Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:To investigate the effect and potential mechanism of circular RNA-centrosome and spindle pole-associated protein 1 (circ-CSPP1) on the malignant biological behavior of hepatoma cells.Methods:Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the expressions of circ-CSPP1 and microRNA-582-5p (miR-582-5p) in hepatoma cells, and Western blotting was used to detect the expression of karyopherins α2 (KPNA2). HepG2 cells were divided into the circ-CSPP1 overexpression group, the circ-CSPP1 overexpression control group, the si-CSPP1 group, the si-NC group, the si-CSPP1+ miR-582-5p inhibition group, and the si-CSPP1+ miR-582-5p inhibition control group. circ-CSPP1 overexpression plasmid, CSPP1 interfering small RNA, CSPP1 interfering small RNA, miR-582-5p inhibition sequence and negative control were transfected respectively in these groups. Cell proliferation in each group was detected by 5-acetylene-2'-deoxyuridine (Edu), invasion ability was detected by Transwell assay, and the binding of circ-CSPP1 and KPNA2 to miR-582-5p was verified by dual-luciferase assay. In the si-CSPP1 group, HepG2 cells transfected with si-CSPP1 lentivirus were subcutaneously injected into the back of nude mice ( n=12), and in the si-NC group, HepG2 cells transfected with negative control lentivirus ( n=12) were injected. The tumor mass, volume, circ-CSPP1 and KPNA2 were detected. Results:In the circ-CSPP1 overexpression group, the relative expression of circ-CSPP1 was (1.68±0.17), the expression of KPNA2 was (1.52±0.16), and the number of invasive cells in the 100-fold field of view was (128.4±13.5), which were all higher than those in the circ-CSPP1 overexpression control group [(1.25±0.16), (1.24±0.15), (128.4±13.5)], while the expression of miR-552-5p was lower than that in the circ-CSPP1 overexpression control group [(0.96±0.11) vs (1.31±0.15)]; The relative expression of circ-CSPP1 in the si-CSPP1 group was (1.02±0.13), KPNA2 was (0.74±0.09), and the number of invasive cells was (53.5±6.7), which were lower than those in the si-NC group [(1.28±0.14), (1.22±0.13), (74.6±8.3)], while the expression of miR-582-5p was higher than that in the si-NC group [(1.71±0.18) vs (1.32±0.14)]; The expression of circ-CSPP1 and KPNA2 and the number of invasion cells in the si-CSPP1+ miR-582-5p inhibition group was higher than that in the si-CSPP1+ miR-582-5p inhibition control group, and the differences were statistically significant (all P<0.05). The results of cell proliferation were consistent with those of invasion. The dual-luciferase gene report showed that, compared with the miR-NC group, the relative luciferase activity in HepG2 cells co-transfected with circ-CSPP1-WT or KPNA2-WT wild-type reporter vectors in the miR-882-5p mimic group decreased [(0.46±0.05) vs (1.03±0.11), (0.42±0.03) vs (1.01±0.09)]. The differences were all statistically significant (both P<0.05). However, there was no statistically significant difference in the relative luciferase activity in HepG2 cells co-transfected with the circ-CSPP1-MUT or KPNA2-MUT mutant reporter vectors (both P>0.05). The tumor weight, volume and circ-CSPP1 and KPNA2 expressions in tumor tissue of nude mice in the si-CSPP1 group were all lower than those in the si-NC group, and the expression of miR-582-5p was higher than that in the si-NC group. The differences were statistically significant (all P<0.05). Conclusion:Inhibition of circ-CSPP1 suppressed the malignant biological behavior of hepatoma cells and tumor growth by upregulating miR-582-5p and downregulating KPNA2.

Objective To investigate the value of geometric parameters of vertebrobasilar artery(VBA)for judging whether vertebral artery(VA)provide cross blood supply of posterior cerebral artery(PCA)blood supply area.Methods MR T2-fluid attenuated inversion recovery(FLAIR),3D time of flight(TOF)MR angiography(MRA)and territorial arterial spin labeling(t-ASL)images of 244 healthy adults were prospectively acquired.The angles between left VA(LVA)or right VA(RVA)and basilar artery(BA)were measured,and the sum and difference between the two angles were calculated(referred to as the sum of VA angles and the difference of VA angles),and the differences of diameters of LVA and RVA were measured and calculated(referred to as the difference of VA diameters).VA perfusion distribution type in PCA blood supply area were observed,and those with type Ⅲ or Ⅵ were enrolled in cross group,while those with type Ⅱ or Ⅴ were enrolled in non-cross group,respectively.The geometric parameters of VBA were compared between groups.Receiver operating characteristic(ROC)curve of parameters being significant different between groups were drawn,and the efficacy of these parameters for judging whether VA provide cross blood supply of PCA area were evaluated.Results There were 34 subjects in cross group and 75 in non-cross group.The sum of VA angles and the difference of VA angles in cross group were both larger than those in non-cross group(both P＜0.05),while the difference of VA diameters were not significantly different between groups(P＞0.05).The AUC of the difference of VA angles for judging whether VA provide cross blood supply of PCA area was 0.676(P＜0.05),while of the sum of VA angles was 0.598(P=0.103).Conclusion The angle differences of LVA and RVA with BA had certain application value for judging whether VA provide cross blood supply of PCA area.

