Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective To investigate the role of Kelch-like-epichlorohydrin-associated protein 1/nuclear factor erythroid-derived factor-2-related factor 2(Keap1-Nrf2)and nuclear factor-κB(NF-κB)signaling pathways in sepsis-associated encephalopathy(SAE).Methods Male C57BL/6J mice of SPF were randomly divided into four groups(n=10):the control group and LPS 6 h,24 h and 48 h groups.The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT).ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum,and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice.Real-time quantitative PCR(qPCR)was adopted to detect the mRNA levels of toll-like receptor4(Tlr4),NF-κB,Keap1 and Nrf2 in the hippocampus,and to determine protein expressions of NF-κB a Nrf2、Keap1 and Tlr4 with Western blotting.Results Compared to the control group,the serum concentrations of interleukin 6(IL-6)in lipopolysaccharide(LPS)groups increased at 6 h,and reached the peak at 24 h and 48 h(P＜0.01).The levels of serum interleukin 18(IL-18)in the LPS groups increased significantly at 6 h and 24 h(P＜0.01)but there was no statistically significant difference compared with the 48h group.The results indicated the activity of superoxide dismutase(SOD)and glutathione(GSH)in brain tissues in LPS groups increased(P＜0.01).OFT results showed the time spent in the center of the open field,the distance covered around the center,and total distance covered by mice in LPS groups were significantly reduced(P＜0.01),except for the time spent in the center of the open field in the LPS 24 h group.The mRNA expressions of Tlr4 and(LPS 6 h,48 h)NF-κB in the hippocampus tissue of mice in LPS groups were elevated(P＜0.05),so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group.Additionally,the protein expressions of NF-κB,Keap1 and Tlr4 increased in LPS groups,so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P＜0.05).Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.

Objective To investigate the influencing factors of unplanned rehospitalization within one year after surgery among adult renal transplant recipients. Methods The clinical data of 299 recipients who underwent renal transplant surgery in the Department of Organ Transplantation of the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2022 were retrospectively analyzed. The recipients were divided into unplanned rehospitalization group and non-rehospitalization group based on whether they experienced unplanned rehospitalization within one year after surgery. Univariate analysis and binary Logistic regression analysis were performed to explore the influencing factors of unplanned rehospitalization within one year after renal transplantation. Results Among the 299 recipients, 102 experienced unplanned rehospitalization, with an incidence rate of 34.11%. Univariate analysis revealedstatistically significant differences were noted between the two groups in terms of gender, occupational status, preoperative underlying disease, rejection reactions, nosocomial infections, immunosuppressive medication regimens, serum creatinine, cystatin C, serum phosphorus, serum potassium, and initial hospitalization duration (P < 0.05). Binary Logistic regression analysis showed that having ≥3 kinds of preoperative underlying disease (OR=2.122, 95%CI, 1.198 to 3.759) and experiencing rejection reactions (OR=3.162, 95%CI, 1.217 to 8.218) were independent risk factors for unplanned rehospitalization within one year after renal transplantation (P < 0.05). Conclusion The rate of unplanned rehospitalization within one year after surgery is relatively high among adult renal transplant recipients. Having ≥3 preoperative underlying disease and experiencing rejection reactions are independent risk factors for unplanned rehospitalization within one year after surgery. Transplantation healthcare teams can develop corresponding strategies targeting these risk factors to reduce the rate of unplanned rehospitalization and alleviate the burden of disease.

