Background Asthma poses a serious threat to children's growth, development, and mental health, thus there has been an increasing focus on the control of asthma morbidity in children and the assessment of its risk factors. A growing body of research has found that exposure to ambient air pollutants an significatly increase the risk of childhood asthma. Objective To understand the changes of ambient air pollutant concentrations in Nanjing and asthma outpatient visits to Nanjing Children's Hospital, and to quantitatively analyze the effects of exposure to different ambient air pollutants on children's asthma outpatient visits. Methods Daily data of ambient air pollutants fine particulate matter (PM_2.5), inhalable particle (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), ozone (O₃), meteorological factors (air temperature & relative humidity), and outpatient visits due to asthma in the hospital from January 1, 2019 to December 31, 2023 were collected, and a generalized additive model based on quasi poisson distributions was used to quantitatively analyze the short-term effects of ambient air pollutant exposure on outpatient visits due to asthma in the hospital. Results The annual average concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ in Nanjing from 2019 to 2023 did not exceed the national limits. For single-day lagged effects, the single-pollutant model showed that the effects of PM_2.5, PM₁₀, NO₂, and CO on children's asthma outpatient visits were greatest for every 10 units increase at lag0, with excess risk (ER) of 1.39% (95%CI: 0.65%, 2.14%), 1.46% (95%CI: 0.97%, 1.95%), 5.46% (95%CI: 4.36%, 6.57%), and 0.18% (95%CI: 0.11%, 0.26%), respectively, and SO₂ reached the maximum effect at lag1, with an ER of 23.15% (95%CI: 13.57%, 33.53%) for each 10 units increase in concentration. Different pollutants reached their maximum cumulative lag effects at different time. The PM₁₀, PM_2.5, SO₂, NO₂, and CO showed the largest cumulative lag effects at lag01, lag01, lag02, lag02, and lag03, respectively, with ERs of 1.35% (95%CI: 0.77%, 1.92%), 0.96% (95%CI: 0.10%, 1.83%), 28.50% (95%CI: 15.49%, 42.98%), 6.92% (95%CI: 5.53%, 8.33%), and 0.31% (95%CI: 0.20%, 0.42%), respectively. The influences of PM_2.5 and PM₁₀ on outpatient visits due to asthma in the hospital became more pronounced with advancing age, while the associations with NO₂, SO₂, and CO were weakened as children grew older. Conclusion Ambient air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, CO) can increase childhood asthma visits, and different pollutants have varied effects on the number of asthmatic children's visits at different ages.

Objective To establish the model of goat intervertebral disc degeneration （IDD） induced by controllable axial compressive stress and evaluate its imaging and pathological characteristics. Methods Twenty goats were randomly divided into 4 groups (control group, 4-week pressure group, 8-week pressure group, 12-week pressure group, n=5, 40 N pressure). Disc height index (DHI) was used to evaluate the change of intervertebral disc height by X-ray, Pfirrmann classification method was used to observe the degree of intervertebral disc degeneration by magnetic resonance imaging (MRI), and histopathological observation and evaluation for intervertebral disc were conducted by HE staining and immunohistochemistry. Results DHI in control group showed no significant changes with the extension of pressure time, while DHI in the experimental group gradually decreased. There was no significant change in Pfirrmann classification in control group. In experimental group, with the extension of time, the higher the degeneration aggravated with the Pfirrmann classification increasing. In experimental group, HE staining showed that the disc nucleus pulposus decreased in volume and nucleus pulposus cells, which were gradually replaced by fibrous tissues. Immunohistochemical staining showed that type I collagen in the nucleus pulposus gradually increased, type Ⅱ collagen gradually decreased, and intervertebral disc degeneration occurred. Conclusions A certain axial compressive stress can lead to degeneration of goat lumbar intervertebral disc, and the degree of degeneration is gradually increased with the extension of time.

