Erratum: Author correction to "Coordinated regulation of BACH1 and mitochondrial metabolism through tumor targeted self-assembled nanoparticles for effective triple negative breast cancer combination therapy" Acta Pharmaceutica Sinica B 12 (2022) 3934-3951

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].

Compliance of sepsis hour-1 bundle strategy for patients with septic shock in emergency department / 中华全科医师杂志

Objective:To investigate the implementation status of sepsis hour-1 bundle strategy for patients with septic shock in emergency department.Methods:A total of 116 septic shock patients admitted to the emergency department from January 2020 to December 2020 were included in this prospective study, and the implementation of sepsis bundles and the clinical outcomes of patients were recorded.Results:Among 116 patients, 20 cases (17.2%) had lactic acid monitored within 1 h, 20 cases (17.2%) had blood culture before antibiotics, 82 cases (70.1%) received broad-spectrum antibiotics, 16 cases (13.8%) received fluid resuscitation ≥30 ml/kg, and 57 cases (49.1%) received vasoactive drugs during resuscitation. Finally, the sepsis hour-1 bundle strategy was fully implemented only in 13 cases (11.2%). Compared with the group with incomplete implementation of sepsis hour-1 bundle strategy, the volume of fluid recovery in the group with full implementation was significantly increased [33.7 (30.0,37.5) vs. 8.9(7.3,10.8) ml/kg, Z=-4.78, P<0.001], mean artery blood pressure significantly increased [70.0 (70.0,76.7) vs. 67.7 (61.7,76.7)mmHg(1 mmHg=0.133 kPa) , Z=-2.00, P<0.001], and lactic acid significantly decreased [3.0 (2.0,3.2) vs. 4.4 (3.7,7.2) mmol/L, Z=-2.76, P=0.006]. However, there were no significant differences in ICU mortality, in-hospital mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Septic shock patients in emergency department have poor compliance with the implementation of sepsis hour-1 bundle strategy, and relevant management training should be strengthened.

Preliminary experience of flexible vacuum-assisted ureteral access sheath(FV-UAS) in retrograde intrarenal lithotripsy / 中华泌尿外科杂志

Objective:Objectives To introduce the preliminary experience of flexible vacuum-assisted ureteral access sheath(FV-UAS) in the treatment of upper urinary calculi in retrograde intrarenal lithotripsy(RIRS).Methods:The clinical data of 11 patients with upper urinary calculi who were treated in Jiangxi Provincial People's Hospital from August to September 2021 were analyzed retrospectively. There were 6 males and 5 females, with the mean age of 48 years (32-72 years), the mean size of stone of 15.5 mm (11-20mm), and the mean stone volume of 1 958 mm3 (1 108-4 036 mm3), including 1 case with upper ureteral calculi, 10 cases with renal calculi, and 2 cases with calculi in multiple renal calyces. Ureteral stents were placed in 2 cases preoperatively. There were 2 cases of grade Ⅱ hydronephrosis according to Grignon classification. All patients were treated by retrograde intrarenal lithotripsy, and the FV-UAS(F12/14) was used during the operation. FV-UAS can be passively bent(>90°) with the bending of the flexible ureteroscopy(f-URS), and connect vacuum suction devices. The method of placing the FV-UAS during the operation was the same as traditional ureteral access sheath. The FV-UAS should be as close to the target stone as possible by the f-URS during the operation. F6 ureteral stent was routinely indwelled for 2-4 weeks. The operation time, postoperative complications, and stone volume clearance rate were summarized and analyzed, and stone volume clearance rate was calculated as(1-residual stone volume/preoperative stone volume)×100%. The stone volume was obtained by CT 3-D reconstruction preoperatively and first day postoperatively.Results:All patients underwent RIRS successfully at the first stage, with the usage of FV-UAS(F12/14)during the operation. The mean operation time was 57.1 minutes(34-90 minutes), and the mean stone volume clearance rate was 98.9%(94.8%-100.0%)on the first day postoperatively. Seven cases reached 100.0% stone-free rate, and 4 cases presented residual calculi. The mean hemoglobin drop was 0.8 g/L, and 1 case presented vomiting without fever on the first day postoperatively. For the 4 cases with residual calculi, no residual stone was found by B-ultrasound when the ureteral stent was removed.Conclusions:Our preliminary study found that it is feasible and safe to use FV-UAS in RIRS, which can follow the f-URS to extend into the renal pelvis and renal calyces. Vacuum-assist can increase the probability of stone-free.

