Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.

ObjectiveTo explore the application value of probe-based confocal laser endomicroscopy (pCLE) in rapidly detecting and evaluating the morphological characteristics of digestive tract tissues in mice. MethodsTwelve male SPF Kunming mice aged 6 weeks were randomly divided into two groups. Six mice were subjected to gastric gavage with 52% Red Star Erguotou to establish the model, and six were given saline by gastric gavage as a control. After 28 days of modeling, 3 mice were randomly selected from each group. After deep anesthesia induced by inhalation of 3% isoflurane, the mice were sacrificed by cervical dislocation. The stomach, duodenum, jejunum, and rectum tissues were excised and immersed in 1% fluorescein sodium solution for staining. The microstructure of the mucosal surface of each tissue was observed using pCLE. The remaining mice in the model group and the control group were deeply anesthetized by inhaling 3% isoflurane, then cardiac perfusion was performed successively with saline and 4% paraformaldehyde. The stomach, duodenum, jejunum, and rectum tissues were excised for dehydration, section and hematoxylin-eosin (HE) staining, and the morphological changes of the tissues were observed under a microscope. ResultsUnder pCLE imaging, fluorescence staining on the surface of the gastrointestinal mucosa was uniform in the control group; the morphology of gastric pits, intestinal villi, and intestinal crypts was intact, arranged compactly, and had distinct boundaries. In the model group, the gastrointestinal mucosa exhibited mucosal swelling and deformation, with uneven fluorescence staining and fluorescein leakage. Furthermore, some tissues showed defects or cell shedding, and the boundaries between adjacent characteristic structures (e.g., gastric pits, intestinal crypts) were blurred. HE staining showed that the gastrointestinal tissue structure of the control group mice was normal and well-organized, with no structural defects. Moreover, submucosal glands were uniform in size, with no hyperplasia observed, and no obvious inflammatory cell infiltration. In the model group, some gastrointestinal mucosal structures were defective and sparsely arranged; submucosal glands showed atrophy, accompanied by obvious inflammatory cell infiltration. The histological characteristics detected by pCLE were consistent with those of HE staining. ConclusionpCLE can be used to obtain rapid, real-time, large-scale, and high-resolution microscopic imaging of the gastrointestinal mucosa, realistically and comprehensively displaying its physiological and microstructural characteristics. It shows promising prospects and practical utility in the histological evaluation of digestive system injuries in small animals.

This study aims to analyze the main drug resistance mechanism of Salmonella enteritidis induced by polymyxin in vitro.In this study,the resistance of Salmonella enteritidis CMCC(B)50335(ZK)to polymyxin was induced in vitro,and the growth characteristics,exercise ability,ul-trastructure and sensitivity to 16 antimicrobial agents before and after induction were determined by turbidimetry,semi-solid agar method,transmission electron microscope and disk diffusion method,and the whole genome and single nucleotide polymorphism(SNP)were detected by Illu-mina NovaSeq PE150 method.RT-qPCR was used to detect the differences in the expression levels of six drug-resistant related genes.The recombinant strain △phoPE1-128-1,which induced drug-resistant strain E1-128-1,was constructed by homologous recombination of Red Escherichia coli,and its sensitivity to polymyxin was detected.The results showed that three strains of induced drug-resistant bacteria E1-128-1,E1-128-3 and E2-128-3 were screened out,and the MIC increased by 128,64 and 64 times respectively after drug resistance stability test.Induced drug resistance had no significant effect on the growth ability of the tested bacteria and the sensitivity of 16 antibacte-rial drugs.The exercise ability of E1-128-1was significantly increased,and the cell wall and plasma membrane obviously thicken.There was no significant difference in the genome components of E1-128-1 before and after induction,but eight missense mutations of six drug-resistance related genes,including phoP/phoQ,cpxP,lptD,csrA and acrB,were detected,including four missense mutation sites of phoP,namely Leu185Trp,His189Ser,Thr190Tyr and Ile191His.The corresponding genes were sequenced by PCR,and the results were consistent with those of SNP.RT-qPCR results showed that the expression levels of mutant genes of the three induced strains increased signifi-cantly.Compared with E1-128-1,the MIC of △phoP E1-128-1 decreased to 1 mg/L.It is sug-gested that the mutation and increased expression of phoP gene are important factors for inducing polymyxin resistance of Salmonella CMCC(B)50335 in vitro.

