Objective:To explore the role of fibroblast growth factor 21 (FGF21) in rats with severe acute pancreatitis-associated acute lung injury (SAP-ALI) and its related molecular mechanisms.Methods:Twenty-four healthy male SD rats were randomly divided into 4 groups (random number, n=6 per group): Control group, SAP group, FGF21 intervention group (SAP+FGF21 group), and autophagy inhibitor group (SAP+FGF21+3-MA group). The SAP model was established by retrograde injection of 3.5% sodium taurocholate into the pancreatic duct. In SAP+FGF21 group, FGF21 10 mg/kg was intraperitoneally injected at 1 hour before modeling. In SAP+FGF21+3-MA group, FGF21 10 mg/kg and 3-MA 20 mg/kg were intraperitoneally injected at 1 h before modeling. Serum amylase activity was detected by biochemical kit. Plasma levels of tumor necrosis factor alpha (TNF-α) and FGF21 were detected by ELISA. HE staining was used to observe the pathological changes of pancreas and lung tissues. Immunofluorescence was used to detect the protein level of FGF21 in lung tissue. Western blot was used to detect the expression levels of autophagy-related proteins in lung tissue. Autophagosomes in lung tissue were observed by electron microscopy. Results:Compared with the Control group, the plasma and lung tissue FGF21 levels in SAP group were significantly decreased (both P<0.001) , severe pancreatic and lung tissue damage, and elevated plasma TNF-α levels ( P<0.001). Western Blot and transmission electron microscopy showed that: The expression of LC3Ⅱ/Ⅰ in lung tissue of SAP group was down-regulated [(0.912±0.052) vs. (0.700±0.135), P<0.001], and P62 protein level was up-regulated [(0.475±0.068) vs. (0.687±0.070), P<0.001] , and reduced autophagosome counts in the SAP group. In contrast, the SAP+FGF21 group showed elevated FGF21 levels (both P<0.01), attenuated pancreatic and lung injury ( P<0.001), decreased TNF-α levels [(280.10±49.36) pg/mL vs. (86.32±66.00) pg/mL, P<0.001]. Lung tissue of LC3 Ⅱ/Ⅰ levels increase [(0.700±0.135) vs. (0.853±0.073), P<0.01], P62 protein levels cut [(0.687±0.070) vs. (0.538±0.030), P<0.01] ], and increased autophagosomes and autolysosomes under electron microscopy. Compared with SAP+FGF21 group, the expression levels of FGF21 in plasma and lung tissue in SAP+FGF21+3-MA group were not significantly changed, and the level of autophagy was decreased. Pancreas and lung tissue injury was severe ( P<0.001), Plasma TNF-α level obviously higher [(86.32±66.00) pg/mL vs. (212.90±11.56) pg/mL, P<0.05]. Conclusion:FGF21 may play a protective role in SAP-ALI by up-regulating the level of autophagy.

Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P＜0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P＜0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P＜0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of＜0.505×10-3 mm2/s and a postoperative D value of＜0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.

Erectile dysfunction has a high incidence rate and is a difficult-to-treat condition in male urology.The synergistic effect of nerves,endothelium,and smooth muscles plays a crucial role in penile erection.However,the role of the many fibroblasts in the corpus cavernosum of the penis during erection is often overlooked.Fibroblasts are at the center of the cellular and molecular network in the corpus cavernosum of the penis,regulating the dynamic balance of the cavernosal microenvironment and mediating penile erection,thus providing a novel target for treating erectile dysfunction.Blood stasis primarily causes erectile dysfunction,thereby serving as a crucial pathological factor leading to the imbalance of the cavernosal microenvironment.Blood stasis also corresponds to the microscopic pathological changes in the corpus cavernosum of patients with erectile dysfunction.Therefore,this study explored the correlation between fibroblast-mediated penile erection and traditional Chinese medicine theories,integrating it with clinical practice.This study proposes that activating blood and resolving stasis can regulate the cavernosal microenvironment and improve fibroblast-mediated erectile dysfunction.This study also provides novel insights for treating erectile dysfunction with traditional Chinese medicine.

