OBJECTIVE To investigate the effects of renally inappropriate medication （RIM） on the frailty of elderly patients with diabetes. METHODS The data of elderly patients with diabetes mellitus admitted to a third-grade class A hospital in Yunnan province from January to December 2022 were collected， and Beers criteria （2019 edition） and Chinese version of FRAIL scale were used to evaluate RIM and the frailty of the patients； the patients were divided into the trial group （with RIM） and the control group （without RIM） according to whether there was RIM. The propensity score matching was used to balance confounding factors between two groups， and the influence of RIM on the frailty of elderly diabetic patients was analyzed by the Logistic regression model. RESULTS Among the 367 patients， 80 patients （21.80%） had RIM， the drugs involved RIM were spironolactone （82.56%）， rivaroxaban （13.95%） and gabapentin （3.49%）. After reaching the balance between groups using the propensity score matching method， the incidence of frailty was 77.94% in trial group and 27.94% in control group （P＜0.001）； the difference was not statistically significant in other confounding factors between the two groups （P＞0.05）. Results of Logistic regression analysis showed that the risk of frailty in the experimental group was 3.118 times that of the control group （odds ratio was 3.118，95% confidence interval was 1.758-5.530， P＜0.001）. CONCLUSIONS RIM is a risk factor for the frailty of elderly patients with diabetes， which can be considered as an indicator for early identification and screening of the frailty of elderly diabetes patients.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

This study utilized the CCK-8 assay to examine the effects of various concentrations of CoCl2(0,50,100,200,300,400 μmol/L)and different treatment durations(0,6,12,24,48 h)on the viability of adipocytes,in order to determine the most suitable treatment conditions.Western blot analysis was employed to investigate the impact of different concentrations of CoCl2(0,50,100,200,400 μmol/L)on the expression of hypoxia and its downstream key proteins in adipocytes.The results indicated that higher concentrations of CoCl2 led to lower adipocyte viability,with sig-nificant decreases in cell viability observed in the 300,400 μmol/L treatment groups(P＜0.01),while the 200 μmol/L group exhibited the highest cell viability.Compared to the control group,the 200 μmol/L CoCl2 treatment group showed a significant upregulation in the expression of hypoxia and its downstream signaling pathway key molecules:hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter type 4(GLUT4),vascular endothelial growth factor receptor 1(FLT-1),prolyl hydroxylase 2(PHD2),and vascular endothelial growth factor(VEGF)(P＜0.01).Addi-tionally,the 200 μmol/L CoCl2 treatment group exhibited higher levels of key lipolytic enzymes,including adipose triglyceride lipase(ATGL),perilipin 1(PLIN1),protein kinase A(PKA),and increased phosphorylation levels of hormone-sensitive lipase(HSL)in the 300 and 400 μmol/L groui ps(P＜0.01).CoCl2-mediated hypoxia in the 200 μmol/L treatment group also in-creased the protein expression of phosphatidylinositol 3-kinase(PI3K)and the phosphorylation level of protein kinase B(Akt).These findings suggest that adding 200 μmol/L CoCl2 can enhance the expression of hypoxia-related proteins,lipolytic enzymes,and insulin-related signaling proteins in primary bovine adipocytes.

Objective To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods A total of 41338 women delivered in the 15 hospitals during the 6 months,195 women with PGDM(PGDM group) and 195 women with normal glucose test result(control group)were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results (1)The incidence of PGDM was 0.472%(195/41338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI), prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration((6.3±1.3)% vs (5.2±0.4)%), fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test(OGTT)-1 h glucose((12.6±2.9) vs (7.1± 1.3) mmol/L)and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3)The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher((3159±700) vs (3451±423) g, P<0.01). And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036).(4)In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU(NICU)admission rate (24.2% vs 9.6% , P<0.01). Conclusions The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

