Objective: To understand the distribution of tobacco retailer within 100 meters outside middle schools in Wuhan City and its impact on smoking behavior of middle school students, so as to provide basis and feasible suggestions for the development of tobacco control policy for adolescents. Methods: From February to May 2023, a multi stage stratified cluster random sampling method was used to select 20 middle schools from 4 districts in Wuhan City. To investigate the distribution of tobacco retailer within 100 metres outside the school and the sale of tobacco to minors. A total of 4 882 students were surveyed using the core questions of the 2021 Chinese Adolescent Tobacco Prevalence Questionnaire. Fisher exact probability test, Chi square test and Chi square trend test were used for statistical analysis. Results: Nearly 70.00% of middle schools had tobacco retailer within 100 metres, with an average of (1.10±0.97) per middle school. The awareness rate (100.00%) and labeling rate (87.50%) of licensed tobacco retailer were higher than those of non licensed tobacco retailer (33.33%, 16.67%) ( P <0.05). The rates of tried smoking, current smoking and buying cigarettes within 30 days were 7.13%, 1.99% and 2.54%, respectively. The rates of students who tried smoking ( 8.58 %), current smoking (2.29%) and buying cigarettes within 30 days (2.85%) in schools with tobacco retailer within 100 metres were higher than those in schools without tobacco retailer (3.79%, 1.28%, 1.83%)( χ 2=35.80, 5.37, 4.37 , P <0.05). And as the grade increased, the rates of tried smoking, current smoking and buying cigarettes among middle school students all showed an upward trend ( χ 2 trend =66.20, 36.10, 16.17, P <0.05). Conclusions Middle school students in Wuhan City have high tobacco availability. The findings suggest that school ban should be extended from 50 meters to 100 meters, and the regulatory authorities must strictly prohibit selling tobacco products to minors at tobacco retailer.

Objective To investigate the clinical efficacy and safety of nivolumab(PD-1 inhibitor)in combination with lenvatinib and FOLFOX regimen[5-fluorouracil(5-FU),oxaliplatin(L-OHP),and calcium folinate(LV)]in the treatment of intermediate and advanced hepatocellular carcinoma(HCC)via hepatic arterial infusion chemotherapy(HAIC).Methods A total of 160 patients with intermediate and advanced HCC admitted to the Second Affiliated Hospital of Guilin Medical University from January 2021 to January 2023 were randomly divided into the control group and the observation group,with 80 patients in each group,using a random number table.The control group received once-daily oral lenvatinib and intravenous carrizumab infusions for 12 weeks as part of transcatheter arterial chemoembolization(TACE)therapy.The observation group was administered with FOLFOX regimen via HAIC chemotherapy,plus intravenous infusion of carrizumab for 12 weeks and once-daily oral lenvatinib.All the patients were followed up regularly.The clinical efficacy was evaluated using the mRECIST criteria.The objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and incidence of adverse reactions were compared between the two groups.Results There were no significant differences in the objective response rate and incidence of adverse reactions between the groups.The disease control rate,overall survival,and progression-free survival in the observation group were significantly higher than those in the control group(P<0.05).Conclusions The FOLFOX-HAIC regimen in combination with nivolumab and lenvatinib is safe and effective for the treatment of intermediate and advanced HCC,without adverse reactions.It can prolong the overall survival and progression-free survival,and improve the patient's quality of life.