Mechanism of the role of NDUFAF4 in increasing radiation resistance of hepatocellular carcinoma by activating Wnt/β-catenin signaling pathway / 中华放射肿瘤学杂志

Objective:To analyze the association between the expression of ubiquinone oxidoreductase complex assembly factor 4 (NDUFAF4) and clinical prognosis of patients with hepatocellular carcinoma (HCC), evaluate the effect of NDUFAF4 on the radiosensitivity of human HCC cell lines, and unravel the underlying mechanism.Methods:The online database and HCC tissue samples were used to investigate the expression of NDUFAF4, and the correlation between NDUFAF4 expression level and clinical prognosis. The si-NDUFAF4 plasmid which down-regulated the expression level of NDUFAF4 was transferred into HepG2 and Huh7 cells. The radiosensitivity of HCC cell lines was detected by clone formation experiment. Nude mice were prepared for tumor-bearing experiment. The β-catenin level was detected by immunofluorescent staining. The expression levels of E-cadherin and N-cadherin proteins were determined by Western blot.Results:Bioinformatics results confirmed that NDUFAF4 was significantly up-regulated in HCC tissues, and the higher the expression level, the worse the patients' clinical prognosis ( P<0.05). The expression level of NDUFAF4 in HCC tissues was significantly higher than that in the adjacent tissues. Clone formation experiment confirmed that knockdown of NDUFAF4 significantly decreased the survival rate of HCC cells ( P<0.01). In vivo experiment showed that knockdown of NDUFAF4 could prevent the proliferation of HCC cells and down-regualte the expression levels of β-catenin and Ki-67. Knockdown of NDUFAF4 significantly down-regulated the expression level of β-catenin protein in the nucleus of HCC cell lines, suggesting that NDUFAF4 could activate the WNT/β-catenin signaling pathway. Knockdown of NDUFAF4 significantly up-regulated the expression level of E-cadherin and down-regulated that of N-cadherin. Conclusions:Knockdown of NDUFAF4 can significantly enhance the radiosensitivity of HCC cell lines by inhibiting the WNT/β-catenin signaling pathway. The expression level of NDUFAF4 is intimately correlated with clinical prognosis. NDUFAF4 can be considered as a new target for lowering the radiation resistance of HCC.

Toluene diisocyanate induces inflammatory response and autophagy in human bronchial epithelial cells / 中国职业医学

OBJECTIVE: To investigate the effect of toluene diisocyanate(TDI) on the activation of autophagy and expression of inflammatory cytokines interleukin(IL)-4 and IL-6 in normal human bronchial epithelial cells(16 HBE). METHODS: i) We prepared TDI-human serum albumin(HSA) and determined the mass concentration of TDI in TDI-HSA. ii) The cells were treated with TDI-HSA and HSA at concentrations of 0.00-400.00 mg/L for 12 hours. CCK-8 assay was used to determinate the cell viability, and TDI-HSA and HSA doses were selected for subsequent experiments. iii) The cells were treated with TDI-HSA and HSA at doses of 0.00-120.00 mg/L for 12 hours, and the levels of reactive oxygen species(ROS) in the cells were detected by flow cytometry. The levels of IL-4 and IL-6 in the cell supernatant were measured by enzyme-linked immunosorbent assay. iv) The cells were treated with TDI-HSA at doses of 0.00-120.00 mg/L for 12 hours, and the autophagy activity was observed under transmission electron microscope. Western blot was utilized to detect the expression of Beclin1, microtubule-associated protein 1 light chain(LC3β) and P62. RESULTS: i) The mass concentrations of TDI in 40.00, 80.00 and 120.00 mg/L TDI-HSA groups were 0.44, 0.89 and 1.33 mg/L respectively. ii) The results of CCK-8 showed that TDI-HSA and HSA at doses below 120.00 mg/L did not affect cell viability, and 0.00-120.00 mg/L was selected as the TDI-HSA and HSA treatment doses for subsequent experiments. iii) The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells in the TDI-HSA group at 40.00, 80.00, and 120.00 mg/L were higher than that in HSA group at the same dose(P<0.01). The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells increased with the increase of TDI-HSA doses(P<0.01). iv) Transmission electron microscopy showed that the number of autophagic lysosomes in 16 HBE cells increased significantly, and the number of mitochondrial vacuoles increased in 40.00, 80.00, 120.00 mg/L TDI-HSA group compared with 0.00 mg/L group. With the increase of TDI-HSA dose, the relative expression of Beclin1 protein and LC3β-Ⅱ/Ⅰ ratio in 16 HBE cell supernatant increased(P<0.05), and the relative expression of P62 protein decreased(P<0.05). CONCLUSION: TDI-HSA induces increased expression of ROS and inflammatory factors and induces autophagy activation in 16 HBE cells. Autophagy may be an important factor for the development of airway inflammation in TDI-induced occupational asthma.

