[The diagnostic value of genetic testing in familial hypercholesterolemia in patients with premature myocardial infarction].

Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.

[Respiratory virus infection and its influence on outcome in children with septic shock].

Objective: To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes. Methods: The clinical data of children with septic shock in children's PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results: A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs (OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions: The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

[Clinicopathological features of polymorphous low-grade neuroepithelial tumor of the young].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: Two cases of PLNTY diagnosed during January 2016 to December 2019 were collected from Ningbo Diagnostic Pathology Center, Zhejiang, China. The clinical features, histopathological characteristics, immunohistochemical and molecular genetic findings were analyzed and the relevant literature was reviewed. Results: The two patients were both female, at the ages of 14 and 25 years, respectively. Both patients presented with seizure attacks. The imaging study showed a mixed signal in the cerebral cortex, located in the occipital and temporal lobes, respectively. Microscopically, the tumors were characterized by the invariable presence of oligodendroglioma-like appearance, often with calcification. Immunohistochemically, the tumors were diffusely and intensely CD34 positive with ramified, CD34-expressing neural elements in regional cortex. The tumors were positive for GFAP, Olig2 and ATRX, and negative for IDH1, Neu N, nestin and EMA. The Ki-67 labeling index was less than 2%. The case number 2 harbored the BRAF V600E mutation, while the case number 1 was negative for both the BRAF V600E mutation and 1p/19q codeletion. Both patients recovered very well and were free of seizures after the following-up of 2 and 24 months, respectively. Conclusions: PLNTY is an uncommon neuroepithelial tumor. Histopathologic and immunohistochemical examinations are necessary for establishing the diagnosis and for excluding oligodendroglioma. PLNTY should be considered as a benign tumor corresponding to WHO Grade I. The prognosis is overall good after complete tumor-resection.

[Pleural effusion as the first manifestation of pleural isolated myeloid sarcoma: a case report and literature review].

Objective: To analyze the clinic features of isolated myeloid sarcoma (IMS) involving the pleural cavity. Methods: A case of pleural isolated myeloid sarcoma (PIMS) with pleural effusion as the first manifestation was described. The related cases in literatures were reviewed with"myeloid sarcoma"and"pleural effusions"as the keywords to search China HowNet, Wanfang database and PubMed database. Results: A 59-year-old man complained of right chest pain for 2 months and worsening pain with distress and shortness of breath for 2 weeks. The chest CT scan showed pleural effusion on the right side. Flow cytometric analysis of pleural fluid showed that a population of blasts with CD34 expressing was 37.6% of the total nucleated cells. The pleural biopsy through medical thoracoscopy indicated lymphoproliferative lesions by pathological examination. Immunohistochemistry was performed on pleural histological sections and cell blocks of pleural effusions, which showed CD34 and CD117 positive expression. The diagnosis of PIMS was finally made. Two literature papers with 2 complete cases were found and reviewed. The 3 cases were analyzed. There were 2 males and 1 female. The age was 59, 51, 56 years respectively. One case was a patient with 3 weeks of right upper quadrant and epigastric pain, nausea, and weight loss. Cytological examination of the pleural fluid showed numerous poorly differentiated malignant cells. Histology from an open laparotomy in duodenal biopsies, gallbladder, and mesenteric lymph nodes supported the diagnosis of IMS. The other case was a patient with 6 weeks of dyspnea and a large swelling in the upper vestibular region. Thoracentesis showed 82% myeloid blasts in the pleural fluid. A gingival biopsy showed a diffuse infiltration by cells with a blastic appearance and supported IMS. Conclusion: PIMS was a very rare cause of pleural effusions. The cytological and histopathological evidences were useful to diagnose IMS involving the pleural cavity.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge.

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/ß-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/ß-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

[Outcomes of severe primary fetal hydrothorax treated by prenatal intervention].