Objective To dynamic monitor drinking-water-borne fluorosis in Huzhu County and water improvement projects,to know the trend of the disease,and to evaluate the effect of prevention and control measures.Methods Seven townships in Huzhu County including 60 history drinking-water-borne fluorosis villages were selected as investigation sites in 2017,and demographic data were collected.In the villages of the diseased areas where the water had been changed,the operation of the water improvement project was investigated,and 1 tap water sample was collected to determine the fluorine content;for the villages in the diseased areas where the water had not been changed,one water sample was collected from the drinking water source in accordance with the five directions of east,west,south,north and middle to determine the fluorine content.More than 90％ of the children aged 8-12 years old in the surveyed villages were examined and judged for dental fluorosis.According to historical data,1 village with severe illness of children was selected,50 people were selected who were over 25 years old and lived in the villages for more than 5 years.Clinical and X-ray examinations of skeletal fluorosis were performed.Urine samples from adults surveyed were collected for urinary fluoride detection.Results Six of the 60 villages in the 7 townships had been relocated.By 2017,a total of 54 villages in drinking-water-borne fluorosis areas had changed their water.A total of 16 water improvement project were surveyed,among them,there were small water improvement project 6,accounting for 37.50％,large water improvement project 10,accounting for 62.50％;normal operated project 16,accounting for 100.00％;water fluoride content of qualified project 16,the qualified rate was 100.00％,the water fluoride content ranged 0.10-0.66 mg/L,covering a population of about 160 thousand and 846 people.A total of 2 399 children aged 8-12 were examined,117 cases of dental fluorosis were detected,the detection rate of dental fluorosis was 4.88％,dental fluorosis index was 0.13.Among them,89 cases were extremely mild,accounting for 3.71％ of all the children examined,21 cases were mild,accounting for 0.88％ of all the children examined,7 cases were moderate,accounting for 0.29％ of all the children examined,and no severe cases were found.A total of 68 adults over 25 years old were examined for skeletal fluorosis.Twelve patients were found to have clinical skeletal fluorosis.The detection rate was 17.65％.X-ray radiography was used to examine 46 people,and 1 case was detected,the detection rate was 2.17％.Clinical and X ray examinations showed no more than moderate patients.Fifty samples of adult urine were tested,the level of urine fluorine was 0.72 mg/L.Conclusions Water improvement project is working well in Huzhu County,and no serious children with dental fluorosis and adult skeletal fluorosis are detected.The prevention and control measures of drinking-water-bornefluorosis has achieved remarkable results in Huzhu County.We will continue to strengthen water improvement project and disease monitoring,and thoroughly control the prevalence of drinking water fluorosis.

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178–3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404–4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037–1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156–13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000–0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.
Asian Continental Ancestry Group* ; Diabetes Mellitus, Type 2* ; Genotype ; Humans ; Multifactor Dimensionality Reduction ; Obesity ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry

Objective To provide clinical experience in treatment of cook′s fungus infection of evidence‐based medical evidence , separation of medical environment of cook′s bacteria identification and antimicrobial susceptibility test .Methods Collected in the hospital infection of hygiene monitoring ,collection and medical staff hands ,skin and mucous membrane ,air and object surface sam‐ples from 86 strains of cook ,application ATB Expression semi‐automatic bacteria identification of susceptibility analyzer supporting article try ID32 Staph identification and drug susceptibility test Staph 5 ,strain identification and drug sensitive test .Results 86 strains bacteria identification cook 62 strains bacteria ,mutation detection rose cook bacteria strains of 16 ,cook eight strains of bac‐teria .Cook bacterium of norfloxacin(16 .3% ) ,and with nitrofurantoin low because of the sensitive rate(20 .9% ) ,of erythromycin (69 .3% ) and gentamycin(67 .4% ) ,the sensitive rate at nearly 70 .0% ,sensitivity to penicillin and other 12 kinds of antimicrobial a‐gents more than 80 .0% ,even 100 .0% .Conclusion Cook for most still sensitive ,clinicians and microorganism inspection personnel should strengthen the cook .

