[Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis].

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

[Development of a deep learning based prototype artificial intelligence system for the detection of dental caries in children].

Objective: To develop a prototype artificial intelligence image recognition system for detecting dental caries, especially those without cavities, in children. Methods: Seven hundred and twelve intraoral photos, which were taken by dental professionals using a digital camera from October 2013 to June 2020 in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, were collected from the children who received dental treatment under general anesthesia. The well-documented post-treatment electronic dental record of each child was identified as label standard to determine whether the teeth were carious and the type of caries types such as caries that had become cavities (caries with cavities), pit and fissure caries that had not become cavities (pit and fissure caries) and proximal caries which the marginal ridge enamel had not been destroyed (proximal caries). The various teeth and caries types were labeled by pediatric dentists using VoTT software (Windows 2.1.0, Microsoft, U S A). There were five labeled groups: pit and fissure caries, approximal caries, non-carious approximal surfaces, caries with cavities and teeth without caries (including intact fillings). Each group was randomly divided into training dataset, validation dataset and test dataset at a ratio of 6.4∶1.6∶2.0 by using random number table. After using the labeled training dataset for deep learning training, a deep learning-based artificial intelligence (AI) image recognition system for detecting dental caries was established, with the caries probability greater than 50.0% as the criterion for determining caries. Sensitivity and accuracy were used as indicators of recognition specificity. Results: Seven hundred and twelve single-jaw intraoral photographs were segmented and annotated into 953 pit and fissure caries, 1 002 approximal caries, 3 008 caries with cavities, 3 189 teeth without caries and 862 non-carious approximal surfaces, totaly 9 014 labels. The sensitivities and specificities of the test set were 96.0% and 97.0% for caries with cavities, 95.8% and 99.0% for pit and fissure caries and 88.1% and 97.1% for approximal caries. Conclusions: The current AI system developed based on deep learning of the intra-oral photos in the present study showed the ability to detect dental caries. Furthermore, the AI system could accurately verify different types of dental caries such as caries with cavities, pit and fissure caries and proximal caries.

[Deep learning-based dental plaque detection on permanent teeth and the influenced factors].

Objective: To develop an artificial intelligence system for detecting dental plaque on permanent teeth and find the influenced factors. Methods: Photos of the labial or buccal surfaces of the permanent teeth were taken by using an intraoral camera (1 280×960 pixels; TPC Ligang, Shenzhen, China) before and after applying the plaque-disclosing agent (Cimedical, Japan) in 25 volunteers [12 males, 13 femals, aged (23±3) years] recruided in accordance with the inclusion criteria from the students of Peking University School of Stomatology from October 2018 to June 2019. A total of 549 groups of photos were captured and then divided into a training dataset containing 440 groups of photos and a test dataset including 109 groups of photos. The scopes of teeth and dental plaque on photos were labeled using LabelMe (Windows 3.2.1, MIT, U S A). A DeepLab based deep learning system was designed for the intelligent detection of dental plaque on permanent teeth. The mean intersection over union (MIoU) was employed to indicate the detection accuracy. Matlab (Windows R2017a, MathWorks, U S A) was used to extract the plaque edge line of 109 groups of photos and to calculate the number of pixels for the measurement of the complexity of the plaque edge line. The percentage of dental plaque area was calculated. Multivariate linear regression was used to explore whether tooth site, plaque percentage, number of plaque edge line pixels and lens light spot location would influence the detection accuracy, of which P<0.05 was considered statistically significant. Results: The MIoU of the permanent tooth model was 0.700±0.191 when 440 photos were used for training and 109 photos were used for testing. In the regression model of significance test (P<0.05), the percentage of plaque and the number of pixels on the edge of plaque had significant influence on the accuracy of dental plaque detection. The standardized coefficient of the number of pixels of the plaque edge line is -0.289, and the standardized coefficient of the percentage of plaque is -0.551. Conclusions: In the present study, an artificial intelligence system was built to detect dental plaque area on tooth photos collected by family intraoral camera. The system showed the ability to detect the dental plaque of permanent teeth. The more complex the marginal line of dental plaque and higher the percentage of dental plaque are, the lower the accuracy of plaque recognition is.

[China statistics of extracorporeal life support in 2018].