Objective:To research and design a negative pressure environment that can be applied in container type of biological isolation shelter,so as to meet the stable negative pressure environment and dynamic intelligent regulation of pressure difference in the container during multimodal transportation,especially under air freight conditions.Methods:The design specifications and research achievements of pressure differences of negative pressure isolation equipment for infectious diseases at home and abroad were comprehensively analyzed.And then,one kind of power-distributed ventilation system without air duct was designed to achieve.The preseted pressure redundancy,real-time monitoring of sensors and dynamic follow-up of pressure were used to realize stable and intelligent regulation of negative pressure within the container during air freight.Results:After testing,the pressure differences of each region of the"three regions and two channels"included clean region,buffer region,contamination region,medical staff passage and patient passage within container type of biological isolation shelter under the negative pressure environment could meet the preseted requirements.The values of pressure differences at the outside of room of clean region,the toilet of clean region,the toilet of clean region of the second dressing room of the buffer region,the contamination region of the first dressing room of the buffer region,the toilet of contamination region and the outside of the room of contamination region were respectively 34.2,38.8,-8.0,-31.7,-15.1 and-44.6.The conditions of the pressure differences within each region of container,which dynamically met the requirements of Biosafety Level-Ⅲ(BSL-3)laboratory,were tested through the sensors,and intelligent display and control equipment that deployed inside of container.Conclusion:The stable negative pressure environment and intelligent regulation for pressure difference in each region of the container can take container to have more high biosafety characteristics,which can effectively ensure the safe transportation of whole region for patients with severe infectious diseases,and the transport and treatment under air freight condition.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objective:To investigate the effects of compound matrine injection on the proliferation of bladder cancer cell line BIU-87 and bladder orthotopic transplantated tumor in nude mice.Methods:BIU-87 cells in logarithmic growth phase were divided into experimental group (adding 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection 200μl) and negative control group (adding equal volume of culturing medium). The proliferation inhibition rate and the half inhibitory concentration ( IC50) of BIU-87 cells were detected and calculated by methyl thiazole tetrazolium (MTT) method. Twenty BALB/c-nu female nude mice were injected with 100 μl of BIU-87 cell suspension with a cell density of 2×10 7/ml in the bladder to establish an animal model of bladder orthotopic transplanted tumor. After 24 hours of perfusion of BIU-87 cell suspension, intravesical perfusion administration (100 μl per nude mouse) was started, and the mice were divided into compound matrine injection group (intravesical perfusion of matrine solution) and pirarubicin group (intravesical perfusion of 1 mg/ml pirarubicin), model control group (intravesical perfusion of the same volume of sterile water), blank control group (without intravesical perfusion of BIU-87 cell suspension or administration). The observation time was 90 d. The survival status and bladder wet weight of the animals were observed and recorded, and the tumor formation rate, tumor inhibition rate and life prolongation rate were calculated. Results:Different concentrations of compound matrine injection acted on BIU-87 cells for 48 hours, and the absorbance ( A) values ??of 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection group and negative control group were 0.027±0.006, 0.065±0.010, 1.695±0.105, 2.387±0.017, 2.427±0.134 and 2.721±0.080 ( F = 742.67, P < 0.05), the A values ??of each concentration of compound matrine injection group were compared with the negative control group, and the differences were statistically significant (all P < 0.05). The IC50 of compound matrine injection on BIU-87 cells was 70.05 μl/ml. On the 90th day of observation, the bladder wet weights of nude mice in blank control group, model control group, pirarubicin group and compound matrine injection group were (0.018±0.004) mg, (0.422±0.130) mg, (0.219±0.136) mg and (0.237±0.113) mg ( F = 14.01, P < 0.001), and the survival time of nude mice was (90±0) d, (54±12) d, (72±4) d and (69±8) d ( F = 18.53, P < 0.001). The inhibition rates of bladder cancer in the pirarubicin group and compound matrine injection group were 48.10% and 43.84%, and the life prolongation rates of the nude mice were 34.95% and 29.53%. Conclusions:Compound matrine injection can inhibit the proliferation of BIU-87 cells in a concentration-dependent manner. Compound matrine injection can increase the tumor inhibition rate and prolong the survival time of nude mice models of bladder orthotopic transplanted tumor.

Objective:To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score.Methods:We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups.Results:The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS).Conclusions:PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