The diagnostic efficiency of ultrasound-guided biopsy of gastrointestinal lesions / 中国医师杂志

Objective To explore the diagnostic efficiency of ultrasound-guided biopsy in the diagnosis of gastrointestinal lesions.Methods The study retrospectively analyzed 41 cases who underwent ultrasound-guided biopsy and diagnosis were confirmed as gastrointestinal lesions either by surgery resections or by biopsies in our hospital from January 2006 to April 2018.The detection rate and the safety in the diagnosis of gastrointestinal lesions by ultrasound-guided biopsy were evaluated and they were compared with clinical efficiency of the endoscopic biopsy.Results (1) Of the 41 cases underwent ultrasound-guided biopsies,38 cases were confirmed by pathology.A 92.7％ detection rate had achieved by ultrasound-guided biopsies.In the 38 cases,the diagnoses were grouped in benign and malignant,with 29 malignant and 9 benign.(2) Among the 13 cases examined by both of the ultrasound-guided biopsy and endoscopic biopsy,the diagnostic accuracy of ultrasound-guided biopsy was 84.6％ and 61.5％ with endoscopy.No significant difference (P =0.378) between the two modalities.(3) No complication occurred with both of methods.Conclusions Ultrasound-guided biopsy of gastrointestinal lesions is a safe and effective method.It would be an alternative solution to provide clinicians with reliable diagnosis,especially when endoscopic diagnosis is not inapplicable or failed.

Lung fibrosis and changes in autophagy-related proteins in rats exposed to silica dust / 中华劳动卫生职业病杂志

Objective@#To explore the changes in the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) and yeast autophagy-related gene 6 (Beclin1) in rat lungs exposed to free silica (SiO2) dust for different periods.@*Methods@#A total of 72 male specific pathogen-free Wistar rats were randomly divided into solvent control group and SiO2 model group. The SiO2 model group received one-time non-exposed intratracheal instillation of suspension of SiO2 particles to establish a model of silicosis. The solvent control group received an equal amount of saline. Six rats each were sacrificed at 1, 7, 14, 21, 28, and 60 days after model establishment. The pathological changes and fibrosis of rat lungs at different time points were evaluated by H&E staining and Masson staining, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of transforming growth factor-β (TGF-β) , interleukin-1 (IL-1) , and tumor necrosis factor-α (TNF-α) in lung tissue homogenate. Western blot was used to determine the relative expression levels of LC3 and Beclin1 in the lung tissue.@*Results@#The results of H&E staining showed that the model group had continuous inflammation in the lung tissue from day 1 to day 60, and the inflammatory scores were significantly higher in the model group than in the control group (P<0.05) . The results of Masson staining showed that rats in the model group had a small amount of collagen fibers in the lung tissue on day 14 and a large amount of collagen fibers on day 60. The fibrosis score was significantly higher in the model group than in the control group (P<0.05) . No collagen fibrosis was observed in the lung tissue in the control group. The results of ELISA showed that the model group had significantly higher levels of IL-1, TNF-α, and TGF-β in lung tissue homogenate than the control group at each time point after exposure (P<0.05) . The results of Western blot showed that the model group had decreased expression of Beclin1 protein in the lung tissue on days 7, 14, 21, 28, and 60, which was significantly higher than that of the control group (P<0.05) . The model group also had a decreased ratio of LC3II/LC3I on days 1, 7, 14, 21, 28, and 60, which were significantly higher than that of the control group (P<0.05) .@*Conclusion@#In the rat model of silicosis induced by free SiO2 dust, the expression levels of autophagy-related proteins, LC3 and Beclin1, are correlated with different stages of silicosis. In the early stage of silicosis, the lung tissue has inflammation, substantially increased ratio of LC3II/LC3I and expression of Beclin1, and active autophagy. With the progression of silicosis, the ratio of LC3II/LC3I and expression level of Beclin1 gradually decrease and autophagy becomes weak.