Objective: To investigate the effect of intrauterine intervention on severe primary fetal hydrothorax. Methods: Twelve cases with severe fetal primary hydrothorax who underwent prenatal intervention from January 2014 to December 2017 in Guangdong Women and Children Hospital were retrospectively reviewed. Results: The median gestational age of prenatal diagnosis was 30.8 weeks (24.0-33.0 weeks) . All cases were excluded congenital chromosomal abnormalities by prenatal diagnosis, and had no complications of pregnancy during prenatal diagnosis and had hydrothorax. Three cases (3/12) were right hydrothorax, the other 9 cases (9/12) were bilateral. Thoracoamniotic shunting was performed in 7 cases (7/12) . Thoracentesis was performed in 5 cases (5/12) , and the hydrothorax reappeared soon after operation in 4 cases, shunt placement was performed again. The hydrothorax was dissolved in 2 cases, released in 6 cases.Tube falling off occurred in 1 case,treatment was abandoned in 1 case and intrauterine fetal death happened in 1 case, and 1 case wasn't rechecked by ultrasonic due to premature birth following thoracentesis. In 10 cases who had deliveries, 5 newborns (5/10) were premature, 6 newborns (6/10) underwent assisted mechanical ventilation, 8 newborns (8/10) underwent thoracic close drainage, all of them were discharged when hydrothorax resolved. Conclusions: Antenatal intervention may improve the chance of survival in severe primary fetal hydrothorax. Thoracoamniotic shunting is the first-choice for the primary severe fetal hydrothorax.

Drug-loaded nanobubbles for ultrasound-mediated antitumor treatment.

Polylactic acid (PLA) bubbles that can act both as ultrasound contrast agents and drug carriers have the disadvantage of low encapsulation efficiency and do not allow effective extravasation into the tumor tissue. In this regard, PLA and lecithin are considered drug carriers. The present study used a modified ultrasonic double emulsion-solvent evaporation technology in order to prepare paclitaxel-loaded PLA-lecithin nanobubbles. X-ray diffraction analysis (XRD) was used to investigate the state of the drug in the bubbles, whereas the tumor weight and the inhibition rate of tumor bearing mice in the ultrasound-mediated function were further examined. The results indicated that the nanobubbles prepared with a mass ratio of PLA and lecithin at 50:250 were characterized as inner hollow. The size of these particles was approximately 615 nm, and the drug loading and encapsulation reached 8.34±0.67% and 91.42±5.48%, respectively. Paclitaxel was distributed in the shell of the bubbles in an amorphous state, and the in vitro drug release was characterized by sustained release, zero release and ultrasound mediated drug release. The injection of H22 hematoma-bearing mice with ultrasound-mediated drug-loaded PLA-lecithin nano-scaled bubbles could reduce the toxicity and increase the antitumor efficacy compared with paclitaxel.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

[Clinical characteristics of new-onset organ dysfunction in pediatric intensive care unit].

