Objective : To explore the polymorphism of endothelial nitric oxide synthase(eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants. Methods : A total of 254 preterm infants(<37 weeks) who were hospitalized were selected as the study subjects. Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci: rs61722009, rs2070744,and rs1799983. Clinical data of the preterm infants were recorded, and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed. Results: (1) The TC+CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia(BPD) in preterm infants, with an OR(95%CI) of 1.266(1.017-1.577).(2) The GT+TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity(ROP), with an OR(95%CI) of 1.184(1.008-1.391).(3) The AB+AA genotype at locus rs61722009 was also an independent risk factor for ROP,with an OR(95%CI) of 1.335(1.033-1. 726).(4) There was no significant relationship between gene polymorphism and the occurrence of respiratory distress syndrome( RDS) and periventricular-intraventricular hemorrhage( PIVH). Conclusion eNOS gene polymorphism is associated with the occurrence of BPD and ROP in preterm infants. The evaluation of e NOS gene polymorphism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications.

Neuraxial labor analgesia effectively alleviates maternal pain and enhances pain control dur-ing delivery.However,breakthrough pain(BTP)following labor analgesia may occur in some parturients after neuraxial anesthesia,potentially prolonging labor progression,compromising maternal-fetal safety,and in-creasing the risk of cesarean delivery.Therefore,understanding and managing breakthrough pain are crucial in clinical practice.This review synthesizes current evidence on risk factors,neuraxial anesthesia modalities,ma-intenance techniques,and rational use of analgesic drugs to reduce BTP.

Objective To investigate the clinical diagnostic value of plasma RAS association domain family 1A(RASSF1A)gene methylation combined with tumor marker detection in non-small cell lung cancer(NSCLC).Methods A total of 98 NSCLC patients admitted to Qinhuangdao First Hospital from June 2023 to March 2024 were selected as the NSCLC group,and 95 patients who under-went pulmonary examinations during the same period but were not diagnosed with NSCLC were selected as the disease control group.Their general clinical data were collected.The correlations among plasma RASSF1A gene methylation,tumor markers,and clinicopatho-logical features were analyzed.The effects of RASSF1A gene methylation and tumor markers on the diagnosis of NSCLC were analyzed by the multivariate Logistic regression.A predictive model was constructed,and its effectiveness was evaluated by the receiver operating characteristics(ROC)curve and goodness of fit test.Results There were significant differences(P＜0.05)in smoking history,neu-ron specific enolase(NSE),carcinoembryonic antigen(CEA),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and RASSF1A methylation levels between the NSCLC group and non-NSCLC group.There were also significant differences(P＜0.05)in RASSF1A methylation levels,NSE,CEA,and CYFR21-1 levels among NSCLC patients with different clinical characteristics such as tumor diam-eter,differentiation degree,and growth type.The results of multivariate Logistic analysis showed that RASSF1A methylation levels(OR=1.071,95％CI:1.042-1.100),NSE(OR=1.168,95％CI:1.132-1.204),CEA(OR=1.154,95％CI:1.121-1.187),and CYFR21-1(OR=1.089,95％CI:1.023-1.195)were all independent risk factors for the diagnosis of NSCLC.A model predicting the occurrence of NSCLC was constructed using the principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),and the ROC curve analysis results showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the prediction model for the RASSF1A methylation level combined with NSE,CEA,and CYFR21-1 were 0.922(95％CI:0.896-0.948),0.897,and 0.851,respectively,which were higher than those of the RASSF1A methylation level,NSE,CEA,and CYFR21-1 alone.Conclusion The prediction model of plasma RASSF1A gene methylation level combined with tumor markers has high diagnostic value for NSCLC and can be used for the clinical diagnosis of NSCLC.

