acquire knowledge about safe drug use through different ways and forms,but they lacked awareness on safe drug use in terms of purchasing drugs,storing drugs,drug use behavior and drug use education.Multiple linear regression analysis showed that the major of study was an influential factor in medication knowledge(P＜0.01),with pharmacy majors demonstrating better mastery.It also in medication behavior(P＜0.01),with pharmacy majors exhibiting more standardized practices.Gender was an influential factor in attitudes toward medication education(P＜0.05),with females showing more positive attitude.Conclusion The knowledge of drug application among university students in the city is relatively good,and they have good medication habits.However,there are shortcomings in their medication behavior and education.It is necessary to actively carry out targeted medication education activities to promote safe and rational medication among university students.

Noise is a common occupational hazard in workplaces. Long-term exposure to high-intensity noise mainly causes occupational noise-induced hearing loss (ONIHL). The development of ONIHL is irreversible, and there is currently no cure. At present, risk assessment methods based on noise exposure intensities mainly include risk index assessment method, Engineering Professional Council assessment method in United Kingdom (EDC assessment method in UK), National Institute of Occupational Safety and Health assessment method in United State (NIOSH assessment method in US), and International Standardization Organization assessment method (ISO assessment method). However, the risk index assessment method is subjective and does not consider the effectiveness of workers wearing protective equipment. The EDC assessment method in UK defines ONIHL differently from China. The NIOSH assessment method in US and ISO assessment methods have population data sources that deviate from China, which can lead to bias in risk assessment. In the future, it is necessary to further carry out application research on the risk assessment of ONIHL in Chinese noise-exposed workers, compare the applicabilities of various assessment methods, conduct large-sample population epidemiological studies for verification, and fully utilize the risk-prediction function to prevent and control ONIHL.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 30 compounds(including antianginal drugs, anticoagulant, anti-platelet aggregators and anti-inflammatory analgesics) illegally added in Chinese patent medicine for promoting blood circulation and removing blood stasis. METHODS The sample was extracted by ultrasonication with 60% methanol. The analysis was performed on Phenomenex Kinetex C18 column (2.1 mm×100 mm, 2.6 μm) with gradient elution using 0.1% formic acid solution and acetonitrile as the mobile phase at the flow rate of 0.3 mL·min–1, and the column temperature was 40 ℃. Mass spectrometry was collected using electrospray ionization (ESI), simultaneous scanning of positive and negative ions, and multiple reaction monitoring mode. RESULTS The linearity of the 30 compounds was good in the mass range examined, with the correlation coefficients all >0.999. The limits of detection of each compound ranged from 1.3 to 238.4 ng·g–1 and the average recoveries ranged from 63.7% to 108.2% with the RSDs of 1.0% to 6.7%. The method was used to test 90 batches of Shujin Huoxue tablets. Paracetamol was detected in 3 batches, while the rest of the compounds were not detected. The amount of paracetamol detected ranged from 0.16 to 0.93 μg per tablet, which was much lower than the minimum daily dose of the corresponding drug, excluding intentional addition. The probable explanation was the residues caused by incomplete cleaning validation of the enterprise’s collinear production. CONCLUSION This method is rapid, accurate, highly sensitive, and highly selective, and can be used for qualitative screening and quantitative determination of 30 chemical compounds illegally added in Chinese patent medicine for promoting blood circulation and removing blood stasis.

