Aim To observe the effect of gypenosides ( GP) on the expression of receptor for advanced gly-cated endproducts ( RAGE ) and transforming growth factor-β1 ( TGF-β1 ) in human mesangial cells( HMCs) induced by AGEs. Methods HMCs were cultured in DMEM of low glucose containing 15% fetal bovine ser-um in vitro, which were divided into four groups: the normal group, model group, GP group and positive control group. In addition to the normal group, the other groups were stimulated by AGEs ( 200 mg · L-1 );furthermore, GP group was intervened with dif-ferent concentrations(25,75,175 mg·L-1) of GP, while control group was given 10 mmol · L-1 of amin-oguanidine hydrochloride. The expression of RAGE and TGF-β1 protein of each group was detected by Western blot; the expression of RAGE and TGF-β1 mRNA of each group was detected by RT-PCR. Re-sults The expression of RAGE, TGF-β1 protein and mRNA in HMCs induced by AGEs in the model group was significantly higher than that of the normal group ( P<0. 01 );compared with the positive control group ( P<0. 01 ) , GP could obviously reduce the expression of RAGE, TGF-β1 protein and mRNA in a dose-de-pendent manner. Conclusion GP can reduce the ex-pression of RAGE in HMCs induced by AGEs, block AGEs-RAGE signaling pathway and decrease the ex-pression of the downstream factor TGF-β1 , therefore, it plays the role in the resistance of rennal fibrosis in DN.

Objective: To determine the potency of QN-2013, a derivative of quinoxaline 1,4-N-oxide, as a hypoxia-selective cytotoxin or a radiosensitizer. Methods: In vitro cytotoxicity and radiosensitization, as well as in vivo antitumor activity were determined by colony formation and tumor growth delay respectively. The changes in the cell cycle, DNA damage and repair of damaged DNA were assayed by FCM and “comet” assay, separately. Results: ICN250 and ICair50 of QN-2013 for HeLa-S3 cells were 0.08 and 1.7 mmol*L－1 respectively, namely, HCR=21. This suggested that QN-2013 was a fairly hypoxic cytotoxin, but inferior to SR-4233. QN-2013 had an evident radiosensitization either in vitro or in vivo. It was noted, however, that the value of in vitro SERs increased exponentially with increasing concentration of the drug, but the in situ antitumor activity seemed to be independent of doses of the drug. The systemic toxicity of QN-2013 was superior to an LD50 of 265　mg*kg－1 compared with 80　mg*kg－1 for SR-4233. In hypoxic condition QN-2013 induced S retension effect and G2M block in HeLa-S3 cells, caused DNA double strand break, and inhibited the repair of radiation-induced DNA damages. All of these reactivenesses might be involved in the action mechanism of QN-2013. Conclusion: QN-2013 is a fair hypoxia-selective cytotoxin, and has shown improved antitumor activity in vivo in combination with radiation. In general, These results suggest that the series of quinoxaline di-N-oxide derivatives hold out bright prospect for the development of novel bioreductive antitumor drugs.

A 31-year-old male normotensive patient with aldosterone-producmg adenoma complained of thirst,polydipsia,polyuria,and periodical paraplegia.The diagnosis is raised by signs of hypokalemia.Despite the lack of hypertension,primary aldosteronism was confirmed by persistent hypokalemia,increased urinary potassium,increased urinary and plasma aldosterone levels and suppressed plasma rennin activity (PRA).The blood pressure profile was studied by ambulatory monitoring,and the mean blood pressure of 24h was normal and the circadian rhythm remained normal. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia.The patient had a marked fall in blood pressure with mean values of 21/17 mm Hg ( diurnal and nocturnal blood pressure were 19/17 and 22/17 mm Hg respectively)and recovery of normal urinary and plasma aldosterone levels and PRA 6 weeks after surgery.This suggests that excess serum aldosterone induced relative hypertension in those patients whose blood pressure was spontaneously very low.Our observations call for primary hyperaldosteronism assay in patients with hypokalemia and renal potassium leakage.

