[Clinical and pathological features of Dubin-Johnson syndrome].

Objective: To explore the clinical and pathological features of Dubin-Johnson syndrome. Methods: The clinical and pathological characteristics of 18 cases of Dubin-Johnson syndrome diagnosed in the Department of Pathology of the Third Affiliated Hospital of Sun Yat-sen University from 2008 to 2018 were analyzed. Related literature was reviewed. Results: There were 15 male and three female patients. The male-to-female ratio was 5∶1. The age of the patients ranged from 17 to 73 years (median 24 years). Common clinical manifestations were jaundice, anorexia, and abnormal liver function tests. The pathological feature was the deposition of dark brown particles in the hepatocytes, especially those around the central veins. Conclusions: Dubin-Johnson syndrome mainly occurs in young people. The characteristic pathological changes are the deposition of dark brown particles in the hepatocytes around the central veins of the liver. The diagnosis of Dubin-Johnson syndrome mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing. The understanding of Dubin-Johnson syndrome can help reduce the rates of missed diagnosis and misdiagnosis of the disease.

[Inference of start time of resurgent COVID-19 epidemic in Beijing with SEIR dynamics model and evaluation of control measure effect].

Objective: To infer the start time of the resurgent COVID-19 epidemic in Xinfadi wholesale market in Beijing in June 2020 and evaluate the effect of comprehensive prevention and control measures in this epidemic. Methods: SEIR dynamics model was used to fit daily onset infections to search the start date of this resurgent COVID-19 epidemic in Beijing. The number of cumulative infections from June 12 to July 1 in Beijing were fitted considering different levels of control strength. Results: The current reemerged COVID-19 epidemic in Beijing probably started between May 22 and May 28 (cumulative probability: 95%), with the highest probability on May 25 (23%). The R(0) of the current reemerged COVID-19 epidemic was 4.22 (95%CI: 2.88-7.02). Dynamic model fitting suggested that by June 11, the cumulative number of COVID-19 cases would reached 99 (95%CI: 77-121), which was in line with the actual situation, and without control, by July 1, the cumulative number of COVID-19 cases would reach 65 090 (95%CI: 39 068-105 037). Since June 12, comprehensive prevention and control measures have been implemented in Beijing, as of July 1, compared with uncontrolled situation, the number of infections had been reduced by 99%, similar to the fitting result of a 95% reduction of the transmission rate. The sensitivity analysis showed consistent results. Conclusions: For the emergent outbreak of COVID-19, the dynamics model can be used to infer the start time of the transmission and help tracing the source of epidemic. The comprehensive prevention and control measures taken in Beijing have quickly blocked over 95% of the transmission routes and reduced 99% of the infections, containing the sudden epidemic timely and effectively, which have value in guiding the prevention and control of the epidemic in the future.

[Risk assessment of global COVID-19 imported cases into China].

Objective: To assess the risk of COVID-19 foreign imports cases to China. Methods: We collected epidemic data (cumulative daily confirmed cases in each country, cumulative confirmed imported cases), demographic data (population density, population) and information on potential source groups of tourists (the daily estimated number of overseas Chinese, overseas Chinese students, overseas workers, foreign students coming to China and flight passengers) and the global health security index (GHS) to assess and predict risk of imported cases for recent (February 1(st) to April 25(th)) and future (after April 26(th)). Results: Strong positive correlation was found among variables including the number of imported cases, cumulative confirmed cases, attack rate, number of overseas Chinese, number of overseas Chinese students, number of foreign students coming to China, number of flight passengers and GHS. In the recent risk analysis, imported cases of Russian were the highest, followed by United Kingdom, United States, France and Spain. In the future risk prediction, 44 countries including United States and Singapore are evaluated as potential high-risk countries in the future through the attack rate index of each country and the estimated average number of daily passengers. Conclusion: The risk assessment of COVID-19 imported cases can be used to identify high-risk areas in recent and future, and might be helpful to strengthen the prevention and control of the epidemic and ultimately overcome the epidemic.

