[Geographic environment-related research advances on children's myopia: intraocular and environmental exposure factors and analytical methods].

Myopia has become a global phenomenon, transitioning into a significant public health issue of worldwide reach. The escalating prevalence of myopia may lead to an increase in the incidence of related complications, potentially resulting in irreversible vision damage for individuals. This not only causes considerable economic strain on societies but also poses a serious threat to vital sectors like national defense. This review outlines various external and internal exposure factors related to childhood myopia. It places particular focus on the analysis of the interaction between geographical environmental factors and internal exposure factors, and examines the limitations of applying traditional methods in studying the relationship between childhood myopia and geographical environmental factors. The paper also introduces two spatial regression methodologies based on frequency estimation and Bayesian estimation, summarizing their feasibility and merits when applied in the study of external exposure elements related to childhood myopia. Finally, it provides a fresh perspective on regional childhood myopia prevention strategies that are conscious of geographical environmental factors.

[Clinical characteristics and follow-up analysis of 63 cases of silicosis complicated with cavity-pulmonary tuberculosis].

Objective: To investigate the clinical characteristics and prognosis of silicosis complicated with cavity-pulmonary tuberculosis. Methods: The clinical data of 63 patients with silicosis complicated with cavity-pulmonary tuberculosis (group A) and silicosis patients (group B) admitted to Yantaishan Hospital from July 2018 to July 2022 were collected and analyzed. Results: Patients in group A were all male, and the common symptoms were cough, expectoration, chest tightness, shortness of breath, and hemoptysis. CT cavity lesions involving the lung, often occurs in the lung after the tip section, after the back section and basal segment, thick-walled cavity, may be accompanied by satellite lesions, endobronchial spread focal, pneumothorax, pleural effusion, etc. 1225 cases of group B patients haemoptysis of 59 patients, cavity in 3 patients, haemoptysis and/or cavity rate was lower than that in group A, the difference was statistically significant (P<0.05) . In group A, CT reexamination 6-24 months after anti-tuberculosis treatment showed that 52 cases (82.5%) had cavity reduction/healing, 8 cases (12.7%) had recurrence, and 3 cases (4.8%) had damaged lung (2 died) . Conclusion: Silicosis patients with hemoptysis and/or CT in cavity should be more vigilant about combined tuberculosis, anti-tuberculosis treatment and/or dynamic CT follow-up helps laboratory diagnosis negative patients.

[A case of delayed peripheral neuropathy caused by diquat poisoning].

Diquat is a kind of conductive contact-killing herbicides. The damage of central nervous system is relatively common, but the peripheral neuropathy caused by diquat has not been reported yet. In September 2021, we treated a patient with diquat poisoning. During the hospitalization, the patient was diagnosed with peripheral neuropathy. Therapy for peripheral nerve injury was given on the basis of conventional treatment of poisoning. The patient was discharged after his condition was stable. The follow-up showed that the peripheral neuropathy of patient was better than before. According to the condition of this patient, it is suggested that we should not only protect the function of gastrointestinal tract, liver, kidney, and central nervous system early, but should also pay attention to the damage of peripheral nervous system in clinical work. We should intervene earlier to improve the prognosis of patients.

[Epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea from 2013 to 2019 in Pudong New Area, Shanghai].

