BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

Objective: To establish a "regular blood donor red blood cell gene database"(hereafter referred to as the "database") by applying molecular biology techniques for red blood cell antigens genotyping and utilizing information technology software, and to determine the significance and application value of this "database" in precise red blood cell transfusion. Methods: Fifteen antigens [C, c, E, e, M, N, S, s, Fy (a), Fy (b), Jk (a), Jk (b), Le (a), Le (b), P1] across six blood group systems (RHCE, MNS, FY, JK, Lewis and P1PK) were detected among 9 426 regular blood donors using the TaqMan-MGB method combined with an improved U-shaped microplate approach. With the assistance of information technology software, the "database" was integrated into the overall inventory management system of the blood supply chain. This enabled comprehensive management of regular blood donor and patient information, test results, specific antigen screening for regular blood donors, graded antigen matching between donors and patients, and rare blood type donor records. Results: The TaqMan-MGB method successfully detected paired antigens (C/c, E/e, M/N, S/s, Fy /Fy , Jk /Jk ) within a single reaction well using a standardized PCR amplification protocol. This method provided a reliable testing solution for clinical institutions and empowered blood collection and supply organizations with high-throughput screening capabilities. In the blood supply chain, genotyped red blood cells accounted for 13.2% (721/5 462 U) of the total inventory, with 95.34% (348/365) originating from donors who donated two units of blood. Moreover, the “database” fulfilled 94.06% (443/471 U) of compatible transfusion requirements from medical institutions and effectively managed rare blood type donors. Conclusion: The establishment of the "database" facilitated the transition of blood compatibility testing from traditional serological methods to molecular biology-based gold standard techniques, significantly advancing the implementation of precise transfusion strategies based on multi-antigen matching between donors and patients.

Objective: To explore the advantages and disadvantages of a new management model of eye community based nurse-led clinics. Methods: From March 2016 to March 2018, a community clinic of a tertiary eye hospital, Qingdao Eye Hospital was analyzed. The situation of staff and equipment allocation and adjustment in the Clinic during the two years was also reviewed. Results: A total of 17042 patients were admitted to the community clinic of a tertiary eye hospital in the past two years, among whom 44.9% were over 65 years old. Ocular surface diseases (34.4%, 5862), cataracts (31.6%, 5382), and refractive errors (17.2%, 2928) were the top three causes of patient visits. The waiting time for NLC patients was 1~114 (8.5±8.5) min, and the waiting time for outpatients in the main hospital area was 32.0~61.0 (42.4±7.1) min. The difference was statistically significant (Z=-135.172, P<0.01). The per capita cost of NLC patients was ¥ 4.0~153.2 (64.9±22.0), and the per capita cost of outpatients in the main hospital area was ¥ 110.0~586.9 (291.0±160.0), the difference was statistically significant (Z=-136.531, P<0.01). NLC scored higher than the main hospital area in consultation, timeliness and convenience of the disease(Z=-7.278, -7.462, -12.677, P<0.01), and was lower than the main hospital in the disease-solving project (Z=-3.188, P<0.01). Conclusion The NLC model is a new management model that can meet the needs of community clinics and also is a new challenge for nursing staff under the health care reform.

Antiviral Agents ; chemistry ; metabolism ; Crystallography, X-Ray ; Ligands ; Protein Binding ; Protein Structure, Tertiary ; RNA Helicases ; chemistry ; classification ; metabolism ; Static Electricity ; Viral Proteins ; chemistry ; classification ; metabolism ; Zika Virus ; enzymology

The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn(2+) and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn(2+). The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.
Crystallography, X-Ray ; Protein Domains ; RNA Helicases ; chemistry ; RNA, Viral ; chemistry ; Viral Proteins ; chemistry ; Zika Virus ; enzymology

OBJECTIVETo analyze the clinical characteristics of protracted bacterial bronchitis (PBB) in children.

METHODThe clinical data of patients seen from October, 2010 to March, 2014 in Department of Respiratory Diseases of our hospital were retrospectively analyzed. Inclusion criteria were over 4 weeks cough, receiving fiberoptic bronchoscopy, positive bacterial culture and (or) the increased percentage of neutral granulocytes in bronchoalveolar lavage fluid (BALF).

RESULTTwenty eight patients were involved, 26 were male (93%) and two were female (7%). The median age of patients was 8.5 months. The median duration of cough was four weeks. The average length of hospital stay was (8.3 ± 3.9)days. The main clinical feature was wet cough in 28 cases, wet cough with wheezing was seen in 21 cases. The wet cough phase distribution was irregular in 21 cases. The crackles with wheeze (in 21 cases) was main signs of PBB. The percentage of CD3⁻ CD16⁺ 56⁺ cells increased in peripheral blood. The fiberoptic bronchoscopic manifestations of PBB were luminal mucosal edema. Eleven patients also had airway malacia. The neutrophil median in BALF was 0.2. The positive rate of bacterial culture of BALF was 36%. The main bacteria were Streptococcus pneumoniae (50%) and Haemophilus influenzae (30%). The main treatment for PBB patients included amoxycillin/clavulanate potassium and second-generation cephalosporins. The average duration of treatment was (17.3 ± 3.2)days, the prognosis was good.