[Analysis of differences in epidemiology and clinical features of Guillain-Barré syndrome between rural and urban areas of southern China].

Objective: To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China. Methods: The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively. Results: The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas. Conclusions: GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

[MNAT1 expression in non-small cell lung cancer and its biological cellular impact].

Objective: To investigate the expression and significance of MNAT1 in non-small cell lung cancer (NSCLC) and to explore the biological impact of MNAT1 expression in lung cancer cells at the cellular level and related signaling pathway. Methods: Forty-eight cases of NSCLC tissues and paired normal tissues was collected at Nanfang Hospital, Southern Medical University from 2015 to 2017. The expression level of MNAT1 was detected by immunohistochemistry, and the relationship between MNAT1 and clinicopathological features was analyzed. The expression of MNAT1 was detected in lung cancer cells, MNAT1 level was analyzed after knocking down in A549 and H322 cells by siRNA; Plasmid vector of overexpressing MNAT1 was constructed, followed by transfecting H1299 cells and observing proliferation and migration at the cellular level. Flow cytometry was used to analyze the effect of the expression of MNAT1 on cell cycle, and Western blot was used to explore the possible molecular mechanism of MNAT1 on cell proliferation and cell cycle. Results: Immunohistochemistry showed that the expression score of MNAT1 was (4.07±3.55) in normal lung tissue and (7.33±4.09) in NSCLC tissue (P<0.01), and correlated with lymph node metastasis. At the cellular level, MNAT1 promoted cell proliferation(P<0.05), migration(P<0.05) and cell cycle progression(P<0.01). Conclusions: MNAT1 may be involved in the development of non-small cell lung cancer.MNAT1 affects cell cycle and proliferation through the Akt/p21 pathway.

Simvastatin inhibits noradrenaline-induced hypertrophy of cultured neonatal rat cardiomyocytes.

1. Oxidative mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We and others have shown that a HMG-CoA reductase inhibitor preserves endogenous antioxidant enzyme activity and inhibits cardiac hypertrophy in vivo. We therefore have examined whether noradrenaline (NA) induces the generation of reactive oxygen species (ROS) during its induction of neonatal cardiomyocyte hypertrophy and whether simvastatin, a HMG-CoA reductase inhibitor, attenuates ROS production and thus NA-induced hypertrophy of cardiomyocytes. 2. NA increased the intracellular ROS levels in a concentration-dependent manner. This increase of ROS was significantly inhibited by simvastatin and catalase. Prazosin partially suppressed NA-induced increase of ROS and beating, while preincubation with both prazosin and propranolol completely abolished NA-evoked increase of ROS and beating. Simvastatin did not affect NA-induced increase of beating. 3. The NA-induced increase of protein content was partially suppressed by prazosin and completely abolished by preincubation with both prazosin and propranolol. Simvastatin inhibited the increase of NA-induced increase of RNA content and [(3)H]-leucine incorporation in a concentration-dependent manner. Mevalonic acid (MVA) reversed the inhibition of NA-induced RNA and protein increase by simvastatin. Catalase also inhibited the NA-induced increase of RNA and protein. 4. We conclude that the inhibitory effects of simvastatin on myocyte hypertrophy were associated with its antioxidant effects and inhibition of MVA-metabolism pathway in neonatal rat cardiomyocytes. NA-induced increases of intracellular ROS and cardiomyocyte hypertrophy requires both alpha and beta adrenoceptors activation in neonatal rat cardiomyocytes. The increases of ROS induced by NA is required for hypertrophy.

Simvastatin inhibits cardiac hypertrophy and angiotensin-converting enzyme activity in rats with aortic stenosis.