This report described one case of applying liver transplantation (LT) in for liver metastases of unresectable rectal cancer.The recipient had multiple intrahepatic metastases upon a diagnosis of colorectal cancer.FOLFOX chemotherapy plus bevacizumab targeted therapy were offered after a resection of primary lesion.Two years later, intrahepatic metastases expanded while no extrahepatic metastasis or in situ recurrence was noted.After LT, tacrolimus + sirolimus immunosuppression regimen and chemotherapy of rhatitrexed were prescribed.Tumor recurred at 3 years after LT and the survival time was 6 years.For patients with unresectable liver metastases of colorectal cancer, LT in the absence of orthotopic recurrence and other distant metastases may improve patient quality-of-life and achieve better outcomes.

Objective:To apply multiple mandibular anatomical landmark points to establish the mandibular median sagittal plane to find and establish the ideal median sagittal plane of the mandible that is suitable for clinical diagnosis and treatment.Methods:The maxillofacial spiral CT data of 30 normal maxillofacial patients in the Western Theater General Hospital were collected, and the 3D cranial model was reconstructed by using Mimics Research 21.0 software to select different anatomical landmarks to establish multiple mandibular MSPs, and with the whole cranial MSP as a reference, the different MSPs were respectively used as the mirror planes to establish a mirror model. The overlap of the original model and the mirror model were compared qualitatively and quantitatively by the overlap three-dimensional color illustration of 3-Matic software and Friedman′s test, respectively, to evaluate the application effect of different planes as mandibular MSPs.Results:There was a statistically significant degree of overlap between the mandibular mirror model and the original model with the whole head MSP and the different mandibular MSPs as mirror planes, respectively (χ 2=12.34, P<0.05). The mirror model of plane Mf-Go-Sim had the smallest overlap with the original model 0.07 (0.04, 0.18) mm; plane N-ANS-PNS was the second smallest 0.14 (0.09, 0.58) mm; the difference in overlap of plane ANS-SBWG-Mp 0.12 (0.04, 0.40) mm; the difference in overlap of plane Me-B-Sim 0.19 (0.09, 0.44) mm; the difference in overlap of plane Po-B-Go 0.18 (0.06, 0.45) mm. Conclusions:Whole-head MSP cannot completely replace mandibular MSP; plane Mf-Go-Sim can be the ideal MSP for the mandible in clinical applications.

Objective To study the effect of the reinforcing and reducing method of acupuncture reported in first Chapter the Nine Needles and Twelve Yuan of the Miraculous Pivot on interstitial fluid pressure (IFP) in subcutaneous tissue of minipig, and to investigate its biomechanical mechanism of regulating the interstitial fluid. Methods Nine healthy minipigs were randomly selected for reinforcing method (pull or press) and reducing method (wave a big pinhole), and tested on soft skin tissues of the abdomen. The IFP in the normal state (NS), the low volume (LV) state (by extracting interstitial fluid) and the high volume (HV) state (by injecting saline solution) was measured before and after acupuncture. Results In the normal state, pulling and pressing the needle could obviously increase IFP, while reducing method could significantly decrease IFP, leading to a rapid decrease in 5 min after acupuncture. In the LV state, pulling and pressing the needle could increase IFP. However, in 10 min after acupuncture, the descend rates of IFP were relatively slower. In the HV state, the reducing method could significantly decrease IFP, and the changing trend in 5 min after acupuncture was different from that of the control group. Conclusions The reinforcing and reducing method of acupuncture could increase or decrease IFP, which proved that the acupuncture method could regulate IFP in the opposite direction. The research findings provide a new scientific basis for using reinforcing and reducing method of acupuncture in clinic.

