Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm² and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm² and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Objective:To compare the outcomes of the total mandibular inferior border ostectomy and the T-shape genioplasty for chin narrowing combined with mandibular contouring and to assess the indications of the total mandibular inferior border ostectomy.Methods:In this retrospective study, the clinical data were collected from the patients who received mandibular contouring and chin narrowing at the Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2015 to January 2019. According to the surgical procedure, patients were divided into Total inferior border ostectomy (Group I) and T-shaped genioplasty combined with mandibular contouring (Group II). Computed tomography scans, combined with medical records and photographs, were collected preoperatively and in the final follow-up postoperatively. Lower facial height, chin width, chin symmetry, facial proportions as well as patients’ satisfaction and complications were investigated to assess the clinical outcomes. Statistical analyses were performed using IBM SPSS Statistics, version 20.0 (IBM Corp., Armonk, NY, USA). The measurement data were expressed as Mean±SD, and the counting data were expressed as case (%). T-test was performed to compare the age difference, average satisfaction score and the relative measurements between the two groups. Pearson’s chi squared test was used to compare the sex composition ratio and complication ratio between the two groups. P<0.05 was considered statistically significant. Results:102 patients were involved in this study, including 42 patients in group I, 7 males and 35 females; 60 patients in group Ⅱ, 11 males and 49 females. All patients improved lower facial contours. No severe complications were observed during the follow-up period(6~24 months) Regarding appearance satisfaction, 30 cases were very satisfied, 11 cases were satisfied, and 1 case was neutral in group I. 43 cases were very satisfied, 15 cases were satisfied, and 2 cases were neutral in group II. There was no significant difference ( P >0.05) between group I and group II in age, sex, inferior lip numbness, hematoma, severe swelling, infection, soft tissue ptosisand appearance satisfaction.There was a statistically significant difference ( P < 0.01) in preoperative lower facial height [(63.05±4.15) mm vs. (52.87±4.07) mm], Preoperative lower and midfacial height ratio [(107.89±3.11) % vs. (91.29±7.94) %], and preoperative chin width and lower facial height ratio [(90.31±3.19) % vs. (104.32±5.28) %], chin width change [(12.11±2.59) mm vs. (8.39±1.89) mm], postoperative chin deviation [(0.17±0. 09)mm vs. (0.36±0.20) mm] and Postoperative chin width and lower facial height ratio [(76.80±1.85) % vs. (80.95±3.75) %]. No statistical difference ( P>0.05) was found in preoperative chin deviation, midfacial height, postoperative lower facial heigh, postoperative lower and midfacial height ratio. Conclusion:In conclusion, compared to T-shape genioplasty combined with mandibular contouring, total mandibular inferior border ostectomy had a large amount of chin narrowing and better postoperative symmetry and is well suited for a longer, wider, and more asymmetrical chin. The surgical options should be considered and chosen quantitatively to achieve aesthetically satisfactory results.

Objective:To compare the outcomes of the total mandibular inferior border ostectomy and the T-shape genioplasty for chin narrowing combined with mandibular contouring and to assess the indications of the total mandibular inferior border ostectomy.Methods:In this retrospective study, the clinical data were collected from the patients who received mandibular contouring and chin narrowing at the Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2015 to January 2019. According to the surgical procedure, patients were divided into Total inferior border ostectomy (Group I) and T-shaped genioplasty combined with mandibular contouring (Group II). Computed tomography scans, combined with medical records and photographs, were collected preoperatively and in the final follow-up postoperatively. Lower facial height, chin width, chin symmetry, facial proportions as well as patients’ satisfaction and complications were investigated to assess the clinical outcomes. Statistical analyses were performed using IBM SPSS Statistics, version 20.0 (IBM Corp., Armonk, NY, USA). The measurement data were expressed as Mean±SD, and the counting data were expressed as case (%). T-test was performed to compare the age difference, average satisfaction score and the relative measurements between the two groups. Pearson’s chi squared test was used to compare the sex composition ratio and complication ratio between the two groups. P<0.05 was considered statistically significant. Results:102 patients were involved in this study, including 42 patients in group I, 7 males and 35 females; 60 patients in group Ⅱ, 11 males and 49 females. All patients improved lower facial contours. No severe complications were observed during the follow-up period(6~24 months) Regarding appearance satisfaction, 30 cases were very satisfied, 11 cases were satisfied, and 1 case was neutral in group I. 43 cases were very satisfied, 15 cases were satisfied, and 2 cases were neutral in group II. There was no significant difference ( P >0.05) between group I and group II in age, sex, inferior lip numbness, hematoma, severe swelling, infection, soft tissue ptosisand appearance satisfaction.There was a statistically significant difference ( P < 0.01) in preoperative lower facial height [(63.05±4.15) mm vs. (52.87±4.07) mm], Preoperative lower and midfacial height ratio [(107.89±3.11) % vs. (91.29±7.94) %], and preoperative chin width and lower facial height ratio [(90.31±3.19) % vs. (104.32±5.28) %], chin width change [(12.11±2.59) mm vs. (8.39±1.89) mm], postoperative chin deviation [(0.17±0. 09)mm vs. (0.36±0.20) mm] and Postoperative chin width and lower facial height ratio [(76.80±1.85) % vs. (80.95±3.75) %]. No statistical difference ( P>0.05) was found in preoperative chin deviation, midfacial height, postoperative lower facial heigh, postoperative lower and midfacial height ratio. Conclusion:In conclusion, compared to T-shape genioplasty combined with mandibular contouring, total mandibular inferior border ostectomy had a large amount of chin narrowing and better postoperative symmetry and is well suited for a longer, wider, and more asymmetrical chin. The surgical options should be considered and chosen quantitatively to achieve aesthetically satisfactory results.

