Objective:To explore the protective effects of liraglutide on acute lung injury in septic mice and its mechanisms.Methods:Thirty-six male FVB/NJ mice were randomly(random number) divided into three groups: control group (Control, n=12), acute lung injury group (ALI, n=12)and liraglutide intervention group (ALI+LIRA, n=12). Mice model of acute lung injury were prepared by intratracheal instillation of Pseudomonas aeruginosa suspension, while the control group were given intratracheal instillation of equal volume of physiological saline; the mice in ALI+LIRA group were received subcutaneous injection of liraglutide (2 mg/kg) 30 minutes post-induction, while both the mice in control group and ALI group were received subcutaneous injection of equal volume physiological saline. After 24 hours, the mice were euthanized, the lung tissues and bronchoalveolar lavage fluid (BALF) were collected, the lung pathological damage changes were evaluated by hematoxylin eosin staining, the expression of surfactant associated protein D (SP-D)in lung tissue were detected by immunofluorescence assay; total protein concentration in BALF were detected by BCA method, and the levels of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α)levels in BALF were measured by enzyme-linked immunosorbent assay(ELISA), the protein expression of SP-D in BALF and lung tissue were determined by Western blot. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:Compared with the control group, the mice in ALI group had higher lung histopathology injury score, higher total protein concentration, higher IL-6 and TNF-α levels in BALF, and had less SP-D positive cells in lung tissue; and also had lower expression of SP-D in both BALF and lung tissue, with statistical significance (all P<0.05). Compared with ALI group, the mice in ALI+LIRA group had lower lung histopathology injury score, lower total protein concentration, lower IL-6 and TNF- α levels in BALF, and had more SP-D positive cells in lung tissue; and also had higher expression of SP-D in both BALF and lung tissue, with statistical significance (all P<0.05). Conclusions:Liraglutide attenuates the severity of acute lung injury in septic mice, and its protective mechanism may be associated with the promotion of SP-D secretion.

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

Objective:To explore the evolution of CT characteristics of the "reversed halo sign" of pulmonary tuberculosis, and to further improve the recognition of its CT signs.Methods:Clinical and CT data of 12 patients with pulmonary tuberculosis who were clinically and pathologically confirmed and accompanied with CT manifestation of "reversed halo sign" in First Affiliated Hospital of Henan University of Science and Technology from August 2013 to April 2020 were analyzed retrospectively. Pathological and imaging contrastl analysis was performed on 1 patient undergoing surgical treatment.Results:Among 12 cases with "reversed halo sign", there were 2 cases with single lesion in unilateral lung, 2 cases with multiple lesions in unilateral lung, and 8 cases with multiple lesions in bilateral lungs. Three cases showed only "reversed halo sign", 9 cases showed both halo-like sign and uniform fireworks sign. "Tree-in-bud "sign was found in all 12 patients in the outer ring of the "reversed halo sign". Eight patients received three or more CT examinations, and six of them showed reduction of density and volume of the "reversed halo sign" after standardized anti-tuberculosis treatment. Under the natural course of the disease in two cases, the overall enlargement of the lesion was observed in 1 case, and the overall density of the lesion was reduced and the outer ring wall of the "reversed halo sign" was thinned in 1 case. The pathology of one case after surgical lobectomy showed granulomatous inflammatory nodules of varying sizes containing Langerhans nodule giant cells in the lung parenchyma. The typical caseous necrotic granulomatous nodules were rare here. The "reversed halo sign" showed dense Langerhans nodules in the outer ring, sparse central areas with fibrous hyperplasia and alveolar wall thickening.Conclusions:The outer ring of "reversed halo sign" of pulmonary tuberculosis shows as "tree-in-bud" sign, and its center shows as the fine reticulation pattern. After effective anti-tuberculosis treatment, both the overall density of "reversed halo sign" and the lesion size reduced. Finally, the lesions mostly present as as fine grid shadows for a long time.

