ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L^-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg^-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg^-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L^-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Confirmed cases of Lyme disease(LD)in Ji'an City,Jiangxi Province and the clinical manifestations and region-al distribution were assessed to provide a basis for timely diagnosis and treatment.In total,133 serum samples were collected from patients with suspected LD in Ji'an Central People's Hospital from December 2021 to August 2022.Serum antibodies a-gainst Borrelia burgdorferi were detected with a two-step testing process.In addition,a specific gene of B.burgdorferi in samples was identified by nested PCR.Sequencing analysis was conducted to confirm the positive samples.Overall,25(18.80％)serum samples were positive for B.burgdorferi nucleic acid and antibodies,which included 20(15.04％)positive for antibodies and 6(4.51％)positive for nucleic acids.The sequences of the 5S-23S rRNA gene spacer of 6 samples were con-sistent with the corresponding sequences of Borrelia yangtzensis and one of the six samples was also positive for antibodies.The 25 positive samples were collected from 9 counties in Ji'an City,with the majority in Jizhou District(44％).All positive patients may experience symptoms related to LD,including joint disorders,neurological disorders,infectious fever,der-matitis,and/or chest pain.The most common symptom was joint disorders(72％).Six cases positive for B.yangtzensis nucleic acids were mainly collected in the Jizhou District,of which four had joint lesions and two had infectious fever.This study confirms the existence of LD in Jiangxi Province,which may be the first confirmation of human infection with B.yan-gtzensis in southern China.Hence,doctors in this region should consider the possibility of LD for cases presenting with related symptoms.Although LD may occur in this region,further investigations and monitoring are warranted.

This study aims to investigate the function of lmo2363 gene in stress resistance of Liste-ria monocytogenes strain LM83-1.In this study,the lmo2363 gene deletion strain and complement-ation strain of Listeria monocytogenes were constructed using overlapping extended PCR and ho-mologous recombination techniques,and the growth ability,stress survival rate and biofilm forma-tion ability of wild,deletion strain and complementation strain were compared under different stress environments.lmo2363 gene deletion strain and complementation strain of Listeria monocy-togenes were successfully constructed in this experiment.The growth curves showed that the growth capacity of the deletion strain was weaker than the wild strain LM83-1 under 4 ℃,7％NaCl,10％NaCl,3.5％ethanol,4.0％ethanol and pH5 stress(P＜0.001).The results of stress survival test showed that the survival rate of the deletion strain was significantly lower than the wild strain after 1 h treatment with pH3 and 10 mmol/L H2 O2 stress(P＜0.010).The biofilm forming ability of the deletion strain was decreased compared with that of the wild strain(P＜0.050).This study confirmed that lmo2363 gene mediated the adaptation of LM to low temperature,high osmotic pressure,ethanol and acid stress environment and affected the formation of LM bio-film.This study laid a foundation for further exploring the function of lmo2363 gene in the stress resistance process of Listeria monocytogenes.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To investigate the psychological status of the outpatients in the andrology clinic and the effect of risk warning combined with multidisciplinary team(MDT)intervention on their satisfaction.Methods:Using convenience sampling,we enrolled 600 outpatients seeking medical attention in the Department of Andrology of our hospital from July to October 2022.We ran-domized the patients into a control(n=300)and an observation group(n=300),obtained their basic information,evaluated their psychological status with the Hospital Anxiety and Depression Scale(HADS),and assessed their satisfaction with the Xijing Hospital Outpatients'Satisfaction Questionnaire(HOSQ).The controls followed the routine procedure of treatment,while the patients in the ob-servation group received early warning before intervention based on their HADS scores.We provided normal medical care for those with HADS scores≤7,employed empathetic communication for those with HADS scores of 8-10,and conducted MDT intervention for those with HADS scores≥1l,followed by comparison of the patients'satisfaction with the outpatient service between the two groups.Results:There were no statistically significant differences in general conditions between the groups of patients(P＞0.05).The mean prevalence rate of anxiety and depression was 47.83％among the male subjects,lower in the control than in the observation group(47.00％vs 48.67％,P＞0.05),but higher in the patients with the education of junior high school or below(60.99％)than in those with that of senior high school(22.34％)and university or above(16.67％),and also higher in those aged 18-40 years(67.38％)than in those aged 41-60 years(51.82％)and over 60 years old(38.33％).A significantly higher rate of satisfaction with the outpatient service was found in the observation group than in the controls(97.18％vs 90.39％,P＜0.05).Conclusion:Anxie-ty and depression are prevalent among the outpatients in the andrology clinic,with a higher prevalence rate in those with lower educa-tion and at a younger age.Early risk warning combined with MDT intervention can improve the satisfaction of the patients.

Humans ; Infant ; Female ; Dandy-Walker Syndrome/diagnosis* ; Tomography, X-Ray Computed ; Craniocerebral Trauma/complications*