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 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.

OBJECTIVETo screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population.

METHODSSequence-specific primers were designed based on single nucleotide polymorphism (SNP) sites of blood group antigens Fy(b) and s. A specific multiplex PCR system I was established. Multiplex PCR system II was applied to detect alleles antigens Di(b), k, Js(b)1910 and Js(b) 2019 at the same time. The two systems was were used to screen for rare blood group antigens in 4490 randomly selected healthy donors of Guangxi Zhuang ethnic origin.

RESULTSWe successfully made the multiplex PCR system I. We detected the rare blood group antigens using the two PCR system. There are five Fy(a-), three s(-), two Di(b-) in 4490 Guangxi zhuang random samples. The multiplex PCR system I has achieved good accuracy and stability. With multiplex PCR systems I and II, 4490 samples were screened. Five Fy(a-), three s(-) and two Di(b-) samples were discovered.

CONCLUSIONMultiplex PCR is an effective methods, which can be used for high throughput screening of rare blood groups. The rare blood types of Guangxi Zhuang ethnic origin obtained through the screening can provide valuable information for compatible blood transfusion. Through screening we obtained precious rare blood type materials which can be used to improve the capability of compatible infusion and reduce the transfusion reactions.

Blood Group Antigens ; genetics ; Duffy Blood-Group System ; genetics ; Genotype ; Humans ; Multiplex Polymerase Chain Reaction ; methods ; Receptors, Cell Surface ; genetics

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

Objective:To explore the treatment efficacy of neuroendoscope-assisted exploration and release of the outflow tract of the fourth ventricle in patients with Chiari malformation type I.Methods:Ninety-five patients with Chiari malformation type I, admitted to our hospital from January 2016 to January 2020, were chosen in our study. Patients from observation group ( n=57) were treated with posterior cranial fossa decompression+subdural tonsillectomy+endoscope-assisted exploration and release of the outflow tract of the fourth ventricle+enlarged reconstruction of the occipital cistern. Patients from control group ( n=38) were treated with posterior fossa decompression+subdural tonsillectomy+enlarged reconstruction of the occipital cistern. All patients were followed up for one year. Data of surgical duration, intraoperative blood loss, postoperative length of hospital stay, and incidence of complications were retrospectively analyzed in patients from the two groups, and the imaging changes of spinal cavity were observed before surgery and during postoperative follow-up. Chicago Chiari Outcome Scale (CCOS) was used to evaluate the prognoses of all patients (scores of 11-16 were defined as good prognosis). The differences of good prognosis rate among patients with different gender, age, degrees of tonsillar herniation and distributions of spinal cavity segments were analyzed. Results:There was no significant difference in surgical duration, intraoperative blood loss, postoperative length of hospital stay or incidence of complications between the two groups ( P>0.05). As compared with the control group (65.5%), the observation group had higher syringomyelia minification (75.5%) during postoperative follow-up, without significant difference ( P>0.05). The good prognosis rate of the observation group during postoperative follow-up (91.2%) was significantly higher than that of the control group (78.9%, P<0.05). Female patients, patients with age≤45 years, and patients with tonsillar herniation level below the atlas had significantly higher good prognosis rate than male patients, patients with age>45 years, and patients with tonsillar herniation level between the foramen magnum and the atlas during postoperative follow-up, respectively ( P<0.05). Conclusion:As compared with conventional surgery, neuroendoscope-assisted exploration and release of the outflow tract of the fourth ventricle is more effective in patients with Chiari malformation type I, and the good prognosis rate is likely higher in female patients, patients with age≤45 years, and patients with tonsillar herniation level below the atlas.