Objective To optimize the platelet enrichment method,and to analyze the concentration changes of key molecules in platelet-rich plasma(PRP)before and after activation,as well as the impact of its activated products on the proliferation of rat endothelial progenitor cells.Methods The tube double-centrifu-gation method was employed to optimize platelet enrichment,and the platelet count in the enriched PRP was measured.ELISA was used to detect the concentration changes of vascular endothelial growth factor(VEGF),endostatin(ES),and P-selectin(CD62P)in PRP before and after activation.The PRP was activated by using liquid nitrogen freeze-thaw method,and the effect of its activated products on the proliferation of rat endothelial progenitor cells was evaluated by using the methyl thiazolyl tetrazolium(MTT)assay.Results The optimal enrichment coefficient of platelets achieved by the double-centrifugation method was 4.63.After low-speed,long-duration double centrifugation,the platelet count was highest in the upper layer of the buffy coat.For PRP with a platelet count of 500× 109/L obtained by machine collection,the VEGF con-centrations before and after activation were(3 418.12±488.80)pg/mL and(4 530.04±308.30)pg/mL,re-spectively,the ES concentrations were(6 168.98±253.22)pg/mL and(6 594.65±82.47)pg/mL,respec-tively,the CD62P concentrations were(6 678.23±324.15)pg/mL and(17 630.53±746.24)pg/mL,respec-tively,statistically significant differences were observed in the above indicators before and after activation(P＜0.01).The activated PRP was diluted in a gradient manner by using a specialized culture medium for en-dothelial progenitor cells.MTT assay results indicated that,in the basal medium,the optimal volume fraction for promoting endothelial progenitor cell proliferation was 0.25％after 48 hours of culture;in the complete medium,the optimal volume fractions for promoting endothelial progenitor cell proliferation were 0.062 5％after 24 hours and 0.125％after 48 hours.Conclusion The concentrations of VEGF,ES,and CD62P in the optimized,enriched PRP exhibited significant changes before and after activation.The optimal volume fraction for promoting endothelial progenitor cell proliferation in the basal medium was 0.25％.

Nitrogen oxides(NOx=NO+NO2)are important precursors of ozone(O3),and NOx and its oxides together constitute reactive nitrogen oxides(NOy)in the atmosphere.A comprehensive understanding of the total NOy level in the atmosphere is of great significance for a deeper understanding of the atmospheric nitrogen cycle and oxidation,as well as for formulating strategies for air pollution prevention and control.In this work,a thermal decomposition-broadband cavity enhanced absorption spectroscopy(TD-BBCEAS)technique for online measurement of total NOy in the atmosphere was developed.With this method,the NOy was efficiently converted into NO2,and the total NOy concentration in the atmosphere was indirectly obtained by measuring NO2.Focusing on the key factors affecting the measurement of total NOy,the influence of NO titration efficiency and other NOy component TD efficiency on measurement accuracy was emphasized.By changing the oxygen(O2)flow rate through the mercury lamp to alter the O3 concentration for titrating NO,the conversion efficiency of NO was evaluated.At O2 flow rate of 6 mL/min,the conversion efficiency of NO was greater than 99%.TD efficiency testing and analysis on NO2,peroxyacetyl nitrate(PAN),nitric acid(HNO3),and nitrous acid(HONO),which account for a large proportion of atmospheric NOy components,was carried out using 680℃as the optimal TD temperature for efficient conversion of NOy.With NO and HONO sample gases as typical verification gases,the conversion efficiency of NOy and the accuracy of NOy measurement by TD-BBCEAS system were verified by switching the on and off modes of mercury lamp and TD device.At integration time of 60 s,the detection limit of the system for NOy was 2.83×1010 molecules/cm3(60 s,2σ).A comparative measurement of actual atmospheric NOy was conducted between the TD-BBCEAS system and the NOy analyzer.The observation results showed a correlation coefficient(R2)of 0.98 and a slope of 0.93,further verifying the feasibility and accuracy of applying the TD-BBCEAS system to measurement of total NOy.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

Since the introduction of monoamine oxidase and monoamine neurotransmitter reuptake inhibitors for the treatment of major depression in the 1950s, their strengths and limitations have been fully and accurately determined. Therefore, the development of novel drugs for the treatment of depression has become a priority for researchers who aim to address treatment resistance and improve patient outcomes. Panax ginseng C. A. Mey (P. ginseng, Ren Shen) is a Chinese medicine used to treat neurological and psychiatric disorders. Numerous studies have shown that ginsenosides, the primary active constituents of P. ginseng, exert a wide range of effects on the central nervous system. Recent studies have demonstrated that ginsenosides possess significant antidepressant properties in animal models. Ginsenosides, such as Rb1 and Rg1, are steroidal molecules, and steroid derivatives have been successfully used in anesthesia, epilepsy, and more recently, postpartum depression treatment. Based on these findings, ginsenosides are promising candidates for the treatment of depression. This raises the following question: What are the prospects of using ginsenosides to treat depression? To gain a clearer understanding, this review provides a comprehensive analysis of recent research on the antidepressant potential of ginsenosides, along with insights and suggestions for future development in this field.