Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P＜0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P＜0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P＜0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P＜0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.

Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P＜0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P＜0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P＜0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P＜0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.

Objective To investigate the correlation between the appendicular skeletal mass index(ASMI)and os-teoporosis(OP)in postmenopausal patients with type 2 diabetes(T2DM).Methods 164 hospitalized postmeno-pausal elderly T2DM patients were selected and their bone density(BMD)and appendicular skeletal mass were measured using dual energy X-ray absorption method(DXA).ASMI=appendicular skeletal mass/height2(kg/m2),and they were divided into OP group and non OP group based on T value.The general clinical data,blood biochemical indicators,and ASMI between the two groups were compared,and Logistic regression analysis,ROC curve were further used to analyze the correlation and diagnostic power.Results Compared with non OP group,OP group had a higher incidence of sarcopenia(SAC)(P＜0.05);the differences in age,ASMI,body mass index(BMI),and estradiol(E2)had significant differences between the two groups(P＜0.05);Logistic regression analysis showed that the reduction of ASMI[OR=0.133,95％CI(0.029-0.611)],BMI[OR=0.785,95％CI(0.625-0.985)],and E2[OR=0.967,95％CI(0.942-0.993)]were protective factors for OP;receiver operating curve(ROC)suggested that the AUC of ASMI for OP prediction was 0.752[95％CI(0.632-0.872),P＜0.001]with sensitivity 87.5％,specificity 47.8％,and the best diagnostic value was 5.52 kg/m2.Conclusion The reduction of ASMI,BMI,and E2 is positively correlated with the occurrence of osteoporosis.ASMI is an important protective factor for osteoporosis.Early OP screening and risk factor assessment should be conducted for elderly postmenopausal T2DM patients,and early intervention measures should be taken to reduce the risk of falls and fractures.

Objective To investigate the epidemiology and pathogenic characteristics of enterovirus in children with hand, foot and mouth disease (HFMD) in Guangyuan area, and to provide a basis for the development of HFMD prevention and control strategies. Methods A total of 759 children with HFMD clinically diagnosed in Guangyuan area from January 2019 to January 2021 were randomly selected. The seasonal, age, gender, regional distribution and pathogen distribution characteristics of HFMD were analyzed by descriptive epidemiological methods. Results The incidence of HFMD was seasonal and presented a typical bimodal distribution, with the summer peak occurring from April to July (χ²=8.714, P<0.05) and the winter peak from October to December (χ²=7.542, P<0.05). There was a significant difference in the incidence rate between regions, and the incidence rate in urban areas was much higher than that in rural areas (χ²=5.915, P<0.05). P < 0.05). The male-female incidence ratio was 1.63:1. The high incidence group of HFMD was children younger than 5 years old, and the number of reported cases was 730. The high incidence age group was 1-3 years old (χ²=8.455, P<0.05). The incidence rate of HFMD in all age groups ≤5 years old was higher in male than female, and the difference was statistically significant (χ²=5.174, P<0.05). A total of 388 HFMD cases were tested positive for viral nucleic acid, with a positive rate of 51.12%, In mild cases, Cox A16, EV71, and other enteroviruses accounted for 27.64%, 29.54% and 29.54%, respectively. The proportion of EV71 in severe cases was 89.47%. Conclusion HFMD is widely distributed in Guangyuan area, with obvious seasonal and population differences. The prevention and control of HFMD should be strengthened in key areas, high incidence seasons and key populations, and the vaccination of children ≤3 years old should be further promoted to prevent the outbreak of HFMD.