Objective: To investigate the epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea in Pudong New Area, Shanghai. Methods: Active surveillance of diarrhea was conducted in 14 sentinel hospitals (three tertiary-level hospitals, nine secondary-level hospitals, and two primary-level hospitals) from January 2013 to December 2019 in Pudong New Area of Shanghai, China base on their location, catchment area, and patient volume. Cold enrichment method was used to isolate Y. enterocolitica and further detection of bioserotype, virulence genes and antimicrobial susceptibility of the isolates were conducted. The difference of rates was determined using chi-square test or Fisher's exact test. Results: A total of 12 941 diarrhea cases were included, and 0.7% (88/12 941) cases were confirmed with Yersinia enterocolitica infection. 67.0% (59/88) cases were single infection, 33.0% (29/88) cases were mixed infections. Detection rates of Y. enterocolitica increased annually (0.3%-1.2%) and were highest in children<5 years of age (1.1%, 37/3 218) and in spring (1.1%, 32/2 998) (χ2 were 18.64 and 9.76, respectively, P<0.05). 58.0% (51/88) cases had watery diarrhea, 15.9% (14/88) had fever and 14.8% (13/88) had vomiting. The predominant bioserotypes were 3/O:3 (53.4%, 47/88), followed by 1A/O:8 (15.9%, 14/88) and 1A/O:5(6.8%, 6/88), respectively. Bioserotype 3/O:3 counted for the highest proportions (89.2%, 33/37) in children <5 years of age. All the strains of bioserotype 3/O:3 harbored ail, ystA, yadA and virF genes, which encoded pathogenic Y. enterocolitica. 11/14 strain of 1A/O:8 and 4/6 strains of 1A/O:5 harbored ystB gene. Most strains were resistant to ampicillin (80.7%,71/88) and amoxicillin/clavulanic acid (71.6%,63/88), and 63.8% (56/88) strains were multidrug resistance (MDR). The difference of antimicrobial resistance rates between 3/O:3 and non 3/O:3 was statistically significant in ampicillin, cefoxitin, nalidixic acid, tetracycline and ampicillin/sulbactam (χ2 was 14.68, 43.80, 41.86, 30.54 and 5.07, respectively, P<0.05). Conclusion: The detection rate of Yersinia enterocolitica was higher in children than in adults in Pudong New Area, Shanghai. The predominant bioserotype was pathogenic 3/O:3 with multidrug resistance.

Prognostic value of late gadolinium enhancement in arrhythmogenic right ventricular cardiomyopathy: a meta-analysis.

AIM: To assess systematically the prognostic value of cardiac magnetic resonance imaging (CMRI) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). MATERIALS AND METHODS: The full text of studies of the clinical efficacy of late gadolinium enhancement (LGE) in ARVC was retrieved in multiple databases. Stata 14 was adopted for meta-analysis and bias analysis. Heterogeneity was assessed with the I2 statistic. RESULTS: After exclusions, 561 patients were included in five studies, and the eligibility criteria were met. The meta-analysis suggested that there was a significant difference between LGE positive and negative patients with ARVC in all-cause mortality (relative risk [RR] = 4.78, 95% confidence interval [CI] = 1.41, 16.23, p=0.012; p for heterogeneity = 0.692, I2 = 0%); major adverse cardiovascular events (MACE) (RR=2.48, 95% CI = 1.24, 4.96, p=0.010; p for heterogeneity = 0.596, I2 = 0%); ventricular tachycardia (RR=3.13, 95% CI = 1.69, 5.78, p<0.001; p for heterogeneity = 0.825, I2 = 0%); implanted cardiac defibrillators (RR=3.15, 95% CI = 1.69, 5.87], p<0.001; p for heterogeneity = 0.353, I2 = 9.4%). CONCLUSION: LGE in ARVC patients is a predictor of all-cause mortality and MACE.

[Association of hyperuricemia-induced renal damage with sirtuin 1 and endothelial nitric oxide synthase in rats].