Objective: To investigate China statistics of extracorporeal life support (ECLS) in 2018. Methods: The statistics data was collected by provincial coordinators assigned by Chinese Society of Extracorporeal Life Support (CSECLS) in 2019, including cases, centers, indications, and in-hospital survival rate. Results: Three thousand nine hundred and twenty-three cases were reported by 260 ECLS centers. There were an increase of 38.8% in extracorporeal membrane oxygenation (ECMO) cases and an increase of 11.6% in ECMO centers compared with that in 2017 (2 826 cases and 233 centers). Adult, pediatric, and neonatal patients accounted for 88.0%, 9.7%, and 2.3% of total cases, respectively. Centers with more than 20 ECMO cases per year had favorable in-hospital survival rate compared with those less than 20 cases (49.1% vs 44.0%, P=0.005). ECMO cases (r=0.71, P<0.001) and centers (r=0.81, P<0.001) were both associated with regional gross domestic product. Conclusions: There was a growth in ECLS cases, centers, and center scale in China within 2018. The majority of ECLS cases and centers were in developed regions. The ECLS indications, and in-hospital mortality in China were in accordance with that in the Extracorporeal Life Support Organization registry gradually. Large-scale ECLS centers had favorable patient outcomes. The development of ECLS still has tremendous potential in China, especially for pediatric and neonatal patients.

[Role of signaling pathway of long non-coding RNA growth arrest-specific transcript 5/microRNA-200c-3p/angiotensin converting enzyme 2 in the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome].

Objective: To investigate whether long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5)/microRNA-200c-3p/angiotensin converting enzyme 2(ACE2) involved in the regulation of the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome (ARDS). Methods: ARDS rat models were established and were divided into control, ARDS, ARDS+ pcDNA and ARDS+ pcDNA-GAS5 groups. Six hours after the establishment of ARDS rat model, arterial blood and lung tissues of the rats from the four groups were collected. The changes of partial pressure of oxygen (PO(2)) and partial pressure of CO(2) (PCO(2)) were analyzed and the expression of GAS5 in lung tissue was observed in these groups. Then, A549 cells were divided into control, lipopolysaccharide (LPS), LPS+ pcDNA, LPS+ pcDNA-GAS5, LPS+ pcDNA-GAS5+ pre-NC, LPS+ pcDNA-GAS5+ miR-200c-3p mimic groups. Quantitative real-time PCR (qRT-PCR) was conducted to measure lncRNA GAS5, ACE2 and miR-200c-3p levels. RNA immunoprecipitation and RNA pull-down assay were used to detect the combination between GAS5 and miR-200c-3p. Western blotting was used to detect the protein level of ACE2. Flow cytometry was used to observe the apoptosis of A549 cells in those groups. The data between groups were compared by t test. Results: In ARDS rat model, PO(2) value was significantly increased in ARDS+ pcDNA-GAS5 group than that in ARDS+ pcDNA group[(81.5±3.3) vs (57.5±5.1) mmHg, t=4.850, P<0.05], and PCO(2) value was significantly decreased in ARDS+ pcDNA-GAS5 group than that in ARDS+ pcDNA group[(50.6±1.9) vs (64.0±1.9) mmHg, t=5.940, P<0.05]. LncRNA GAS5 level in A549 cells of LPS group decreased significantly than that in control group (0.43±0.01 vs 1.01±0.01, t=0.242, P<0.05). Compared with LPS+ pcDNA group, ACE2 expression increased significantly in LPS+ pcDNA-GAS5 group (0.85±0.04 vs 0.34±0.02, t=1.800, P<0.05). Compared with LPS+ pcDNA-GAS5+ pre-NC group, ACE2 expression decreased significantly in LPS+ pcDNA-GAS5+ miR-200c-3p mimic group (0.62±0.01 vs 0.84±0.02, t=9.440, P<0.05). Compared with control group, the percentage of A549 cell apoptosis promoted significantly in LPS group (25.90±0.61 vs 7.90±0.22, t=0.257, P<0.05). Compared with LPS+ pcDNA group, the percentage of A549 cell apoptosis suppressed significantly in LPS+ pcDNA-GAS5 group (10.50±0.37 vs 26.37±0.45, t=1.760, P<0.05). Compared with LPS+ pcDNA-GAS5+ pre-NC group, the percentage of A549 apoptosis promoted significantly in LPS+ pcDNA-GAS5+ miR-200c-3p mimic group (19.07±0.56 vs 10.87±0.26, t=0.643, P<0.05). Conclusion: In ARDS, down-regulation of lncRNA GAS5 decreases ACE2 expression through increasing miR-200c-3p to promote the apoptosis of A549 cells, thus to promote the progression of ARDS.