Value of intracavitary contrast-enhanced ultrasound via abdomen in fistulas difficult to diagnose before operation / 中国医师杂志

Objective To evaluate the value of intra-cavitary contrast-enhanced ultrasound (IC-CEUS) via abdomen in fistulas difficult to diagnose before operation.Methods Clinical data of 12 patients with preoperative clinical suspicion of Crohn's Disease (CD) complications of fistula were enrolled in the study.Colonoscopy,cystoscope,or CT/MR has not confirmed the diagnosis of intra abdominal fistulas.IC-CEUS were performed by locally-injection of contrast agent in abdominal abscess,observing fistula and the relationship with the adjacent organs in CEUS mode.Diagnostic criteria were surgical findings.Results Fistulas in 10 patients were detected by IC-CEUS,including 7 cases of Ileo-mesenteric fistuls,2 cases of il eo-vesical fistulas,and 1 case of colo-vesical fistula.The accuracy rate of IC-CEUS in diagnosis of fistulas difficult to diagnose before operation in Crohn's disease was 83.3％ (10/12).No severe adverse events occurred during and after IC-CEUS procedure.Conclusions Our preliminary study shows that IC-CEUS is feasible in detecting abdominal fistula with high accuracy.It might be used as the alternative imaging tech nique for detecting fistulas when CT and MR are insufficient.

Relationship Between Serum Concentration of the Active Metabolite and the Efficacy and Safety of Oxcarbazepine / 医药导报

Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg ? L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg?kg-1?d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg?L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg?L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg?L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.

Relationship between ABCA3 gene polymorphisms and susceptibility with neonatal respiratory distress syndrome / 中国小儿急救医学

Objective To investigate ABCA3 gene polymorphism and its relationship with neonatal respiratory distress syndrome (NRDS) in the Guangxi Zhuang Autonomous Region of China by genotyping and haplotype analysis.Methods Using a tagging single nucleotide polymorphism (tSNP) strategy and TaqMan (r) real-time PCR,we genotyped 4 tSNPs (rs4787273,rs 1 50929,rs 11867129,and rs 17135889) and one additional coding SNP(rs13332514) of the ABCA3 gene in preterm infants with NRDS(NRDS group,n =45) and without NRDS (non-NRDS group,n =45) and subsequently predicted the haplotypes.The minor allele frequency and the haplotype 'distribution were compared between the two groups.Results The minor allele A(0.14 vs.0.05,P =0.046) and genotype AG (0.289 vs.0.111,P =0.035) frequency of SNP rs17135889 in NRDS group were significantly higher than those in non-NRDS group.Totally 6 haplotypes occurred at a frequency ≥0.01,among which,the haplotype TGGAG,depended on rs17135889,was significantly higher in NRDS group than that in non-NRDS group (0.061 vs.0.000,P =0.014).Conclusion The results suggested that SNP rs17135889 of ABCA3 gene might be related to NRDS in preterm population of the Guangxi Zhuang Autonomous Region.Allele A contributes to NRDS susceptibility in preterm infants.

Distribution of surfactant protein A2 haplotype and its association with preterm respiratory distress syndrome susceptibility / 中华实用儿科临床杂志