Objective:To investigate the effects of RNA interference on the expression level of leptin and its effect on proliferation, TGF-β 1 and collagen type Ⅰ production in human pathological scar fibroblasts in vitro. Methods:Pathological scar tissues (hypertrophic scar, keloid) were collected from the Department of Burn Plastic Surgery in Affiliated Hospital of North Sichuan Medical College. After primary cell culture and cell passage, passage 3 cells were selected for experimental study. The cells were divided into two groups: the experimental group which was transfected with leptin siRNA, and the negative control group which was transfected with empty vector. Examinations were carried out 48 hours after transfection. Cell proliferation was determined by CCK-8. The transcription levels of leptin, TGF-β 1 and type Ⅰ collagen genes were detected by polymerase chain reaction (PCR). The protein expression levels of leptin, TGF-β 1 and type Ⅰ collagen were determined by immunofluorescence and Western blotting. Student′s t-test was used for comparison between groups, and P<0.05 was considered statistically significant. Results:Five hypertrophic scars and five keloids were included. Compared with the negative control groups, the proliferation ability ( A450) of leptin-SiRNA transfected fibroblasts were not significantly different ( P>0.05). The relative mRNA expression levels of leptin, TGF-β 1 and type Ⅰ collagen in hypertrophic scars and keloids were significantly decreased in the siRNA transfection groups compared with the negative control groups ( P<0.05). Immunofluorescence results showed that the expression levels of leptin, TGF-β 1 and type I collagen in keloids were higher than those in hypertrophic scars, and that siRNA induced leptin downregulation significantly reduced the levels of leptin, TGF-β 1 and type I collagen in both hypertrophic scars and keloids. Western blotting showed that the protein levels of leptin, TGF-β 1 and type Ⅰ collagen were significantly decreased in hypertrophic scar and keloid fibroblasts after leptin siRNA interference ( P<0.05). Conclusions:Downregulation of leptin gene expression by RNA interference inhibited TGF-β 1 and typeⅠ collagen expression, which could be used in treating pathological scar.

Objective:To investigate the effects of RNA interference on the expression level of leptin and its effect on proliferation, TGF-β 1 and collagen type Ⅰ production in human pathological scar fibroblasts in vitro. Methods:Pathological scar tissues (hypertrophic scar, keloid) were collected from the Department of Burn Plastic Surgery in Affiliated Hospital of North Sichuan Medical College. After primary cell culture and cell passage, passage 3 cells were selected for experimental study. The cells were divided into two groups: the experimental group which was transfected with leptin siRNA, and the negative control group which was transfected with empty vector. Examinations were carried out 48 hours after transfection. Cell proliferation was determined by CCK-8. The transcription levels of leptin, TGF-β 1 and type Ⅰ collagen genes were detected by polymerase chain reaction (PCR). The protein expression levels of leptin, TGF-β 1 and type Ⅰ collagen were determined by immunofluorescence and Western blotting. Student′s t-test was used for comparison between groups, and P<0.05 was considered statistically significant. Results:Five hypertrophic scars and five keloids were included. Compared with the negative control groups, the proliferation ability ( A450) of leptin-SiRNA transfected fibroblasts were not significantly different ( P>0.05). The relative mRNA expression levels of leptin, TGF-β 1 and type Ⅰ collagen in hypertrophic scars and keloids were significantly decreased in the siRNA transfection groups compared with the negative control groups ( P<0.05). Immunofluorescence results showed that the expression levels of leptin, TGF-β 1 and type I collagen in keloids were higher than those in hypertrophic scars, and that siRNA induced leptin downregulation significantly reduced the levels of leptin, TGF-β 1 and type I collagen in both hypertrophic scars and keloids. Western blotting showed that the protein levels of leptin, TGF-β 1 and type Ⅰ collagen were significantly decreased in hypertrophic scar and keloid fibroblasts after leptin siRNA interference ( P<0.05). Conclusions:Downregulation of leptin gene expression by RNA interference inhibited TGF-β 1 and typeⅠ collagen expression, which could be used in treating pathological scar.