Objective: To investigate the association of hyperuricemia-induced renal damage with sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in rats. Methods: Using the random number table method, 32 Sprague-Dawley rats were randomly divided into 4 groups: control group, model A group (the model was generated using oxonic acid potassium salt alone), model B group (hyperuricemia model was generated using oxonic acid potassium salt combined with uric acid) and resveratrol group, with 8 rats in each group. The experiment lasted 12 weeks. Serum uric acid and cystatin C levels were monitored regularly. In week 12, serum creatinine and urea nitrogen levels were measured, and the kidneys were extracted. The expression of SIRT1 and eNOS in renal tissues was measured and determined by immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. Immunohistochemistry of alpha-smooth muscle actin combined with Masson staining was employed to evaluate the degree of renal fibrosis, and pathological changes were observed based on hematoxylin and eosin staining. Results: In week 12, the uric acid levels in both the model A and model B groups were higher than those in the control group [(316±43) µmol/L, (297±40) µmol/L vs (118±44) µmol/L, both P<0.05]. The levels of cystatin C in the model A, model B, and resveratrol groups were all higher than those in the control group [(156±20) ng/ml, (143±29) ng/ml, (128±26) ng/ml vs (62±18) ng/ml, all P<0.05]. Creatinine levels were higher in the model A and model B groups than those in the control group [(68.5±10.3) µmol/L, (64.5±13.9) µmol/L vs (43.2±10.6) µmol/L, both P<0.05]. The levels of uric acid, cystatin C and creatinine in the resveratrol group were lower than those in the model A group (all P<0.05). Immunohistochemistry, RT-qPCR, and Western blotting for renal SIRT1 and eNOS showed that the expression in the model A and model B groups was inhibited, while the expression in the resveratrol group was not significantly inhibited, compared with that in the control group. Microscopically, obvious abnormalities were not found in the renal tissue of the control group. Renal inflammatory cell aggregation and edema occurred, and interstitial fibrosis was obvious in both the model A and model B groups, while these lesions in the resveratrol group were significantly improved. Conclusions: Hyperuricemia may cause renal injury by inhibiting the expression of SIRT1 and eNOS.

[Factors influencing poor prognosis of mechanical thrombectomy in time window of acute ischemic stroke].

Objective: Investigate the causes of poor prognosis of mechanical thrombectomy in the time window of acute ischemic stroke (AIS) with anterior circulation. Methods: A retrospective analysis was made on the data of 78 patients with anterior circulation AIS who underwent mechanical thrombectomy in the time window from January 2017 to December 2017 in the Department of Vascular Neurosurgery of Liaocheng Brain Hospital. The modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 3 months after operation. According to the prognosis,the patients were divided into the group with good prognosis (42 cases, mRS<2 points) and the group with poor prognosis (36 cases, mRS<3 points). Univariate and multivariate Logistic regression analysis was used to analyze the related factors of poor prognosis. Results: (1) Univariate analysis showed that the prognosis of patients with good combination and primary stenosis of diabetes mellitus and atherosclerosis was lower than that of patients with poor prognosis (P<0.05). The collateral circulation compensation rate and vascular recanalization rate of patients with good prognosis were higher than those of patients with poor prognosis (P<0.05). Learning significance (P<0.05). (2) Multivariate analysis showed that diabetes mellitus (P=0.035), collateral circulation compensation (P=0.011) and primary atherosclerotic stenosis (P=0.042) were independent risk factors for poor prognosis. Conclusion: Perfect preoperative evaluation and strict screening of patients, good collateral circulation compensation,individualized treatment for patients with primary atherosclerotic stenosis,and strict control of postoperative hyperglycemia can improve the clinical prognosis of endovascular therapy.

[Study on calculating the curative care expenditure of injury in Gansu Province based on "A System of Health Accounts 2011"].

Objective: To study the distribution and related factors of curative care expenditure (CCE) of injury in Gansu Province in 2017. Methods: Based on the "A System of Health Accounts 2011 (SHA 2011)", the curative care expenditure of injury in Gansu Province was calculated and analyzed. The five-stage stratified cluster sampling method was adopted to extract 149 medical and health institutions, 120 township hospitals (including community health service centers), 150 individual clinics and 600 village clinics (including community health service stations). The top-down allocation method was used to calculate the cost of injury treatment in Gansu Province, and the influencing factors were analyzed by multiple linear regression. Results: In 2017, the CCE of injury in Gansu province was 3.831 billion yuan, and the expense in general hospitals was 2.708 billion yuan. Among them, the cost of lower limb injury and head injury were 1.090 and 0.847 billion yuan. People aged 40 to 69 years old spent 1.901 billion yuan on injury treatment, and the CCE of injury treatment for men and women were 2.422 and 1.409 billion yuan respectively. The results of multiple linear regression showed that hospitalization expenditure was significantly associated with length of stay, operation, hospital grade, age, payment method and gender (P<0.001). Conclusion: The economic burden of injury in Gansu Province is relatively heavy, so it is necessary to focus on preventions for different groups and costly injury sites.