BML-111 inhibits the inflammatory response and apoptosis of renal tissue in rats with hemorrhagic shock by inhibiting the MAPK pathway.

OBJECTIVE: The effect of lipoxin receptor agonist BML-111 on acute kidney injury and AKI in rats with hemorrhagic shock (HS) and its mechanism were investigated. MATERIALS AND METHODS: A model of hemorrhagic shock in Sprague-Dawley (SD) rats was established, and recovered after 30 min of shock. 1 mg/kg BML-111 was intraperitoneally injected at the beginning of resuscitation in group BML-111. The concentration of serum creatinine, serum KIM-1 content, NGAL and inflammatory factors were detected. Renal tissue injury was examined by HE staining; TUNEL staining was used to detect the apoptosis of rat kidney cells. Western blot was performed for the detection of the expression level of MAPK (mitogen-activated protein kinase), Bax, cytochrome C and caspase-3,9 in rat renal tissue. RESULTS: HE staining showed pathological changes in groups group comparing to sham group. BML-111 group had a significant decrease in renal tissue injury. The scores of renal injury in each group were in accordance with the histological changes. The expression level of inflammatory factors in HS group was significantly higher than that in sham group (p<0.05). After BML-111 intervention, the levels of inflammatory factors in renal tissue were significantly lower than those in HS group (p<0.05). Meanwhile, NGAL and KIM-1 also showed the same trend. TUNEL staining showed that compared with sham group, the number of apoptotic cells in renal tissue of HS group increased significantly, and the apoptosis rate of renal tissue cells in group BML-111 decreased significantly. Western blot showed that the expression level of JNK, p38MAPK, and apoptosis-related protein in HS group was significantly increased, whereas the expression level of p38MAPK and JNK in group BML-111 was significantly decreased. CONCLUSIONS: BML-111 can reduce the inflammatory response and apoptosis of renal tissue by inhibiting the activation of MAPK signaling pathway in acute renal injury induced by hemorrhagic shock.

Correlation of PICCO/CT on cardiac output index value and prognosis in patients with heart disease.

The aim of this paper is to study the correlation between the cardiac output index value and the prognosis of patients with heart disease with the help of Pulse-induced Contour Cardiac Output (PICCO) and computed tomography (CT). Three hundred eighteen patients with pathologically confirmed heart disease were selected as study subjects. The Sime ns Av anto 1.6T type superconducting magnetic resonance meter and GE Light Speed Pro 48 slice spiral CT were used for the phased array coil scanning and enhanced scanning, respectively and to analyze the relationship between the cardiac output index value and prognosis in patients with heart disease with the help of PICCO and CT. The accuracy rates of PICCO and CT in determining the cardiac output index of heart disease were 93.2% and 76.1%, respectively, which were significantly different (P less than 0.05). The coincidence rate between the results of the cardiac output index and pathological results of heart disease from PICCO and CT were 57.6%and 54.7%, respectively. According to the χ2 test results, the diagnostic results of PICCO were consistent with the pathological results of the heart disease group (Kappa = 0.039, 0.496, P less than 0.05). The coincidence rate for the five-year survival rate of PICCO/CT with the total survival rate and the results of the patients were 56.7% and 43.8%, respectively. The coincidence rate of PICCO and CT diagnosis results with the cardiac output index values, as well as prognosis results, was high. In judging the value of the cardiac output index and the prognosis of patients with heart disease, PICCO was superior to CT. The diagnostic results of PICCO have a strong correlation with the pathological results, therefore, PICCO can be used to accurately determine the cardiac output index and the prognoses of patients with heart disease.

Efficacy of Tiopronin in treatment of severe non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome of which the main feature is diffuse macrovesicular hepatic steatosis caused by deposition of excessive free fatty acid and triglyceride in liver parenchyma. AIM: To observe the efficacy of Tiopronin in treatment of severe nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: 30 patients with severe NAFLD were treated with Tiopronin for 3 months. 30 healthy people were selected as control. The body mass index (BMI) and plasma levels of endotoxin (ET), leptin, IL-6 and IL-8 were measured before and after treatment. RESULTS: The serum levels of ET, leptin, IL-6 and IL-8 in severe NAFLD group were significantly higher than those in control group (p < 0.05). After treatment with Tiopronin, these indexes were significantly lower than before (p < 0.05). CONCLUSIONS: The intestinal endotoxemia (IETM) occurs in patients with severe NAFLD. Leptin, IL-6 and IL-8 play important roles in pathogenesis of NAFLD. Tiopronin can reduce the levels of ET, leptin, IL-6 and IL-8 for treatment of NAFLD.