Objective:To investigate the effect of low molecular weight heparin (LMWH) on the inflammatory response of PC12 cells induced by oxygen glucose deprivation (OGD) and its related mechanism.Methods:The PC12 cells were cultured in vitro were randomly divided into sham(control) group, OGD group, LMWH group and blocking agent group. The latter group was divided into six groups: Eritoran+ OGD group, LMWH+ Eritoran+ OGD group, ST2825+ OGD group, LMWH+ ST2825+ OGD group, pyrrolidinedithiocarbamate (PDTC)+ OGD group and LMWH+ PDTC+ OGD group. OGD cell model was established. Cell counting kit-8 (CCK-8) assay was used to detect cell activity. The expressions of toll-like receptor 4 (TLR4), MyD88 and nuclear factor κB (NF-κB) mRNA and protein were detected by real time polymerase chain reaction (qRT-PCR) and Western blot. The concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α(TNF-α) and S100β were determined by enzyme linked immunosorbent assay (ELISA). Results:The cell activity of OGD group was significantly lower than that of control group on the first, second, third day ( P<0.05). Compared with OGD group, the activity of LMWH group was increased on the second, third day ( P<0.05), but lower than that of control group ( P<0.01). The mRNA expression of TLR4, MyD88 and NF-κB was significantly increased in OGD group compared with the control group ( F=144.9, F=710.5, 79.51, P<0.01). Compared with OGD group, the mRNA expression of TLR4, MyD88 and NF-κB were significantly decreased after treatment with LMWH ( P<0.01), and the specific inhibitor of TLR4, MyD88 and NF-κB enhanced the anti-inflammatory effect of LMWH. The protein expression of this pathway was consistent with that of the gene. The concentration of IL-1β, IL-6, TNF-α and S100β in OGD group was significantly higher than control group ( P<0.05). After treatment with LMWH, the concentrations of inflammatory factors and S100β were significantly decreased compared with OGD group ( P<0.01). When hinder TLR4, MyD88 and NF-κB respectively by Eritoran, ST2825 and PDTC, the concentrations of inflammatory factors and S100β were significantly decreased, but it was still higher than control group ( P<0.05). Conclusions:OGD can cause pathological damage of PC12 cells, including high expression level of S100β and aggravation of inflammatory reaction. LMWH can improve cell activity, down-regulate inflammatory reaction degree and protect the cells. Using inhibitors of TLR4/MyD88/NF-κB pathway to inhibit the corresponding target, the up-regulation of inflammatory factors by OGD can be inhibited in varying degrees. These suggested that LMWH may regulate inflammatory reaction of PC12 cells induced by OGD through TLR4/MyD88/NF-κB pathway.

Objective To explore the clinical effect of new type rectal cancer radiotherapy individualized fixation device in the radiotherapy of rectal cancer. Methods From June 2015 to December 2016,60 patients with rectal cancer who accepted the external irradiation in Zhejiang Tumor Hospital were divided into two groups by random number table method. A group(31 cases) received new type rectal cancer radiotherapy position fixation devices with thermoplastic film. B group(29 cases) received simple foam pad with thermoplastic film. Before each treatment,Cone beam CT(CBCT) scan was conducted. The applied CBCT image and the planned reconstruction image were compared in the direction of X(left and right),Y(upper and lower)and Z(front and rear) axis. The setup error was recorded, and the correlation between the two groups was analyzed. Results The average setup error of patients in A group in X (left and right),Y(upper and lower),Z(front and rear) axis were (1. 61 ± 0. 18)mm,(1. 82 ± 0. 13)mm,(1. 91 ± 0. 11)mm,respectively. The average setup error of patients in B group in X(left and right),Y(upper and lower),Z (front and rear) axis were (2. 22 ± 0. 13)mm,(2. 43 ± 0. 14)mm,(2. 36 ± 0. 13)mm,respectively. There were statistically significant differences between the two groups(t=14. 958,17. 501,11. 283,all P＜0. 001). Conclusion The new type of rectal cancer radiotherapy position fixing device is more comfortable than the simple foam pad,and the setting error is smaller than the simple foam pad.

