Objective:To investigate the effects of Penehyclidinehydrochloride(PHCD) on endotoxin-induced cerebral edema.Methods:one handred and five S-D male rats(200～220g)were randomly divided into 5 groups(n=21):groupC control;groupL LPS;group DL,DM and DH received intraperitoneal PHCD 0.05,0.15 or 0.45mg/kg 10min before lipopolysaccharide(LPS) administration.Cerebral edema was induced by internal carotid arterial LPS 150?g.Seven animals each group were decapitated at 4、6 and 12h after operation and their brains were immediately removed for determination of water content of brain and microscopic examination.Results:Administration of LPS caused severe brain damage and significantly increased water content of the brain.The LPS-induced changes were mitigated by pretreatment with different doses of PHCD in groupDM and DH,but there was no significant difference between the two groups.Conclusion:Pretreatment with PHCD can attenuate LPS-induced cerebral edema.

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on expression of NF-κB and iNOS in rats with LPS-induced brain injury. Methods One hundred and five male SD rats weighing 200-220 g were randomly divided into 5 groups (n=21 each): group Ⅰ normal saline (NS);group Ⅱ LPS (L);group Ⅲ,Ⅳ,Ⅴ PHCD 0.05, 0.15, 0.45 mg/kg (D1,2,3). The animals were anesthetized with chloral hydrate 350 mg/kg. Brain injury was induced by intra-arterial LPS 150 μg administered via left internal carotid artery in group Ⅱ-Ⅴ. In group Ⅲ,Ⅳ, and Ⅴ PHCD 0.05, 0.15 and 0.45 mg/kg were given intraperitoneally (IP) at 10 min before intra-arterial LPS. The animals were decapitated at 4, 6 and 12 h after administration of PHCD (n=7 at each time point in each group). The brains were immediately removed for determination of water content, expression of NF-κB and iNOS protein and examination with light and electron microscope. Results Water content of the brain and expression of NF-κB and iNOS protein were significantly higher in group L, D1, D2 and D3 than in group NS and were significantly lower in group D2 and D3 than in group L. Intra-arterial LPS produced severe damage to the brain which was significantly attenuated by PHCD in group D2 and D3. Conclusion PHCD 0.15,0.45 mg/kg pretreatment can attenuate LPS-induced brain injury by inhibiting the up-regulation of expression of NF-κB and iNOS.

Objective To analyze the multi-slice computed tomography (MSCT) enhanced findings in the patients with primary small intestinal stromal tumor(SIST),and to probe the relationship between the imaging findings and the pathologic risk in order to improve the diagnostic accuracy.Methods Thirty patients with primary SIST confirmed by surgical pathology were enrolled in this study.Characterization and compassion of the clinical manifestations and MSCT enhanced findings were carried out between the pathologic low-and high-risk groups.Furthermore,the relationship was analyzed between the enhanced findings and the pathologic risk.Results Among all 30 patients with primary SIST,the lesion was located at duodenum in 5 patients (16.7％),at jejunum in 16 (53.3％),and at ileum in 9 (30％).14 patients were classified in the low risk group with the lesion with the average length of (3.8±0.9) cm,and other 16 in the high-risk group with lesion with the average length of (7.0 ± 1.4) cm.There were no statistical differences between the low-and high-risk groups in CT value in plain and venous phase,and in added value in arterial,venous and delayed phases.However,the significantly differences were observed in CT value in arterial and delayed phases between two groups (P＜0.05).Conclusion MSCT may effectively evaluate the pathologic risk of primary SIST.There are significant differences of the enhanced findings between the low and high-risk groups,which can provide important apreoperative classification for the therapy.

Objective To investigate the effect of propofol on the learning and memory function in neonatal rats under hypoxic conditions. Methods Eighty-four 7-day-old SD rats were randomly divided into 6 groups (n = 14 each): propofol + 18% oxygen (propofol-hypoxia, group PH), propofol + air (group PA), propofol +100% oxygen (propofol-oxygen, group PO), 0.9% normal saline (NS) + 18% oxygen (group CH), NS + air (group CA), NS + 100% oxygen (group CO). The rats received injection of intraperitoneal propofol 50 mg/kg or NS 5.0 ml/kg once a day for 7 consecutive days and they were exposed to 18% oxygen, air or 100% oxygen at the end of each injection. SaO2 and respiratory rate (RR) were monitored and recorded after administration. The rats were returned to the cage after recovery of the righting reflex. Six rats in each group were sacrificed 24 h after the 7th injection, and the brain tissues were taken to observe the apoptosis in hippocampal neurons. Morris water maze test was used to test the learning and memory function 2 weeks after administration in the other rats. Results RR was significantly lower and the escape latency at T1.2 longer in group PO than in group CO (P ＜ 0.05). RR and SaO2 were significantly decreased, apoptotic index was increased, the escape latency was prolonged and the frequency of crossing the original platform was reduced in group PA compared with group CA, and in group PH compared with group CH (P ＜ 0.05). Compared with group PO, SaO2 was significantly decreased, apoptotic index was increased, the escape latency was prolonged and the frequency of crosing the original platform was reduced in group PA (P ＜ 0.05). Conclusion Propofol induces apoptosis in hippocampal neurons and decreases the learning and memory function in neonatal rats under hypoxic conditions.

Objective:To observe the protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy.Methods:Seventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Müller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT- qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively.Results:The weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression ( t=38.318, P<0.001) in the retina of mice in the DM group was increased and GS expression ( t=29.737, P<0.001) was decreased compared with the control group. The GFAP expression ( t=13.677, 19.387, 16.305; P<0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression ( t=5.170, 19.399, 6.705; P<0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group. Conclusion:Zhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response.

