[Role of hyperglycemia-induced 5-hydroxytryptamine degradation of hepatic stellate cells in hepatic inflammation and fibrosis induced by type 2 diabetes mellitus].

OBJECTIVE: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis. METHODS: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe. RESULTS: There were up-regulated expressions of 5-HT2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H2O2) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor ß1 (TGF-ß1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-ß1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2. CONCLUSION: Hyperglycemia-induced myofibroblastization and TGF-ß1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT2AR is involved in the regulation of 5-HT synthases and MAO-A expression.

[Application of artificial intelligence-assisted diagnosis for cervical liquid-based thin-layer cytology].

Objective: To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening. Methods: A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao'an People's Hospital(Group) and Changsha Yuan'an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared. Results: The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual. Conclusions: Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.

[The evaluation of severity and treatment for OSAHS by acoustic pharyngometry which in different postures].

Objective: To investigate the optimal position in application of acoustic pharyngometry to detect the pharyngeal condition and to assess its therapeutic effect on obstructive sleep apnea hypopnea syndrome(OSAHS). Method: Eight adult males were assigned to the normal group, and 57 male patients with OSAHS diagnosed by polysomnograhy(PSG) were assigned to the snoring group. Of the snoring group, 11 patients who were diagnosed severe OSAHS underwent low-temperature plasma uvulopaltopharyngoplasty(UPPP) and coblationchanneling of the tongue(CCT), were assigned to the operation subgroup; 8 patients underwent continuous positive airway pressure(CPAP), which was assigned to the CPAP subgroup. And remainders underwent conservative treatment, including weight loss and position change. Acoustic pharyngometry (three positions including sitting position, supine position and lateral position) and PSG exam were performed in all participants. Additionally, acoustic pharyngometry under three positions was conducted again in patients in the operation and CPAP subgroups three months after treatment. Result: The minimum cross-sectional area was negatively associated with both AHI and the percentage of time with oxygen saturation below 90%(SIT90)( P<0.01). The correlation coefficient of the minimum crosssectional area insupine position with AHI and SIT90 were r=-0.569,r=-0.478, respectively. Under supine position, the minimum crosssectional area was negatively correlated with body mass index(BMI)(r=-0.265, P=0.033), and the minimum crosssectional area was negatively associated with neck circumference(r=-0.309, P=0.012). The minimum cross-sectional area was significantly increased after treatment of OSAHS(both operation and CPAP), which was statistically different before and after treatment compared to the control group(P<0.01). Conclusion: ①The minimum cross-sectional area is significantly correlated with AHI and SIT90, respectively. The acoustic pharyngometry can be used to screen OSAHS patients. ②In this study, the minimum cross-sectional area under supine position is significantly smaller than that under sitting position. In addition, the minimum cross-sectional area under supine position harbored a better correlation with AHI and SIT90, which could better reflect the narrowness of pharyngeal cavity during sleep. ③Acoustic pharyngometry could be a simple, rapid and non-invasive technique that can objectively evaluate the efficacy of surgical and CPAP methods, and provided a more favorable basis for future clinical work..

Development of neutralizing antibodies and group A common antibodies against natural infections with human rotavirus.

We determined the levels of group A common and neutralizing antibodies against human rotavirus in paired serum specimens obtained from 38 infants within 12 days of the onset of diarrhea. Thirty of the infants excreted rotavirus in stools, and eight did not. Nine patients (30%) with rotavirus diarrhea and seven patients (88%) with diarrhea due to other causes had detectable levels (greater than or equal to 1: 80) of immunoglobulin (IgG) common antibodies in acute-phase sera. All the patients with rotavirus diarrhea showed at least fourfold rises in titers of IgG or IgM common antibodies or both, while only two control patients showed significant rises in either IgG or IgM common antibodies in their convalescent-phase sera. Of the 19 patients excreting "short" electropherotypes of rotavirus, 18 showed at least fourfold rises in titers of neutralizing antibodies against serotype 2 human rotavirus but not against serotype 1, 3, or 4. Nine of the ten patients excreting "long" electropherotypes showed significant rises in neutralizing antibodies against serotype 3, and the other patient showed a significant rise in neutralizing antibodies against serotype 1. One patient excreted long and short electropherotypes simultaneously, and he also showed a significant rise in neutralizing antibodies against serotype 2 and 3 viruses. The control patients with diarrhea did not show significant changes in titers of antibodies against any of the serotypes. These results demonstrated that the neutralizing antibody response within 2 weeks after clinical onset is specific for the infecting serotype of rotavirus.

Rotavirus infection of the oropharynx and respiratory tract in young children.

Oropharyngeal aspirates were obtained from 89 infants hospitalized with respiratory illnesses accompanied or not by diarrhea and 33 control patients without the diseases. Rotavirus was detected from 25 of these patients by immunocytology, isolation of the virus in cultures of MA104 cells, or both. None of the control patients gave a positive result. The infection involves squamous cells and globlet cells probably originating from the oropharynx, and ciliated columnar epithelial cells from the respiratory tract. The virus from 2 specimens was propagated by repeatedly passaging in the cultures and found to have characteristic morphology of rotavirus. The electrophoretic patterns of the viral RNA extracted from them are closely similar to those obtained with the rotavirus genome extracted from the stool of the same patients. Repeated stool specimens were also obtained, and sera were paired from some of these subjects. All but one of the patients who gave a positive virology for their aspirates also showed a significant rise in the titres of common group A rotavirus antibody, neutralizing antibody against one or more of serotypes of rotavirus, or both. Patients who excreted rotavirus in their stools were younger and had significantly lower titres of rotavirus antibodies in their acute sera, than those who shedded the virus in the oropharynx but did not excrete the virus in repeated stool specimens. The prevalence of rotavirus in the oropharyngeal aspirates from these patients surpassed that of adenovirus, respiratory syncytial virus, influenza virus, and herpes simplex virus combined.