Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.

ObjectiveTo understand the visual environment sanitation in primary and secondary school classrooms in Minhang District， Shanghai， and to investigate the factors affecting the decline in students’ visual acuity. MethodsIn 2020， among all the primary and secondary schools in Minhang District， according to different types of classroom structures， levels， orientations， unilateral lighting， and bilateral lighting， a total of 20 231 students from 674 classrooms in primary and secondary schools were selected through stratified cluster sampling. Each monitored classroom was regarded as a research unit， and the naked eye vision of students was tested using a standard logarithmic vision chart during the 2020 and 2021 academic years. The change in average visual acuity between the two measurements was taken as the dependent variable， and the visual environment indices were considered as independent variables. The relationship between classroom visual environment indices and the decline in students’ naked eye vision was analyzed. ResultsThe qualification rates for per capita classroom area， window to floor area ratio， average illuminance of the blackboard， uniformity of blackboard illuminance， average illuminance of the desks， uniformity of desk illuminance， lighting coefficient of classroom， blackboard reflection ratio， back wall reflection ratio， and distance between lamps and desks were 79.53%， 88.58%， 46.74%， 70.33%，64.69%， 80.86%， 71.81%， 20.30%， 1.63%， and 97.53%， respectively. The average naked eye vision of primary and secondary school students in the 2020 academic year was 4.75±0.37 （right eye） and 4.76±0.37 （left eye）， while in the 2021 academic year， it was 4.70±0.39 （right eye） and 4.71±0.38 （left eye）. There was a significant decrease in the naked eye vision of primary and secondary school students in the 2021 academic year compared to that of 2020 （P<0.05）. Univariate linear regression analysis showed a significant correlation between grade， average illuminance of the blackboard， average illuminance of the desks， uniformity of desk illuminance， lighting coefficient， and distance between lamps and desks， and the decline of students’ naked eye vision within one academic year （P<0.05）. After adjusting for grade， multiple linear regression analysis revealed a significant correlation between the average illuminance of the blackboard， uniformity of desk illuminance， lighting coefficient， and distance between lamps and desks， and the decline of students’ naked eye vision within one academic year （P<0.05）. Higher average illuminance of the blackboard， uniformity of desk illuminance， lighting coefficient， and distance between lamps and desks were protective factors for naked eye vision. ConclusionThe visual environment of primary and secondary school classrooms in Minhang District is a matter of concern. Average illuminance of the blackboard， uniformity of desk illuminance， lighting coefficient， and distance between lamps and desks are related to the degree of visual impairment in students over a year.

Objective To explore the analgesic effect of different doses of dezocine combined with ropivacaine for thoracic paravertebral block(TPVB)on patients undergoing thoracoscopic radical resection of lung cancer and the influence on hemodynamics and immune function of patients.Methods Patients with lung cancer who underwent thoracoscopic radical resection were divided into low-dose group and high-dose group according to random number table method.Both groups of patients were given total intravenous anesthesia to complete the surgery.At 15 min before general anesthesia induction,the low-dose group was given TPBV with 0.1 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL,and the high-dose group was given TPBV with 0.15 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL.Comparisons were performed on both groups in terms of analgesic effect,hemodynamic parameters,immune function and occurrence of adverse drug reactions.Results There were 48 cases in low-dose group and 46 cases in high-dose group.In low-dose group,the heart rate values before TPVB,before skin incision,at 5 min after sectioning and at the end of surgery were(78.52±6.54),(70.79±7.07),(74.48±6.68)and(76.69±7.29)beat·min-1,the mean arterial pressure values were(93.16±5.72),(86.38±7.51),(92.15±6.36)and(91.14±6.13)mmHg.In high-dose group,the heart rate values at the above time points were(79.36±7.11),(71.68±6.49),(74.76±7.06)and(76.57±6.52)beat·min-1;the mean arterial pressure values were(93.89±7.18),(85.27±7.41),(90.34±6.52)and(92.43±6.34)mmHg,there were no statistical differences between the two groups(all P＞0.05).The resting state scores at 2,6 and 12 h after surgery were(1.38±0.19),(1.54±0.21)and(1.72±0.16)points,the pain scores at motion state were(1.88±0.15),(2.36±0.37)and(3.26±0.38)points in low-dose group;in high-dose group,the resting state scores were(1.32±0.17),(1.58±0.22)and(1.81±0.18)points,the pain scores at motion state were(1.81±0.13),(2.11±0.31)and(3.03±0.36)points,respectively,there were no statistical differences between the two groups(all P＞0.05).The number of analgesic pump compressions at 24 h after surgery and the number of cases with analgesic remedy were(5.12±1.26)times and 15 cases in low-dose group and were(4.74±1.03)times and 10 cases in high-dose group,with no statistical differences between the groups(all P＞0.05).The percentages of CD3+cells in low-dose group at the end of surgery and at 12 h and 24 h after surgery were(68.51±6.76)％,(54.22±5.43)％and(51.47±6.58)％,the percentages of CD4+cells were(40.29±5.02)％,(34.94±4.79)％and(30.48±5.11)％,CD4+/CD8+ratios were 1.54±0.34,1.36±0.28 and 1.16±0.23;the percentages of CD3+cells in high-dose group were(67.92±7.11)％,(56.58±6.36)％and(54.47±6.89)％,percentages of CD4+cells were(41.33±5.75)％,(35.86±5.21)％and(32.27±4.78)％,the CD4+/CD8+were 1.53±0.35,1.40±0.30 and 1.22±0.26,all with no significant difference(all P＞0.05).The incidence of postoperative adverse drug reactions in high-dose group and low-dose group were 32.61％and 14.58％,with significant difference(P＜0.05).Conclusion When TPVB regimen of dezocine combined with ropivacaine is used in thoracoscopic radical resection of lung cancer,the analgesic effect of low-dose dezocine is comparable to that of high-dose dezocine,with lower risk of adverse drug reactions.