Objective:To investigate the clinical effect of endoscopic injection of norepinephrine on cerebral infarction complicated by stress-induced gastrointestinal bleeding.Methods:A total of 150 patients with cerebral infarction complicated by stress-induced gastrointestinal bleeding who were admitted to the Intensive Care Unit of Lishui City People's Hospital from October 2020 to October 2021 were included in this study. These patients were randomly divided into a control group and an observation group using the random number table method, with 75 patients in each group. Patients in the control group received routine clinical treatment, while those in the observation group received endoscopic injection of norepinephrine in addition to routine clinical treatment. The hemostatic time, blood transfusion volume, and length of hospital stay were compared between the two groups. The stress index and inflammatory index were compared between the two groups before and after treatment. The hemostatic effect and adverse reactions were evaluated in each group.Results:The hemostatic time, blood transfusion volume, and length of hospital stay in the observation group were (16.16 ± 4.36) hours, (385.35 ± 41.28) mL, and (5.35 ± 1.28) days, respectively, which were significantly shorter or less than (27.27 ± 6.34) hours, (447.07 ± 32.07) mL, and (7.07 ± 2.07) days in the control group ( t = 12.50, 10.22, 6.12, all P < 0.001). After treatment, the levels of cortisol, norepinephrine, antidiuretic hormone, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were (288.33 ± 19.53) mmol/L, (29.17 ± 4.26) μg/L, (4.08 ± 1.08) mU/L, (38.27 ± 8.72) ng/L, (6.69 ± 1.35) μg/L, and (6.37 ± 1.51) mg/L, respectively, which were significantly lower than (327.22 ± 22.01) mmol/L, (39.32 ± 5.54) μg/L, (5.36 ± 1.22) mU/L, (51.24 ± 13.23) ng/L, (8.67 ± 2.29) μg/L, and (11.44 ± 3.13) mg/L in the control group ( t = 11.44, 12.57, 6.80, 7.08, 6.45, 12.63, all P < 0.001). The overall response rate of hemostasis in the observation group was 94.67% (71/75), which was significantly higher than 82.67% (62/75) in the control group ( χ2 = 5.37, P < 0.05). The incidence of adverse reactions in the observation group was 8.00% (6/75), which was slightly, but not significantly, lower than 14.67% (11/75) in the control group ( χ2 = 1.66, P > 0.05). Conclusion:Endoscopic injection of norepinephrine for the treatment of cerebral infarction complicated by stress-induced gastrointestinal bleeding can rapidly stop bleeding, effectively reduce inflammation,improve stress index, and be highly safe.

OBJECTIVE: To explore the mediating effect of college counselors' empathy between perceived demand and behavior of helping others. METHODS: Three hundred and eleven college counselors were selected as study subjects by a convenient sampling method. The Perceived Needs Ability Questionnaire,Interpersonal Reactivity Index-C Questionnaire and Helping Behavior Questionnaire were used to assess the perceived needs,empathy ability and helping behavior of college counselors. RESULTS: The score of the empathy ability of college counselors was( 3. 4 ± 0. 4),the median scores of perceived demand ability and helping behavior were 3. 1 and 3. 3 respectively. The perceived demand ability of college counselors was positively correlated with both empathy ability and helping behavior [Spearman rank correlation coefficient( rS) = 0. 25,0. 27,P < 0. 01) ],and empathy ability was positively correlated with helping behavior( rS) = 0. 30,P <0. 01). Empathy ability has partial intermediary effect between perceived demand ability and helping behavior under the circumstances of medium-level dilemma and high-level dilemma,with the ratio of mediating effect to total effect accounting for 14. 6% and 13. 2% respectively. CONCLUSION: The perceive demand ability can directly or indirectly promote the behavior of helping others. Empathy ability plays partial mediating effects between perceived demand ability and helping behavior.

Liquid biopsies have made a great progress in malignant tumors research.Circulating tumor cells,circulating tumor DNA and exosomes can be regarded as biomarkers to be applied in diagnosis of epithelial ovarian cancer,monitoring progress dynamically,estimating prognosis and drug resistance in chemotherapy,which can help doctors provide patients with individual treatment to realize precision medicine in epithelial ovarian cancer.

Currently, electronic health records (EHR) are largely created and maintained by physicians, and used just as an electronic record. In future, EHR will be a tool of information sharing and patients may participate in decision making for their own health with this tool. This article summarizes the concept of EHR, the problems it faces and how the mobile internet and cloud computing can promote the development of EHR.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*