Objective To investigate the clinical diagnostic value of plasma RAS association domain family 1A(RASSF1A)gene methylation combined with tumor marker detection in non-small cell lung cancer(NSCLC).Methods A total of 98 NSCLC patients admitted to Qinhuangdao First Hospital from June 2023 to March 2024 were selected as the NSCLC group,and 95 patients who under-went pulmonary examinations during the same period but were not diagnosed with NSCLC were selected as the disease control group.Their general clinical data were collected.The correlations among plasma RASSF1A gene methylation,tumor markers,and clinicopatho-logical features were analyzed.The effects of RASSF1A gene methylation and tumor markers on the diagnosis of NSCLC were analyzed by the multivariate Logistic regression.A predictive model was constructed,and its effectiveness was evaluated by the receiver operating characteristics(ROC)curve and goodness of fit test.Results There were significant differences(P＜0.05)in smoking history,neu-ron specific enolase(NSE),carcinoembryonic antigen(CEA),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and RASSF1A methylation levels between the NSCLC group and non-NSCLC group.There were also significant differences(P＜0.05)in RASSF1A methylation levels,NSE,CEA,and CYFR21-1 levels among NSCLC patients with different clinical characteristics such as tumor diam-eter,differentiation degree,and growth type.The results of multivariate Logistic analysis showed that RASSF1A methylation levels(OR=1.071,95％CI:1.042-1.100),NSE(OR=1.168,95％CI:1.132-1.204),CEA(OR=1.154,95％CI:1.121-1.187),and CYFR21-1(OR=1.089,95％CI:1.023-1.195)were all independent risk factors for the diagnosis of NSCLC.A model predicting the occurrence of NSCLC was constructed using the principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),and the ROC curve analysis results showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the prediction model for the RASSF1A methylation level combined with NSE,CEA,and CYFR21-1 were 0.922(95％CI:0.896-0.948),0.897,and 0.851,respectively,which were higher than those of the RASSF1A methylation level,NSE,CEA,and CYFR21-1 alone.Conclusion The prediction model of plasma RASSF1A gene methylation level combined with tumor markers has high diagnostic value for NSCLC and can be used for the clinical diagnosis of NSCLC.

Objective To investigate the expression changes of interferon gene stimulating factor(STING)and E-box zinc finger binding protein 1(ZEB1)in elderly cervical cancer(CCA)patients and their correlation with human papillomavirus(HPV)infection.Methods Sixty-two patients with CCA who underwent patho-logical examination in this hospital from January 2021 to September 2022 were selected as the CCA group,65 patients with cervical intraepithelial neoplasia(CIN)as the CIN group,and 63 patients with normal cervix as the control group.The positive expression rates of cervical STING and ZEB1 and high-risk HPV infection in each group were observed and recoraded.The correlation of STING and ZEB1 levels with clinicopathological features of CCA and high-risk HPV infection was analyzed.Results The positive expression rates of STING and ZEB1 in CCA group were higher than those in CIN group and control group,and the level of ZEB1 in CIN group was higher than that in control group,with statistical significance(P＜0.05).The detection rates of HPV16 and 18 in CCA group were higher than those in CIN group and control group,and the detection rates of HPV16 and 18 in CIN group were higher than those in control group,the differences were statistically sig-nificant(P＜0.05).The infiltration depth and FIGO stage of CCA patients were correlated with the positive expression rates of STING and ZEB1,the degree of tumor differentiation and lymph node metastasis were cor-related with the positive expression rates of STING(P＜0.05),and the positive expression rates of STING and ZEB1 in CCA patients were positively correlated with the infection rates of HPV16 and 18(P＜0.05).Conclusion The positive expression levels of STING and ZEB1 proteins in the CCA group are higher than those in the control group and CIN group,and their expression levels were related to FIGO staging and depth of cervical cancer infiltration.STING and ZEB1 proteins are positively correlated with HPV16 and 18 infec-tion,and STING and ZEB1 proteins may jointly act with HPV16 and 18 on the occurrence and development of CCA.