Objective To study the distribution of surfactant protein A2 (SP-A2) haplotype and its association with preterm respiratory distress syndrome (RDS) susceptibility in a local Chinese cohort.Methods Using population base and case-control study cohorts,genotyping for four single nucleotide polymorphism (SNP) was performed,rs1059046,rs17886395,rs1965707,rs1965708,in 80 term infants,50 preterm infants with RDS (RDS group) and 50 preterm infants without RDS(control group) by using TaqMan (R) real-time polymerase chain reaction.Infants in RDS group and control group were matched according to gender and gestational age.Frequency of each haplotype was compared between preterm infants with RDS and without RDS,term infants and preterm infants without RDS.Results Most common haplotypes in term infants were 1A0,1A5,1A1.In each preterm infants groups with RDS and without RDS,1A0,1 A5,1 A1 were also the most common haplotypes.Among these three common haplotypes,frequency of 1A0 was lower in preterm infants,including RDS group and control group,than that in term infants.No significant difference was found between preterm groups with RDS and without RDS (P ＞ 0.05),neither in preterm infants with gestational age ≥32 or ＜ 32 weeks.Haplotype 1A0 frequency(0.542) in term infants was significantly higher than that in preterm infants ＜ 32 weeks without RDS (0.329) (x2 =6.06,P =0.01).Conclusions SP-A2 haplotype distribution in a local Chinese population shows ethnic characteristics to some extent.Only SP-A2 does not contribute to the susceptibility for preterm RDS.

Relationship between SLCO1B1 521T ＞ C genovariation and severe toxicity during high-dose methotrexate chemotherapy / 中华实用儿科临床杂志

Objective To investigate the relationship between severe toxicity during high-dose methotrexate (HD-MTX) chemotherapy and 29 related factors including SLCO1B1 521T ＞ C genovariation,and to enhance drug safety.Methods Eighty-two children with acute lymphoblastic leukemia (ALL) received HD-MTX chemotherapy.The regimen was MTX 3-5 g/m2 continuous infusion for 24 hours.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the patients' genotypes of SLCO1B1 T521C polymorphism,which was the coding gene of organic anion transporting polypeptide 1 B1 (OATP1 B1).Haematological,gastrointestinal and hepatic toxicities in 1-10 days after HD-MTX administration were observed and graded according to Common Terminology Criteria for Adverse Events (CTCAE,version 4.02).The patients were divided into two groups based on toxicity grades:case group (grades Ⅲ-Ⅴ) and normal group (grades 0-]]).The differences of 29 variates including biology features,biochemical indicators,SLCO1B1 T521 C polymorphism and etc.were compared between the two groups by univariate analysis,and the significant factors were found out.The final predictive model of severe HD-MTX-related toxicity was set up through Logistic regression analysis.Receiver operating characteristic (ROC) curve of predictor was drawn based on final model in order to evaluate its predictive ability.Results There were only 4 significant different variates between case group and normal group (P ＜ 0.05),including SLCO1B1 T521C polymorphism,serum MTX concentrations at 72 hours after starting MTX infusion (C72h),the ratios of 7-hydroxy-MTX (the metabolin of MTX) to MTX concentrations at 48 hours (k48 h),and frequency of k48 h ≤2.Based on a multivariate logistic regression analysis,only SLCO1B1 521T＞ C genovariation (odds ratio 18.489,95％ confidence interval 5.413-63.157)was the significant independent predictor for severe HD-MTX-related toxicity.The area under ROC (95％ confidence interval) of SLCO1B1 521T ＞ C genovariation as the predictor for severe HD-MTX-related toxicity was 0.776 (0.653-0.899),which had significant diagnositic value (P ＜ 0.05).Conclusions There is higher risk of severe HD-MTX-related toxicity while patients having SLCO1B1 521T ＞ C genovariation.Clinician should consider it and take some protective measures.

