Objective To investigate whether the effect of transient high glucose on inflammatory factors expression could be continuous in rat glomerular mesangial cell,and its relation with histone methylation modification.Methods Rat glomerular mesangial cells (HBZY-l) were divided into three groups:the high glucose group (25.0 mmol/L glucose),the hypertonic group (MA,5.5 mmol/L glucose+ 19.5 mmol/L mannitol) and the normal-glucose control group (5.5 mmol/L glucose),which were cultured for 24 h respectively.All 3 groups were then changed with normal-glucose medium to culture for 24 h,48 h and 72 h.Their protein,mRNA and supernatant were harvested.The protein expressions of mono-methylation of H3 lysine 4 (H3K4mel) was measured by Western blotting,and the mRNA expressions of NF-κB subunit p65 and set7/9 were determined by real timequantitative PCR.The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) were detected by enzyme-linked immunosorbent assay.Results (1)Compared with those in normal control group,the expressions of H3K4mel protein and set7/9 mRNA were first up-regulated in high glucose group,then gradually down-regulated in the following 48 h normal-glucose medium (as compared with those at 0 h,all P ＜ 0.05).At 72 h there was no statistic difference between high glucose group and normal control group (all P ＞ 0.05).(2) Compared with those in normal control group,the up-regulated p65 mRNA,VCAM-1 and MCP-1 sustained at least for 72 h in high glucose group.Conclusions Transient high glucose can induce persistent inflammatory factors expression in rat glomerular mesangial cells,which may via histone modification.

Objective To analyze the effects of valproic acid(VPA),a histone deacetylase(HDAC)inhibitor,on macrophage polarization in?duced by paraquat(PQ)or lipopolysaccharide(LPS). Methods Mouse RAW264.7 cells were cultured at 37℃with 5%CO2,passaged,and then given one of the following treatments:(1)PQ;(2)PQ+VPA(classⅠandⅡa HDAC inhibitor);(3)PQ+apicidin(classⅠHDAC inhibitor);(4)PQ+MC1568(classⅡa HDAC inhibitor);(5)LPS;(6)LPS+VPA;(7)LPS+apicidin;(8)LPS+MC1568. The cells and culture supernatants were harvested after 8 h of treatment. RT?PCR,ELISA,and flow cytometry were conducted to assess the expression levels of macrophage phenotyp?ic markers. Results Both PQ and LPS skewed the macrophage functional polarity toward proinflammatory phenotype. VPA,apicidin,and MC1568 all inhibited PQ?and LPS?induced macrophages polarizing toward pro?inflammatory phenotype ,but the inhibitory effects were different in some ways. Conclusion VPA inhibits the proinflammatory function of macrophages induced by PQ and LPS ,but the effect of VPA on PQ?and LPS?induced macrophages has its own characteristics.

OBJECTIVEA multiplex PCR system for screening rare blood group antigens K and Yt(b) was constructed to study the distribution of the two blood groups in a Uygur population in Xinjiang, China.

METHODSSequence-specific primers (SSP) were designed based on single nucleotide polymorphism sites of KEL and ACHE alleles encoding the two blood group antigens. The system was designed for simultaneously detecting the two antigens by optimizing the PCR reaction. Three hundred and sixty-two randomly selected healthy individuals were screened. Products of PCR were further analyzed for heterozygosity.

RESULTSThe system was set up successfully. No KK sample was identified and 9 K+ k+ , 41 Yt (a+ b+ ), 4 Yt (a- b+ ) were found among the 362 samples.

CONCLUSIONThe established PCR-SSP based multiple PCR system is efficient to screen the rare blood group antigens K and Yt(b). The information of rare blood donors obtained from the screening can be used to improve the capability of compatible transfusion.

