Objective To investigate the association of C3435T genetic polymorphism of MDR1 gene with paliperidone plasma concentration in the patients with schizophrenia by detecting the paliperidone plasma concentration change and C 3435T genetic pol‐ymorphism of MDR1 gene during medication process .Methods The paliperidone plasma concentration in 61 patients with schizo‐phrenia was detected by adopting the liquid chromatography tandem mass spectrometry at the end of 1 ,2 ,4 ,6 weeks after medica‐tion .Meanwhile C3435T MDR1 genotype was determined by adopting the LDR‐PCR method .The paliperidone plasma concentra‐tions in the patients with different genotypes and different alleles were compared .Results Among 61 patients with schizophrenia , CC ,CT and TT genotypes accounted for 24 .59% (15/61) ,63 .30% (38/61) and 13 .11% (8/61) respectively ,in which the propor‐tion of heterozygote CT was significantly higher than that of homozygote CC and TT (P<0 .05) .The proportion of C and T allele were 55 .74% and 44 .26% respectively(P<0 .05) .The paliperidone plasma concentration at 4 detection time points in the patients with TT genotype at 4 time points was significantly higher than that in the patientis with CC genotype ,and paliperidone plasma concentration only at the end of 1 week in TT genotype was significantly higher than that in CT genotype ,CT genotype was higher than CC genotype (P<0 .05) .The paliperidone plasma concentration at 4 detection time points in the patients of T allele was higher than that in the patients with C allele ,but statistically significant difference was only found at the end of 1 week (P<0 .05) .Conclu‐sion The C3435T genetic polymorphism of MDR1 gene has certain relationship with paliperidone plasma concentration in the pa‐tients with schizophrenia .

Objective To investigate clinical value of inflame factors in child patients with sepsis at different time points before the diagnosis time.Methods A retrospective model was performed in this study.24 child patients with sepsis in Department of Paediatrics from January 2014 to October 2016 were selected.At the time 72 h(group A),48 h(group B),24 h(group C) before the diagnosis time,plasma levels of HBP and serum levels of IL-6,IL-10 were detected by ELISA,and pre calcitonin (PCT) and high sensitive C reactive protein (hs-CRP) were detected by immunofluorescence.Compared to the same period,22 healthy cases were selected as the control.Repeated measure anova and Receiver operating characteristic curve analysis were performed.Results The plasma levels of HBP were (9.69 ± 1.30) μg/L,(12.82 ±2.03) μg/L,(15.46 ± 1.02) μg/L,(18.60 ± 1.10) μg/L at group A,group B,group C before the diagnosis time respectively.The plasma levels of HBP at all time points before the diagnosis time were significantly higher than the control (t =6.27,P ＜ 0.01;t =16.82,P ＜ 0.01;t =25.16,P ＜ 0.01).The serum levels of HBP at group B,group C were significantly higher than the last time point (t =5.62,P ＜0.01;t =10.25,P ＜ 0.01).Receiver operating characteristic curve(ROC) revealed that the areas of HBP at group A(0.823),group B (0.898),was significantly higher than the other inflame factors(Z =2.41,P ＜0.01;Z=2.02,P＜0.05;Z=0.38,P＞0.05;Z=0.32,P＞0.05)(Z=0.43,P＞0.05;Z=0.46,P＞0.05;Z =0.26,P ＞ 0.05;Z =0.57,P ＞ 0.05).It also revealed that at group C,area of PCT(0.941) was significantly higher than the other inflame factors (Z =0.12,P ＞ 0.05;Z =0.08,P ＞ 0.05;Z =0.03,P ＞0.05;Z-0.10,P ＞ 0.05).Conclusions HBP has a wide diagnostic window period for sepsis.IL-6,IL-10,PCT and hs-CRP have diagnostic value in partial periods of sepsis.

