Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

In order to investigate the chemical constituents of glycosides in Piper sintenense Hatusima, column chromatographic techniques such as silica gel, ODS, MCI GEL CHP20P, Sephadex LH-20, and semi-preparative high performance liquid chromatography were used to afford nine glycosides from the n-butanol part of the 95% ethanol extract of Piper sintenense Hatusima. Based on the physicochemical properties and NMR data, the above compounds were identified as (2S)-2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone-2-O-β-D-glucopyranoside (1), 2-phenylethyl β-D-glucopyranoside (2), benzyl α-L-arabinopyranosyl-(1''→6')-β-D-glucopyranoside (3), benzyl β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (4), phenethyl β-D-apiofuranosyl-(1''→ 2')-β-D-glucopyranoside(5), salidroside (6), phenethanol β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (7), (Z)-hexenyl-O-α-L-arabinopyranosyl-(1''→6')-O-β-D-glucopyranoside (8), (Z)-hexenyl-O-β-D-xylopyanosyl-(1''→6')-O-β-D-glucopyranoside (9). Compound 1 was identified as a new compound, and compounds 3-9 were isolated from the genus Piper for the first time.

ObjectiveTo investigate the prevalence of Staphylococcus aureus in patients with diarrhea, and to analyze the genes carriage of enterotoxin in the strains of these patients in Jiading District, Shanghai. MethodsFrom 2021 to 2023, anal swabs of diarrhea outpatients from one sentinel hospital and nine community health service centers in different townships in Jiading District, Shanghai, were tested for Staphylococcus aureus, from which five enterotoxin virulence genes such as SEA, SEB, SEC, SED, and SEE were tested simultaneously. ResultsA total of 1 080 anal swabs were collected, 81 of which were tested positive for S. aureus, with a detection rate of 7.50%, and the detection rate of S. aureus was similar in patients with diarrhea from 2021‒2023. There was no statistically significant difference in detection rates between males and females (χ²=0.821, P=0.365). S. aureus detection rate was highest in infants and young children with diarrhea (29.51%), followed by 14.06% in the people aged between 4‒<31 years, and 2.99% in those aged ≥31 years. Significant differences were observed in the detection rate of S. aureus in the diarrhoeal patients from different townships of Jiading District(χ²=66.134,P<0.05). The carriage rates of the 5 enterotoxin genes, namely SEA, SEB, SEC, SED, SEE, were 13.58%, 14.81%, 11.11%, 7.41%, and 0, respectively. ConclusionThe prevalence of S. aureus among the patients with diarrhea in Jiading District is relatively stable but with distinct geographical patterns. Children and adolescents are high-risk groups. SEB were the dominant gene, followed by SEA.

Chemical constituents of n-butanol part of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied.Eight glycosides were separated and purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography.Based on the physicochemical properties and spectral data, these compounds were 3-ethyl-4-methyl-pentyl ester-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1), juglanoside E (2), (4S)-α-terpineol-8-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (3), (4S)-α-terpineol-8-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (4), eugenyl-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucuronopyranosyl methylester (6), kaempferol-3-O-β-D-glucuronopyranoside (7), and quercetin-3-O-β-D-glucuronopyranoside (8).Among them, compound 1 was a new compound, and compounds 2-6 were isolated from the genus Cyclocarya for the first time.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a kind of endogenous tissue engineering technology that lengthens the jaw and opens airway so that a patient can breathe safely and comfortably on his or her own. Endothelial progenitor cells (EPCs) are crucial for MDO-related angiogenesis. Moreover, emerging evidence suggests that heat shock protein 20 (Hsp20) modulates angiogenesis under hypoxic conditions. However, the specific role of Hsp20 in EPCs, in the context of MDO, is not yet known. The aim of this study was to explore the expression of Hsp20 during MDO and the effects of Hsp20 on EPCs under hypoxia. METHODS: Mandibular distraction osteogenesis and mandibular bone defect (MBD) canine model were established. The expression of CD34, CD133, HIF-1α, and Hsp20 in callus was detected by immunofluorescence on day 14 after surgery. Canine bone marrow EPCs were cultured, with or without optimal cobalt chloride (CoCl2 ) concentration. Hypoxic effects, caused by CoCl2 , were evaluated by means of the cell cycle, cell apoptosis, transwell cell migration, and tube formation assays. The Hsp20/KDR/PI3K/Akt expression levels were evaluated via immunofluorescence, RT-qPCR, and western blot. Next, EPCs were incorporated with either Hsp20-overexpression or Hsp20-siRNA lentivirus. The resulting effects were evaluated as described above. RESULTS: CD34, CD133, HIF-1α, and Hsp20 were displayed more positive in the callus of MDO compared with MBD. In addition, hypoxic conditions, generated by 0.1 mM CoCl2 , in canine EPCs, accelerated cell proliferation, migration, tube formation, and Hsp20 expression. Hsp20 overexpression in EPCs significantly stimulated cell proliferation, migration, and tube formation, whereas Hsp20 inhibition produced the opposite effect. Additionally, the molecular mechanism was partly dependent on the KDR/PI3K/Akt pathway. CONCLUSION In summary, herein, we present a novel mechanism of Hsp20-mediated regulation of canine EPCs via Akt activation in a hypoxic microenvironment.

