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Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.
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The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around CD274 and CD273 was discovered, which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2. The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1. After transcription, the PD-L1 is tightly regulated by miRNAs and RNA-binding proteins via the long 3'UTR. At translational level, PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination. In addition, PD-L1 can be secreted via exosome to systematically inhibit immune response. Therefore, fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.
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OBJECTIVE: To analyze the status and influencing factors of the health literacy(HL) of college students in a comprehensive university. METHODS: A total of 3 360 students from in a comprehensive university of Xinjiang Production and Construction Corps was selected using multi-stage stratified cluster random sampling method. The HL level of college students was investigated and evaluated with self-edited Xinjiang Construction Corps College Students Health Literacy Questionnaire. RESULTS: The HL level of college students was 17.1%. The HL level of medical students was higher than that of non-medical students(35.4% vs 10.0%, P<0.01). Logistic regression analysis results showed that among the medical students in grade three or four, those with medium and excellent academic achievement, and Han nationality had a positive effect on their HL level(P<0.01). Among the non-medical students, female and medicine related optional courses had a positive effect on their HL level(P<0.05). Students in the sophomore year had a negative effect on their HL level(P<0.05). CONCLUSION: There is a big difference in the level of HL between medical students and non-medical students. Medical college students and non-medical college students have different factors affecting HL, medical education is related to improving HL.
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Objective To investigate the time relationship of the change,and diagnostic accuracy and sensitivity between retinal light threshold fluctuations (LTF) and retinal nerve fiber layer (RNFL) and ganglion cell complex(GCC) thickness on high-risk primary open-angle glaucoma (POAG).Methods Totally 319 patients (319 eyes) with high-risk in POAG from the First Affiliated Hospital of Kunming Medical Universityand during December 2009 and December 2017,50 healthy individuals (50 eyes) as control were collected in this longitudinal cohort study.Visual field and OCT were reviewed every 6 months on the high-risk group and every 12 months on the control group.High-risk groups inclusion criteria:vertical C/D≥0.6;early visual field defect (according to glaucoma visual field damage GSS2 quantitative grading standards,mean deviation and pattern standard deviation of central field exceeds the border as an early visual field defect);continuous repeatable results.The first field and OCT results in the absence of visual field defects and C/D≥0.6,which were conformed reliability indicators and removed learning effects as a baseline.When patients achieve POAG diagnosis criteria first time which was recorded as a turning point.And they were divided into early group meanwhile were ended of follow-up.After the last follow-up,the inspection data was segmented counted in yearly interval.The changes of LTF,thickness of RNFL and GCC during the follow-up period in the early POAG group and the control group were observed.The loss rate and change rate in each period were compared for the assessment of their trends with time.Followed by calculation of the area under receiver operating curves (AUC) to compare the predicted value of POAG and the sensitivity at 95％ specificity in each period.Results After last follow-up,totally 67 patients 67 eyes (early POAG group,37 males and 30 females) were entered the turning point.The mean follow-up of the early POAG group and the control group were 6.6 and 6.4 years.The average RNFL thickness was 79.05± 8.09 μm,GCC thickness was 71.58 ± 8.41 μm,LTF was -6.05 ± 7.02 dB in early POAG group.The average RNFL thickness was 93.49± 6.24 μrm,GCC thickness was 79.72± 6.32 μm,LTF was-0.31 ± 0.58 dB in the control group.The differences of LTF and the thickness of RNFL and GCC were statistically significant (t=-5.97,-10.42,-5.60;P＜0.001).The AUC of RNFL,GCC thickness and LTF increased with time in the early POAG group.The sensitivity was gradually increased at 95％ specificity:5th year before to at turning point,RNFL thickness AUC was 0.15,0.65,0.71,0.77,0.85,0.92,and sensitivity was 20％,56％,61％,65％,70％,76％,respectively;GCC thickness AUC was 0.12,0.53,0.69,0.74,0.82,0.90,and sensitivity was 14％,53％,69％,74％,82％,90％,respectively;the AUC of LTF was 0.10,0.21,0.33,0.75,0.86,0.91,and sensitivity was 7％,17％,44％,65％,78％,87％,respectively.Conclusions The earliest time of structural functional damage of POAG is at the 4th year before confirmed,simultaneous RNFL diagnosis accuracy and sensitivity are better than GCC and LTF.The earliest time of visual functional damage of POAG is at the 2th year before confirmed,simultaneous LTF diagnosis accuracy and sensitivity are better than RNFL and GCC.