Clinical and molecular insights into Glanzmann's thrombasthenia in China.

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder characterized by spontaneous mucocutaneous bleeding. The disorder is caused by quantitative or qualitative defects in integrin αIIbß3 (encoded by ITGA2B and ITGB3) on the platelet and is more common in consanguineous populations. However, the prevalence rate and clinical characteristics of GT in non-consanguineous populations have been unclear. We analyzed 97 patients from 93 families with GT in the Han population in China. This analysis showed lower consanguinity (18.3%) in Han patients than other ethnic populations in GT-prone countries. Compared with other ethnic populations, there was no significant difference in the distribution of GT types. Han females suffered more severe bleeding and had a poorer prognosis. We identified a total of 43 different ITGA2B and ITGB3 variants, including 25 previously unidentified, in 45 patients. These variants included 14 missense, 4 nonsense, 4 frameshift, and 3 splicing site variants. Patients with the same genotype generally manifested the same GT type but presented with different bleeding severities. This suggests that GT clinical phenotype does not solely depend on genotype. Our study provides an initial, yet important, clinical and molecular characterization of GT heterogeneity in China.

[HER2 gene status and mRNA expression in immunohistochemistry 1+ breast cancer].

Objective: To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer. Methods: Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion. Results: Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17>2 and average HER2 copy number>4 and 2 cases of HER2/CEP17<2 and average HER2 copy number>6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17>2 and average HER2 copy number<4 were found in all patients, which included 2 cases of high in situ mRNA expression (3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression (2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P>0.05). Conclusions: A small number of HER2 IHC 1+ patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.

[Detection and application of bcl-2/IgH gene translocation and immunoglobulin gene rearrangement in follicular lymphoma].

Objective: To evaluate the application of FISH testing of bcl-2/IgH gene translocation and IgH/L gene rearrangement in different stages of follicular lymphoma. Methods: In 32 follicular lymphoma cases, which were collected at Guangdong General Hospital from September 2014 to December 2016, the bcl-2/IgH gene ectopic state was detected by FISH while the IgH/L gene rearrangement was tested using PCR-GeneScan to analyze the relationship between bcl-2/IgH gene translocation, different stages of follicular lymphoma and clonal immunoglobulin (IgH/L) gene rearrangements. Results: From the paraffin sections of all 32 follicular lymphomas, 17 cases showed bcl-2/IgH gene translocation, and the percentages of FL1, FL2 and FL3 translocation were 12/13, 3/5 and 2/14, respectively. Among the 24 cases of IgH/L gene arrangements identified from the total sample, the occurrence rates of FL1, FL2 and FL3 gene arrangement were 7/13, 4/5 and 13/14, respectively. Spearman's rank correlation analysis and χ(2) analysis showed that bcl-2/IgH gene translocation was negatively correlated with follicular lymphoma stage and the association was statistically significant. In more advanced stages of follicular lymphoma, the occurrence of bcl-2/IgH gene translocation tended to decrease with distinct FL1, FL2 and Fl3 gene expression (P<0.05). As IgH/L gene rearrangement in FL3 was higher than that in FL1 and FL2, its detection may be complimentary to FISH test for bcl-2/IgH gene translocation in diagnosing follicular lymphoma. Conclusions: The combined use of FISH and PCR-GeneScan increases the positive rate of follicular lymphoma diagnosis, and this combination is more sensitive than FISH or clonal analysis only to detect the chromosomal abnormality or the gene rearrangement.

Facilitating the measurement of circulatory hydrogen sulfide with fluorescence probe-coated microplates.