Objective:To investigate the value of serum vascular endothelial growth factors (VEGF), pepsinogen ratio (PGR) combined with magnifying chromoendoscopy in the diagnosis of Epstein-Barr virus associated gastric carcinoma (EBVaGC).Methods:A retrospective case control study was conducted. The clinical data of 314 patients with gastric cancer who were confirmed by pathological examination in Baoji Central Hospital from January 2018 to January 2023 were retrospectively collected. All patients were divided into EBVaGC group (34 cases) and EB virus negative gastric cancer (EBVnGC) group (280 cases) according to the result of EB virus quantitative real time polymerase chain reaction in serum before treatment, while 50 healthy volunteers who underwent the physical examination in the same period were selected as the control group. The level of VEGF was detected by using enzyme-linked immunosorbent assay (ELISA), and serum levels of pepsinogen (PG) Ⅰ and PGⅡ were detected by using fluorescence immunochromatography. PGR was calculated by PGⅠ-to-PGⅡ ratio. Electronic magnification gastroscopy was performed, suspicious lesions were stained and the pathological state of gastric tissues was observed. Taking the pathological results of living tissues as the gold standard, the diagnostic efficacy of each index alone and the combination detection for EBVaGC was calculated. Multivariate logistic regression model was used to analyze the independent risk factors of the incidence of EBVaGC.Results:The age of patients in EBVaGC group, EBVnGC group and the healthy control group was (61±10) years, (63±12) years and (61±12) years, respectively; and there were 28 males (82.4%), 228 males (81.4%) and 41 males (82.0%), respectively. There were no statistically significant differences in age and gender among the 3 groups (all P>0.05). The serum VEGF level and the proportion of positive patients detected by endochromatography in EBVaGC group were higher than those in the EBVnGC group and the healthy control group [VEGF: (253±48) pg/ml vs. (183±38) pg/ml, (92±25) pg/ml; positive proportion: 94.1% (32/34) vs. 77.9% (218/280), 2.0% (1/50)], and the PGR in EBVaGC group was lower than that in EBVnGC group and the healthy control group (2.1±1.0 vs. 3.1±1.1, 14.1±1.9), and the differences were statistically significant (all P<0.05). The sensitivity of serum VEGF in the diagnosis of EBVaGC was higher than that of PGR [73.5% (25/34) vs. 66.9% (22/34)]. The diagnostic specificity of PGR [78.2% (219/280) vs. 69.3% (194/280)] and accuracy [76.8% (241/314) vs. 69.8% (219/314)] were higher than those of VEGF. The sensitivity [85.3% (29/34)], specificity [82.9% (232/280)] and accuracy [83.1% (261/314)] of magnifying chromoendoscopy in the diagnosis of EBVaGC were higher than those of VEGF and PGR. The sensitivity [94.1% (32/34)], specificity [95.7% (268/280)] and accuracy [95.5% (300/314)] of the 3 combined detection were higher than those of single and pairwise detection. Multivariate logistic regression analysis showed that the independent risk factors for the incidence of EBVaGC included alcoholism ( OR = 2.310, 95% CI: 1.243-3.581, P = 0.007), spicy food preference ( OR = 1.516, 95% CI: 1.084-2.142, P = 0.026), irregular diet ( OR = 1.448, 95% CI: 1.013-2.104, P = 0.043), family history of gastric cancer ( OR = 2.732, 95% CI: 1.312-4.894, P = 0.001). Conclusions:Serum VEGF and PGR combined with magnifying chromoendoscopy can improve the diagnostic efficiency of EBVaGC, and developing good eating will be helpful to prevent or slow down the progression of stomach diseases.

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Humans ; Rabies Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Rabies virus ; Vaccination ; Rabies/prevention & control*

Objective: To explore the effectiveness of preventive treatment for latent tuberculosis infection (LTBI) patients, so as to provide reference for the management and preventive treatment of clustered epidemic in schools. Methods: Data came from the school tuberculosis outbreak of a boarding high school in Kaizhou District, Chongqing, which occurred between June 2017 and March 2018 among 2016 grade high school teachers and students for investigation and analysis. The total incidence, LTBI patients, and the incidence after preventive treatment for 5 years were followed up. Results: A total of 34 cases of pulmonary tuberculosis from June 2017 to March 2018. A total of 1 357 individuals were screened for 6 concentrated contact screenings, with a confirmed tuberculosis rate of 2.43%, a tuberculosis skin test (TST) positive rate of 27.41%, and a strong TST positive rate of 7.39%. Among them, the confirmed tuberculosis rate and TST positive rate in the first case class were much higher than those in other classes, with statistically significant differences ( χ 2=286.30, 98.59, P ＜0.01). 88 cases of LTBI were found, with 31 cases receiving preventive treatment (35.23%), of which 28 completed preventive treatment (90.32%). After five years of follow-up, 73 cases of pulmonary tuberculosis were diagnosed in 2016 by the school senior high school, with a incidence rate of 0.98/10 2 (person/person years). Fifteen of the 88 LTBI patients were diagnosed with pulmonary tuberculosis, and the incidence rate was 3.33/10 2 (person/person years). The incidence rate of the preventive treatment group was 0.7/10 2 (person/person years)lower than that of the medical observation group 4.5/10 2 (person/person years), with a statistically significant difference ( χ 2=4.31, P ＜0.05). Conclusion The classes with higher TST positive rate and strong positive rate have higher incidence rate. Improving the preventive treatment rate of LTBI patients can effectively reduce the incidence rate of tuberculosis.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Objective:The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored.Methods:(1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed.Results:(1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions:Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

Objective:To explore the effect of the demand-oriented system training in the training of advanced nurses in the Chest Pain Center Cardiac Catheterization Laboratory.Methods:From January 2018 to December 2020, convenience sampling was used to select nurses who were trained in the Chest Pain Center Cardiac Catheterization Laboratory of Hunan Provincial People's Hospital as the research subject. The nurses who engaged in advanced studies from January 2018 to June 2019 were set as the control group ( n=57) , and the nurses who engaged in advanced studies from July 2019 to December 2020 were set as the observation group ( n=60) . The control group conducted traditional training, and the observation group carried out demand-oriented system training on the basis of the control group. The theoretical and operational assessment scores, comprehensive ability and satisfaction were compared between the two groups of nurses before and after advanced studies. Results:After the intervention, the nurses in the observation group had higher scores in theoretical and operational assessment, clinical skill and management in comprehensive ability and the satisfaction score than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The effect of the demand-oriented system training in the advanced nurses in the Chest Pain Center Cardiac Catheterization Laboratory is better than the traditional training, and it is worthy of clinical promotion.