A cross-sectional study was conducted in Heilongjiang in a representative sample of 2 875Chinese adults aged from 20 to 74 years. Questionnaire was conducted. Their height, weight, waist circumference,blood pressure, blood glucose, serum insulin, lipids, and other indexes were determined. The criterion of International Diabetes Federation was applied for metabolic syndrome (MS) diagnosis. The results showed that the preliminary prevalence rate of MS was 19.34% and the age-adjusted prevalence rate of MS was 21.92% ( male 20.41% , female 23.11% ). The prevalence rate of MS increased with the age. The prevalence rate in the urban area was higher than that in the town and rural area ( both P < 0.05 ). The result of multiple factor logistic regression analysis showed that body fat content, insulin resistance, age, residential difference, drinking habit,daily staple food quantity, urine albumin, education, family history of obesity, and gender were related with MS.

Background and purpose:Adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2), which has been found over-expressed in a variety of cancer cells, takes part in the drug resistance of cancer through effux of anticancer drugs. The purpose of this study was to investigate the mechanisms of human glioblastoma cells sensitivity to pyropheophorbide-a methyl ester (MPPa)-mediated photodynamic therapy (PDT) eradicating tumour cells and its relationship to ABCG2.Methods:U87 and A172 glioma cell lines in the logarithmic growth phase were selected and exposed to the treatment of MPPa-PDT and MPPa-PDT+fumitremorgin C (FTC) respectively. The cell viability was measured with the use of CCK-8 assay. The expression of ABCG2 was detected by Western blot. The intracellular contents of MPPa in each group without illumination were tested by lfow cytometry. Flow cytometry with AnnexinⅤ-FITC/PI double staining was used to detect the cell apoptotic rate. DCFH-DA staining was used to assess the generation of intracellular reactive oxygen species (ROS).Results:The MPPa-mediated PDT could eradicate A172 and U87 cancer cells in an energy-dependent manner. The light energy density in A172 was 8 times of that in U87 when the cell viability reached median lethal dose after MPPa-mediated PDT. The high expression of ABCG2 in A172 cells affected the accumulation of intracellular MPPa. Inhibition of ABCG2, not only could enhance the eradicating effect of MPPa-PDT on A172 cells, but also could increase the yield of ROS triggered by MPPa-PDT and the accumulation of intracellular MPPa.Conclusion:The human glioblastoma cell line A172 is insensitive to MPPa-mediated PDT. The mechanism may relate to ABCG2, which decreases the MPPa content in cancer cells through effux of MPPa, resulting in decline of cytotoxicity.

Day surgery can effectively improve the utilization of medical resources. In October 2015, an obstetrics and gynecology hospital established a gynecological day surgery center to centrally manage gynecological day surgery and continuously optimize the management process. In July 2019, the hospital established an intelligent information platform for gynecological daytime surgery managemen. Based on this platform, the " evaluation-appointment-hospitalization-follow-up-chronic disease management" information management process was implemented, the " pre hospital-in hospital-post hospital" full process medical quality and safety monitoring was carried out to form a centralized closed-loop management mode for gynecological day surgery led by gynecologists. Under this management mode, the number of gynecological day surgeries in the hospital has increased from 2 866 cases in 2019 to 4 065 cases in 2021, providing convenient medical services and personalized chronic disease management services, and ensuring the quality and safety of gynecological day medical care, for reference for promoting the high-quality development of day surgeries in specialized hospitals.

OBJECTIVES: Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury. METHODS: Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)]. RESULTS: There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05). CONCLUSIONS Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.
AMP-Activated Protein Kinases/metabolism* ; Acute Kidney Injury/pathology* ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/pharmacology* ; Autophagy ; Caspase 3/metabolism* ; Caspase 9/metabolism* ; Female ; Humans ; Ischemia ; Kidney/pathology* ; Leptin/pharmacology* ; Male ; Mammals/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Reperfusion/adverse effects* ; Reperfusion Injury/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVE: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer. METHODS: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study. RESULTS: Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of α-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol. CONCLUSION Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition (EMT) signaling pathways.