Hepatitis B is one of the major diseases that affect the health of Chinese people, and chronic hepatitis B virus (HBV) infection can lead to disease progression. Programmed death-1 (PD-1) discovered in recent years is an important coordinated stimulus molecule which belongs to the B7/CD28 family. After its binding with programmed death ligand (PD-L), it can regulate the activation, differentiation, and proliferation of T lymphocytes. PD-1 and its ligand are differently expressed in different stages of chronic HBV infection. The interaction between PD-1 and its ligand in different immune cells induces immune tolerance in human body and finally leads to the chronicity of HBV infection. Blocking the PD-1/PD-L signaling pathway through different ways can improve T cell exhaustion, suggesting that this might be one of the directions of antiviral therapy in future.

At present, nucleos(t)ide analogues and interferon-α still have limited effects in patients with chronic hepatitis B (CHB), and therefore, it is of vital importance to develop more effective therapeutic strategies to improve the treatment outcome of CHB patients. This article introduces the immunotherapy for CHB, including therapeutic vaccines (protein vaccines, DNA vaccines, and dendritic cell vaccines) and cell regulation therapy, and points out that immunotherapy is considered a promising treatment regimen for HBV infection. With further studies on the clinical outcome after HBV infection, significant advances have been achieved in immunotherapy for CHB.

Doxycycline is a broad-spectrum antimicrobial agent used in clinical for a long time. In recent years, many studies showed that its pharmacological activities of anti-tumor, heart function improvement, nerve protection and antiasthma depended on its inhibition of matrix metalloproteinase ( MMPs) . In the present paper,the new pharmacological actions of doxycycline were reviewed to promote the applications in clinics.

Objective To investigate the expression pattern and significance of two importantoocyte-secreted factors:growth differentiation factor 9(GDF9)and bone morphogenetic protein 15(BMP15)during oocyte maturation in women with polycystic ovary syndrome(PCOS)and infertile women due to husband factors.Methods Total of 25 oocytes[9 at germinal vesicle GV stage,9 at M Ⅰ stage and 7 at M Ⅱ stage]were obtained from 12 patients with PCOS and 82 oocytes(29 at GV stage,26 at M Ⅰ stage and 27 at M Ⅱ stage)were from 56 controls.The nested quantitative real time(RT)PCR was uscd to detect the abundance of GDF9 and BMP15 mRNA in each oocyte.Results(1)The expression level of GDF9 mRNA at the GV stage,M Ⅰ stage and M Ⅱ stage in PCOS group were 44.8(4.2-529.0),27.6(9.8-172.7)and 49.0(0.2-65.9)respectively,the expression in were 149.9(55.4-387.9),29.9(2.5-205.8)and 657.8(149.4-1376.2)in control group,respectively.The expression of GDF9 mRNA at M Ⅱ stage was significantly lower in PCOS group than in controls(P ＜ 0.01),however,the differences didn't reach statistical significant at GV or M Ⅰ stage between the two groups(P ＞ 0.05).The expression of GDF9 mRNA displayed some changes at different maturation stage in controls(P ＜ 0.05,P ＜ 0.01),however,the expression didn't demonstrate any dynamic changes in PCOS group(P ＞ 0.05).(2)The expression level BMP15 mRNA at the GV stage,M Ⅰ stage and M Ⅱ stage in PCOS group were 0.1(0.1-22.0),3.2(0.6-55.0)and 6.4(3.2-8.5),respectively,the expression were 41.6(6.5-96.1),4.0(2.0-10.4)and 49.7(2.3-139.5)in control group,respectively.The expression of BMP15 mRNA at GV stage was significantly lower in PCOS group than in controls(P ＜ 0.01),however,the differences were not significant at M Ⅰ or M Ⅱ stage between the two groups(P ＞0.05).The expression of BMP15 mRNA also displayed some changes at different maturation stage in controls(P ＜ 0.05),however,the level didn't demonstrate any dynamic changes in PCOS group(P ＞ 0.05).Conclusion It was suggested that the low expression of oocyte secreted factors in mature oocytes from PCOS patients might be associated with impaired oocyte quality and developmental competence in PCOS.