Objective:To analyze the splicing mutation site of COL4A5 gene in a family with X-linked dominant Alport syndrome and explore the possibility of exon specific U1 small nuclear RNA (snRNA) gene therapy. Methods:The clinical data of the proband and family members of Alport syndrome were collected, and the gene mutations in the whole exon of a series of nephropathy genes in the proband were detected by high-throughput sequencing. The splice site changes and pathogenicity caused by COL4A5 c.546+5G>A mutation were analyzed by online software. Minigene experiment was used to verify and analyze the effect of COL4A5 gene mutation site c.546+5G>A in the proband of Alport syndrome family, and transient transfection and introduction of modified U1 snRNA to correct splicing mutation. Results:The results of gene sequencing showed that there was a hemizygous variation of COL4A5 gene in the proband and his half brother, and the variation site was c.546+5G>A. The results of online software for analyzing the pathogenicity of splice variation showed that the original donor splicing site could not be detected after mutation, suggesting that there was a great possibility of affecting splicing. The abnormal splicing mode of COL4A5 gene with c.546+5G>A mutation—deletion of exon 9 was verified by hybridized small gene detection. The abnormal splicing mutation could be partially corrected by the modified U1 snRNA. The correction ratios of ExSpeU1 (MT), ExSpeU1(E9+1), ExSpeU1(E9+9) and ExSpeU1(E9+11) to exon 9 deletion caused by c.546+5G>A were 0, 43.81%, 52.09% and 48.12%, respectively. Conclusions:The pathogenicity of the new splicing mutation of COL4A5 is verified, and the modified U1 snRNA can partially correct the abnormal splicing.

OBJECTIVE: To develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma and investigate the pharmacokinetics of atorvastatin and the changes in voriconazole concentration in rats after administration. METHODS: Plasma samples were collected from rats after intragastric administration of atorvastatin alone or in combination with voriconazole. The samples were treated with sodium acetate acidification, and atorvastatin and voriconazole in the plasma were extracted using a liquidliquid extraction method with methyl tert-butyl ether as the extractant. The extracts were then separated on a Thermo Hypersil Gold C18 (2.1×100 mm, 1.9 μm) column within 6 min with gradient elution using acetonitrile and water (containing 0.1% formic acid) as the mobile phase; mass spectrometry detection was achieved in selective reaction monitoring (SRM) mode under the positive ion scanning mode of heated electrospray ion source (H-ESI) and using transition mass of m/z 559.2→440.2 for atorvastatin and m/z 350→280 for voriconazole, with m/z370.2→252 for lansoprazole (the internal standard) as the quantitative ion. RESULTS: The calibration curves were linear within the concentration range of 0.01-100 ng/mL (=0.9957) for atorvastatin and 0.025-100 ng/mL (=0.9966) for voriconazole. The intra-day and inter-day precisions were all less than 13%, and the recovery was between 66.50% and 82.67%; the stability of the plasma samples met the requirements of testing. The AUC of atorvastatin in rat plasma after single and combined administration was 438.78±139.61 and 927.43±204.12 h·μg·L, CLz/F was 23.89±8.14 and 10.43±2.58 L·h·kg, C was 149.62±131.10 and 159.37±36.83 μg/L, t was 5.08±1.63 and (5.58±2.11 h, and T was 0.37±0.14 and 3.60±1.52 h, respectively; AUC, CLZ/F and T of atorvastatin in rat plasma differed significantly between single and combined administration. The HPLC-MS/MS system also allowed simultaneous determination of voriconazole concentration in rat plasma after combined administration. CONCLUSIONS The HPLC-MS/MS system we established in this study is simple, rapid and sensitive and allows simultaneous determination of atorvastatin and voriconazole in rat plasma. Some pharmacokinetic parameters of atorvastatin are changed in the presence of voriconazole, and their clinical significance needs further investigation.
Administration, Oral ; Animals ; Atorvastatin ; Chromatography, High Pressure Liquid ; Rats ; Tandem Mass Spectrometry ; Voriconazole