Objective: To investigate the incidence and clinical characteristics of new-onset organ dysfunction of patients in pediatric intensive care unit (PICU). Method: A retrospective observational study identified all patients admitted to the PICU of Shengjing Hospital Affiliated to China Medical University from January 2015 to January 2016. The functional status score (FSS) was evaluated at admission and hospital discharge respectively, and the difference defined as ΔFSS between the FSS at hospital discharge and the FSS at admission was calculated. According to the initial FSS, the patients were divided into normal group (6-7 scores), mildly abnormal group (8-9 scores), moderate abnormal group (10-15 scores), severe abnormal group (16-21 scores) and extreme severe abnormal group (22-30 scores). According to the primary disease, all cases were divided into cardiovascular disease group, urinary disease group, surgery group, digestive disease group, neurological disease group, respiratory disease group, hematological disease group, poisoning group and other group. According to the FSS domain, all cases were divided into mental status group, sensory group, communication group, motor group, feeding group, respiratory group. The incidence of new-onset organ dysfunction, the case fatality rate and the FSS of each group were calculated. Comparisons were performed using a chi-square test, t test and analysis of variance. Result: The study population included 928 patients (561(60.5%) male, mean age (31.1±1.3) months). The incidence of new-onset organ dysfunction was 8.8%(82/928) and the case fatality rate was 1.3%(12/928). The FSS at hospital discharge(scores), ΔFSS (scores) and the incidence of new-onset organ dysfunction were significantly less in patients in the normal group (6.38±0.17, -0.20±0.17 and 1.3%(3/229), respectively) compared to patients in the mildly abnormal group (7.09±0.27, -1.39±0.27 and 7.2%(12/170), respectively, t=2.36, 3.93, χ(2)=7.39, all P<0.05), patients in the moderately abnormal group (8.86±0.28, -2.76±0.28 and 10.6%(38/359), t=6.56, 6.91, χ(2)=17.14, all P<0.05), patients in the severely abnormal group(13.56±0.88, -4.39±0.88 and 24.6%(19/79), t=12.29, 7.13, χ(2)=42.43, all P<0.05) and patients in the extreme severely abnormal group(18.68±0.99, -6.59±0.91 and 10.9%(10/91), t=18.15, 10.10, χ(2)=13.27, all P<0.05). Significant difference was found regarding the incidence of new-onset organ dysfunction among patients in cardiovascular disease group (27.3%, 24/88), surgery group (9.2%, 6/65), digestive disease group (8.2%, 8/97), neurological disease group (7.7%, 23/299), respiratory disease group (6.9%, 17/248), hematological disease group (3.9%, 2/51) and toxic group (0, 0/61) (χ(2)=37.75, all P<0.05). There were significant differences among primary disease groups regarding the FSS at admission, the FSS at hospital discharge, ΔFSS, Δmental status FSS, Δsensory FSS, Δcommunication FSS, Δmotor FSS, Δfeeding FSS, and Δrespiratory FSS (F=13.56, 8.97, 10.84, 6.30, 7.37, 7.84, 7.47, 9.97, 10.50, all P<0.05). Conclusion: The incidence of new-onset organ dysfunction in PICU was high. The case fatality rate in patients with new-onset organ dysfunction was high. The functional status at hospital discharge was strongly associated with the functional status at admission. Patients in the cardiovascular disease group had the highest incidence of new-onset organ dysfunction and the most severe deterioration of functional status.More attention must be paid to motor function and respiratory function in cardiovascular disease, respiratory disease and hematological disease.

[Clinical characteristics of 13 neuroendocrine prostate cancer patients].

Objective: To explore the radiological, pathological features and clinical characteristics of neuroendocrine prostate cancer patients(NEPC). Methods: The clinical characteristics and pathology data of 13 neuroendocrine prostate cancer patients treated in the Affiliated Hospital of Tianjin Medical University from January 2004 to January 2015 were analyzed retrospectively. Results: Of all 13 patients, three cases were primally diagnosed small cell cancer, and 10 cases were translated to neuroendocrine type from adenocarcinoma after endocrine therapy. Frequent urination, urgency, nocturia, and dysuria were main symptoms. Serum prostate-specific antigen (PSA) was (14.5±3.2)µg/L; the volume of prostate was enlarged, mean volume, range 28-176(45±4)ml. The lesion was moderately low signal intensity in T(2)WI, while slightly higher signal in DWI. Signal characteristic of dynamic enhanced MRI was "fast in fast out" . The expression of Synaptophysin, Chromogranin A , CD56 and Ki-67 in NEPC were highly expressed by immunohistochemistry analysis. Among them, five patients accepted intravenous chemotherapy, two cases received external radiation therapy, three cases received cryoablation and three cases received palliative therapy. Median survival time in all 13 patients was 10 months, while median survival time in patients treated by chemotherapy was 16 months . Conclusion: NEPC is a highly aggressive subtype of prostate cancer characterized by rapid disease progression, lack of treatment and worse prognosis. Therefore, patients with NEPC may benefit from early diagnosis and comprehensive treatment with chemotherapy.

[Effects of high-intensity focused ultrasound on apoptosis-associated gene expression in xenografts with human pancreatic cancer].