1. In the present study, we tested the hypothesis that long-term administration of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin may regress hypertrophy and the possible effect of simvastatin on angiotensin-converting enzyme (ACE) activity in rats with pressure-overload cardiac hypertrophy. 2. Pressure-overload left ventricular hypertrophy (LVH) of rats was induced by part coarctation of the abdominal aorta; a sham-operated group served as the control. Six weeks after operation, animals were divided into three groups and an 8 week treatment period was insitgated as follows: (i) the simvastatin treatment group received simvastatin at 3.6 mg/kg per day, p.o.; (ii) the ACE inhibitor group received captopril at 50 mg/kg per day, p.o.; and (iii) the LVH control group received no drug treatment. 3. At the end of the treatment period, left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were monitored in vivo. Diastolic pressure-volume relationships were evaluated in a Langendorff preparation with a balloon-in-left ventricle (LV) heart. Myocyte cell width was measured. Angiotensin-converting enzyme activity and angiotensin (Ang)II and hydroxyproline contents of the LV were determined. 4. At the end of the experiments, LVH was established in the LVH control group by increases in LV weight, LV weight/body-weight ratio, LV weight/right ventricle weight ratio, LV myocyte cell width, LVSP and LVEDP by 40, 26, 19, 61, 56 and 59%, respectively (all P < 0.01), compared with the sham-operated group. In the simvastatin-treated and ACE inhibitor groups all these parameters were significantly reduced compared with sham-operated controls. In the LVH control group, ACE activity and AngII and hydroxyproline contents of LV tissue increased by 180, 123 and 70, respectively (all P < 0.01), compared with the sham-operated group. Compared with the LVH group, in the simvastatin-treated and ACE inhibitor groups ACE activity was reduced by 36 (P < 0.05) and 48% (P < 0.01), respectively, AngII content was reduced by 11 (P < 0.05) and 43% (P < 0.01), respectively, and hydroxyproline content was reduced by 23 (P < 0.01) and 10% (P < 0.05), respectively. 5. For the first time, the results of the present study demonstrate that simvastatin significantly reduces LVH, cardiac tissue ACE activity and improves LV performance in pressure-overloaded rats. Because, compared with captopril, simvastatin is more potent in its reduction of LVH and less potent in its inhibition of ACE activity, the mechanism of its antihypertrophic action, in addition to ACE inhibition, may involve inhibition of the mevalonic acid pathway, the main target of action of statins. Thus, HMG-CoA reductase inhibitors may be beneficial for the clinical treatment of cardiac hypertrophy.

Effects of simvastatin on left ventricular hypertrophy and function in rats with aortic stenosis.

AIM: To investigate the effects of simvastatin (Sim) on left ventricular hypertrophy in rats with pressure-overload cardiac hypertrophy. METHODS: The left ventricular hypertrophy (LVH) of rats was induced by partly occluding abdominal aorta below right renal artery. The rats were given i.g. Sim (1.8 and 3.6 mg.kg-1.d-1) for 8 wk. Three days after operation, left ventricular function was measured. Then the left ventricle (LV) + septum and the right ventricle (RV) were weighed. Hydroxyproline content of LV was measured. RESULTS: Eight weeks later, in the LVH group, LV weight (LVW), LVW/body weight (BW), LVW/RV weight (RVW), LV ending diastolic pressure (LVEDP), and hydroxyproline content increased by 36%, 51%, 28%, 92%, and 23%, respectively (all P < 0.01) compared with the sham group. LV + dp/dtmax and -dp/dtmax decreased by 39.2% and 39.4% (all P < 0.01). After the rats were given i.g. Sim 3.6 mg.kg-1.d-1, LVW, LVW/BW, LVW/RVW, left ventricle ending diastolic pressure (LVEDP), and hydroxyproline content decreased by 22%, 21%, 23%, 24%, and 11% compared with LVH group (all P < 0.01), LV + dp/dtmax and -dp/dtmax increased by 60% and 32% (all P < 0.01). CONCLUSION: Sim inhibited development of LV hypertrophy and improved LV function in rats with aortic stenosis.

Cytokines as mediators of autoimmune diabetes and diabetic complications.