Objective:To explore the proportions of Th17 cells in the peripheral blood and levels of IL-17,IL-23 in the serum of patients with Graves′disease ( GD ) and their clinical significance.Methods: We studied 29 patients with GD ( GD group ) , and reevaluated the GD group after therapy ( euthyroid GD group ).29 gender-and age-matched volunteers were selected as the normal control ( NC group).The proportions of Th17 cells were investigated by flow cytometry.The levels of IL-23,IL-17 in the serums were measured by ELISA.The levels of FT3,FT4,TSH were determined by ECLIA and the levels of TrAb were tested by RRA.Results:There were no significant difference among 3 study groups in sex and age match ( F=0.0075 , P>0.05;χ2=0.4213 , P>0.05 ).The proportions of Th17 cells and the levels of IL-17 , IL-23 were increased in the GD and euthyroid GD patients compared with the control group (respectively,P<0.05).The proportions of Th17 cells and the concentrations of IL-23 in euthyroid GD group were significantly lower than those of GD group ( respectively , P<0.05 ) , but there were no significance in the concentrations of IL-17 between euthyroid GD group and GD group(P>0.05).Correlation analysis revealed that the proportions of Th17 cells ,and the levels of IL-17,IL-23 were positively correlated with the levels of FT3,FT4,TrAb(r=0.588 2,0.337 2,0.371 0;0.549 6,0.287 5,0.342 7;0.361 0,0.420 8, 0.330 8;P<0.05 ,for all parameters ) ,and were negatively correlated with the levels of TSH ( r=-0.319 7 ,-0.472 8 ,-0.428 2;P<0.05,for all parameters).Conclusion:Th17 cells and their related cytokines IL-17,IL-23 are highly expressed in the serum of patients with GD.Th17 cells and their relative cytokines have certain relevance with 4 thyroid function parameters of the patients with GD , which can be used as biological markers for GD.

Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography-tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile-water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00-1000 ng/mL (r (2)>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of -4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.

Objective:To explore the role of cytokines in the pathogenesis of Graves′disease(GD),by detecting the levels of IFN-γ,IL-6,IL-17 and TGF-β1 in GD patients who were newly diagnosed.Methods:A total of 23 patients with new onset GD and 23 gender-and age-matched healthy controls were examined.The levels of serum IFN-γ, IL-6, IL-17 and TGF-β1 were measured by ELISA,FT3,FT4 and TSH levels were determined by ECL IA;TrAb levels were tested by RRA.Results: There were no significant difference among GD and NC group in sex and age match ( t=0.334 8 ,P>0.05;χ2=0.410 7 ,P>0.05 ).The levels of serum IFN-γ,IL-6,IL-17 and TGF-β1 in the GD group were significantly higher than the control group ( P<0.05 ) .Correlation analysis revealed that IFN-γ,IL-6,IL-17 and TGF-β1 were positively correlated with FT3,FT4(r=0.324 6,0.453 2,0.431 0,0.463 8;0.413 2,0.441 5, 0.436 2,0.467 1;P<0.05 ).Conclusion: IFN-γ, IL-6, IL-17 and TGF-β1 are highly expressed in the newly diagnosed GD patients.They play an important role in the pathogenesis of GD ,and provide helpful evaluation indices of immune dysfunction to Graves disease.

Objective To study the incidence of low triiodothyronine (T3) syndrome in critical patients,and compare the prognosis evaluation value between low T3 syndrome and acute physiology and chronic health evaluation (APACHE) Ⅱ score.Methods A total of 160 critical patients were enrolled.APACHE Ⅱ score of patients were recorded at admission,and thyroid hormone levels were measured on the first and the third day after admission.The patients who were low T3 level were enrolled into observation group,and the patients who were normal T3 level were as control group.The patients were followed up for 28 d,then were divided into death group and survival group according to the prognosis.The prognosis evaluation value was compared between T3 and APACHE Ⅱ score by receiver operating characteristic (ROC) curve.Results The incidence rate of low T3 syndrome was 25.6％ (41/160).During the follow-up phase,the fatality rate in observation group was 41.5％(17/41),and in control group was 29.4％ (35/119),there was statistical difference (P ＜ 0.05).The ROC area under curve of T3 was 0.657 (95％ CI:0.712-0.846),APACHE Ⅱ score was 0.672 (95％ CI:0.721-0.857),and there was no statistical difference (P ＞ 0.05).Best cut-off value of T3 was 0.41 μ g/L resulting in 76.9％(40/52) sensitivity and 78.7％(85/108) specificity.Conclusion Critical patients complicated with low T3 syndrome has poor prognosis,and T3 may be a predictive marker in evaluating the prognosis of critical patients.