OBJECTIVE: The hydrogen sulfide (H2S) role in pathogenesis of various diseases were wildly addressed in recent decade. The circulatory (plasma or serum) and biological fluid H2S measurement is still an enormous issues due to the technical limitation. This paper aimed to develop a novel measurement method based on fluorescence probe. METHODS: Firstly, 20 µL ethanol was used to dissolve 100 pmol fluorescence probe, then added in a 96-well plate. An equal volume of ethanol was also added to the blank well of the plate. The plate was placed in a dark room for about 1 h until the fluorescence probe was evenly coated in the 96-well microplate and dried. The plate was frozen at -20 °C for later use. Secondly, the plasma or serum sample was added with saturated ammonium sulfate buffer (pH 7.8) and then centrifuged to remove the proteins. The equal volume supernatant liquid was added to the probe-coated well and the probe-uncoated well. The plate was incubated in a dark environment at 37 °C for 2 h. Finally, after incubation, the fluorescence density was acquired at ΛEx/ΛEm 340/445 nm in a microplate reader. The differences of the fluorescence density values between the probe-coated well and probe-uncoated well were counted and H2S concentration of plasma/serum was calculated by standard curve with NaHS. RESULTS: The method had high sensitivity (from 0.3 to 100 µmol/L) and specificity for measuring H2S as compared with other biologically relevant reactive sulfur species and sulfur-containing amino acid. Serum H2S concentrations were assayed in 188 health volunteers using this method [(12.1±3.5) µmol/L, 95%CI: 4.6-19.8 µmol/L], and the frequency distribution showed a normal tendency(one-sample Kolmogorov-Smirnov test, P>0.1). The serum H2S concentrations in 30 hypertension patients were decreased compared with 22 age- and gender-matched health individuals (paired-samples t test, t=9.937, P<0.001). There were no differences of H2S concentration in serum [(19.66±2.32) µmol/L] or plasma [(18.67±2.07) µmol/L], between the samples acquired from artery [(19.34±0.51) µmol/L] or vein [(18.99±0.50) µmol/L] of male Wistar rats (repeated measurement of ANOVA, P=0.38). One week frozen samples did not affect the detection. The values of the repeated measurement did not differ (two-way ANOVA, P>0.05). CONCLUSION: The present method is easily performed with high sensitivity, specificity and repeatability for circulatory H2S. It is also quick and may apply for large samples.

[Analysis of the impact of job characteristics and organizational support for workplace violence].

Objective: To analyze the effect of job characteristics and organizational support for workplace violence, explore the influence path and the theoretical model, and provide a theoretical basis for reducing workplace violence. Methods: Stratified random sampling was used to select 813 medical staff, conductors and bus drivers in Chongqing with a self-made questionnaire to investigate job characteristics, organization attitude toward workplace violence, workplace violence, fear of violence, workplace violence, etc from February to October, 2014. Amos 21.0 was used to analyze the path and to establish a theoretical model of workplace violence. Results: The odds ratio of work characteristics and organizational attitude to workplace violence were 6.033 and 0.669, respectively, and the path coefficients were 0.41 and-0.14, respectively (P<0.05). The Fitting indexes of the model: Chi-square (χ(2)) =67.835, The ratio of the chi-square to the degree of freedom (χ(2)/df) =5.112, Good-of-fit index (GFI) =0.970, Adjusted good-of-fit index (AGFI) =0.945, Normed fit index (NFI) =0.923, Root mean square error of approximation (RMSEA) =0.071, Fit criterion (Fmin) =0.092, so the model fit well with the data. Conclusion: The job characteristic is a risk factor for workplace violence while organizational attitude is a protective factor for workplace violence, so changing the job characteristics and improving the enthusiasm of the organization to deal with workplace violence are conducive to reduce workplace violence and increase loyalty to the unit.

Rab3A, Rab27A, and Rab35 regulate different events during mouse oocyte meiotic maturation and activation.