Objective:To explore the application effect and learning experience of the medical MOOCs teaching design model based on live streaming platform constructed by the research group in its previous research.Methods:The preparation of the design patterns from the teaching, teaching activities and teaching evaluation of the three dimensions based on the questionnaire, and 368 junior undergraduates majoring in clinical medicine in Batch 2018 of Army Medical University who had applied the online teaching of medical MOOC instructional design mode based on live broadcast platform were selected as the survey objects. And learners' satisfaction and learning experience with this teaching model was analyzed. SPSS 25.0 was used for t test. Results:In the study, 74.2% (273/368) of the learners believed that the teaching design model of medical MOOCs based on live streaming platform had good effect and was helpful to themselves; 60.6% (223/368) of the learners had a high degree of satisfaction, with good teaching effect feedback. In terms of the mastery of MOOCs knowledge content, the final English score of the experimental group (429.03±35.86) was better than that of the control group (401.87±25.85), with statistical significance ( P<0.05). Conclusion:The teaching design model of medical MOOCs based on live streaming platform is applicable, and helpful to improve online learning experience, solve the problem of insufficient interaction in MOOCs learning, and provide practical basis and method reference for the innovative application of teaching model in medical colleges and universities in China.

Chemical constituents from the air dried parts of Cichorium glandulosum were studied. The chemical constituents of C. glandulosum were separated and purified by means of silica gel, Sephadex-LH 20, ODS column chromatography and semi-preparative high performance liquid chromatography. The structure was elucidated by physicochemical characteristics and spectral data. One new flavonoid glycoside was isolated from C. glandulosum, and identified as quercetin-3-O-［6″-O-(3-ethoxy-1, 3-dioxopropyl)］-β-D-glucopyranoside(1).

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

Objective To investigate the changes of fibrinogen and D -dimer levels in patients with severe burn and their relationship with prognosis .Methods 90 patients with severe burn were selected as the subjects .The patients were divided into the dead group (30 cases) and the survival group (60 cases) according to the prognosis of the patients.The differences and changes of fibrinogen and D -dimer at the same time after admission were compared between the two groups .Results At each time point after admission , the fibrinogen levels of the death group were significantly higher than those of the survival group at the same time [(5.9 ±1.5)g/L vs.(5.1 ±1.3)g/L,(8.8 ± 2.2)g/L vs.(7.4 ±2.5)g/L,(7.6 ±2.8)g/L vs.(5.7 ±1.2)g/L,(7.1 ±2.5)g/L vs.(4.3 ±1.7)g/L],the differences were statistically significant(t =3.892,4.762,5.436,6.987,all P <0.05).At each time point after admission,the D-dimer levels of the death group were significantly higher than those of the survival group at the same time[(743.4 ±226.2)ng/mL vs.(704.1 ±214.6)ng/mL,(935.4 ±256.9)ng/mL vs.(834.6 ±256.2)ng/mL, (846.3 ±291.5)ng/mL vs.(712.1 ±251.3) ng/mL,(756.7 ±232.8) ng/mL vs.(601.5 ±168.7) ng/mL],the differences were statistically significant (t=3.895,5.477,4.743,5.746,all P<0.05).The level of D-dimer in the survival group showed a rise firstly ,then showed a decrease trend after admission ,while the levels of fibrinogen and D-dimer of the death group were altered in double -peak change .Conclusion There is an obvious impairment of coagulation function in severe burn patients , and the level of D -dimer and fibrinogen is higher , the prognosis of patients is worse .