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Single tumor marker(TM)for cancer diagnosis with both satisfactory sensitivity and specificity has not been found.Therefore, it is necessary to identify the biomarkers to make the TM panel and establish the corresponding multiparameter predictive model through fuzzy mathematics methods.Recent studies using the big data technology showed that the integration of the biomarkers panel and prediction score model could provide the effective and accurate diagnosis for the cancer patients and be in favor of making the scheme for personalized therapy,treatment-monitoring and prognosis prediction.A reliable and efficient TM score prediction model will provide the novel perspectives and procedures for the diagnosis and treatment of cancer patients.
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Objective To evaluate the relationship between placental expression of Gab1 and neonatal birth weight in mothers with gestational diabetes mellitus (GDM).Methods From the singleton and full-term cesarean delivered women in Shengjing Hospital Affiliated to China Medical University between October 2014 and May 2015,30 macrosomia babies with maternal GDM were selected as GDM macrosomia group,30 cases of GDM with normal neonatal birth weight as GDM normal group,30 cases without GDM but with macrosomia as normal macrosomia group,and 30 cases without GDM and with normal neonatal birth weight as the normal control group.Gab1 protein and mRNA expression in placentas were detected using immunohistochemistry,Western blot and real-time quantitative-polymerase chain reaction.Analysis of variance,LSD,Dunnett's T3,Chi-square test and Pearson's correlation analysis were used for statistical analysis.Results (1) Gab 1 protein location and positive expression rate:Gab 1 protein expression in human placenta tissue was located in the nucleus.The positive epression rate of Gab 1 protein in the GDM macrosomia group was higher than in the GDM normal group and normal macrosomia group [93％(28/30),73％(22/30) vs 73％(22/30)] and those in the normal macrosomia group and GDM normal group were higher than in the normal control group[47％(14/30)](x2=4.320,4.320,4.444 and 4.444,all P＜0.05).(2) The expression levels of Gabl protein and mRNA:The expression level of Gab1 protein in the GDM macrosomia group was higher than in the GDM normal group and normal macrosomia group (1.43 ± 0.58 vs 1.05 ± 0.67 and 0.95± 0.59),and that in the normal macrosomia group and GDM normal group were higher than in the normal control group (0.64±0.38) (LSD test,all P＜0.05).The expression levels of Gab1 mRNA showed the same trend as the expression levels of Gab1 protein in the four groups.(3) Gab 1 protein expression level was positively associated with neonatal birth weight (r=0.320,P=0.320).Conclusions The expression of Gab1 in placenta is involved in the regulation of birth weight in GDM mothers.
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ObjectiveTo observe the clinical effects of mirabilite external application and neostigmine injection at Zusanli acupoint combined with Xuebijing intravenous injection on patients with severe sepsis.Methods A history-prospective controlled study was conducted. Patients with severe sepsis admitted to the Fourth People's Hospital of Jiangsu University from January 2012 to November 2015 were enrolled. Twenty-one cases admitted from January 2014 to November 2015 were assigned as a research group and treated with application of mirabilite external application, Zusanli acupoint injection of neostigmine combined with intravenous Xuebijing injection; 22 patients with Xubijing treatment from January 2012 to November 2015 were included in a Xubijing group; 21 patients with routine therapy from January 2012 to November 2013 were included in a control group. The changes of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), mean arterial pressure (MAP), oxygenation index (OI), serum creatinine (SCr), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, sequential organ failure assessment (SOFA), gastrointestinal function score, blood platelet count (PLT), plasma prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimmer in three groups before and after treatment were observed; the length of stay in ICU and the 28-day mortality were compared among the three groups. Results Compared with those before treatment, WBC, PCT, CRP, SCr, APACHE Ⅱ score, SOFA score, gastrointestinal function score, APTT, PT, and D-dimer were all obviously lower after treatment for 7 days in various groups; OI, MAP, PLT were significantly higher, and the improvement degree of WBC, PCT, CRP, SCr, APACHE Ⅱ score, SOFA score, gastrointestinal function score, OI in research group was more significant than those of control group and Xubijing group [WBC (×109/L): 7.52±0.75 vs. 12.87±4.13, 10.88±0.66, PCT (μg/L): 1.14±0.55 vs. 6.32±1.39, 3.47±1.94, CRP (mg/L): 21.0±9.2 vs. 65.0±13.6, 35.0±13.9, OI (mmHg, 1 mmHg = 0.133 kPa): 357.0±20.4 vs. 295.0±20.4, 309.0±21.4, SCr (μmol/L): 7.89±2.35 vs. 14.33±9.17, 11.27±4.65, APACHE Ⅱ score: 10.38±0.75 vs. 18.27±2.57, 13.09±4.10, SOFA score: 1.05±0.66 vs. 6.01±2.33, 3.26±1.03, gastrointestinal function score: 0.31±0.11 vs. 2.01±0.46, 1.85±0.29, all P 0.05]. Conclusions The treatment of mirabilite external application and neostigmine injection at Zusanli acupoint combined with Xuebijing intravenous injection can obviously improve the clinical symptoms, blood coagulation indexes and organ functions, reduce the levels of inflammatory indexes, shorten the time of the length of stay in ICU and elevate the survival rate of patients with severe sepsis.