Rab family members play important roles in membrane trafficking, cell growth, and differentiation. Almost all components of the cell endomembrane system, the nucleus, and the plasma membrane are closely related to RAB proteins. In this study, we investigated the distribution and functions of three members of the Rab family, Rab3A, Rab27A, and Rab35, in mouse oocyte meiotic maturation and activation. The three Rab family members showed different localization patterns in oocytes. Microinjection of siRNA, antibody injection, or inhibitor treatment showed that (1) Rab3A regulates peripheral spindle and cortical granule (CG) migration, polarity establishment, and asymmetric division; (2) Rab27A regulates CG exocytosis following MII-stage oocyte activation; and (3) Rab35 plays an important role in spindle organization and morphology maintenance, and thus meiotic nuclear maturation. These results show that Rab proteins play important roles in mouse oocyte meiotic maturation and activation and that different members exert different distinct functions.

Slater Insulator in Iridate Perovskites with Strong Spin-Orbit Coupling.

The perovskite SrIrO_{3} is an exotic narrow-band metal owing to a confluence of the strengths of the spin-orbit coupling (SOC) and the electron-electron correlations. It has been proposed that topological and magnetic insulating phases can be achieved by tuning the SOC, Hubbard interactions, and/or lattice symmetry. Here, we report that the substitution of nonmagnetic, isovalent Sn^{4+} for Ir^{4+} in the SrIr_{1-x}Sn_{x}O_{3} perovskites synthesized under high pressure leads to a metal-insulator transition to an antiferromagnetic (AF) phase at T_{N}≥225 K. The continuous change of the cell volume as detected by x-ray diffraction and the λ-shape transition of the specific heat on cooling through T_{N} demonstrate that the metal-insulator transition is of second order. Neutron powder diffraction results indicate that the Sn substitution enlarges an octahedral-site distortion that reduces the SOC relative to the spin-spin exchange interaction and results in the type-G AF spin ordering below T_{N}. Measurement of high-temperature magnetic susceptibility shows the evolution of magnetic coupling in the paramagnetic phase typical of weak itinerant-electron magnetism in the Sn-substituted samples. A reduced structural symmetry in the magnetically ordered phase leads to an electron gap opening at the Brillouin zone boundary below T_{N} in the same way as proposed by Slater.

The efficacy of high-intensity, focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva.

Non-neoplastic epithelial disorders of the vulva (NNEDV) are common types of vulval lesions. Although corticosteroids represent a first-line treatment for NNEDV, concerns exist about the safety associated with long-term topical corticosteroid use. Recently, several clinical trials have identified high-intensity focused ultrasound (HIFU) as a promising treatment modality for NNEDV. The aim of this multi-center, randomized, controlled clinical trial was to investigate the efficacy of HIFU therapy in women with NNEDV based on histological alterations. We enrolled patients who were clinically diagnosed with NNEDV. They were randomized into 2 treatment groups: 1) halcinonide for 3 months or 2) HIFU once. A total of 123 patients were biopsied both prior to and after the therapy, and 62 and 61 patients were assigned to the HIFU and halcinonide groups, respectively. The histological changes were then analyzed. After the treatments, the therapeutic effects were observed in both groups. Comparing the diagnosis and alterations in lichenoid and sclerotic patterns and in chronic inflammation, we found statistically significant differences. Furthermore, when compared with the halcinonide group, the HIFU group exhibited enhanced curative effects that were statistically significant (P = 0.039). Based on the histological evidence from this randomized, controlled trial, HIFU represents an effective method for the treatment of NNEDV.

Association of NF-κB1 gene polymorphisms with coronary artery disease in a Han Chinese population.