Antigens, Bacterial ; genetics ; Antigens, Surface ; genetics ; Blood Donors ; Blood Group Antigens ; genetics ; Blood Transfusion ; methods ; China ; Humans ; Multiplex Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide

Objective:To explore the efficacy and safety of camrelizumab combined with apatinib as the second-line treatment for patients with advanced gastric cancer.Methods:The clinical data of 19 patients with advanced gastric cancer in Hebei General Hospital from August 2019 to March 2022 were retrospectively analyzed. All patients received camrelizumab combined with apatinib as the second-line treatment. The treatment efficacy and adverse reactions were evaluated; the survival analysis was performed using Kaplan-Meier method; Cox proportional hazards model was used to analyze the influencing factors for overall survival (OS) of patients.Results:Among 19 patients, no one achieved complete remission, 4 patients (21.1%) achieved partial remission, 9 patients (47.4%) had stable disease. The objective response rate (ORR) and disease control rate (DCR) were 21.1% (4/19) and 68.4% (13/19), respectively. The ORR of patients with deficient mismatch repair (dMMR) was higher than that of patients with proficient mismatch repair (pMMR) [100.0% (2/2) vs. 11.8% (2/17), P < 0.05], and patients with programmed death receptor ligand 1 (PD-L1) combined positive score (CPS) ≥1 had a higher DCR than patients with PD-L1 CPS < 1 [100.0% (5/5) vs. 25.0% (1/4), P < 0.05]. The median follow-up time of 19 patients was 14.7 months (12.0-17.4 months), the median progression-free survival time and OS time were 2.8 months and 5.7 months (95% CI 2.4-8.9 months). Increased lactate dehydrogenase (LDH) was negatively correlated with OS ( χ2 = 10.262, P = 0.001). Multivariate Cox regression analysis showed that LDH was an independent influencing factor for the OS of patients (<250 U/L vs. ≥250 U/L: HR = 0.149, 95% CI 0.039-0.657, P = 0.005). The most common treatment-related adverse reactions were fatigue (52.6%, 10 cases), anemia (47.4%, 9 cases), thrombocytopenia (36.8%, 7 cases), rash (36.8%, 7 cases), and reactive capillary hemangioma (36.8%, 7 cases). Conclusions:Camrelizumab combined with apatinib as the second-line treatment for advanced gastric cancer have good efficacy and safety.

Objective To explore the effects of three-grade prevention and nursing when used in caring hematological malignancies (HM) patients with oral mucositis (OM).Methods Totally 128 HM patients who received chemotherapy in the Third Affiliated Hospital of Wenzhou Medical University from January 2015 to June 2016 were divided randomly into an observation group (64) and a control group (64). Patients in both groups received conventional chemotherapy nursing,and on this basis,patients in the observation group were treated with three-grade prevention and nursing,which was followed by a comparison in incidence of oral mucositis (OM), Fungous infection of lower respiratory tract (FILRT) and oral cavity fungus infection (OCFI) between patients in the two groups.Results As for OM incidence,patients in the observation group were better than those in the control group (P<0. 05). The FILRT incidence of patients in the observation was lower than that of patients in the control group (P<0.05);and the OCFI incidence of patients in the observation group were higher than that of patients in the control group (P<0. 05).Conclusions Three-grade prevention and nursing effectively reduces the incidence of OM and FILRT among HM patients during perichemotherapy,and is worthy of clinical expansion and application.

Objective:To explore the quantitative analysis value of diffusion tensor imaging (DTI) for early changes of calf muscle in type 2 diabetes mellitus (T2DM) patients without peripheral ischemia.Methods:From September 2018 to March 2019, 20 male T2DM patients (age: 45-64 years) without peripheral ischemia and 20 matched male healthy controls (age: 46-62 years) who performed lower limb DTI in Wuxi Second Hospital Affiliated to Nanjing Medical University were prospectively analyzed. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and λ 1, λ 2, λ 3 values of medial head of gastrocnemius (GM), lateral head of gastrocnemius (GL), tibialis anterior(TA) and soleus muscles(SOL) were measured respectively. The differences of DTI diffusion characteristics between 2 groups were compared by using independent-sample t test, and the correlation between FA, ADC and body mass index (BMI), fasting blood glucose (FBG), hemoglobin A 1c (HbA1c), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG) were analyzed by Pearson correlation analysis. Results:The ADC of TA and SOL in T2DM group ((1.77±0.15) and (1.83±0.10)×10 -3 mm 2/s) was higher than that in control group ((1.66±0.11) and (1.75±0.16)×10 -3 mm 2/s); λ 1, λ 2, and λ 3 of TA in the T2DM group ((2.30±0.21), (1.63±0.17) and (1.38±0.13)×10 -3 mm 2/s) were higher than those in control group ((2.17±0.12), (1.51±0.13) and (1.31±0.12)×10 -3 mm 2/s); λ 2 and λ 3 of SOL were also higher than those in control group ((1.74±0.11) vs (1.64±0.18)×10 -3 mm 2/s and (1.53±0.12) vs (1.44±0.15)×10 -3 mm 2/s; t values: 2.65-3.91, all P<0.05). There were no significant correlations between FA, ADC and BMI, FBG, HbA1c, HDL, LDL and TG ( r values: from -0.15 to 0.08, all P>0.05). Conclusions:Quantitative parameters of DTI, especially ADC, can sensitively detect the microstructural changes of calf muscle in T2DM patients without peripheral ischemia. TA and SOL have high sensitivity to the diffusion of T2DM-related microstructural changes.

