BACKGROUND: Recently,liver transplantation technique has been developed rapidly,and prevention of ischemia/reperfusion injury and protection of liver regeneration have become a research focus.Ischemic preconditioning(IPC)is an effective method for protecting liver ischemic injury.However,the mechanism remains controversial.OBJECTIVE: To investigate the mechanism of IPC on hepatic injury and regeneration after reduced-size rat liver transplantation.METHODS: Animals were randomly divided into 3 groups.Rat reduced-size liver transplantation model was established in liver transplantation group.IPC+liver transplantation group underwent first porta hepatis blocking for 10 minutes before liver graft reperfusion,followed by reperfusion for 15 minutes.The ligament around the liver was dissociated in the sham-surgery group.The samples were collected 0.5,2,6 and 24 hours post-operation.The hepatic injury was examined by the serum alanine aminotransferase(ALT)and hepatic tissue histopathology analysis of grafts.Semi-quantitative immunohistochemistry and westernblotting were used to examine the redox factor-1(Ref-1)protein expression.The hepatic regeneration of the grafts was examined by the expression of proliferating cell nuclear antigen(PCNA)in hepatic cells.RESULTS AND CONCLUSION: Compared with liver transplantation group,the ALT values at 6 and 24 hours after operation in IPC group decreased significantly(P < 0.05; P < 0.01).Pathological analysis indicated that there were lots of inflammation cells around the portal veins,the serious sinus hepaticus dilation and damage of hepatic tissue in liver transplantation group.However,the tissue injury observed in IPC group was comparatively slight.Semi-quantitative immunohistochemistry revealed that Ref-1 protein was more abundant in IPC grafts tissue compared to liver transplantation group.These observations were supported by westernblotting studies where Ref-1 protein was shown to be over-expressed in IPC specimens at 24 hours after reduced-size liver transplantation(P < 0.05).In addition,the number of PCNA-positive cells in IPC group was more than liver transplantation group at 2,6 and 24 hours after operation(P < 0.05).IPC improves hepatic regeneration and relieves grafts injury in earlier period after reduced-size rat liver transplantation,which is associated with the over-expression of Ref-1protein.

Objective To investigate the clinical feature,diagnosis and therapy of isolated Langerhans cell histiocytosis(histiocytosis X) with unusual localization.Methods A case of isolated Langerhans cell histiocytosis of the infundibulum was reported.The endocrinic tests,imaging,immunohistochemical and pathological examinations of this case were detected.Through literature review,the pathological and clinical feature,diagnosis,therapy of isolated Langerhans cell histiocytosis of the infundibulum were overviewed.Results Magnetic resonance imaging(MRI) of the brain showed a 9 mm homogeneously enhancing mass in the region of the infundibulum.No other lesion was found in other organ systems.The patient underwent an occupying lesion resection of the infundibulum via right pterion approach.Langerhans cell histiocytosis was diagnosed through pathologic analysis.She was on hormone replacement therapy and close follow-up visit postoperatively.Conclusion Isolated Langerhans cell histiocytosis of the infundibulum in adult is extremely rare.Understanding of this disease should be improved to avert misdiagnosing.

Objective To investigate the potential effect of glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) on immune function of T lymphocytes via neuroendocrine modulation mechanism in mice following severe burns.Methods Male BALB/C mice were randomly (ramdam number) divided into thermal injury group (n =50) and sham-thermal group (n =30).The thermal injury model was made by exposing the back skin of 15％ total body surface area (TBSA) to 95 ℃ water for 7 seconds,while in sham-thermal model the mice were immersed in 37 ℃ water instead.The expression of GLP-1 receptor (GLP-1 R) was determined in sorted CM + T cells from normal mice by immunofluorescence method.In ex vivo experiment,the mice were sacrificed at 24 h post-bum,then the mononuclear cells (MNC) from spleen were separated from both groups and cultured in RMPI 1640 with 10％ FCS (fetal calf serum) in presence of ConA (concanavalin A,5 μg/mL).Cells were pretreated with catecholamine receptor antagonist propranolol (prop) for 1 hour,followed by consecutive dose of Ex-4 for another 48 h.In in vivo experiment,prop (30 mg/kg) was i.p.injected 30 minutes before thermal injury,then Ex-4 (2.4 nmol/kg) was injected i.p.immediately after scalding.Mice were sacrificed at 6 h and 24 h after thermal injury,then the serum and the spleens were collected.Results GLP-1R was expressed on splenic CD4 + T cells from normal micc.Ex-4 exerted no marked effect on the functions of T cells in terms of proliferation and IL-2 secretion at all doses examined ex vivo,which was not affected by pretreatment with prop.In vivo,T cell functions were suppressed by Ex-4 in thermal mice (P ＜ 0.05),but was restored by pretreatment with prop.Regardless of ex vivo or in vivo,Ex-4 could induce T cells switched to Th2 response (P ＜ 0.05).Moreover,the Th2 switch by Ex-4 was greatly potentiated by prop intervention in thermal mice in vivo other than ex vivo.Norepinephrine level was increased and epinephrine was decreased by Ex-4 in thermal mice.Both norepinephrine and epinephrine levels were obviously enhanced by pretreatment with prop.Conclusions Ex-4 can inhibit the proliferation and IL-2 secretion of splenic T lymphocytes through the sympathetic nervous system,however,it might induce Th2 switch from Th cells by acting directly on GLP-1R.

