Objective V-raf murine sarcoma virus oncogene homologous gene B (BRAF) gene plays an important role in mitogen-activated protein kinase signaling pathway by encoding RAF family serine/ threonine protein kinase.Mutations in the BRAF gene can lead to tumorigenesis.About 10％ of metastatic colorectal cancers have BRAF gene mutations.The prognosis of this type of cancer is poor,with a median overall survival of 12 months.Recent studies have shown that FOLFOXIRI regimen combined with bevacizumab can be used as a first-line treatment.In addition,simultaneous targeting inhibition of multiple signaling pathways can bring survival benefits to these patients.

Objective To study treatment of massive variceal bleeding secondary to localized pancreatitis-associated portal hypertension (MVBPAPH).Methods A retrospective study on the clinical data of patients with MVBPAPH was carried out.Of 24 patients with MVBPAPH,20 had pancreatic pseudocysts.12 were operated after failure of treatment with endovascular intervention for variceal bleeding (including 10 patients with splenectomy and gastric fundus-body peripheral vessels amputation and 2 patients with pancreatic pseudocystogastrostomy).8 patients underwent partial splenic embolization and left gastroepiploic artery embolization.4 patients directly underwent splenectomy and gastric fundus-body peripheral vessels amputation for variceal bleeding.Results Left pleural effusion developed in 5 patients who underwent arterial embolization.Left pleural effusion and lung infection occurred in 2 patients who underwent operation.All patients recovered well and were discharged home.During the follow-up period of 2 to 72 months,no rebleeding occurred in these patients (including 2 patients had passed little interval melena).Gastroscopy re-examination showed that variceal veins were not found in 18 patients.Variceal veins which were detected in the remaining 6 patients were obviously less severe.Conclusion Individualized treatment should be given to patients with MVBPAPH and according to the specific type of pancreatitis and the onset time of any accompanying pseudocyst.

Objective To explore the effects of acupuncture and individualized occupational therapy on the rehabilitation of patients with unilateral spatial neglect ( USN ) after stroke.Methods Stroke patients with hemiplegia were evaluated by neuropsychological tests,including line bisection,a cancellation test,clock drawing,and figure and shape copying.Sixty-nine right hemispheric stroke patients identified with USN were randomly assigned to 3 groups:20 patients as a control group received conventional rehabilitation therapy ; another 22 patients as an occupational group received type-specific individualized occupational therapy combined with conventional rehabilitation therapy; the remaining 23 patients as an acupuncture combined with occupational therapy group received acupuncture in addition to both conventional rehabilitation therapy and occupational therapy.These three groups were evaluated with neuropsychological tests and the modified Barthel index (MBI) before and after treatment.Results ①MBI scores in the occupational therapy group and the combined group were significantly higher after treatment,but no significant difference was observed in the control group.②The increased MBI scores in the combined and occupational groups were higher than those in the control group.At the same time the increase in MBI scores in the combined group was significantly greater than in the occupational therapy group.③The assessment results with both line bisection and cancellation tests in all three groups were significantly different after treatment.The line bisection results in the occupational therapy group and the combined group were significantly better than in the control group.The cancellation test results in the combined group were significantly better than in the control group.Conclusion These findings show that acupuncture combined with occupational therapy can have a positive effect on neglect recovery and greatly improve the daily life of USN patients.

Objective To explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis.Methods Analysis was conducted on data from genome-wide association studies(GWASs)on Omega-3 fatty acids and breast cancer.The selected instrumental variables(IVs)comprised genetic loci associated with Omega-3 fatty acids.Various Mendelian randomization analysis methods,including inverse-variance weighted(IVW)method,MR-Egger regression analysis,weighted median,simple models,and weighted models,were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer.Results A total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs.The analysis methods,including IVW method,revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer(P>0.05).Analysis methods,such as MR-Egger regression analysis,did not detect significant gene-level pleiotropy(P=0.319),which indicates the high sensitivity and robustness of analysis results.Conclusion The findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.

The integration of MRI and linac has realized real-time MRI-guided radiotherapy and accelerated the progress of precision radiotherapy. Electrons are subjected to Lorentz force in the magnetic field, especially the electron cyclotron effect occurs at the tissue-air interface, which changes the original electron equilibrium state and brings challenges to dosimetry with MRI-Linac. In recent years, a series of studies carried out through Monte Carlo simulation and experimental measurement have suggested that the conventional dosimetry devices can be used for the dosimetry with MRI-Linac after replacing the magnetic materials, but corresponding correction factors should be introduced according to the magnetic field intensity, placement angle of the measuring device, type of the measuring device. The standardization, streamlining, and real-time dosimetry with MRI-Linac need to be further studied.

Cerebral small vessel disease (CSVD) is a prevalent disease in elder people, which is related to cognitive dysfunction, neuropsychological disorder, motor and gait dysfunction, and urinary incontinence. The imaging markers of CSVD mainly include recent subcortical small infarct, lacuna, white matter hyperintensity, enlarged perivascular space, cerebral micro-bleed, cerebral micro-infarct, and cerebral atrophy. At present, the correlation and interaction of CSVD imaging markers and their synergistic effects on clinical symptoms have gradually become the research focus. This article reviews the correlations of cerebral micro-infarct with other CSVD imaging markers to further clarify the pathogenesis of coexistence of a variety of CSVD imaging markers and guide the prevention and treatment of CSVD.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