ObjectiveTo observe the potential effects of microcystin-LR (MC-LR) to open field behaviors and cognitive functions of rats after low-dose and 60 days exposure.Methods20 SD male rats (4 weeks old) were grouped into control ( double distilled water),0.2,1.0 and 5.0 μg/kg groups by random number table.Rats were exposed to microcystin-LR intragastrically every two days for 60 d.Open fields and Morris water maze were employed to observe the spontaneous behavior and spatial learning and memory capacity of rats.ResultsFor each group,the duration in the central area of open field were ( 8.86 ± 3.38 ) s,( 3.09 ± 1.22 ) s,( 1.68 ± 0.24) s,(1.22 ±0.93) s,frequencies in central area were (4.80 ± 1.16) times,(4.40 ± 1.91 )times,( 1.40 ±0.23)times,(3.80 ± 1.02 ) times,movement duration were ( 137.30 ± 5.25 ) s,( 122.97 ± 9.50) s,( 108.86 ± 6.38 ) s,( 129.35 ± 9.40) s,the escape latency were ( 23.17 ± 4.28 ) s,(77.00 ± 8.31 ) s,(59.00 ± 11.89) s,( 63.80 ±16.09) s,respectively.Compared to control,the duration in the central area of open field decreased and escape latency increased significantly (P ＜ 0.05 ) in all the MC-LR treated groups; and frequencies in central area and movement duration of 1.0 μg/kg treated rats decreased significantly.No significant differences were observed between expsoured group and control group in spacial probe tests(P＞0.05).ConclusionMC-LR exerts effects on the spontaneous behavior and spatial cognitive ability of rats.The further study on neurobehavior effects of MC-LR is necessary.

Objective To dynamically monitor the base excess(BE) in traumatic brain injury(TBI) patients within 3 d after admission,and to assess the impact of the early BE on prognosis.Methods Blood BE was monitored for 3 d in 56 TBI patients.Patients were classified into mild group(15 patients),moderate group (22 patients) and severe group (19 patients) according to the scores of Glasgow coma scale(GCS).Patients were classified into survival group(42 patients) and dead group(14 patients) according to prognosis.Patients were classified into high BE group (35 patients,BE≥-8 mmol/L) and low BE group (21 patients,BE ＜-8 mmol/L).The relations among BE,degree of injury and prognosis were analyzed.Results The level of BE in mild group,moderate group and severe group was increased after treatment for 1,2,3 d than that before treatment.The level of BE was consistent with the degree of injury [mild group:(-3.02 ± 0.21)mmol/L; moderate group:(-8.49 ± 1.44) mmol/L;severe group:(-9.64 ± 1.19) mmol/L].The level of BE in mild group and severe group had significant difference than that in moderate group (P＜ 0.01).The level of BE in dead group before treatment and after treatment for 1,2,3 d was significantly lower than that in survival group [(-11.97 ±2.13) mmol/L vs.(-6.29 ± 1.16) mmol/L,(-9.84 ± 1.33) mmol/L vs.(-4.89 ± 1.78)mmol/L,(-8.78 ± 2.01) mmol/L vs.(-3.61 ± 1.43) mmol/L,(-7.84 ± 1.42) mmol/L vs.(-3.10 ±0.98)mmol/L] (P ＜0.01).The scores of APACHE Ⅱ before treatment and fatality rate in low BE group were significantly higher than those in high BE group [(24.84 ± 3.68) scores vs.(16.27 ± 2.21) scores,52.4％ (11/21) vs.8.6％(3/35)] (P ＜ 0.01).The scores of GCS before treatment in low BE group was significantly higher than that in high BE group [(7.56 ± 3.09) scores vs.(10.51 ± 2.43) scores](P ＜ 0.01).Conclusion The level of early BE is a good factor on evaluating the condition and prognosis in TBI patients.