Changes in brain content of nociceptin/orphanin FQ and endomorphin 2 in a rat model of neuropathic pain.

Orphanin FQ (OFQ) and endomorphins (EM) are newly characterized members of opioid peptide family. OFQ has been shown to antagonize morphine analgesia at supraspinal level, whereas endomorphins are highly selective endogenous ligands for mu receptor, showing analgesic effect at both spinal and supraspinal level. OFQ and EM-2 (EM2) immunoreactivity (ir) was measured by radioimmunoassay in nociception-related brain areas of rats subjected to L5/L6 spinal nerve ligation, using sham operated rats as control. It was found that: (1) the content of EM2-ir of spinal nerve ligated rats showed a significant increase (778%) in periaqueductal gray (PAG), and a significant decrease (43%) in striatum, compared with the control group. (2) a significant increase of the content of OFQ-ir was found in amygdala (+841%) and PAG (+459%), respectively in spinal nerve ligated rats. High pressure liquid chromatography showed that the EM2-ir and OFQ-ir were both heterogeneous with the major part eluting at the position of EM2 and OFQ standard, respectively. These results suggest that spinal nerve ligation induces significant changes in the content of EM2-ir and OFQ-ir in some discrete brain areas, which may play a role in nociceptive modulation.

Nocistatin, a peptide reversing acute and chronic morphine tolerance.

It has been reported that intracerebroventricular (i.c.v.) injection of nociception/orphanin FQ (OFQ) can antagonize morphine analgesia, whereas i.c.v. OFQ antibody can reverse morphine tolerance. Nocistatin (NST) is a recently characterized neuropeptide possessing an antagonizing effect on OFQ. Here we examine whether i.c.v. NST would result in a reversal of morphine tolerance. The results showed that: (1) i.c.v. NST at doses of 0.005, 0.05, 0.5, 5 or 50 ng per rat produced a bell-shaped dose-dependent reversal of chronic morphine tolerance, with maximum response at 0.5 ng. (2) Acute morphine tolerance could also be reversed, albeit partially, by i.c.v. NST at 0.5 ng. (3) The reversal of acute and chronic morphine tolerance by NST was completely abolished when NST (0.5 ng) was co-injected with (8 microg) OFQ. Since OFQ and NST are derived from the same preprohormone, the profile of its splicing in the CNS may play an important role in determining the effectiveness of morphine analgesia.

Saponins from Oxytropis bicolor.

Two new trace saponins were isolated from Oxytropis bicolor by column chromatography and preparative TLC on silica gel. The structures were elucidated as 16-O--[beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranosyl]-(20S, 24S)-3 beta, 16 beta, 20,24,25-pentahydroxy-9,19-cyclolanostane and 16-O-[beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranosyl-20-O-alpha-L -arabinopyranosyl-(20S,24X)-3 beta, 16 beta,20,25-pentahydroxy-9, 19-cyclolanostane on the basis of chemical evidence and spectral analysis.

Four saponins from Oxytropis ochrocephala.

From Oxytropis ochrocephala Bunge, four saponins 1, 2, 3, and 4 were isolated. Saponins 1 and 2 are new compounds. The common genuine aglycone of the saponins is soyasapogenol B. The structures of those saponins were established by means of 13C-NMR, MS analyses, and chemical methods. In addition, a new interesting artifact aglycone 6 was obtained from the hydrolysate of these saponins and its structure was elucidated by spectral analyses and chemical transformations.

Three saponins from Oxytropis species.

Three flavonoids and three saponins have been isolated from Oxytropis species. Their structures were determined as isorhamnetin-3-O-beta-D-glucoside, rhamnetin-3-O-beta-D-galactoside, apigenin, 3-O-[alpha-L-rhamnopyranosyl (1----2)-beta-D-glucopyranosyl(1----4)-beta-D-glucuronopyranosyl]+ ++soyasapogenol B, 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucuronopyranosyl] azukisapogenol and a new saponin 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucopyranosyl]-25-O-alpha-L- rhamnopyranosyl-(20S,24S)-3 beta,16 beta, 20,24,25-pentahydroxy-9,19-cycloanostane.