CONCLUSIONPBB is common in male infants. Persistent wet cough with wheezing was the main characteristic of PBB. PBB is commonly accompanied by immune dysfunction and airway malacia, and the pathogens were Streptococcus pneumoniae and Haemophilus influenzae.

Bacterial Infections ; drug therapy ; pathology ; Bronchitis ; drug therapy ; microbiology ; pathology ; Bronchoalveolar Lavage Fluid ; Bronchoscopy ; Cough ; Female ; Haemophilus influenzae ; isolation & purification ; Humans ; Infant ; Male ; Respiratory Sounds ; Retrospective Studies ; Streptococcus pneumoniae ; isolation & purification

Objective To evaluate the effects of sub anesthetic dose of ketamine combined with sufentanil on postoperative patient-controlled intravenous analgesia (PCIA)in patients undergoing radical resection of esophageal cancer.Methods Ninety patients,ASAⅠorⅡ,aged 55-75 years old,se-lected for radical resection of esophageal cancer were randomly divided into three groups:group S1,group S2,group SK,30 patients in each group were treated with PCIA.Group S1,2 μg/kg sufentanyl;group S2,2.5 μg/kg sufentanyl;group SK 2 μg/kg sufentanyl+90 μg·kg-1·h-1 ketamine.6 mg of granisetron was added to each group,and then diluted into 100 ml of normal saline.All patients were administered load-ing doses of 5 ml analgesics 30 min before the end of the operation.The VAS score,Ramsay sedation score, SBP,DBP,HR,SpO2 and adverse effects were recorded respectively at 4,8,24 and 48 hours after opera-tion.The total times of pressing PCIA were also recorded in 48 h after operation.Results There was no statistically significant difference in Ramsay sedation score,SBP,DBP,HR and SpO2 at 4,8,24,48 hours after operation in the three groups.Compared with group S1,the VAS score and total number of pressing PCIA times in groups SK and S2 were significantly lower in 48 h after operation (P <0.05).Compared with group S2,VAS score and the total number of pressing PCIA times in group SK were significantly de-creased in 48 h after operation (P <0.05).Two patients from group SK occurred respiratory depression 48 h after operation.There was no statistically significant difference in incidence of adverse effects in the three groups.Conclusion Sub anesthetic dose of ketamine combined with sufentanil on PCIA can reduce postoper-ative sufentanil consumption and significantly relieve the postoperative pain in patients undergoing radical re-section of esophageal cancer.The analgesic effect is better than using sufentanil alone.

Objective To investigate and compare the different effects of soluble adult wornl antigen(SWA)and soluble egg antigen(SEA)of Schistosoma japonicum on the apoptosis and cell-cycle of routine CD4~+T cells.Methods Purified CD4~+T ceUs from normal C57BL/6 mice were cultured with CFSE labeled antigen presenting clls in the presence of different stimuli for 36 h.Flow cytometry(FCM)was used to detect the apoptosis of CD4~+T cells by fluorescence conjugated caspase-3 antibodie staining.The flow cytometry was used to analyze the cell-cycle of CD4~+T cells cultured as described above for 96 h by propidium iodide staining.Results Compared with the apoptosis percentage of CD4~+T cells[(1.24±0.29)%]in the SEA stimulated group,that in the SWA stimulated group[(1.52±0.38)%]did not show statistically significant difference(P>0.05).Compared with the cell percentages in G1 phase[(78.91±2.98)%],S phase[(7.39±0.85)%]and G2/M phase[(10.69±1.05)%] in the SWA stimulated group,that of the G1 phase[(59.42±1.32)%]was significantly lower,but those in the S phase[(21.07±O.88)%] and G2/M phase[(18.88±1.21)%]were significantly increased in the SEA stimulated group(P<0.01).Conclusions There is no statistically significant difference between the apoptosis levels of CD4~+T ceHs stimulated by SWA and SEA.However,SEA significantly promotes the progression of the cell-cycle of CD4~+T cells compared with SWA.

Objective To observe the apoptosis of Th1 and Th2 cells in C57BL/6 mice chronically infected with Schistosoma japonicum.Methods The apoptotic Th1 and Th2 cells in spleen and lymph node from C57BL/6 mice infected with Schistosoma japonicum for 13 weeks were examined by three-color and indirect flow cytometery with staining surface molecule and intracellular cytokines.Results Compared with the normal mice,the proportion of apoptotic Th1 and Th2 cells of 13-week post-infection was significantly high,and the apoptotic Th1 cells increased more than apoptotic Th2 cells in the infected C57BL/6 mice,and the Th1 cells were more susceptible to apoptosis than Th2 cells.Conclusions Unequal susceptibility to apoptosis in Th1 and Th2 cells may be one of the reasons leading to Th2 polarization on mice chronically infected with Schistosoma japonicum,which provides the new proof of Th polarization.