The pandemic of coronavirus disease 2019 (COVID-19) has had a serious impact on global health. COVID-19 vaccines may be one of the most effective measure to end the pandemic. High infection risk and higher serious incident and mortality rates have been shown in cancer patients with COVID-19. Therefore, cancer patients should be the priority group for COVID-19 prevention. Until now, data of COVID-19 vaccination for cancer patients is lacking. We review the interim data of safety and immune-efficacy of COVID-19 vaccination in cancer patients based on the latest studies. Due to the complicated immune systems of cancer patients caused by the malignancy and anticancer treatments, we proposed preliminary specific COVID-19 vaccination recommendations for cancer patients with different anticancer treatments and at different stages of the disease. Preventing COVID-19 with vaccinations for cancer patients is crucial, and we call for more large-scale clinical trials and real-world studies, for further COVID-19 vaccination recommendations development.
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Objective To compare the differences in the intestinal microflora of WHBE rabbit and JW rabbit models of diarrhea-predominant irritable bowel syndrome(IBS). Methods 16 WHBE rabbits and 16 JW rabbits were randomly divided into normal control(NC)group and IBS model group, respectively(n=8). The diarrhea-predominant IBS model was established by wet-heat stress combined with intragastric gavage of senna decoction. The abdominal circumference index,water content of feces and colonic transit function were observed. After sacrifice,colon tissue samples were taken for histopathological examination and colon contents for intestinal flora diversity analysis. Results Compared with the NC group,the IBS model rabbits showed an increased abdominal circumference index and fecal water content,and a shortened colon transit time, but no obvious pathological changes were observed in the colon tissues. Meanwhile, the Shannon index and Chao1 index of IBS model rabbits were significantly decreased(P<0.05). According to the result of OTU classification analysis,Firmicutes and Bacteroidetes are the dominant bacteria in the intestinal microflora of rabbits. Compared with the NC group, the Firmicutes, Verrucomicrobia, Chloroflexi, Akkermansia, and Streptococcus in the WHBE rabbit IBS model group were significantly reduced(P < 0.05, P < 0.01), while Bacteroidetes and rc4-4 significantly increased(P < 0.05, P < 0.01). However, in the JW rabbit IBS model group, Eubacterium and Subdoligranulum were significantly increased(P< 0.05),while Lactobacillus,Coprobacter,Veillonella and Streptococcus were markedly decreased(P<0.05). Compared with the JW rabbit NC group,the abundance of Firmicutes,Odoribacter, Veillonella,Streptococcus,Oscillospira and Pseudoflavonifractor were significantly decreased(P<0.05, P<0.01), but Bacteroidetes,Verrucomicrobia,Eubacterium,Akkermansia and Coprobacter were significantly increased(P<0.05,P<0.01)in the WHBE rabbit NC group. Compared with the JW rabbit IBS model group, the abundance of rc4-4, Bacteroidetes,Coprobacter and Clostridium were significantly higher(P < 0.05, P < 0.01), while the Firmicutes, Dorea, Coprococcus and Subdoligranulum were significantly lower(P <0.05)in the WHBE rabbit IBS model group. Conclusions There is an intestinal microflora imbalance in rabbits with IBS, resulting in a decrease of microflora diversity. The changes of intestinal microflora in the WHBE rabbits and JW rabbits with IBS have their own characteristics, and have apparent differences.

Objective To observe the pathological changes of brain tissues in the WHBE rabbit model of sporadic Alzheimer disease (AD). Methods Thirty 3 -4-month old male WHBE rabbits were randomly divided into 3 groups:normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water ( HCD+ Cu2+) group, 10 in each group. Another 10 senile (36-48-month old) male WHBE rabbits were taken as senile group. The NC group and the senile group were fed a normal basic diet, the HCD group fed a 2% cholesterol diet, and the HCD+Cu2+group fed a 2% cholesterol diet plus 0. 12 PPM copper drinking water for 12 weeks. The levels of total cholesterol (TC) and β-amyloid protein (Aβ) 1-42 were measured at 12 weeks. The activity of superoxide dismutase ( SOD) and the content of malondialdehyde (MDA) in the cortex and the hippocampus were detected. In addition, the covered area of Aβ, β-site APP cleaving enzyme 1(BACE1) and phosphorylated tau (p-tau) protein in coronal sections of brain tissues were also observed by immunohistochemical staining. The senile plaques and the neurofibrillary tangles were observed by Congo red and Bielschowsky staining, respectively. Results The body weight of WHBE rabbits in the senile group was significantly higher than that of the NC group ( P ＜ 0. 01 ), and the plasma TC and Aβ1 -42 in each group were significantly higher than that in the NC group (P ＜ 0.05, P ＜ 0.01). The activity of SOD in brain tissues was significantly lower than that of NC group (P＜ 0. 05), and the MDA content was significantly higher than that of NC group (P＜ 0. 05, P ＜ 0. 01). Immunohistochemical staining showed that the covered area of Aβ, BACE1 and p-tau in brain tissues of all groups were significantly higher than that of NC group (P ＜ 0. 05, P ＜ 0. 01), and the covered area of BACE1 and p-tau protein in the brain tissues of HCD + Cu2+group was also significantly higher than that of the HCD group (P ＜ 0. 05, P ＜ 0. 01). Congo red and Bielschowsky staining showed that the number of senile plaques and neurofibrillary tangles were observed in the brain tissues of the HCD, HCD+Cu2+and senile groups. Conclusions High cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in WHBE rabbit models of sporadic AD with obvious oxidative damage, increased Aβ deposition and senile plaque in the brain, and pathological changes of tau. WHBE rabbit can be used in the study of animal models of neurodegenerative diseases.