Objective To evaluate the role of infliximab trough levels(IFX-TL)and C reactive protein(CRP)concentration in prediction secondary loss of response(LOR)to infliximab(IFX)in patients with Crohn′s disease(CD)during IFX maintenance therapy since 14 weeks after induced treatment.Methods From November 2015 to October 2016,43 CD patients received IFX treatment were enrolled.IFX was initially given at zero,two,and six weeks at 5 mg/kg as induced therapy,and then the same dose was given every eight weeks as long-term maintenance treatment.Serum IFX-TL and CRP concentration were measured at 14thweek after the first IFX injection.The disease activity of CD was assessed by the Harvey-Braddshaw index.According to the follow-up results,the enrolled patients were divided into LOR group and continuous response group,and then the differences in IFX-TL and CRP concentrations at the 14thweek after induced therapy were compared between two groups.Mann-Whitney U test and receiver operating characteristic(ROC)curve were performed for statistical analysis.Results After a median 54 weeks of follow-up,18(41.9%)of 43 CD patients achieved a sustained response to IFX therapy,while 11 patients(25.6%)were LOR to IFX therapy.At the 14thweek after induced therapy,serum IFX-TL of LOR group was 2.30 μg/mL(0.52 μg/mL,2.92 μg/mL),which was lower than that of continuous response group(5.10 μg/mL(3.54 μg/mL,9.34 μg/mL)),and the difference was statistically significant(Z= -3.236,P=0.001).The CRP concentration of LOR group was 3.10 mg/L (0.38 mg/L,21.70 mg/L),which was higher than that of continuous response group(0.51 mg/L(0.27 mg/L, 1.50 mg/L)),and the difference was statistically significant(Z= -1.732,P=0.015).The results of ROC curve analysis indicated that at 14thweek after induced therapy the area under curve(AUC)value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864(95% confidence interval(CI)0.728 to 0.999),sensitivities were 83.3% and 81.8%,specificities were 94.4% and 54.5%,cut-off values of accuracies were 3.115 μg/mL and 5.93 mg/L.Conclusion IFX-TL<3.115 μg/mL and CRP concentration>5.93 mg/L at 14thweek since IFX induced therapy might be used as effective predictors of LOR in CD patients during maintenance therapy.

Objective:To evaluate the relationship between the phthalate ester exposure and the population obesity with Meta-analysis, and to provide a new idea for prevention and control of obesity. Methods:A comprehensive search was performed in English databases (Pubmed, Web of Science, The Cochrane Library, Elsevier Science Direct and OVID) and Chinese databases (Sinomed database, CNKI database, VIP database, Wanfang database).The studies about the relationship between phthalate ester exposure and the population obesity were retriveded.The Chinese and English studies were selected according to the inclusion criteria and exclusion criteria.Meta-analysis was performed using RevMan 5.3 software.Results:Six studies were finally obtained, involving 1259 samples.The Meta-analysis results showed that the monobutyl phthalate (MBP) level in urine of the obesity population was increased 4.1 times compared with the normal population (95%CI:1.43-6.76);while the combined effect values of dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP) and diethyl phthalate (DEP) level in serum of the population in two groups were 1.17 (95%CI:0.64-1.69), 0.80 (95%CI:0.13-1.48), and 0.72 (95%CI:-0.19-1.63);the combined effect values of monoethylhexyl phthalate (MEHP) and monoethyl phthalate (MEP) levels in urine were 1.75 (95%CI:-0.45-3.96) and 2.75 (95%CI: 0.36-5.15);there were no significant differences (P>0.05).Conclusion:The elevated MBP levels in the urine may be a risk factor for obesity in the population, suggesting that MBP may contribute to obesity.

Background:With the extensive use of infliximab (IFX)in treatment of patients with Crohn's disease (CD),some of the patients had losing of response to IFX treatment. The specific mechanism is not clear yet,and may be related to the formation of antibodies to infliximab (ATI). However,there is no report on the positivity rate of ATI in China so far. Aims:To investigate the clinical effects of serum IFX trough levels (IFX-TLs)and ATI in CD patients treated with IFX. Methods:A total of 76 CD patients receiving IFX treatment from Jan. 2016 to Mar. 2017 at Shanghai Renji Hospital were enrolled. Serum IFX-TLs and ATI were detected. CD patients were divided into active stage group and remission group according to CDAI score,and serum IFX-TLs,ATI,C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR) levels were analyzed. Results:Of the 76 patients with CD,positive ATI was found in 2 patients (2. 6%). Forty-five (59. 2%)patients were in remission,while 31 (40. 8%)in active stage. No significant differences in IFX-TLs [2. 84 (1. 30,4. 96)μg/ mL vs. 4. 08 (1. 29,6. 72)μg/ mL,P =0. 484],ATI [8. 00 (5. 27,14. 89)ng/ mL vs. 7. 00 (4. 40, 25. 00)ng/ mL,P = 0. 454]were found between active CD and remission CD. Serum CRP,ESR levels were significantly increased in active CD than in remission CD (P = 0. 038,P = 0. 009). Logistic regression analysis showed that activity of CD was related to CRP (OR = 6. 082,95% CI:1. 348-27. 436,P = 0. 019),but not related to IFX-TLs,ATI and ESR (P > 0. 05). Conclusions:The activity of CD may be correlated with CRP,but not with IFX-TLs,ATI and ESR.