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Objective To explore the the expression of Klotho mRNA and protein in placenta of macrosomia and its relationship with the birth weight of neonates. Methods The cases were from November 2014 to March 2015 in Shengjing Hospital of China Medical University, divided into 4 groups:the gestational diabetes with macrosomia group (GM), the gestational diabetes with normal birth weight group (GN), the normal pregnancy with macrosomia group (NM) and the normal pregnancy with normal birth weight group (NN). Klotho mRNA and protein expression in the placenta were detected by immunohistochemistry SP method, real-time fluorescent quantitative PCR and western blot, respectively, and were compared among the 4 groups. Results (1) Immunohistochemical detection showed the positive rate of Klotho protein was significantly higher in the placenta of GM (93%,28/30) than in the GN (73%,22/30;P0.05). Conclusions The up-regulation of Klotho gene may be associated with macrosomia. The relationship is not affected by the complication of gestational diabetes.
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Objective To observe the effects of aerosol imiquimod on the level of Interleukin-12 (IL-12) and interleukin-13 (IL-13) in bronchial alveolar lavage fluid(BALF) and serum immunoglobulin E(IgE) level in mouse asthma models.Methods Thirty BALB/c mice were divided into 3 groups, control group, asthma group and imiquimod group, ten in each group.The asthma group and imiquimod group were established by sensitization and challenge with ovalbumin (OVA) ,imiquimod group was interfered with aerosol imiquimod 30 min before challenge.Serum in each group was collected by excising eyeball 24 h after the last challenge.The level of IgE in serum was measured by ELISA.Bronchoalveolar lavage fluid (BALF) was performed, and total cell counts,cell differential were examined.The level of IL-12 and IL-13 in BALF was measured by ELISA and total cell counts, cell differential were examined in BALF.The inflammation changes of lung was observed by HE staining.Results (1) By hematoxylin-eosin (HE) staining, the result of asthma mice were small airway wall thickening ,secretion increased, epithelial cells fall off, arranging disorderly, and submucosal had plenty of inflammatory cells infiltration, mainly with lymphocytes.But imquimod group attenuated the airway inflammation of asthmatic mice.(2) Total cell counts and all kinds of inflammatory cells of asthma group were increased greatly compared with normal group;Eosinophil and lymphocyte cells were much lower in imquimod group than those in asthma group (P ＜0.05).(3) The level of IL-13 in BALF and the level of IgE in serum in imiquimod group was obviously higher than that in control group,IL-13 level were positively correlated with IgE level(r =0.774 ,P ＜ 0.05), but imiquimod group was greatly decreased compared with control group and increased in comparison with that in group A;The level of IL-12 in asthma group was reduced and the level of IgE was increased compared with normal group.IL-12 level in imiquimod group was evidently higher and IgE level was lower than that in asthma group.IL-12 level negatively correlated with IgE level(r =-0.802, P ＜ 0.05).Conclusion Imiquimod aerosol inhalation may up-regulate the level of Th1 chemokine IL-12,down-regulates the level of Th2 chemokine IL-13 and decrease the level of IgE in serum so that it may suppress antigen-induced airway inflammation.