Objective To investigate the clinical characteristics of tubal stump pregnancy, and to assess the value of interventional embolization in preventing tubal stump pregnancy. Methods Among the patients who were planned to receive preoperative treatment of hydrosalpinx before the performance of in vitro fertilization-embryo transfer (IVF-ET) at authors' hospital, 35 patients had stump of fallopian tube. Of the35 patients, previous surgery of unilateral fallopian tube was present in 28 and previous surgery of bilateral fallopian tubes in 7. The length of tubal stump ranged from 10mm to 45mm, with a mean of 25mm. Interventional embolization with micro-coils was carried out in all patients, after which IVF-ET was performed. The pregnancy rate and ectopic pregnancy rate were calculated. Results Embolization of both fallopian tubes was successfully accomplished in all 35 patients. The IVF-ET pregnancy rate was 48.5％ (17/35), and no tubal stump pregnancy occurred. Conclusion The use of interventional embolization to occlude tubal stump can effectively avoid the occurrence of tubal stump pregnancy.

Objective To analyze the correlations of commonly used biometric parameters of normal fetal brain with fetal gender and gestational age (GA) and to evaluate the feasibility of establishing MRI reference standards for normal fetal brain biometry in second and third trimesters. Methods MRI measurements of 263 fetuses without central nervous system abnormalities were retrospectively collected from the Obstetrics and Gynecology Hospital of Fudan University from June 2012 to April 2017. MRI measurements of fetal biparietal diameter (BPD), occipital-frontal diameter (OFD), head circumference cross-sectional area (HCS), transverse cerebellar diameter (TCD), anterior-posterior diameter of the vermis (APDV), vermian height (VH) and vermian cross-sectional area (VS) were obtained in every standard plane. Head circumference (HC) and (BPD+OFD)/2 were calculated. Spearman correlation analysis, independent samples t-test, Pearson correlation analysis and linear regression analysis were used for statistic analysis. Results Fetal BPD, OFD and HCS were statistically correlated with gender in second and third trimesters (r= － 0.155, － 0.149 and－ 0.159; P=0.032, 0.038 and 0.027). The mean values of BPD, OFD and HCS of male fetuses were greater than those of female ones [(7.25±1.22) vs (6.87±1.28) cm, (8.59±1.38) vs (8.18±1.41) cm, (53.62±16.82) vs (48.48±16.84) cm2; t=2.101, 2.011 and 2.102; all P<0.05] and the mean differences between them were 0.38 cm, 0.41 cm and 5.14 cm2, respectively. BPD, OFD, HCS, HC, (BPD+OFD)/2, TCD, APDV, VH and VS were positively correlated with gestational age (r=0.950, 0.947, 0.962, 0.957, 0.957, 0.976, 0.931, 0.943 and 0.960, respectively; all P<0.001). Among them, TCD (r=0.976) was the closest relating factor, followed by HCS (r=0.962) and VS (r=0.960). The linear regression equations were as follows: BPD (cm)=0.276×GA－0.453, R2=0.903; OFD (cm)=0.308×GA+0.010, R2=0.896; (BPD+OFD)/2 (cm)=0.292×GA － 0.222, R2=0.916;HC (cm)=0.473×GA － 0.359, R2=0.916; HCS (cm2)=3.795×GA － 52.232, R2=0.926; TCD (cm)=0.180× GA－1.858, R2=0.952; APDV (cm)=0.047×GA－0.353, R2=0.867; VH (cm)=0.071×GA－0.592, R2=0.890;VS (cm2)=0.143×GA－2.396, R2=0.919, all P<0.001. Conclusions Some fetal brain biometric parameters are correlated with fetal gender. It is essential and conducive to establish different reference values for male and female fetuses to achieve accurate prenatal evaluation and diagnosis. Fetal BPD, OFD, HCS, HC, (BPD+OFD)/2, TCD, APDV, VH and VS have strong linear relationship with gestational age in second and third trimester and can be served as good indicators for evaluating fetal brain growth and development. MRI quantitative measurement of fetal brain biometric parameters can provide more reliable reference data for prenatal evaluation of fetal brain growth and development. It is feasible to establish MRI reference standards for fetal brain biometry.