SLCO1B1c. 521T>C gene polymorphisms are associated with high-dose methotrexate pharmacokinetics and clinical outcome of pediatric acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To provide guidance for the high-dose methotrexate (HD-MTX) treatment of pediatric acute lymphoblastic leukemia (ALL), and to understand the impact of SLCO1B1c.521T>C (rs4149056) variant on methotrexate (MTX) pharmacokinetics and clinical outcome in children with ALL.</p><p><b>METHOD</b>Eighty-two children with ALL in Division of Hematology of Wuhan Children's Hospital from January 2008 to February 2013 were enrolled. All patients were genotyped for rs4149056 single nucleotide polymorphism (SNP) into wild-type group (TT genotype) and variant group (TC/CC genotype). According to the ALL-BFM 2000 protocol, all patients received intravenous infusion of MTX every ten days at 3 to 5 g/m(2). Leucovorin rescue was performed after 36 hours of the MTX administration and its dose was adjusted according to the MTX plasma concentration at 48 hours. The concentrations of MTX and its metabolite at 24, 48 and 72 h were determined by high performance liquid chromatography with solid phase extraction. Population pharmacokinetic parameters were estimated by the NLME software. The pharmacokinetics, toxicity and leucovorin rescue was compared. The relapse rate within 5 years and event-free survival were followed up.</p><p><b>RESULT</b>Eighty-two pediatric patients were classified into two groups: variant group including 20 TC genotype carriers and one CC genotype carrier, wild-type group included 61 patients with TT genotype. Compared with wild-type group, plasma concentration of MTX at 48 and 72 h increased significantly [48 h: (1.00±1.41) vs.(0.34±0.17) µmol/L, t=2.131, P=0.046; 72 h: (0.31±0.26) vs.(0.08±0.04) µmol/L; t=3.995, P=0.001]. Area under the concentration time curve (AUC48-∝) of MTX significantly increased in variant group [(23.18±19.91) vs.(5.66±2.01) h·µmol/L] (t=4.025, P=0.001). Time above the MTX safety threshold (TC>0.1 µmol/L) increased significantly in variant group [(95.3±22.0) vs.(67.1±7.5) h, t=5.880, P<0.001]. Rescue dosage of leucovorin in variant group was higher than that in wild-type group [(312.7±287.8) vs.(140.6±27.5) mg/m2, t=2.614, P=0.017]. The children carrying rs4149056 C allele suffered from a higher frequency of serious adverse effect [gastrointestinal toxicity: 33% (7/21) vs. 5% (3/61);hepatic toxicity: 24% (5/21) vs. 2% (1/61)]. The difference was statistically significant (χ2=9.275, 8.289, all P<0.05). Hospital stay of variant group was significantly longer than that of wild-type [(4.95±1.43) vs. (4.05±0.22) d, t=2.881, P=0.009]. The relapse rate within 5 years of variant group and wild-type group were 9% (2/21) and 13% (8/61), respectively. There were no significant differences in the event-free survival between the two groups (χ2=0.001, P=0.971).</p><p><b>CONCLUSION</b>The SLCO1B1 c.521T>C variant was an important determinant of MTX pharmacokinetics. An appropriate leucovorin dose raise in variant group was beneficial to reducing the serious toxicity and did not affect the long-term clinical outcome.</p>

Recombinant human interferon alpha 2b broad-spectrum anti-respiratory viruses pharmacodynamics study in vitro / 药学学报

This study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. At the cellular level, the effect of the recombinant human interferon alpha 2b on influenza A virus was detected using real-time fluorescence quantitative RT-PCR. The effects of the recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus, respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic effect (CPE) method. In this study, the therapeutic index of recombinant human interferon alpha 2b anti-HPIV was 1476.63, the therapeutic index of recombinant human interferon alpha 2b anti-RSV was 141.37, the therapeutic index of recombinant human interferon alpha 2b anti-coronavirus was more than 2820.76, and the antiviral effect of recombinant human interferon alpha 2b was better than ribavirin (RBV). Recombinant human interferon alpha 2b has a stronger inhibitory effect on different influenza A virus RNA than drug control. The therapeutic index of recombinant human interferon alpha 2b anti-influenza B virus was 2.74, with modest effect. Recombinant human interferon alpha 2b in vitro has broad spectrum antiviral activities, low toxicity and high therapeutic index. Recombinant human interferon alpha 2b is expected to become the efficient medicine in clinical against respiratory viruses, as well as provide better services for prevention and treatment of respiratory viruses' infections.

Relationship Between Serum Concentration at 48 h and Pharmacokinetic Characteristics and Toxic Reactions at Terminal Elimination Phase After Starting High Dose Methotrexate Infusion / 医药导报

Objective To recheck the reliability of methotrexate ( MTX) serum concentration at 48 h ( C48 h ) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia (ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3 -5 g·( m2 ) -1 ] in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h (C24 h ,C48 h and C72 h ) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1 group and C48 h<1 μmol·L-1 group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 h and AUC48-∞ were significantly higher in C48 h ≥1 μmol · L-1 group than in C48 h <1 μmol·L-1 group (P<0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1 group than in C48 h < 1 μmol · L-1 group ( P < 0. 05). Conclusion C48 h can predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1 can be used as a marker of MTX elimination delay event to guide later rescue regimen.