Objective:To investigate the current status of anticoagulant therapy and the incidence of ischemic and bleeding events in hospitalized patients aged 90 years and over with non-valvular atrial fibrillation(NVAF).Methods:We retrospectively collected clinical data, antithrombotic treatment strategies, in-hospital ischemic stroke and bleeding events from NVAF patients(≥90 years)who were admitted to our hospital from June 2014 to August 2018.Based on the CHA 2DS 2-VASc score(2, 3, and ≥4 respectively), patients were divided into three ischemic risk groups, and antithrombotic treatment strategies and in-hospital ischemic stroke events were compared between the three groups.Alternatively, patients were divided into the high bleeding risk group(HAS-BLED score ≥3, )and the non-high bleeding risk group(HAS-BLED score ≤2), and antithrombic treatment strategies and the major bleeding events were compared between the two groups. Results:Among the 223 hospitalized NVAF patients aged 90 years and over, 42.6% of them received anticoagulant treatment, 25.6% received antiplatelet drugs, and 31.8% received non-antithrombotic treatment.With the increase of the CHA 2DS 2-VASc score, there was a trend of declined rates of non-antithrombotic treatment among the three ischemic risk groups(47.4%, 42.9%, 26.4%, P=0.06), and the rates of in-hospital ischemic stroke were similar among groups(10.5%, 12.2%, 15.5%, P=0.75). Moreover, compared with the non-high bleeding risk group, patients in the high bleeding risk group more frequently received anticoagulant treatment(47.2% vs.38.3%)and less frequently received non-antithrombotic therapy(28.7% vs.34.7%). There was no significant difference in antithrombotic treatment strategies( P=0.39)or rate of in-hospital major bleeding events(13.0% vs.10.2%, P=0.51). However, the rate of in-hospital major bleeding events was significantly higher in those with concurrent infections(16.8% vs.6.4%, P=0.02)or respiratory failure(21.3% vs.8.0%, P=0.01). Conclusions:The rate of anticoagulant use in NVAF patients aged 90 years and over is too low during hospitalization, and anticoagulant therapy should be standardized.In addition to the HAS-BLED score, we should consider the complications that increase the bleeding risk, such as infections and respiratory failure, when evaluating the bleeding risk.

Objective:To evaluate the pharmacodynamics of remimazolam tosilate inducing loss of consciousness (LOC) when combined with sufentanil in children.Methods:American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ pediatric patients of either sex, aged 3-6 yr, undergoing electronic bronchoscopy, were included in this study. ECG monitoring was carried out in all children after admission, sufentanil 0.1 μg/kg was intravenously injected slowly, and 3 min later remidazolam tosilate was intravenously injected. The dose of remimazolam tosilate was determined by the modified Dixon′s up-and-down sequential experiment, and the initial dose of remimazolam tosilate was 0.30 mg/kg. The dose of remimazolam tosilate in the next child was determined according to the the loss of consciousness, and the successive dose gradient was 0.05 mg/kg. Loss of eyelash reflex and Modified Observer′s Assessment of Alertness/Sedation Scale score reaching 0 and the occurrence of 8 crossover points where consciousness transitioned from non-disappearance to disappearance after 1 min of remimazolam tosilate injection were considered to be signs of LOC. The median effective dose (ED 50), 95% effective dose (ED 95), and their 95% confidence interval ( CI) of remimazolam tosilate inducing LOC were calculated using probit method. Results:When combined with sufentanil, the ED 50 and 95% CI of remimazolam tosilate inducing loss of consciousness were 0.461 (0.429-0.493) mg/kg, and the ED 95 and 95% CI were 0.515 (0.487-0.689) mg/kg. Conclusions:When combined with sufentanil, the ED 50 of remimazolam tosilate inducing LOC is 0.461 mg/kg and the ED 95 is 0.515 mg/kg in children.