Hypofractionated radiotherapy, which provides equivalent efficacy and dose not increase toxicity compared with conventional fractionated radiotherapy following breast-conserving surgery, has become a preferred choice for whole breast irradiation. Given the low local recurrence risk and long survival time for early breast cancer survivors, radiation-associated toxicities are the focus of clinical practice. However, in the era of hypofractionated radiotherapy, the risk factors for radiation-associated toxicity remain undefined and further research is warranted. In this review, we aim to provide an overview of the toxicities of hypofractionated radiotherapy following breast-conserving surgery.

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.

Objective:To evaluate the clinical efficacy of radiotherapy in the treatment of extracranial metastatic breast cancer, and to investigate the significance and prognostic factors of whole-lesion radiotherapy (WLRT).Methods:Clinical data of 85 patients with extracranial metastatic breast cancer treated with radiotherapy between 2014 and 2019 were retrospectively analyzed. Thirty-six patients were assigned into the WLRT group and 49 in the non-WLRT group. The local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan- Meier method, log-rank test and univariate prognostic analysis. Cox proportional hazards model was used for multivariate prognostic analysis. Results:The median follow-up time was 26.7 months. The 2-year LC, PFS, OS rates were 77%, 26%, 77%, respectively. The 2-year LC (91% vs. 67%, P=0.001), PFS (47% vs. 8%, P<0.001), OS rates (84% vs. 71%, P=0.010) in the WLRT group were significantly higher than those in the non-WLRT group, respectively. Multivariate analysis demonstrated that WLRT was an independent favorable prognostic factor for the LC, PFS and OS. Furthermore, bone metastasis alone was associated with improved LC and positive hormone receptor status was correlated with improved OS. Conclusions:WLRT has the potential to prolong the survival of patients with extracranial metastatic breast cancer. The patients with bone metastases alone obtain better LC, whereas those with negative hormone receptor status has worse OS.

Distant metastasis is the leading cause of death for breast cancer patients, and advanced metastatic breast cancer is mainly considered incurable. Oligometastasis is an" intermediate stage" between local primary tumor and extensive metastasis. As a local treatment approach, radiotherapy plays an important role in the management of oligometastatic breast cancer. The development of stereotactic body radiotherapy (SBRT) allows the delivery of ablative doses to the targets without exceeding the dose constraints of organs-at-risk. Studies have shown that SBRT is safe and effective, with local control rates of more than 80% for breast cancer oligometastasis to the bone, lung, liver, brain, and lymph nodes. However, how to screen the true oligometastasis remains controversial. Randomized clinical trials will be essential to confirm whether SBRT can improve the survival outcomes.

Multi-disciplinary team(MDT)mode is regarded as the key to standardized diagnosis and treatment of malignant tumors. The model, however, encounters such roadblocks in the current form of MDT organization, as costly clinical resources and time consumption, low efficiency, poor management of participating experts in MDT, and lack of enforceability of the therapeutic decisions made. This paper summarized the practical MDT experiences of the Affiliated Cancer Hospital of Shandong First Medical University. It introduced the construction of an intranet-based MDT system covering a large proportion of newly diagnosed malignant tumor patients, and the practices and achievements of such MDT management system under hospital administrative guidance. The authors proposed to use reporting ratio as the main assessment indicator in promoting MDT, and that to define the performance, responsibilities and rights in MDT practice. These measures aim at to upgrading individual behaviors of doctors to organizational behaviors of hospitals, and providing cancer patients with more standardized, comprehensive and personalized diagnosis and treatment decisions.