Objective To investigate the ability and underlying mechanism of hepatitis B virus X protein (HBx)regulationofPolo-likekinase 1 (Plk1)expression.Methods The human HCC cell line HepG2 was transfected (transiently and stably) with an HBx plasmid expression vector (pCMV-HA-HBx) or empty plasmid vector (control),with and without expression plasmids with the Plk1 promoter.Effects on Plk1 expression were assessed by western blotting.Functional effects on the Plk1 promoter were assessed by luciferase reporter assay.Effects on the mRNA level of Plk1 in S phase HepG2 cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction.After blocking protein synthesis by treatment with cycloheximide (CHX),the turnover rate of Plk1 was assessed by western blotting.Lastly,the effect of HBx on cell cycle was assessed by flow cytometry.Results HBx did not increase the protein expression of Plk1 in non-synchronized HepG2 cells,but did significantly up-regulate the Plkt protein level in the synchronized S phase cells (P =0.026 and P =0.003,respectively).Ectopic expression of HBx did not increase the mRNA level of Plk1 in HepG2 cells,but did inhibit the degradation of Plk1,as evidenced by an increased half-life of Plk1 protein (from 30 to 90 minutes).The HBx-expressing HepG2 cells showed more trequent entry into the S or G2/M phase than the control cells (31.65％ vs.24.56％ or 9.43％ vs.4.47％,respectively) and less in the G0/G1 phase (decrease from 70.97％ to 58.92％ for the HBx-expressing HepG2 cells).Conclusion HBx is able to up-regulate the expression of Plk1 in HepG2 cells by a mechanism involving stabilization of the Plkl protein primarily in the S phase of the cell cycl.

CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
Animals ; CD146 Antigen ; genetics ; metabolism ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Fibrosarcoma ; metabolism ; pathology ; Male ; Melanoma, Experimental ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B ; metabolism ; Neovascularization, Physiologic ; drug effects ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Retinal Vein ; growth & development ; pathology ; Signal Transduction ; drug effects ; Transplantation, Homologous ; Vascular Endothelial Growth Factor A ; pharmacology ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient （DTP） pharmacies and propose measures for pre-emptive risk management， providing references for the quality risk management of cold chain medicines. METHODS Based on the requirements of national regulations， a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024， focusing on the receipt， storage， distribution， and delivery processes， using questionnaires， telephone interviews， and on-site visits. Common quality management issues in the operation of cold chain medicines were identified， and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures. RESULTS & CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey， and personnel from 30 DTP pharmacies participated in on-site and telephone interviews. Typical problems were identified in some DTP pharmacies， including insufficient personnel allocation or training， incomplete or inadequate implementation of quality system documentation， inadequate provision or management of cold chain facilities and equipment， and non-compliant storage and distribution of cold chain medicines. These issues posed certain risks to the quality management of cold chain medicines. It is recommended that DTP pharmacies strengthen personnel allocation and training， improve quality system documentation， enhance the provision and management of facilities and equipment， standardize storage and transportation operations， and strengthen supervision and assessment as pre-emptive measures. In addition， all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation， in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.

China has entered a stage of deep aging. The expanding aging population and subsequently an aging labor force pose significant challenges to China’s social and economic development. European Union (EU) countries have entered the aging phase earlier and to a greater extent. To address the labor shortage and the rising dependency ratio, the EU has implemented a series of policies and measures, including raising retirement age, promoting flexible retirement, enhancing work flexibility, improving welfare for elderly workers, creating age-friendly environments, focusing on occupational health, strengthening knowledge and skills training, and leveraging digital technologies in the workplace. These measures aim to prevent premature exit of elderly workers, better balance their work and life needs, improve occupational health and skills, and enhance overall work efficiency of companies. This review discussed the experience and lessons learned from the EU countries in addressing the aging workforce from the perspectives of occupational health and occupational skills development, aiming to provide rational suggestions to assist China in better adapting the challenges of aging workforce after steadily and orderly advancing the gradual reform of the statutory retirement age, thereby improving the efficiency of the overall workforce and the stability of the labor market, driving the talent dividend of highly educated and skilled middle-aged and elderly employees, and ultimately promoting sustained economic and social development.

Objective: To investigate the effect of G protein-coupled receptor 108(GPR108) gene knockout on systemic inflammation in lipopolysaccharide(LPS)-induced sepsis mice. Methods: Male C57BL/6 mice and GPR108 gene knockout mice were randomly divided into 4 groups: WT group, WT-LPS group, KO group, KO-LPS group. The physiological characteristics of mice in different groups were observed, and the morphological changes of liver and lung tissues were observed. Macrophages were extracted from bone marrow and subjected to flow cytometry to detect their M1 polarization status. The expression levels of IL-6 in liver and lung tissues, macrophages, and serum were also measured. Results: KO-LPS group mice showed significant liver and lung tissue damage, with a significantly greater number of bone marrow-derived macrophages polarizing towards M1 in the KO-LPS group compared to the WT-LPS group. Additionally, at the tissue, cellular, and serum levels, the expression of IL-6 in the KO-LPS group mice was significantly higher than that in the WT-LPS group mice(P<0.05). Conclusion During the systemic inflammatory infection induced by LPS in mice, the lack of GPR108 exacerbates the systemic inflammatory response. GPR108 has an inhibitory effect on the inflammatory response in mice with LPS-induced sepsis.