Objective To observe the morphological structures of WHBE rabbit brain in vivo based on 3.0 T magnetic resonance imaging system (MRI), accumulate the basic biological data of WHBE rabbit brain imaging, and provide a background information to further expand the WHBE rabbit application.Methods Nine healthy adult male WHBE rabbits were intravenously anesthetized with 3% pentobarbital sodium.3.0 T MRI plus rabbit brain dedicated coil was used to perform routine transverse and sagittal scans, and the size of brain structures were measured.Results MRI scanning can be successfully performed to obtain sagittal and transverse T2WI or T1WI images of WHBE rabbit brain in vivo, and can be clearly observed the basic structures of WHBE rabbit brains in vivo, such as olfactory bulb, cerebrum, cerebellum and pituitary gland.In addition, high signal was found in the hippocampus of the left and right temporal lobes in 4 rabbits with T2WI, but also low signal appeared in the corresponding regions in T1WI, and the others were not abnormal.Meanwhile, the reference data of frontal lobe, hippocampus, cerebrum, lateral ventricles, pituitary gland and other related anatomical structures were also obtained.Conclusions Using the 3.0 T magnetic resonance imaging system and rabbit brain coil,the morphological and anatomical structures of rabbit brain can be clearly observed, and the basic imaging data of WHBE rabbits brain have been established preliminarily.

Objective To investigate precise and regulable animal model of benign bile duct strictures.Methods Mini pigs were divided into four groups as sham surgery group, conventional surgery group, small caliber group and large caliber group according to random number table, with 6 pigs in each group.For the small caliber group, outside diameter 3.0mm catheter were inserted into bile duct and partial sutured.For the large caliber group, outside diameter 6.0mm catheter were inserted into bile duct and partial sutured.Conventional surgery group were treated with 5-0 absorbable suture on distal bile duct and controlled stricture severity visually.For sham surgery group, bile duct were exposed without suture.Observe the general condition of four groups.Test liver function on 1st, 3rd, 7th, 14th, 21st and 28th day postoperative.Perform cholangiography on 30th day postoperative.All four groups were put to death to observe the histological changes of liver and bile duct.Results Liver function of sham surgery group showed no obvious change during observation.On 28th day postoperative, compared to conventional surgery group, the liver enzymes ALT, AST, γ-GT, ALP, bilirubin level of small caliber group elevated(P<0.05)and the liver enzymes ALT, AST, γ-GT, bilirubin level of large caliber group elevated(P<0.05),while ALP level lowered(P<0.05).Cholangiography showed bile duct stenosis of different degree on 6 pigs of small caliber group with average diameter 2.7mm (from 2mm to 4mm).As for large caliber group, 5 pigs showed stenosis with average diameter 5.5mm (from 5mm to 7mm).3 pigs of conventional surgery group showed no obvious bile duct stenosis.The 6 pigs of sham surgery group showed no bile duct stenosis.According to designed stenosis standard, the success rate of small caliber group and large caliber group are both higher than conventional surgery group.(P<0.05).30 days after surgery, all 6 pigs of small caliber group had postoperative intraperitoneal adhesion, hepatomegaly, obvious expansion of intrahepatic bile duct and gallbladder expanded by 4~5 times.5 pigs of large caliber group had hepatomegaly, slight dilation of intrahepatic bile duct, obvious expansion of gallbladder, clear choledochal edema, sutured tissue thickening and visible bile duct stenosis.HE staining with the small caliber group showed hepatocyte spotty degenerative necrosis, expanded cholestatic intrahepatic small bile duct, swelling hepatocyte and fibrous septa.HE staining with the large caliber group showed intrahepatic small bile duct slightly expanded and hepatocyte arranged basically normal.VG staining with the small caliber group showed excessive accumulaton of collagen fibers outside bile duct mucous cells, randomly and densely arranged and irregularly shaped.VG staining with the large caliber group showed increased collagen fibers in bile duct submucosa, densely and banded arranged.Conclusion This animal model of mini pig is an relatively ideal large animal model of biliary stricture with high surgical success rate and few postoperative complications.

