OBJECTIVETo explore the feasibility of establishing an isolated porcine liver machine perfusion model and assess its value in high-intensity focused ultrasound studies.

METHODSTwenty-one isolated porcine livers were perfused with autologous blood for 4 h through dual vessels (portal vein and hepatic artery) cannulation using an extracorporeal circulation machine under a sub-normothermic perfusion condition. The perfusion model was assessed by monitoring the liver color, texture, liver weight gain, hemodynamic parameters, color Doppler flow imaging, bile output and histopathology.

RESULTSNineteen isolated porcine livers were successfully cannulated with dual vessels, and failure of hepatic artery intubation occurred in two porcine livers. After machine perfusion for 4 h, the isolated livers maintained a soft texture with stable hemodynamic levels within relative normal physiological ranges. The bile output was more than 3 ml/h within the initial 3 h of perfusion. Histopathological examination demonstrated no morphological or structural changes of the liver tissues.

CONCLUSIONThe isolated porcine liver perfusion model is stable and feasible, and can be used for high-intensity focused ultrasound studies.

Animals ; Equipment Design ; Extracorporeal Circulation ; instrumentation ; methods ; Hemodynamics ; Liver ; blood supply ; diagnostic imaging ; Liver Circulation ; physiology ; Swine ; Ultrasonography

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.
Adenine/analogs & derivatives* ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy* ; Piperidines ; Proto-Oncogene Proteins c-bcl-2 ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use* ; Recoverin ; T-Lymphocytes

To report the first case of chronic disseminated paracoccidioidomycosis in China. A 49-year-old male patient presented with papules and nodules of the skin for 1 year, and papules and ulcers on the oral mucosa for 2 months. Skin examination showed the edema of the left foot, multiple crusting ulcers on the sole of the left foot, ulcers with a granular base in the interdigital regions between the third and fourth toes as well as fourth and fifth toes of the left foot, accompanied by punctate hemorrhage and exudation; there were multiple papules, nodules, and plaques on the dorsum and medial side of the left foot and the left knee, with ulcers and crusts in the center; 2 papules were observed on the left wrist, and 1 papule on the left upper lip with a crusted surface; red plaques with ulcers and punctate hemorrhage were observed on the gingival mucosa, buccal mucosa, labial mucosa, and palate, and the lesions mainly occurred on the left side. Ultrasonography of superficial lymph nodes showed bilateral cervical and supraclavicular lymph node enlargement, which was more obvious on the left side. Computed tomography of the chest and abdomen showed diffuse miliary nodular shadows, and cordlike, cloudy flocculent and nodular high-density shadows in both lungs, as well as obvious thickening of the left adrenal gland in the abdomen. Yeast cells were observed by immunofluorescent staining of biopsy tissues from the oral mucosa and left lower limb. Histopathological examination of biopsy tissues from the oral mucosa and left lower limb showed granulomatous inflammation, and refractive double-membrane yeast cells could be observed inside or outside the multinucleated giant cells, without or with a single bud or multiple buds; periodic acid-Schiff staining and hexamine silver staining of the above biopsy tissues were positive. Fungal culture of the left lower limb lesion in Sabouraud dextrose agar medium at 25℃ and 37℃ both yielded fungal hyphae. Metagenomics sequencing of the oral mucosal tissue and alveolar lavage fluid indicated the infection with Paracoccidioides brasiliensis. The diagnosis of chronic disseminated paracoccidioidomycosis was confirmed. After 1-month oral treatment with itraconazole capsules at a dose of 400 mg/d, the lesions on the skin and oral mucosa markedly improved, and computed tomography imaging of the lung and left adrenal gland also showed obvious improvement. The dose of itraconazole was reduced to 200 mg/d after 3 months. The patient′s condition further improved during a 10-month follow-up.

Objective To investigate the changing curve of mean lung density (MLD)in normal preschool children based on CT quantitative measurement.Methods Chest CT data of 409 preschool children were reviewed retrospectively from the "digital lung"database.A computerized algorithm based on the "digital lung"was applied to all examinations in a batch manner.The MLD values of total lung,right lung,left lung and each lobe were obtained automatically.Results There was no correlation between the gender and MLD,however a moderately negative correlation was found between the age of month and MLD (P＜0.05).No significant difference of MLD was found between genders of the same age of month group,except in left lower lobe of 49-60 months of age (P=0.043). The MLD was decreased gradually with age (P＜0.05).Conclusion There is not a statistical difference in MLD between the preschool boys and preschool girls of the same age of month.With the growth of preschool children,the MLD is gradually decreased.

The phosphatidylinositol 3-kinase (PI3K) and its downstream target protein kinase B (Akt/PKB) can be activated by a variety of extracellular and intracellular signals. They are important signaling molecules and key survival factors involved in cell proliferation, differentiation, apoptosis and other cellular processes. Recently, many reports demonstrate that type I PI3K/Akt signaling pathway plays an important role in maintenance of self-renewal and pluripotency of embryonic stem (ES) cells. Further studies with regard to the self-renewal and pluripotency of ES cells and underlying molecular mechanisms are crucial to its application in cell replacement therapy, regenerative medicine and tissue engineering. The present review focuses on the recent progress on the mediation of PI3K/Akt signaling pathway on the maintenance of self-renewal and pluripotency of ES cells.
Cell Differentiation ; Cell Proliferation ; Embryonic Stem Cells ; cytology ; Humans ; Phosphatidylinositol 3-Kinases ; physiology ; Pluripotent Stem Cells ; cytology ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction

Objective: To detect the expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia (B-ALL) in newly diagnosed cases, and to investigate the relationship between CRLF2 and the general clinical characteristics, efficacy and prognosis. Methods: 103 cases of newly diagnosed adult B-ALL patients were investigated from Apr 2016 to Dec 2017 in the Department of Hematology, Henan Cancer Hospital. Bone marrow samples was used to detect the expression of CRLF2 in leukemic cells. The expression of CRLF2 ≥20% was defined as CRLF2-high group and <20% was defined as CRLF2-low group. The clinical characteristics and prognosis of the two groups were compared. Results: The Median overall survival (OS) and disease free survial (DFS) in CRLF2-high group were 9.0 months and 4.25 months, respectively. CRLF2-low group were 15.5 months and 10.25 months, respectively. There was a statistically significant difference in median OS and DFS between the two groups (P=0.007, P=0.000) . The 18-month OS and DFS in CRLF2-high group were 38.6% and 25.1%, respectively. CRLF2-low group were 57.8% and 42.3%, respectively. Multivariate analysis showed high expression of CRLF2 was an independent risk factor for OS (HR=2.991, 95% CI 1.429-6.261, P=0.004) and DFS (HR=2.374, 95%CI 1.146-4.960, P=0.041) in patients. Conclusion: Patients with high expression of CRLF2 had poor prognosis.
Adult ; Disease-Free Survival ; Humans ; Leukemia, B-Cell ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Receptors, Cytokine ; Risk Factors

Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.
Diabetes Mellitus ; diagnosis ; physiopathology ; therapy ; Exosomes ; metabolism ; Humans ; Insulin Resistance ; physiology ; MicroRNAs ; metabolism ; RNA, Messenger ; metabolism

Objective: To compare the therapeutic efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This is a multicenter randomized controlled trial. From March 2017 to July 2019, moderate to severe OSAHS patients from three clinical center in Shanghai who were intolerant to continuous positive airway pressure (CPAP) and with velopharyngeal and glossopharyngeal plane obstruction were enrolled in this study. According to the surgical type, they were 1∶1 randomized to HUPPP plus radiofrequency ablation of tongue base group (Ablation group) or HUPPP plus traction of tongue base group (Traction group). All patients completed over-night standard Polysomnography (PSG), upper-airway assessment (Friedman classification, Müller test, CT and cephalometric examination), preoperative routine examination, Epworth Sleepiness Scale (ESS) and Quebec sleep questionnaire (QSQ). Six to 12 months after operation, all the above-mentioned examinations were repeatedly performed. Changes of aforementioned variables before and after operation were assessed. Results: A total of 43 patients with moderate to severe OSAHS were enrolled in this study. One patient lost to follow-up, the remaining 21 were allocated to Ablation group and 21 were allocated to Traction group. The total therapeutic efficacy of all patients was 69.05% (61.90% in Ablation group and 76.19% in Traction group), but there was no statistical significance between the two groups (P= 0.317). The value of sleep scale score (ESS and QSQ), objective sleep variables (apnea-hypopnea index, oxygen saturation, percentage of time with blood oxygen less than 90% in total sleep time, oxygen desaturation index and micro-arousals) and upper airway cross-sectional area (palatopharyngeal and retrolingual area) of the two groups were improved (P<0.05), but the differences between the two groups were not statistically significant (P>0.05). Conclusion: For moderate to severe OSAHS who had glossopharyngeal plane obstruction, both HUPPP plus radiofrequency ablation of tongue base or HUPPP plus traction of tongue base are effective treatment for OSAHS, and the curative effect is similar. The choice of surgical type could be selected according to patient's or surgical conditions.
China ; Humans ; Oxygen Saturation ; Radiofrequency Ablation ; Sleep Apnea, Obstructive/surgery* ; Tongue/surgery* ; Traction

Objective: To investigate the prevalence and associated risk factors of metabolic syndrome (MS) in patients with obstructive sleep apnea (OSA). Methods: From July 2007 to June 2017, a total of 8 155 adult subjects, including 6 484 males and 1 671 females, aged 18-90 (43.13±12.28), body mass index 14.61~59.56 (25.59±3.98) kg/m²,who were admitted to the Department of Otorhinolaryngology head and Neck surgery of The Sixth People's Hospital affiliated to Shanghai Jiao Tong University, were retrospectively analyzed. All patients underwent polysomnography and biochemical tests. Subjects were divided into four groups (non-OSA, mild OSA, moderate OSA, and severe OSA) according to OSA severity. The prevalence of MS was expressed as percentage, and the correlation between OSA and MS and its characteristic pathophysiological indicators was evaluated by logistic regression model after adjusting for factors such as gender, age, BMI, neck circumference, hip circumference, smoking and alcohol consumption, and was expressed by odds ratio (OR). SPSS 25.0 software was used for statistical analysis. Results: The overall prevalence of MS was 43.6%, and that of non-/mild/moderate/severe OSA group was 18.6%, 30.4%, 43.8%, 57.1%.Logistic regression showed that patients with mild/moderate/severe OSA had an increased risk of MS compared with non-OSA patients, with adjusted OR values and confidence intervals of 1.27 (1.05-1.54), 1.84 (1.53-2.22), and 2.08 (1.76-2.46), respectively (P<0.01).In addition, indicators of OSA anoxic burden [oxygen drop index(T_oxygen=7.1), minimum blood oxygen(T_minimum=56.3), blood oxygen saturation below 90% cumulative time ratio (T_CT90=10.6) ]were closely associated with MS disease(P<0.01), but sleep fragmentation index (arousals index) was not significantly associated with MS disease. Conclusion: The risk of MS gradually increases with the severity of OSA, and the indicators reflecting OSA hypoxia burden are closely related to MS disease.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Female ; Humans ; Male ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Oxygen Saturation ; Retrospective Studies ; Sleep Apnea, Obstructive/epidemiology* ; Young Adult