Nuclear factor (NF)-κB is a transcription factor that controls cell proliferation, differentiation, and immunity. Activated NF-κB1 is associated with the pathogenesis of coronary artery disease (CAD) and genetic polymorphisms in NF-κB1 have a plausible role in modulating the risk of CAD. To identify markers that contribute to the genetic susceptibility to CAD, we examined the potential association between CAD and single nucleotide polymorphisms (SNPs; rs28362491, rs230531, rs230528, rs1005819, rs4648055, rs3774964, and rs3774968) in the NF-κB1 gene using SNaPshot SNP genotyping assay. Participants included 361 patients with CAD and 385 healthy controls. The genotype and allele frequencies of the rs28362491 (promoter region) polymorphism in the CAD patients were significantly different from those in the healthy controls. The frequency of the D allele was significantly higher in CAD patients than in the healthy controls (P = 0.005 after Bonferroni correction). Strong linkage disequilibrium was observed in one block (D' > 0.9). Haplotype analysis revealed that haplotypes in block 1 of the NF-κB1 gene did not display a risk or protective effect (P > 0.05). These data suggest that NF-κB1 gene polymorphisms confer susceptibility to CAD and also support the notion that dysfunction of NF-κB1 is involved in the pathophysiological process of CAD.

Association between interleukin-17A polymorphism and coronary artery disease susceptibility in the Chinese Han population.

Coronary artery disease (CAD) is a major global health problem. In China, the incidence of CAD and the rate of mortality arising from it have increased every year. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by activated T cells, and it may be involved in the development of CAD. Genetic polymorphisms in functional regions of the IL17A gene have a plausible role in modulating the risk of CAD. To evaluate the role of IL17A polymorphisms as a risk factor for CAD, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory regions of IL17A. This study examined the potential association between CAD and five SNPs (rs8193037, rs8193036, rs3819024, rs2275913, and rs3748067) of the IL17A gene. The allelic or genotypic frequencies of the rs8193037 (promoter region) and rs8193036 (promoter region) polymorphisms in CAD were significantly different from those in healthy controls. The CAD subjects had a significantly lower frequency of the A allele of rs8193037 (P = 0.009, OR = 1.772, 95%CI = 1.146- 2.742) and the T allele of rs8193036 (P = 0.010, OR = 1.754, 95%CI = 1.139-2.701). Strong linkage disequilibrium was observed in one block (D' > 0.9). Significantly fewer T-G-G-A haplotypes (P = 0.045) were found in CAD subjects in block 1. These data suggest that IL17A gene polymorphisms confer susceptibility to CAD, and support the notion that dysfunction of IL-17A is involved in the pathophysiological process of CAD.

TRAF3IP3, a novel autophagy up-regulated gene, is involved in marginal zone B lymphocyte development and survival.

Tumour necrosis factor receptor-associated factor 3 (TRAF3) interacting protein 3 (TRAF3IP3; also known as T3JAM) is expressed specifically in immune organs and tissues. To investigate the impact of TRAF3IP3 on immunity, we generated Traf3ip3 knock-out (KO) mice. Interestingly, these mice exhibited a significant reduction in the number of common lymphoid progenitors (CLPs) and inhibition of B cell development in the bone marrow. Furthermore, Traf3ip3 KO mice lacked marginal zone (MZ) B cells in the spleen. Traf3ip3 KO mice also exhibited a reduced amount of serum natural antibodies and impaired T cell-independent type II (TI-II) responses to trinitrophenol (TNP)-Ficoll antigen. Additionally, our results showed that Traf3ip3 promotes autophagy via an ATG16L1-binding motif, and MZ B cells isolated from mutant mice showed a diminished level of autophagy and a high rate of apoptosis. These results suggest that TRAF3IP3 contributes to MZ B cell survival by up-regulating autophagy, thereby promoting the TI-II immune response.

PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with ß2 AR agonists by a natural agent arctigenin.

BACKGROUND: Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, ß2 adrenergic receptor (ß2 AR) agonists bind to the ß2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the ß2 AR agonist, but the target for this remained elusive. METHOD: Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. RESULTS: Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PDE4D resulted in cAMP accumulation in human bronchial smooth muscle. The inhibition of PDK1 showed a synergistic function with ß2 AR agonists and relaxed the constriction of segregated guinea pig tracheal muscle. CONCLUSIONS: The PDK1/Akt/PDE4D axis serves as a novel asthma target, which may benefit airflow obstruction.