Objective: To identify the expression of apoptosis-associated genes of high- intensity focused ultrasound(HIFU) in xenograft with human pancreatic cancer. Methods: Mice implated with human pancreatic cancer cells (YY-1) were divided into HIFU group or control group. Tumor cell apoptosis was verified by TUNEL. The expression of the apoptosis-associated genes was analyzed by Agilent Human Gene Expression. Selected genes was validated by quantitative real-time PCR(RT-PCR)and Western blot. Results: The rate of tumor cell apoptosis in HIFU group was higher than that of control group at 7, 14 days after HIFU treatment ((63.6%±15.2%)vs (19.0%±2.4%), P<0.01)and ((41.4%±7.3%)vs(18.0%±2.4%), P<0.01). Gene expression profiling revealed a total of 69 differentially expressed genes in related to apoptosis pathway, among which 44 genes were up-regulated, and 25 genes down-regulated. The RT-PCR results of selected 4 genes were consistent with those of gene expression profiling. The results of Western blot analysis at 7, 14 days after HIFU treatment showed that the expressions level of Bax protein in HIFU group was greater that of in control group ((0.39±0.11)vs (0.20±0.09), P<0.05)and ((0.46±0.12)vs(0.24±0.10), P<0.05), while the expressions level of Bcl-2 protein in HIFU group was lower than that of in control group ((0.68±0.14)vs(1.56±0.21), P<0.05)and((0.51±0.16)vs(1.57±0.22), P<0.05). Conclusions: HIFU could induce apoptosis and results in dramatic changes in gene expression, indicating that multiple pathways are involved. Although intrinsic pathway might be predominantly involved in HIFU-elicited apoptosis, further research is needed to clarify the detailed mechanisms.

[Comparison between poly hydroxy acrylic acid and Van-clear replacing the traditional reagents to detect the cervical hTERC genes by adopting FISH technique].

OBJECTIVE: To observe the difference of the human telomeres RNA component (hTERC) genes' amplification in the cervical tissue by applying the environment-friendly fixative poly hydroxy acrylic acid and the transparent dewaxing solution Van-clear separately or jointly to replace the traditional fixative 4% (volume fraction) neutral buffered formalin and the conventional transparent dewaxing solution xylene in the use of fluorescence in situ hybridization (FISH) for detection. METHODS: In the study, 255 cases of cervical tissue specimens submitted by the Department of Gynecology in Zhongshan Boai Hosipital were collected from Mar. 2013 to Apr. 2015. Four samples were taken from the same lesion site. All the cases were divided into 4 groups and named group A, B, C, and D. Group A used 4% neutral buffered formalin fixed and xylene dewaxing to make slices. Group B used poly hydroxy acrylic fixed and xylene dewaxing to make slices. Group C used 4% neutral buffered formalin fixed and Van-clear transparent to make slices. Group D used poly hydroxy acrylic fixed and Van-clear transparent dewaxing to make slices. The amplification of hTERC genes in the four groups of cervical specimens was also detected by FISH technique. RESULTS: When the hTERC genes were detected by FISH method under the fluorescence microscope, it was obvious that the tissue profile and the background of group A, B, C and D were all clear. The probe was fixed in the accurate position so that the bright red or green fluorescence signals were easily found in these four groups. Compared with the positive rate of group A, there was no statistical significance in that of group B, C and D (P>0.05). At the same time, the coincidence rate of the FISH results was high, which showed that the new environment-friendly reagent had no significant difference in the detection of cervical hTERC genes by FISH technique. CONCLUSION: It is possible for the environment-friendly reagent poly hydroxy acrylic acid and Van-clear to replace 4% neutral buffered formalin and xylene separately or jointly to detect the cervical hTERC genes by adopting FISH technique.

Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats.

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

The gender difference in effect of sevoflurane exposure on cognitive function and hippocampus neuronal apoptosis in rats.