The chimeric antigen receptor T cell(CAR-T)therapy products approved for market and under development mainly targets the B-cell receptor-related protein CD19.This paper relies on the pharmacovigilance database during clinical trials of the Center for Drug Evaluation National Medical Products Administration.We retrospectively analyzed the 113 individual case safety expedited reports of suspected unexpected serious adverse reactions of CAR-T cell therapy products containing B-cell receptor-rolated protein CD19 from domestic clinical trials received from January 1,2021 to May 20,2024.Strengthen risk management according to product characteristics.It is expected that through this paper,the sponsors can improve the pharmacovigilance regime and system,timely report according to the requirements,strengthen the risk communication with the regulatory authorities,form a joint force with the regulatory authorities,and jointly do a good job in risk management during clinical trials.

In recent years,chimeric antigen receptor T cell(CAR-T)therapeutic products have shown good efficacy in the treatment of blood tumors,and breakthroughs have also been made in the treatment of solid tumors and autoimmune diseases.In order to further understand the clinical research and development progress of CAR-T products,this paper mainly uses the drug clinical trial registration and information publication platform of the Center for Drug Evaluation National Medical Products Administration as the information source,and focuses on the statistical analysis of the clinical trial progress of domestic CAR-T cell therapy products containing the targeted B-cell receptor-related protein CD19.It is hoped to further improve the quality and efficiency of clinical research and development of CAR-T cell therapy products,strengthen the sponsor's awareness of main responsibility,and timely update trial information to protect the rights and interests of subjects during clinical trials.

Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM_2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM_2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM_2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO₄+NaCl and anhydrous Na₂SO₄+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~1000 ng·mL⁻¹ with the correlation coefficients all greater than 0.96. The method detection limits (MDLs) ranged from 0.01 to 0.29 ng·m⁻³. The spiked recoveries of SCCPs, MCCPs, and LCCPs at the low, medium, and high concentrations were 77.38%-81.64%, 93.11%-99.78%, and 87.41%-101.39%, respectively, and the relative standard deviations (RSDs) were 2.90%-12.84%. This method was used to determine the CPs levels in 11 PM_2.5 samples from Shijiazhuang. The positive rates of ∑SCCPs, ∑MCCPs, and ∑LCCPs were all 100%, the concentration ranges were 0.24-2.18 ng·m⁻³ (mean 0.84 ng·m⁻³), 0.17-1.67 ng·m⁻³ (mean 0.70 ng·m⁻³), and 0.01-0.16 ng·m⁻³ (mean 0.04 ng·m⁻³), respectively, and the percentages to ΣCPs were 52.95%, 44.39%, and 2.66%, respectively. Conclusion The method established in this study is simple, time-saving, solvent saving, and can simultaneously detect SCCPs, MCCPs, and LCCPs in PM_2.5, which is suitable for the determination of PM_2.5 samples in large quantities, and can also provide a reference for the detection methods of other halogenated organic compounds in PM_2.5.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway.Methods:A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting.Results:Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 vs. 248.90±12.76 at 6 hours of modeling, 80.13±7.94, 190.40±9.56 vs. 288.90±6.01 at 12 hours of modeling; all P < 0.05]. Western blotting showed that compared with the sham operation group, the protein expressions of iNOS, LC3, and p62 in the sepsis model group were significantly higher at 6 hours and 12 hours after modeling; compared with the sepsis model group, the protein expressions of iNOS, LC3, and p62 in the MB treatment group and MB prevention group were significantly lower at 6 hours and 12 hours after modeling (iNOS/GAPDH: 0.38±0.04, 0.60±0.04 vs. 0.77±0.04 at 6 hours of modeling; 0.38±0.02, 0.66±0.04 vs. 0.79±0.05 at 12 hours of modeling; LC3/GAPDH: 0.13±0.07, 0.42±0.07 vs. 1.05±0.16 at 6 hours of modeling; 0.08±0.02, 0.25±0.03 vs. 0.48±0.09 at 12 hours of modeling; p62/GAPDH: 0.17±0.05, 0.44±0.10 vs. 1.19±0.07 at 6 hours of modeling; 0.07±0.00, 0.28±0.08 vs. 0.69±0.02 at 12 hours of modeling; all P < 0.05). Conclusion:MB can reduce myocardial oxidative stress by inhibiting iNOS expression and mitochondrial autophagy in septic rats, thereby alleviating myocardial damage in sepsis, and has protective effect on myocardial damage in sepsis.