Objective To investigate the metabolic profile of uric acid and the significance of the altered renal expression of urate trans-porter 1(URAT1) in patients with uric acid nephrolithiasis. Methods The data of 24 patients in our hospital from January 2012 to October 2013 were analyzed retrospectively. Participants in the research were divided into three groups:patients with uric acid nephrolithiasis,other patients with nephrolithiasis and normal participants. The basic clinical data and the related data of uric acid metabolition of participants were collected,URAT1 gene expression in renal tissures of three groups was detected by Real-time PCR technique. All data were statistically ana-lyzed and compared between these groups. Results Uric acid levels in plasma,body mass index and age were significantly higher in patients with uric acid nephrolithiasis than other two groups (P<0. 05),but urine PH value was significantly reduced in patients with uric acid neph-rolithiasis. Urine and uric acid output of 24 hours urine were no significant difference among the three groups (P>0. 05). The result of Real-time PCR suggested that the URAT1 renal expression was significantly higher in patients with uric acid nephrolithiasis than other two groups (P<0. 05). Conculusion Patients with uric acid nephrolithiasis are closely related with hyperuricemia,but unrelated with renal over-ex-cretion of uric acid. The upregulated URAT1 expression in the kidney may be an important molecular mechanism of the clinical features.

Objective To evaluate the curative effect of polyscope modular flexible ureteroscope combined with Holmium laser lithotrip-sy in the treatment of renal calculi. Methods 53 patients with renal calculi were performed CTU to detect the position of renal calculi before operation. The patients were treated with polyscope modular flexible ureteroscope combined with Holmium laser, and the double J tube were routinely indwelled 4 to 12 weeks after surgery. Results All the 52 patients has successfully completed the operation in the frist stage. The mean operative time was about 38 minutes. 6 patients were treated with flexible ureteroscope for second stage operation. One week after oper-ation, the review showed that there were residual calculi existed in 24 cases and there were 56 cases of post-operative infection, including 17 cases of sepsis or sepsis shock. Conclusion Polyscope modular flexible ureteroscope can be used for all kinds of kidney stones surgery and is characterized by safety and mild tissue injury. But we should pay more attention to the post-operative infection especially urosepsis.

The guanine-nucleotide exchange factor (GEF) RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thus regulating various downstream cellular processes. RalGPS1a is composed of an Nterminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal pleckstrin homology (PH) domain. The Cdc25 domain of RalGPS1a, which shares about 30% sequence identity with other Cdc25-domain proteins, is thought to be directly engaged in binding and activating the substrate Ral protein. Here we report the crystal structure of the Cdc25 domain of RalGPS1a. The bowl shaped structure is homologous to the Cdc25 domains of SOS and RasGRF1. The most remarkable difference between these three Cdc25 domains lies in their active sites, referred to as the helical hairpin region. Consistent with previous enzymological studies, the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding. A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras complex. However, analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.
Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Cloning, Molecular ; Crystallography, X-Ray ; Escherichia coli ; Guanosine Diphosphate ; metabolism ; Guanosine Triphosphate ; metabolism ; Humans ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; Plasmids ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; genetics ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; ral GTP-Binding Proteins ; chemistry ; genetics ; metabolism ; ral Guanine Nucleotide Exchange Factor ; chemistry ; genetics ; metabolism

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of TNF-α was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.
Animals ; Collagen ; Constriction ; Fibrosis* ; Gene Expression ; Heart ; Histone Deacetylases ; Hypertrophy ; Injections, Intraperitoneal ; Melatonin* ; Myocytes, Cardiac ; Rats* ; Smad4 Protein

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Corona Virus Disease 2019 (Corona Virus Disease 2019,COVID-19) has become a public health emergency that has attracted global attention because of its large-scale outbreak resulting in numerous human infections and deaths. COVID-19 is a highly contagious respiratory disease caused by novel coronavirus 2019-nCoV. Due to a large number of infections and fast transmission speed, it's significant to diagnose the infected people quickly and detect the asymptomatic infected people as soon as possible. At present, the preliminary screening is judged by the clinical manifestations of the patients, mainly involving the respiratory system, but recent studies have found that the patients infected with COVID-19 have unique oral manifestations, such as taste disturbance, xerostomia, halitosis, inflammation of salivary glands, necrotizing periodontal disease and some of them are earlier than typical symptoms such as dry cough, fever, etc. Paying attention to the oral manifestations of patients can further improve the COVID-19 screening procedure. At present, symptomatic treatment is mainly used for these oral symptoms.