Objective:To study the diagnostic value of combined detection of IAA,ICA and GADA in the classification of diabetes mellitus.Methods:30 cases of patients with type 1 diabetes who were treated in our hospital from June 2015 to June 2016 were selected as A group,60 cases of patients with type 2 diabetes were selected as B group,50 cases of healthy people were selected as C group.The IAA,ICA and GADA of the three groups were detected by ELISA,and the positive rate of the three groups were compared.Results:The fasting glucose of A group was (10.12± 3.68) mmol/L,B group was (11.23± 3.26) mmol/L,A group and B group were significantly higher than that of C group (P＜0.05),but there was no significant difference between A group and B group (P＞0.05);the positive rates of GADA,ICA and IAA in A group and B group were significantly higher than those in C group (P＜0.05),and the positive rates of GADA,ICA and IAA in A group were significantly higher than those in B group (P＜0.05);the sensitivity and specificity of combined detection of IAA,ICA and GADA in type 2 and type 1 diabetes mellitus were significantly higher than that in the single test (P＜0.05).Conclusions:The combined detection of IAA,ICA and GADA has a high diagnostic value in the classification of diabetes mellitus,which is worth clinical application.

Objective To establish a rabbit model of facial skin lifting and to evaluate the skin lifting effects of absorbable soft tissue plastic belt, and to provide experimental basis for clinical application of this plastic belt.Methods 36 Japanese white rabbits were randomly divided into model control group (n=6) and plastic belt lifting group (n=30). The model control group received only facial skin resection surgery, while the plastic belt lifting group had facial skin resection and plastic belt implantation.The changes of rabbit general status, skin lifting effects, performance of plastic belt and pathological changes of subcutaneous tissue after implantation were determined during the 4 weeks after surgery. Results The rabbit skin wound was healed within 3-7 days after surgery without infection.Meanwhile, the plastic belts did not show shifting or rupture, and only whitening around the perforations was observed in the two groups.Compared with the model control group, the MA and MB distances in the plastic belt lifting group were significantly lower ( P<0.01 ) , while the biological tension of plastic belts in the facial skin lifting rabbit models was significantly increased with the extension of time after implantation (P<0.01), and the biological tension was 18.62 N at 4 weeks after transplantation. In addition, the tensile intensities of perforations and plate in the two groups were significantly reduced at 4 weeks postoperatively (P<0.01), the tensile intensity of perforations and plate in the two groups were maintained at 35.07 N and 53.31 N, respectively, and the perforations/plate tensile intensity ratio of the two groups remained unchanged during 4 weeks after transplantation ( P >0.05 ) .Moreover, the molecular weight ( Mw ) , peak molecular weight ( Mp ) , Z molecular weight (Mz) and viscosity were gradually decreased along with the time passing after implantation (P<0.01), and its dispersion Mz/Mw ratio was also gradually decreased from 2 weeks after implantation (P<0.01), and no obvious pathological changes were found after subcutaneous implantation of the plastic belts.Conclusions We have successfully established a facial skin lifting rabbit model, and the plastic belt can obviously lift the facial skin fascia system and keep intact more than 4 weeks in the body.Therefore, this plastic belt can be applied for anti-wrinkle facial soft tissue lifting against the skin damage caused by aging.