Clinical analysis of Crohn's disease in the elderly / 中华老年医学杂志

Objective To analyze clinical characteristics of crohn's disease in the elderly in order to reduce the rate of misdiagnosis in Crohn's disease in elderly people.Methods Patients with Crohn's disease were divided into elderly group (n=80) and young and middle-aged group (n=100).Clinical manifestations,complications,laboratory test results and misdiagnosis rate were retrospectively analyzed.Results Diarrhea rate was higher in elderly group than in young and middle-aged group (62.5％ vs.28％,x2 =21.54,P＜0.05).The incidence of bloody/pus stools was lower in elderly group than in young and middle-aged group (16.3％ vs.30.0％,x2 =4.621,P＜0.05).Ileus and perianal diseases incidence rates were lower in elderly group than in young and middle-aged group (20.0％ vs.36.0％,1.3％ vs.8.0％,x2=5.538 and 4.263,P＜0.05).Crohn's disease showed more decreased serum albumin,decreased hemoglobin and ESR in elderly group,which accounted for 48.8％,41.3％,and 38.8％ respectively,but there were no differences between the two groups (all P＞0.05).Compared with young and middle-aged group,Crohn's disease was more likely misdiagnosed as colon cancer and ischemic bowel disease in elderly group (x2 =16.05 and 16.07,both P＜ 0.05).Crohn's disease was more likely misdiagnosed as appendicitis,intestinal tuberculosis and ulcerative colitis in young and middle-aged group than in elderly group (x2=4.707,6.210,4.792,respectively,all P＜0.05).Conclusions Crohn's disease in elderly people occurs with more severe diarrheas,less blood and pus stools,less obstruction and perianal lesions as compared with young group,to which we should pay more attention.

Clinical and endoscopic follow-up of infliximab with azathioprine combination therapy in Crohn's disease / 中华消化杂志

Objective To inspect the efficacy and mucosa healing condition of infliximab with azathioprine combination therapy in Crohn's disease (CD) and its correlation with prognosis.Methods A total of 20 active CD patients who received infliximab and azathioprine combination therapy at The First Affiliated Hospital of Sun Yat-sen University were objects of this study.The clinical efficacy was evaluated at 10 weeks,30 weeks,54 weeks and 2 years respectively according to CD activity index.The efficacy was evaluated under endoscopy at 10 weeks,30 weeks,54 weeks and 2 years respectively according to mucosal response situation under endoscopy.The data were analyzed by analysis of variance or Fisher's exact test between two groups.The factor affecred mucosal healing was analyzed by Logistic regression analysis.Results The clinical remission rate of patients without steroid at week 10,30,54 and 2 year were 12/20,16/20,15/20 and 15/20 respectively.Mucosal healing rate at week 10,30 and 54 weeks were 8/20,12/20 and 10/20 respectively.Logistic regression analysis indicated that age was the only factor affected mucosal healing at 30 weeks (OR =0.774,95％ CI:0.630 to 0.950).There was significant differences in clinical remission between mucosa response patients and invalid under endoscopy at 30 weeks and 2 years without steroid (at 30 weeks:14/14 vs 2/6; at 2 years:14/14 vs 1/6; all P＜0.01).Infliximab were withdrawn in 4 of 16 patients who was in non-steroid clinical remission at 30 weeks,and the other 12 patients were continued with infliximab therapy.There was no significant difference in non-steroid clinical remission rate (4/4 vs 11/12) and mucosa healing rate (2/4 vs 7/12) between withdrawal and continue of infliximab therapy (all P＞0.05).Conclusions Infliximab with azathioprine combination therapy can effectively promote and maintain mucosa healing in CD.The mucosa response patients can maintain long time non-steroid clinical remission.