BACKGROUND:How to improve the hematopoietic microenvironment is a hot topic in the treatment of aplastic anemia. OBJECTIVE:To explore the action mechanism of Angelica sinensis polysaccharide in the treatment of aplastic anemia by combining GEO sequencing analysis,network pharmacology,and experimental validation. METHODS:Aplastic anemia-related differentially expressed genes were obtained from GEO database,and gene ontology and gene set enrichment analysis were performed.The active components and targets of Angelica sinensis polysaccharide were obtained by combining the literature with PubChem,SwissTargetPrediction,and PharmMapper databases.After the intersection targets were taken,STRING and Cytoscape were used to construct protein-protein interaction network,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed.Mouse model of aplastic anemia was established,and the effect and action mechanism of Angelica sinensis polysaccharide on aplastic anemia were verified by blood cell analyzer,flow cytometry,ELISA,immunohistochemistry,immunofluorescence,and western blot assay. RESULTS AND CONCLUSION:(1)A total of 834 differentially expressed genes were screened,which were involved in biological processes such as cell development,hematopoiesis,and myeloid cell differentiation.(2)347 targets related to Angelica sinensis polysaccharide were retrieved and 77 potential therapeutic genes were screened.Among them,the degree values of angiogenic,apoptotic,and immune-related factors such as VEGFA,EGLN1,Bcl-2,interferon-γ,interleukin-2,interleukin-4,and interleukin-6 were significant.(3)KEGG pathway enrichment analysis revealed that the therapeutic targets were mainly enriched in Th17 cell differentiation,NK-related cytotoxicity,cell adhesion factors such as interferon-γ,interleukin-2,and interleukin-4 related signaling pathways.(4)Animal experiments showed that Angelica sinensis polysaccharide significantly improved bone marrow haematopoiesis,increased peripheral blood cell,and bone marrow single nucleated cell counts,and improved the survival rate of mice.Compared with the model group,mice in the Angelica sinensis polysaccharide group showed a significant decrease in the ratio of Th1/Th2 cells(P<0.01),a decrease in the expression level of interferon-γ(P<0.01),an increase in the level of interleukin-4(P<0.05),a significant increase in the level of VEGFA(P<0.01),a significant decrease in EGLN1(P<0.01),a significant decrease in apoptosis rate of bone marrow single nucleated cells and reactive oxygen species level(P<0.01),and a significant increase in cleaved Caspase-3 protein expression(P<0.01),and a significant decrease in Bcl-2/Bax ratio(P<0.01).(5)These findings show that Angelica sinensis polysaccharide can improve hematopoiesis of aplastic anemia mice by regulating aberrant T-cell subsets and promoting angiogenesis to improve hematopoietic microenvironment,and inhibiting apoptosis of bone marrow mononuclear cells.

Objective To explore the relationship of quality of life with optimisms and sense of coherence in adult kidney transplant recipients. Method A total of 295 kidney transplant recipients participated in the study by a self-designed general questionnaire, revised life orientation test (LOT-R), sense of coherence (SOC-13) and the MOS 36-item short form health survey (MOS SF-36). Results The mean score of mental health scale (PCS) was 47.02±7.30, which differed with different age, employment status and transplant vintage (P ＜0.01). The mean score of phyical health scale (MCS) was 46.87 ±11.14, which differed with education, economic burden and transplant vintage (P ＜0.05). PCS and MCS were positively correlated with the total score of sense of coherence (52.05％) and optimism (23.45％) (P＜0.001). Optimism played a partially mediating role in the relationship between sense of coherence and quality of life. Conclusions The quality of life of kidney transplant recipients needs to be improved, which was at a low level.Optimism (medium to high level) and sense of coherence (medium to low level) are influencing factors of the quality of life. Improving accessment of mental state of patients with kidney transplant receients, paying more atentent and support to their mental change can improve their optimism and sense of coheherce and then life quiality.

Objective:To evaluate the detective effect of double inversion recovery (DIR) sequence on cerebral white matter hyperintensities (WMH) in patients with acute ischemic stroke, and compare with those of T2WI and FLAIR sequences.Methods:Seventy-three acute ischemic stroke patients with WMH within 14 d of onset, admitted to Department of Neurology, Beijing Shijitan Hospital, Capital Medical University from November 2018 to March 2021, were chosen. MRI T2WI, FLAIR and DIR sequences were used to detect WMH. According to Fazekas scale, patients with periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH) were divided into mild group (score of 0-1) and moderate to severe group (scores≥2); the differences in WMH volume detected by T2WI, FLAIR and DIR sequences, and signal intensity, cross-sectional area and contrast of isolated lesions were compared.Results:(1) Seventy-three patients were with PVWMH (36 into the mild group and 37 into the moderate to severe group); in patients from the moderate to severe group, PVWMH volume detected by FLAIR sequence was statistically larger compared with that by DIR sequence, and PVWMH volume detected by T2WI sequence was significantly smaller compared with that by FLAIR sequence ( P<0.05). Fifty-seven patients were with DWMH (44 into the mild group and 13 into the moderate to severe group); the DWMH volume detected by FLAIR and T2WI sequences was significantly larger than that by DIR sequence ( P<0.05). (2) A total of 60 isolated lesions were detected, ranged 5.0-9.1 mm in length; isolated lesions enjoying significantly larger cross-sectional area, higher signal intensity, and lower contrast detected by FLAIR and T2WI sequences compared with those by DIR sequence ( P<0.05); isolated lesions enjoying significantly higher signal intensity and contrast detected by T2WI sequence compared with those by FLAIR sequence ( P<0.05). Conclusion:DIR sequence enjoys better effect in detecting WMH than FLAIR and T2WI sequences; the mismatch area of DIR sequence with FLAIR or T2WI sequences suggests WMH penumbra.