Over the last several years, there has been a considerable and rapid expansion in our understanding of the cytokines. Insights into cytokine functions gained from basic biological studies are currently being applied to the study of autoimmune diabetes. It has become clear that cytokines are critical regulating elements involved in the processes of initiating, promoting, and effecting beta-cell destruction. It is also evident that cytokine functions in IDDM are determined by timing of appearance and local synthesis, as well as the prevailing cytokine and cellular milieu. Elucidating individual cytokine responses in IDDM may offer new insights into mechanisms of disease pathogenesis and may lead to novel cytokine-based therapies for the treatment of IDDM. It may also be possible that the intensity or character of a patient's cytokine response to islet injury or to the metabolic changes inherent to diabetes may influence the ultimate expression of IDDM or its complications. Clearly, this rapidly expanding field of study should have a major impact on our understanding of diabetogenesis, our ability to intervene in our understanding of diabetogenesis, our ability to intervene in the disease process itself, and ultimately our capacity to care for individuals with IDDM.

Renal TGF-beta regulation in spontaneously diabetic NOD mice with correlations in mesangial cells.

Diabetic nephropathy is characterized by excessive glomerular matrix accumulation, basement membrane thickening and sclerosis. Although it is clear that systemic metabolic disturbances precipitate such renal changes, the signals and pathways involved in this process are not fully elucidated. Recent evidence suggests that growth factors/cytokines are intimately involved in the pathogenesis of diabetic nephropathy. Because of its prosclerotic properties, transforming growth factor-beta (TGF-beta) is a prime candidate mediator of diabetic nephrosclerosis. We examined perfused kidney tissues isolated from spontaneously diabetic, non-obese diabetic mice (NOD) for TGF-beta content. By using murine isotype specific TGF-beta probes, we demonstrate that within 5 to 10 days of hyperglycuria renal TGF-beta 2 mRNA and protein content increases. By immunohistochemical analysis, de novo TGF-beta immunoreactivity was detected within both glomeruli and the interstitium. In order to determine the signals involved in promoting kidney TGF-beta content in vivo, TGF-beta regulation was examined in renal mesangial cells in vitro. Murine mesangial cells stimulated with glycosylated protein secrete bioactive TGF-beta and demonstrate a disproportionate increase in the steady state levels of TGF-beta 2 mRNA. These data suggest that a major early renal response in NOD mice to hyperglycemia or to glycosylated proteins is characterized by increases in TGF-beta.

A protective NOD islet-infiltrating CD8+ T cell clone, I.S. 2.15, has in vitro immunosuppressive properties.

Type 1, insulin-dependent diabetes mellitus (IDDM) appears to result from a T cell-dependent destruction of insulin-producing pancreatic beta cells. In non-obese diabetic (NOD) mice and in other rodent models of human IDDM, final expression of disease may be controlled by protective, as well as, destructive T cell influences. Previously, a CD8+ T cell clone, I.S. 2.15, was isolated directly from islets of disease-resistant male NOD mice. Upon transfer to young NOD recipients, the non-cytolytic I.S. 21.5 T cell clone, confers in vivo protection from two forms of accelerated IDDM. The present study demonstrates that I.S. 2.15 T cells induce in vitro immunosuppression. The suppressive effects of I.S. 2.15 T cells are mediated through soluble factor(s) and are independent of T cell activation, cell contact, antigen specificity or the major histocompatibility complex (MHC). By polymerase chain reaction (PCR), I.S. 2.15 T cells contain mRNA species encoding for the potentially immunosuppressive cytokines, interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). The T cell suppressive effects engendered by I.S. 2.15 T cells closely mimic those observed with TGF-beta. Moreover, I.S. 2.15-induced immunosuppression correlates with intracellular levels of TGF-beta mRNA. These results establish that immunoregulatory T cells are present within islets in IDDM-resistant NOD mice and may impact on final disease expression through the production of soluble mediator(s).