Objective To investigate the impact of human leukocyte antigen(HLA)functional epitope mismatch(EM)on the efficacy of platelet transfusion in patients with hematological diseases.Methods HLA genotyping was performed on platelet donors and patients with hematological diseases who applied for platelet serological cross-matching and HLA antigen matching from June 2021 to June 2023 by PCR-SBT method.HLA platelet matching was based on the principle of CREG to se-lect donors for patients.HLA Matchmaker 4.0 software was used to analyze donor-recipient HLA EM information.The expres-sion level and gene distribution of related HLA functional epitope(Eplet)were searched from the international HLA Epitope registry website(www.Epregistry.com.br).Retrospective analysis was conducted on clinical platelet transfusion data to evalu-ate the impact of HLA EM on platelet transfusion effectiveness.Results Platelet transfusion efficacy showed no correlation with gender and age,but it was associated with platelet matching strategy.When the total number of HLA EMs was less than 20,a lower total number of donor-recipient HLA EMs resulted in higher platelet transfusion efficiency(χ2=19.311,P=0.001)and higher average value of 24 h corrected count increment(CCI)(F=7.737,P<0.001).The total number of donor-recipient HLA EMs had negative correlation with actual 24 h CCI(Rho=-0.322,P<0.001).Further statistical analysis re-vealed that 17 Eplets were related to the effectiveness of platelet transfusion.The locus distribution of 17 Eplets might be u-nique to HLA-A(17.6%)or-B(64.7%)or shared between HLA-A and-B(17.6%),and its expression may be high(58.8%)or intermediate(41.2%).Conclusion The total number of donor-recipient HLA EMs is a crucial factor influencing platelet transfusion effectiveness,and several HLA Eplets associated with this effectiveness have been identified.

Objective To evaluate the utility of combined liver stiffness measurement (LSM) and spleen stiffness measurement (SSM),by transient elastography,along with measurement of portal vein width (PVW) for evaluating risk of bleeding in patients with esophageal and gastric varices (EV).Methods A total of 73 patients with cirrhosis who were treated in the Department of Gastroenterology of the Second Affiliated Hospital of Xi'an Jiaotong University between April 2014 and March 2015 were included in the study.Child-Pugh classifications were obtained,portal vein widths were measured by ultrasound,liver and spleen stiffness were measured by transient elastography using FibroTouch(R).Patients were examined by electronic endoscopy,upper abdominal computed tomography and standard serum testing.The serum indexes of fibrosis (aspartate aminotransferase (AST) to platelet ratio index (APRI),and AST to alanine aminotransferase ratio (AAR)) were calculated.Patients were grouped according to the results of gastroscopy,with severe (EV) and high risk of bleeding comprising group A and no or mild-to-moderate EV and low risk of bleeding comprising group B.Statistical analysis was carried out with t-test for continuous variables and x2 test for categorical variables to first screen out variables different between groups then the correlation with severe EV was assessed by generating receiver operating characteristic (ROC) curves.Lastly,binary logistic regression was used to evaluate the performance of combined variables for diagnosing severe EV and their predictive value for risk of bleeding.Results Group A and B showed significant differences for LSM,SSM and PVW (all P ＜ 0.05).The cutoffvalues for diagnosing severe EV were 23.4 kPa for LSM,40.3 kPa for SSM and 11.5 mm for PVW,with areas under the ROC curve (AUROC) as 0.655,0.788 and 0.709 respectively.For combined measurements,the AUROC was 0.773 for LSM plus PVW and 0.840 for LSM plus PVW (with highest diagnostic performance).Conclusions Combination of SSM plus PVW measurement shows high diagnostic performance for evaluating severe EV,and better performance than LSM plus SSM plus PVW and LSM plus PVW,with good predictive value for risk of EV bleeding.