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Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.
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Alzheimer's disease （AD） is a common degenerative disease of the central nervous system in the elderly， with memory impairment and behavioral changes as the main clinical manifestations. Modern research has demonstrated that many herbs with both medicinal and edible values have anti-oxidation and anti-aging activities. In addition， these herbs are naturally safe and play a role in disease prevention and health care. The 110 medicinal and edible herbs announced by the National Health Commission of the People's Republic ofChina in 2021 were studied. The relevant papers published in the last five years were searched against CNKI， VIP， Wanfang Data， PubMed and other databases. The effects， mechanism， and active ingredients of the medicinal and edible herbs against Alzheimer's disease were summarized. The results showed that more than 30 herbs including Ginseng Radix et Rhizoma， Curcumae Longae Rhizoma， Astragali Radix， Corni Fructus， Gastrodiae Rhizoma， Angelicae Sinensis Radix， Cistanches Herba， Croci Stigma， Glycyrrhizae Radix et Rhizoma， Ganoderma and their active ingredients were effective in the prevention and treatment of Alzheimer's disease. Among them， ten herbs that met the requirements were screened out for analysis. The medicinal and edible herbs and their active ingredients can act on multiple targets and treat Alzheimer's disease via multiple signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase 5 （MEK5）/extracellular signal-regulated kinase 5 （ERK5）， cytochrome C （CytC） and cysteine aspartate-specific protease （Caspase）-3/（Caspase）-9， Wnt/β-catenin， and brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， thus improving learning， cognitive ability， and memory ability. Most of the medicinal and edible herbs have the tropism to the heart， spleen， liver， and kidney meridians and tonifying effect.
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Objective:To retrospectively analyze prognostic factors and patterns of recurrence in locally advanced gastric cancer patients receiving chemoradiotherapy (CRT) after radical gastrectomy, aiming to provide reference for postoperative CRT of locally advanced gastric cancer.Methods:Clinical data of 171 patients with curatively resected gastric carcinoma who received postoperative CRT in our hospital between 2008 and 2020 were retrospectively analyzed. The disease-free survival and overall survival (OS) rates were calculated by Kaplan- Meier method. Univariate prognostic analysis was performed by log- rank test. Multivariate prognostic analysis was conducted by Cox model. Results:The median follow-up duration was 63 months. The follow-up rate was 93.6%. 31.0% and 66.7% of the enrolled patients were classified in pathological stage Ⅱ and Ⅲ. The acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 8.8% and 9.9%, respectively. In total, 166 patients completed the entire CRT regimen. No toxicity-related death occurred. Regarding patterns of recurrence, 17 patients had locoregional recurrence, 29 had distant metastasis and 12 had peritoneal metastasis. The 1-, 3-and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, while the 1-, 3-and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. In the multivariate analysis, pathological T stage, perineural invasion and lymph node ratio (LNR) were found to be the independent predictors of OS.Conclusions:Postoperative intensity-modulated radiation therapy and chemotherapy are well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. LNR can be used as an independent prognostic indicator for OS. Adjuvant CRT should be considered for all patients with a high risk of locoregional recurrence.
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Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.
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Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.
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Objective:To investigate the effects of microRNA-10a(miR-10a)on the proliferation and migration of tumor-associated fibroblasts(TAFs)in the liver microenvironment, as well as on the mRNA expressions of interleukin(IL)-6, IL-8 and IL-1β in TAFs.Methods:The normal liver tissues adjacent to cancer and focal tissues of metastatic colon cancer to the liver from the same patient were collected, and then primary normal fibroblasts(NFs)and the primary cell line of TAFs were established by tissue cultivation.The NFs and TAFs were identified by morphological observation and immunofluorescence staining, and their purity was determined by flow cytometry.The real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of miR-10a in NFs and TAFs, and then miR-10a was over-expressed in the lower ones.Subsequently, the effects of miR-10a on cell proliferation, migration and the mRNA expression levels of IL-6, IL-8 and IL-1β were detected by the cholecystokinin(CCK-8)test, wound healing assay and RT-qPCR.Results:Immunofluorescence staining showed that human cytokeratin 18(CK-18)was neither expressed in NFs nor in TAFs, while fibroblast-specific protein 1(FSP-1)was expressed in NFs and TAFs, and alpha-smooth muscle actin(α-SMA)was weakly expressed in NFs but strongly expressed in TAFs.The results of flow cytometry showed that the positive rates of α-SMA in NFs and TAFs were 95.6% and 95.3%, respectively.The mRNA expression of miR-10a in TAFs was 0.65 times of that in NFs( P<0.01). After overexpression of miR-10a, the proliferation abilities at the 3th, 4th and 5th day were lower in TAFs than in NFs( P<0.05 and 0.01), the migration abilities at 24 h and 48 h were 25% and 15% lower in TAFs than in NF group( P<0.01 and 0.05), and the mRNA levels of IL-6, IL-8, IL-1 β were 54%, 27% and 42% lower in TAFs than in NFs, respectively( P<0.01, 0.01 and 0.05). Conclusions:The overexpression of miR-10a in TAFs inhibits the cell proliferation and migration and reduces the mRNA expressions of inflammatory factors IL-6, IL-8 and IL-1β, which may be an important factor for TAFs’ inhibiting liver metastasis.