OBJECTIVE To observe the effect of Huangjing Jiangya Decoction on blood pressure and sleep in patients with hy-pertension of qi-deficiency type accompanied by insomnia.METHODS 73 patients with hypertension of qi-deficiency type accompa-nied by insomnia who met the inclusion criteria were selected and randomly divided into an observation group of 36 cases and a control group of 37 cases.The control group was treated with amlodipine besylate tablets,and the observation group was given Huangjing Jian-gya Decoction oral treatment on the basis of the control group.Both groups were treated continuously for 8 weeks.The changes in TCM syndrome scores,office blood pressure monitoring(OBPM),home blood pressure monitoring(HBPM),24-hour ambulatory blood pressure monitoring(ABPM),Pittsburgh Sleep Quality Index(PSQI)scores and clinical efficacy of the two groups of patients before and after treatment were observed.RESULTS After treatment,the TCM syndrome scores in the observation group were significantly decreased(P<0.05,P<0.01),which were better than the control group(P<0.01);OBPM and HBMP in both groups were signifi-cantly reduced(P<0.05,P<0.01),the observation group was better than the control group(P<0.05,P<0.01);the ABPM of the observation group was significantly reduced(P<0.01),which was better than the control group(P<0.05,P<0.01);the sleep quali-ty,sleep latency,sleep duration,daytime dysfunction score and PSQI total score of the observation group were significantly decreased(P<0.01),which were better than those in the control group(P<0.05,P<0.01);the clinical efficacy of hypertension and insomnia in the observation group was both better than the control group(P<0.01).CONCLUSION Huangjing Jiangya Decoction combined with amlodipine can improve the symptoms of patients with hypertension of qi-deficiency type accompanied by insomnia,lower blood pressure,improve sleep quality,shorten sleep latency,alleviate daytime dysfunction,and has good clinical efficacy.

Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

In order to reveal the intestinal absorption mechanism of saikosaponin d (SSd) in vitro and in vivo, the current research investigated the effects of different experimental conditions (time, concentration, temperature, pH, intestinal segments), transporter inhibitors, paracellular pathway enhancer, metabolic enzyme inhibitors on the intestinal absorption of SSd, in Caco-2 monolayers and a single pass perfusion model in rats.The results showed that the apparent permeability coefficient (Papp) and effective permeability coefficient (Peff) of SSd were 4.75 × 10-7 - 6.38 × 10-7 cm/s and 0.19 × 10-4- 0.27 × 10-4 cm/s, respectively, indicating that it was a low permeability compound, and that the transmembrane transport of SSd was concentration-dependent (0.5-5 μmol/L) and time-dependent (0-180 min).Ileum was the main absorption site for SSd. Experimental results based on Caco-2 monolayers showed that the P-gp inhibitor and paracellular permeability enhancer significantly increased the absorption of SSd (P < 0.05), which was consistent with the results obtained in rats. Inhibitors of OATPs and OCTs showed different results in vitro and in vivo, which may be related to the lower expression of them in jejunum.In summary, the intestinal absorption of SSd occurs through a carrier-mediated and energy-dependent transport, as well as passive diffusion, and P-glycoprotein plays an important role in the active transport of SSd.

By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.

Objective:To investigate and compare the value of cross-sectional area measurement and width measurement by high frequency ultrasound in the diagnosis of congenital adrenal hyperplasia (CAH) in infants.Methods:The abdominal ultrasound images of 20 infants who were diagnosed as CAH in Tianjin Children′s Hospital and clinical diagnosised from November 2013 to August 2018 were analyzed retrospectively. The maximum cross-sectional area of adrenal gland and the maximum width of single limb were measured respectively to assess the size of adrenal gland. Fifty normal full-term infants were selected as control group at the same period. The differences of maximum cross-sectional area of adrenal gland, the maximum width of single limb between CAH group and control group were compared. ROC curve was plotted to compare the diagnostic values of cross-sectional area measurement and width measurement.Results:①There was significant difference in maximum cross-sectional area of adrenal gland between infants with CAH and normal infants[(129.47±37.39)mm 2 vs (54.42±20.85)mm 2; t=10.004, P<0.001]. There was significant difference in maximum width of adrenal gland between infants with CAH and normal infants [(4.56±1.20)mm vs (3.25±0.66)mm; t=5.445, P<0.001]. ②The area under ROC curve(AUC) of cross-sectional area measurement was 0.966, the best cutoff value was 87.5 mm 2, the sensitivity was 95.0%, and the specificity was 92.5%. AUC of width measurement was 0.817, the best cutoff value was 5.25 mm, the sensitivity was 90.0%, and the specificity was 62.5%. The difference of AUC between cross-sectional area measurement and width measurement was 0.149, which was statistically significant ( Z=2.309, P=0.021). Conclusions:Both cross-sectional area measurement and width measurement by high frequency ultrasound have diagnostic values for CAH in infants, with the former more valuable than the latter.