Clinical and colonoscopic characteristics of Crohn disease and intestinal tuberculosis / 中华消化内镜杂志

ObjectiveTo unify the definitions of colonoscopic characteristics of Crohn disease (CD) and intestinal tuberculosis ( ITB),and to evaluate colonoscopic and clinical features in the differential diagnosis of CD and ITB.MethodsA collaborative group composed of 10 experts from 5 hospitals voted to identify and confirm the colonoscopic characteristics.Clinical and colonoscopic characteristics were analyzed,thereafter,characteristics were scored based on different diagnostic specificity.ROC curve was used for determining the cutoff point to differentiate CD from ITB.ResultsFirstly,standard endoscopic images and descriptions were determined.Secondly,colonoscopic parameters which were significantly different between the CD and ITB patients included the follows:involvement of more than four intestinal segments,anorectal involvement,longitudinal ulcers,cobblestone appearance and transverse ulcers.Clinical findings which were significantly different between the CD and ITB patients included active pulmonary tuberculosis,PPD-test strong positive,anal fistula/perianal abscess and extra-intestinal manifestations in CD.4.4％(6/136) patients were confirmed by histological evidence of caseating granulomas.By using our scoring system,39.7％ (54/136) confirmed diagnoses and 18.4％ (25/136) suspected diagnoses were made in patients without histological evidence.ConclusionIdentification of colonoscopic characteristics and unification of the colonscopic diagnostic criteria were helpful in the differential diagnosis between CD and ITB.The differential diagnosis rate could he improved by using the scoring system.Half cases could not be confirmed even with combined pathology and the scoring system,so a more comprhensive scoring system would be warranted.

Association between gene polymorphism of plasminogen activator inhibitor and ischemic cerebrovascular disease in aged people of Henan Han nationality / 中华老年医学杂志

Objective To investigate the association between gene polymorphism of plasminogen activator inhibitor (PAI-1)and ischemic cerebrovascular disease in aged people of Henan Han nationality.Methods A case control method was used,including 408 patients with ischemic cerebrovascular disease and 418 age and gender matched healthy controls.Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequencies of PAI-1 844G/A.Results In patient group,the gene frequencies of AA,AG,GG were 18.1％,41.4％,40.4％,and the A and G allele frequencies were 38.8％ and 61.2％,respectively.In the control group,the gene frequencies of AA,AG,GG were 15.8％,47.4％,36.8％,and the A and G allele frequencies were 39.5％ and 60.5％.There were no significant differences in the frequencies of genotypes and alleles between the two groups (P＞0.05).The different genotypes of 844G/A of PAI-1 gene were not associated with hypertension,hyperglycemia,plasma homocysteic acid levels (P ＞ 0.05).Conclusions PAI-1 gene-844G/A polymorphism may not be independent risk factor of ischemic cerebrovascular disease in aged people of Henan Han nationality.

Clinical and endoscopic evaluation of anti-tuberculosis trial for differentiation between intestinal tuberculosis and Crohn's disease / 中华消化内镜杂志

Objective To investigate the evaluation standard and proper time point of anti-tuberculosis trial for differential diagnosis between intestinal tuberculosis (ITB) and Crohn's disease (CD). Methods Clinical data and endoscopic changes of 28 patients with confirmed ITB and 11 with confirmed CD,who underwent anti-tuberculosis trail, were retrospectively analyzed. Results No significant difference could be found in clinical characteristics of ITB and CD patients on baseline, such as active pulmonary tuberculosis, strong positive skin test and anal fistula/perianal abscess. Clinical symptoms were relieved in both groups right after anti-tuberculosis treatment. After 3 months of treatment, the no-improvement rate in ITB group was 0, whereas that of CD group was 27.3% (P =0. 004). The disappearance rate plus improvement rate of ulcer in ITB group was 90. 9% (20/22) plus 9. 1% (2/22) and 100% ( 28/28 ) plus 0 at 3 and 6 months of treatment, respectively. The disappearance rate plus improvement rate of nodular lesion was 58. 8% (10/17) plus 41.2% (7/17) and 76. 5% (13/17) plus 23.5% (4/17), respectively. There was no obvious improvement of active ulcer or nodular transformation in CD group at any time point ( P ＜ 0. 01 ).Conclusion With deficiency of special index for differential diagnosis of ITB and CD, some cases hard to differentiate still have to accept anti-tuberculosis treatment. Three months of anti-tuberculosis treatment is a proper time point to evaluate the efficacy. Disappearance of active ulcer and nodular transformation, together with cure or obvious improvement in clinic are taken as effective for treatment trail.