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Objective To evaluate the effect of dexmedetomidine and tramadol on perioperative insulin resistance in patients undergoing radical resection of rectal carcinoma.Methods Sixty ASA I or II patients undergo-ing radical resection of rectal carcinoma were randomly divided into 3 groups(n =20 each):dexmedetomidine group (group D),tramadol group(group T),control group(group C).Group D was given dexmedetomidine intravenously at 1μg/kg 15min before induction of anesthesia followed by a continuous infusion of 0.5μg·kg -1 ·h -1 until the abdo-men was closed,and group T was given tramadol intravenously at 1.5mg/kg 15min before induction of anesthesia fol-lowed by a continuous infusion of 0.5mg·kg -1 ·h -1 until the abdomen was closed,whereas group C received the same volume of normal saline.Venous blood samples were taken at 30min before anesthesia induction(T1 ),1 h after the beginning of the operation(T2 ),1h after operation(T3 ),24h after operation(T4 )for determination of blood con-centrations of glucose(BG),insulin(INS),interleukin -6 (IL -6),tumor necrosis factor -α(TNF -α).Insulin resistance(HOMA -IR)and insulin sensitivity index(QUICKI)were calculated.The numbers of patients with PONV were studied respectively.Results The serum IL -6,TNF -α,BG,INS concentrations and HOMA -IR were signifi-cantly lower while ISI was significantly higher in both group D[t =7.71,3.37,8.78,8.73,11.45,2.82(T2 ),3.04, 2.95,12.75,10.73,16.09,2.92(T3 ),11.26,2.45,11.40,5.10,14.5,2.51(T4 ),all P <0.05]and group T[t =3.02,2.59,2.93,7.76,6.32,2.03(T2 ),8.78,2.27,4.14,8.83,7.68,2.12(T3 ),6.10,2.05,3.71,2.35,7.12, 2.09(T4 ),all P <0.05]at T2 ,T3 and T4 than those in group C.The serum TNF -αconcentration and HOMA -IR were significantly lower while ISI was significantly higher in group D[t =6.68,4.58,2.05 (T2 ),9.01,6.66,2.23 (T3 ),7.54,5.5,2.02(T4 ),all P <0.05]at T2 ,T3 and T4 than those in group T.The numbers of patients with PONV were significantly higher in group T than those in group D and group C (χ2 =26.13,18.75,all P <0.05 ). Conclusion Both dexmedetomidine and tramadol can attenuate perioperative insulin resistance in patients undergo-ing Radical Resection of Rectal Carcinoma,and the decrease the consentrations of IL -6 and TNF -αmay be involved in the mechanism.The roles of prevention of perioperative insulin resistance in dexmedetomidine group are superior to tramadol group.The incidence of PONV is less in a dexmedetomidine group than that in a tramadol group.
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Objective To evaluate the value of neutrophil CD64 positive cells percentage(CD64%)detec-tion to stop using antibiotic in patients with severe pneumonia.Methods 60 accepted antibiotic therapy patients with severe pneumonia,in accordance with the random number table,were separated into observation group(n =30)and control group(n =30).Antibiotics were stopped according to CD64% in observation group,while it according to the clinical symptoms,the plasma level of white blood cell and C -reactive protein in control group.The main observation indexes included the days of antibiotics use,the length of Intensive Care Unit(ICU)stay,clinical efficacy and the case fatality rate.Results The days of antibiotics use in the observation group was (10.3 ±5.2)d,while it was (16.8 ± 5.8)d for patients in the control group,and it had significant difference(t =-4.570,P 0.05).Conclusion Stop using antibiotics according to the neutrophil CD64 % is safe,reliable,and can effectively reduce the excessive use of antibiotics and shorten the length of ICU stay in patients with severe pneumonia.
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Objective To investigate the effect of silent information regulator 1 (SIRT1)on cigarette smoke extract (CSE)-induced apoptosis of human alveolar epithelial cell (AECs).Methods The expression levels of SIRT1 protein were examined by Western Blotting in A549 cells that were treated with CSE at different concentrations.The impairment models of A549 cells induced by CSE were established.The concentration of CSE was 20.0％ and the treatment time of CSE was 24 hours.A549 cells were pretreated with 20 μmol/L resveratrol(Res)or 5 mmol/L nicotinamide (NAM) for 2 h before CSE treatment.The protein levels of SIRT1,Bax and Bcl2 were further explored by Western blotting.The proportion of apoptotic A549 cells was measured using MTT.Results The expression of SIRT1 was reduced after treatment with CSE in a dose-dependent manner(P＜0.05).Compared with the control group,the group of CSE treatment with 2.5％,5.0％,10.0％,20.0％and 40.0％ CSE for 24h showed that the expression of SIRT1 in A549 cells was decreased by 25.6％(P＜0.05),35.2％(P＜0.05),38.7％ (P＜0.05),57.9％ (P＜0.05)and 64.0％(all P＜0.05)separately; that A549 cell viability was decreased in a dose-dependent manner; and that A549 cell viability was decreased by 10.2％(t=2.035,P＜0.05),18.4％(t=4.269,P＜0.05),27.7％ (t=5.963,P＜0.05),59.0％(t=21.140,P＜0.05)and 88.1％(t=58.827,P＜0.05)separately.CSE plus 20 μmol/L Res pretreatment reversed the expression levels of SIRT1,Bax and Bcl2 in A549 cells (all P＜0.05)and reduced the apoptosis of A549 cells.The effects of CSE on inhibiting SIRT1 pathways were aggravated by NAM (an inhibitor of SIRT1) in the A549 cells (P＜ 0.05).Conclusions SIRT1 plays important role in regulating the apoptosis of human alveolar epithelial A549cell induced by CSE.SIRT1 may inhibit apoptosis by up-regulating Bcl2 expression and downregulating Bax expression,which has a protective effect on A549 cells apoptosis induced by CSE.