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Objective To investigate the diagnostic effect of diffusion tensor imaging (DTI) on spinal neurotype brucellosis spondylitis (BS).The characteristics of apparent diffusion coefficient (ADC) value and fractional anisotropy (FA) value of spinal neurotype BS in different disease stages were quantitatively analyzed to evaluate the different forms of spinal neurofibrillary tract injury.Methods A prospective design was used to collect data of BS patients with spinal neurological symptoms from June 2015 to July 2017 in the First Affiliated Hospital of Hebei North University as the brucellosis group (n =39),including 23 males and 16 females,aged (20.8 ± 15.3) years old.Healthy subjects were selected as the control group (n =30),including 20 males and 10 females,aged (25.2 ± 4.0) years old.The brucellosis group was divided into acute stage (＜ 3 months),subacute stage (3-6 months) and chronic stage (＞ 6 months),with 12,10 and 17 cases,respectively.Routine spinal scans and DTI scans were performed using a 3.0T superconducting magnetic resonance imaging (MRI) scanner,DTI used Fiber Trak package to measure ADC value and FA value and perform quantitative analysis [receiver operating characteristic (ROC) curve],and reconstructed the changed form of the spinal neurotype BS nerve fiber bundle.Results A total of 39 patients' data were collected in the brucellosis group.Among them,5 patients showed segmental thickening of spinal nerves on conventional MRI,high signal on T2 weighted imaging (T2WI) and short time inversion recovery (STIR),and color code changes on DTI scan FA imaging.Routine MRI of 34 patients showed spinal cord compression,spinal cord morphological changes or cauda equina nerve aggregation and displacement,while DTI scan FA imaging showed spinal cord or cauda equina nerve morphological changes,but no color code changes.The ADC values of patients in the acute and subacute stages were higher than that of the control group [(1.41 ± 0.05),(1.31 ± 0.05),(1.23 ± 0.05) × 10-3 mm2/s,P ＜ 0.05],and the FA values were lower than that of the control group (0.40 ± 0.04,0.68 ± 0.08,0.76 ± 0.05,P ＜ 0.05).There were no statistically significant differences in ADC and FA values between patients with chronic spinal neurotype BS [(1.25 ± 0.04) × 10-3 mm2/s,0.72 ± 0.04] and the control group (P ＞ 0.05).ROC curve analysis showed that the area under curve (AUC),specificity,sensitivity and accuracy of ADC were 0.912,0.942,0.930 and 0.924,respectively.The AUC,specificity,sensitivity and accuracy of FA were 0.901,0.937,0.928 and 0.943,respectively.The change forms of spinal neurotype BS were:① color code change;② loss/fracture;③ displacement and pressure;④ rarity.Conclusion DTI plays a diagnostic role in spinal neurotype BS,and can quantitatively analyze the characteristics of changes in ADC value and FA value in different periods,and can clearly display the forms of changes in spinal neurofiber,providing a reliable basis for the diagnosis of spinal neurotype BS.

Objective To explore the differential diagnosis of breast ductal carcinoma in situ (DCIS)and breast ductal carcinoma in situ with microinvasion (DCIS-Mi)by ADCMin ,ADCDR and DCE-MRI,and to analyze the correlation between DCIS-Mi and biological factors. Methods Preoperative breast MRI examinations were performed in 41 patients with DCIS-Mi and 3 7 patients with DCIS.DCIS-Mi and DCIS patients were compared in terms of ADCMin ,ADCMax ,ADCDR ,early enhancement rate (EER)and the morphological characteristics of DCE-MRI.The optimal diagnostic variables were determined by binary Logistic regression,the threshold value of the optimal diagnostic variables was ensured by ROC,and the correlation between DCIS-Mi and biological factors was analyzed by Spearman.Results ADCMin of DCIS-Mi patients was lower than that of DCIS (t＝6.294,P＝0.033),and ADCDR was higher than that of DCIS (t＝9.246,P＝0.020).70.7 3% DCIS-Mi showed non-tumor-like enhancement,inclined to segmental distribution,and internal heterogeneous or cluster ring enhancement;29.27% manifested tumor-like enhancement,internal heterogeneous or ring enhancement,and unclear margin.64.86% DCIS showed non-tumor-like enhancement,inclined to linear distribution,internal homogeneous/heterogeneous enhancement;35.14% expressed tumor-like enhancement,internal homogeneous enhancement,and clear margin.The accuracy,sensitivity and specificity of ADCMin , ADCDR ,tumor or non-tumor internal enhancement features in the diagnosis of DCIS-Mi were higher (84.0%,9 5.3%,9 2.4%;89.3%, 9 5.3%,9 2.4%;85.1%,9 2.5%,9 3.8%;87.4%,9 6.8%,84.7%, respectively).ADCMin and ADCDR threshold value were 1.1 1× 10－3 mm2/s and 0.35×10－3 mm2/s,respectively.ADCMin of patients with DCIS-Mi was positive correlation with ER(－)and PR(－), and negative correlation with HER-2(+)(P＜0.05).ADCDR ,non-tumor distribution,and non-tumor internal enhancement characteristics,the tumor edge and internal enhancement characteristics were negative correlation with ER(－)and PR(－),and positive correlation with HER-2 (+)(P＜0.05).Conclusion ADCMin ,ADCDR and DCE-MRI can be used for the differential diagnosis of DCIS-Mi and DCIS, and provided evidence for clinical treatment plan.