Objective:To investigate the recurrence and influencing factors of diabetic foot ulcer in patients with type 2 diabetes mellitus.Methods:Totally 185 type 2 diabetes patients with new-onset of diabetic foot ulcers admitted to Fuyang People′s Hospital of Anhui Province from January 2011 to December 2015 were enrolled in this study, including 120 males and 65 females, aged 40-79 years. All the patients were followed up for 3 years, and their clinical data were retrospectively analyzed by the case-control study. The Kaplan-Meier cumulative recurrence curve was drawn according to the 3-year cumulative recurrence rate of diabetic foot ulcers. The time to visit, toe involvement, and amputation of involved toes in patients with recurrent diabetic foot ulcer were counted at the initial onset and the recurrence of the ulcers, respectively, and the data were statistically analyzed with t test and chi-square test. According to the recurrence of diabetic foot ulcers, the patients were divided into foot ulcer recurrence group and foot ulcer non-recurrence group. The gender, age, course of diabetes mellitus, length of hospital stay, visit time, body mass index, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, hemoglobin, white blood cell count, toe involvement, toe amputation, ankle-brachial index, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), history of hypertension, cardio-cerebrovascular disease, smoking, residence, solitary life, and walking disorder of patients between the two groups were compared, and the data were statistically analyzed with t test and chi-square test. Log-rank test was performed on the indexes with P<0.1 in comparison between two groups, and the indexes with statistically significant differences in Log-rank test were analyzed by multivariate Cox regression analysis to screen the influencing factors of recurrence of diabetic foot ulcer. Results:(1) The 3-year cumulative recurrence rate of diabetic foot ulcers in 185 patients with type 2 diabetes mellitus was 47.0% (87/185). (2) For 87 patients with diabetic foot ulcer recurrence, compared with that at the initial onset of the ulcers, the visit time was significantly shorter ( t=10.593, P<0.01), the toe amputation rate was significantly increased ( χ2=5.118, P<0.05), but there was no obvious change in toe involvement at the recurrence of the ulcers. (3) There were statistically significant differences in age, course of diabetes mellitus, length of hospital stay, body mass index, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, cholesterol, LDL, HDL, hemoglobin, white blood cell count, gender, toe amputation, ankle-brachial index, DR, history of cardio-cerebrovascular disease, solitary life, and walking disorder of patients between foot ulcer recurrence group (87 patients) and foot ulcer non-recurrence group (98 patients) ( t=5.123, 4.242, 5.324, -24.572, 6.102, -1.984, -9.747, 3.226, 3.076, 3.646, -4.683, -7.502, 8.095, χ2=5.621, 18.433, 4.546, 5.785, 9.655, 7.625, 7.886, P<0.05 or P<0.01), while the rest of the indexes of patients between the two groups were similar. Log-rank test showed that the two groups had statistically significant differences in age, course of diabetes mellitus, length of hospital stay, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, ankle-brachial index, DPN, and walking disorder ( χ2=210.046, 44.837, 34.107, 98.685, 66.532, 294.451, 260.554, 5.012, 6.818, 11.160, P<0.05 or P<0.01). Age, total bilirubin, albumin, DPN, and walking disorder were the influencing factors for the recurrence of diabetic foot ulcers in patients with type 2 diabetes mellitus (hazard ratio=1.024, 0.678, 0.849, 2.335, 4.099, 95% confidence interval=1.001-1.047, 0.558-0.823, 0.797-0.904, 1.280-4.258, 2.044-8.223, P<0.05 or P<0.01). Conclusions:The 3-year cumulative recurrence rate of diabetic foot ulcers in patients with type 2 diabetes mellitus is relatively high, with the influencing factors being age, total bilirubin, albumin, DPN, and walking disorder.

Objective To investigate the effect of atorvastatin on blood lipid and carotid atherosclerosis in patients with hyperlipidemia and cerebral infarction.Methods 98 patients with hyperlipidemia and cerebral in-farction in our hospital from September 2014 to February 2017 were selected and divided into observation group(49 cases)and control group(49 cases)according to the random number table method.The control group was treated with conventional treatment,the observation group was treated with atorvastatin on the ba-sis of the control group.The two groups were treated for 4 weeks.The ADL score,NIHSS score,blood lipid index,carotid IM T and carotid plaque area were compared between the two groups before and after treatment. Results ADL score of the patients in the observation group after treatment higher was than the control group (t=12.7783,P<0.05),NIHSS score was lower than the control group(t=10.941,P<0.05);LDL-C,TC and TG levels after treatment in the observation group were than in the control group(t= 17.239,9.216, 9.800,P<0.05),while the HDL-C level was higher than the control group(t=7.683.P<0.05);the patients in the observation group were treated by carotid artery IM T and carotid plaque area was higher than that of the control group(t=8.919,6.344,P<0.05).Conclusion Atorvastatin can improve hyperlipidemia in pa-tients with cerebral infarction and carotid atherosclerosis,dyslipidemia,has the important research signifi-cance.