Objective:To investigate the etiology, clinical manifestations, clinicopathological features of cystic neutrophil granulomatous mastitis (CNGM).Methods:From Jan 2019 to Dec 2020, 95 CNGM cases diagnosed by biopsy pathology at Chongqing Hospital of Traditional Chinese Medicine and Chongqing Liangping District Hospitol of Traditional Chinese Medicine were reviewed.Results:There were 95 female patients, aged 21 to 50 years, with a median age of 32 years. Laboratory examination showed that 56% (53/95) cases had elevated rheumatoid antibody level, 27 % (26/95) had increased level of serum thyroid antibody, 15% (14/95) had elevated antineutrophil antibody, 35% (33/95) had increased ESR, 38% (36/95) had increased C-reactive protein. The positive rate of Gram-stained bacilli was 82% (78/95). Histology: pyogenic granuloma with lobule of breast as the center, the center of granuloma was cystic vacuole.Immunohistochemistry showed that the inflammatory cells in and around granuloma were mainly CD3 + cells, and CD4 + cells were more than CD8 + cells. Conclusions:The cystic neutrophilie granulo matous mastitis is a rare type of idiopathic granulomatous mastitis. The diagnosis of CNGM is dependent on its specific pathological features.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

Objective To evaluate Aedes albopictus infestation status in the central urban area of Shanghai,and analyze the related epidemic risk of mosquito-borne infectious disease.Methods Consecutive mosquito surveillance was conducted in the green lands and residential areas in the central urban area of Shanghai during 2012-2014,the Aedes albopictas density and its seasonal fluctuation were observed;the sequence ofAedes albopictus in Shanghai was aligned with that in other epidemic area abroad,and the susceptibility ofAedes albopictus to mosquito-borne virus and endemic risk were analyzed.Results No Aedes aegypti was found in the central urban area of Shanghai.As predominant species in both the residential area and the green lands,the proportion ofAedes albopictus in the residential area was significantly higher than that in the green lands (78.53％ vs.19.99％,x2=15 525.168,P＜0.001),and so was the density (11.91,42.02 pcs/day· site in the residential area vs.3.65,2.18,2.73 pcs/day· site in the green lands,all P value＜0.001).In 2014,the density reached 42.02 pcs/day · site and the proportion reached 94.69％ in the residential areas.Phylogenetic tree analysis showed that the genetic distance between Aedes albopictus in Shanghai and Aedes albopictus in Africa was quite far.Conclusion No Aedes aegypti was found in Shanghai and its surrounding areas,while Aedes albopictus infestation in the central urban area of Shanghai was serious.Strict measures should be taken to reduce the Aedes albopictus density for the effective control Zika virus spread.

BACKGROUND: Limb allograft is a sort of composite tissues allotrans plantation(CTA), some researches showed that the apoptosis of target cell is one of the main mechanism of the dysfunction of allograft.OBJECTIVE: To investigate the characteristic of cell apoptosis in acute rejection of limb allograft in rats based on limb allograft model.DESIGN: A randomized controlled trial using the experimental animals as the objects.SETTING: Experimental animal center Laboratory of a hospital of a medical university MATERIALS: The experiment was done in the Experimental Animal Central Laboratory of the First Affiliated Hospital of Harbin Medical University from November 2003 to May 2004. Totally 56 healthy and male SD rats and 28 Wister rats were involved with body mass of 200 to 250 g. The rats were provided by the Experimental Animal Center of the First Affiliated Hospital of Harbin Medical University. They were randomly divided into two groups:transplantation group with 28 Wistar rats and 28 SD rats and control group with 28 SD rats.INTERVENTIONS: The transplantation group of SD rats underwent limb allotransplantation from allogenetic Wistar. The control group of SD rats underwent limb replantation. The expression of acute rejected in limb allografts was observed. The limb grafts were harvested atday 1, 3, 5 or 7 after transplantation. Histopathological rejection grade of each tissue rejection was performed with hematoxylin-eosin staining. Apoptotic cells were detected by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) and apoptotic index(AI) was calculated.MAIN OUTCOME MEASURES: Primary results: ① istopathological grade of acute rejection in limb allografts ② The relationship between apoptosis and acute rejection in limb allograft in rats; Secondary results:General condition of rats in each group.RESULTS: The limb grafts showed edema and erythema and the skin became red at day(3.43 ±0.79) after transplantation. The average survival time was(7.42 ± 1.72) days. The acute rejection in skin was the strongest. On the day 3, 5 and 7 after operation, the histopathological rejection grades of skins in the transplantation group were(1.14±0.38) ,(2.28 ±0.48) and(2.86 ±0.38) grades respectively. They were significantly different from that of muscle and nerve( P ＜ 0.05 ) . The apoptotic cells in allografts were mainly infiltrating lymphocytes in subcutaneous tissues and then the muscle cells. All was positively correlated with acute rejection grade in limb allograft .CONCLUSION: Apoptosis was involved in acute rejection of limb allograft in rat. The apoptotic index can be used as a quantitative index to estimate the injury of grafts.