OBJECTIVE: Anesthesia and surgery can induce postoperative cognitive dysfunction. Ser-133 phosphorylation sites of cAMP-response element binding protein (CREB) is a key gene that mediate a variety of downstream transcription initiation factors, regulate neuronal survival and promote the expression of a large number of genes. Thus, CREB may play a role in this impairment. We hypothesize that and sevoflurane-induced cognitive impairment possibly via inhibiting the expression of CREB downstream genes and proteins. MATERIALS AND METHODS: To test this hypothesis, adult Sprague-Dawley rats were subjected to sevoflurane exposure and were tested with a series of behavioral experiments (open field, passive avoidance test and Morris water maze test) at different time (1 d to 95 d). Besides, blood gas changes and expiratory sevoflurane concentrations were examined at 2 h; the levels of phosphorylated CREB 1, the protein Bcl-2, Caspase-8 and Caspase-3 were assessed at 1 week and 3 months after anesthesia. We also conducted a comparison in sevoflurane-induced cognitive impairment between male and female rats. RESULTS AND CONCLUSIONS: Here, we found that sevoflurane anesthesia can impair short-term cognitive function, which may be via down-regulating p-CREB1 and Bcl-2 expression and up-regulating Caspase-8 expression to reduce hippocampus neuronal apoptosis, and male rats suffered a more severe cognitive dysfunction than female rats. In addition, sevoflurane can produce a reversible long-term cognitive dysfunction in rats.

The treatment of paravertebral malignant mesenchymal tumor pain with cryoablation.

OBJECTIVE: The purpose of this study was to evaluate the feasibility, safety, and efficacy of cryoablation to treat pain from paravertebral malignant mesenchymal tumors. METHOD: Cryoablation was performed on 15 patients who suffer from unresectable painful paravertebral malignant mesenchymal tumors and whose pain was poorly controlled by conventional treatment methods. The sizes of the tumors varied from 3 to 20 cm. The patients' pain at baseline before the cryoablation and the pain they felt 1 day, 1 week, 1 month, and 3 months after the cryoablation were assessed respectively by the Brief Pain Inventory (BPI). RESULT: BPI scores are divided into two categories: the influence of pain and the severity of pain. Both results showed a decline after the cryoablation. The evaluation score of pain severity decreased significantly (P=0.001, P=0.031) on the observation of 1 day and 1 month after the cryoablation; that of pain influence decreased significantly (P=0.016, P=0.036) in the cases of 1 day and 1 week after cryoablation. Two patients (13.33%) had mild complications, but no serious complications occurred. CONCLUSION: Cryoablation is a low risk, well-tolerated topical treatment for the pain of patients with unresectable paravertebral malignant mesenchymal tumor.

Effect of transcatheter renal arterial embolization combined with cryoablation on regulatory CD4+CD25+ T lymphocytes in the peripheral blood of patients with advanced renal carcinoma.

OBJECTIVE: To analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4+ CD25+ T cell (Treg) and its implication in patients with renal carcinoma. METHODS: Seventy seven patients are included in the study, and divided into two groups: TRAE group (n=45, receiving TRAE only) and TRAE+cryoablation group (n=32, receiving cryoablation 2-3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD4+T, CD8+T, and CD4+T/CD8+T) in the peripheral blood is measured by flow cytometry previous to the therapy and 3 months after therapy. Meanwhile, the extent of tumor necrosis is measured by MRI or CT 1 month after therapy. RESULTS: The percentages of Treg cells of patients in TRAE + cryoablation group decrease from (6.65±1.22)% to (3.93±1.16)%, (t=42.768, P<0.01), and the percentages of CD4+T and CD4+T/CD8+T increase significantly (P<0.01). However, the results of patients in TRAE group show that the percentages of Treg, CD4+T, CD8+T and CD4+T/CD8+T increase slightly although the differences had no statistical significance (P>0.05). The tumor necrosis rate of TRAE+cryoablation group is 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t=6.784, P<0.01). The median survival duration of the TRAE+cryoablation group is 20 months, significantly longer than that of the TRAE group (χ² = 7.368, P<0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r=0.90, P<0.01) and life time (r=0.67, P<0.01). CONCLUSION: The therapy of TRAE combined with cryoablation contributes to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, which consequently increase tumor necrosis rate and prolong the patients' survival duration.

Curcumin attenuates airway hyperreactivity induced by ischemia-reperfusion of the pancreas in rats.

OBJECTIVES: Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. METHODS: Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. RESULTS: The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. CONCLUSIONS: I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.