Objective To explore the feasibility of needle-embedding therapy in the treatment of chronic myocardial ischemia using a miniature pig model established by placement of an Ameroid constrictor at the left anterior descending branch (LAD) of coronary artery in Bama miniature pigs during surgery. Methods The miniature pig model of chronic myocardial ischemia was established by placement of an Ameroid constrictor at the left anterior descending branch of the left coronary artery in Bama miniature pigs. The pig models were randomly divided into the treatment group (the"Neiguan " group) and the control group (the "Zusanli " group), and were treated with needle- embedding electroacupuncture at the"Neiguan" (PC6) and "Zusanli" (ST36) acupoints, respectively. Myocardial samples were taken at 6 weeks after surgery for light and electron microscopic examinations. Results Gross pathology showed that ischemic area in the myocardium appeared in both experimental groups. The ischemic area in the "Zusanli "group was larger than that of the"Neiguan"group. Histopathology showed that the acupuncture treatment at the"Neiguan"acupoint reduced the ischemic injury in the pig myocardial tissues. Ultrastructural observation of the myocardium showed mitochondrial vacuolization in cardiomyocytes and myocardial fibrosis in both groups. Conclusions Acupuncture therapy at the"Neiguan"acupoint of pericardial channel may exert protective effect on the myocardial ischemia by reducing the ischemia-injury of cardiomyocytes, but can not inhibit the already existed ischemia-induced cardiomyocytic injuries. Our findings suggest that the establishment of miniature pig model of chronic myocardial ischemia by surgically placing an Ameroid constrictor on the left anterior descending branch of left coronary artery and the needle-embedding in acupoints is feasible for the treatment of chronic myocardial ischemia in this pig model.

Objective To analyze the efficacy and safety of CyberKnife combined with temozolomide (TMZ) in treatment of brain metastasis of non-small cell lung cancer (NSCLC). Methods From March 2013 to March 2016, 62 NSCLC patients with brain metastases in department of oncology of the 187th Hospital of PLA were divided into two groups according to the random number table method, the CyberKnife combined with TMZ group (CyberKnife + TMZ group, 31 cases) and simple CyberKnife group (CyberKnife group, 31 cases). Hypofractionated radiation of CyberKnife was given 18-36 Gy in 1-5 fractions of 5-25 Gy. CyberKnife+ TMZ group was given temozolomide 150 mg·m-2·d-1 for 5 days in first cycle, then every 28 days they received temozolomide therapy from the second to the sixth cycles: 200 mg·m-2·d-1 for 5 days. The clinical symptom remission rate after the treatment of CyberKnife in one week, the effective rate after CyberKnife in 3 months, the median intracranial progression-free survival time, overall survival, and the incidences of adverse reaction were comparatively analyzed. Results The clinical symptom remission rates of CyberKnife+TMZ group and CyberKnife group after the treatment of CyberKnife in one week were 93.6 ％ (29/31) and 96.8 ％ (30/31). There was no significant difference in the clinical symptom remission rates (χ2= 1.207, P=0.547). The effective rates of the two groups after CyberKnife in 3 months were 93.6 ％ (29/31) and 90.3 ％(28/31). There was no significant difference in the effective rates (χ2 = 0.695, P= 0.706). The median intracranial progression-free survival time in CyberKnife + TMZ group (14.0 months) was significantly higher than that in the CyberKnife group (9 months) (χ2=8.977, P=0.003), and the median overall survival time in CyberKnife + TMZ group (15.0 months) was also significantly higher than that in the CyberKnife group (12.0 months) (χ2 = 5.190, P= 0.023). There was no significant difference in the adverse reaction of the central nervous system between the two groups (χ2=0.746, P=0.689), but the adverse reactions of the digestive system (χ2 = 6.062, P= 0.014) and the hematologic system (χ2 = 6.613, P= 0.010) in CyberKnife + TMZ group were significantly higher than those in the CyberKnife group. Systemic adverse reactions of the two groups were tolerated by most patients. Conclusions CyberKnife combined with TMZ is a feasible therapeutic option for NSCLC patients with brain metastases. This therapy can improve the median survival time to cerebral progression of the disease and the median overall survival time.