OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Background Preterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years. Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth. However, whether sleep status could mediate the association between heat exposure and preterm birth remains unclear. Objective To evaluate the association between maternal heat exposure in early pregnancy and preterm birth, and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth. Methods A birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital (Guangzhou Panyu District He Xian Memorial Hospital) from 2017 until now. Pregnant women (with gestational age between 8 and 13 weeks) were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent. Then they were followed up until delivery. A total of 3 268 pregnant women were included for the final analysis. Questionnaires were distributed to collect the demographic characteristics, lifestyles, and sleep status of pregnant women. Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy. The 75th, 80th, 85th, 90th, and 95th percentiles (P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅) of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure. Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status (sleep duration, night sleep timing, and wake up timing). The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed. Results Among all the included participants, 165 newborns were preterm births with an incidence rate of 5.0%. Heat exposures with thresholds of P₉₀ and P₉₅ increased the risk of preterm birth, with ORs (95%CIs) of 1.66 (1.04-2.57) and 1.90 (1.03-3.33), respectively (P<0.05). Heat exposures with thresholds of P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅ decreased the sleep duration (<9 h vs. ≥9 h, control group: ≥9 h), and the ORs (95%CIs) were 1.51 (1.25-1.83), 1.44 (1.17-1.77), 1.35 (1.08-1.70), 1.43 (1.09-1.87), and 1.45 (1.00-2.13), respectively. Heat exposures with P₇₅ and P₈₀ thresholds resulted in earlier wake up timing (<8: 00 vs. ≥8: 00, control group: <8: 00), with ORs (95%CIs) of 0.77 (0.63-0.93) and 0.76(0.61-0.93), respectively. No significant association was observed between heat exposure and night sleep timing. The mediation analyses showed that under heat exposure with P₉₀ threshold, a statistically significant mediation effect was observed for sleep duration, and the proportion mediated was 6.07% (95%CI: 0.17%-25.00%) (P<0.05). No significant mediation effect was observed for night sleep timing and wake up timing. Conclusion An elevated risk of preterm birth after heat exposure in early pregnancy may be partly mediated through reducing sleep duration.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Objective To develop a new type of lumbar prosthesis,movable artificial lumbar vertebral body (MALV) and evaluate the stability and activity of the prosthesis by in vitro biomechanical test.Methods Fifteen adult fresh lumbar spine specimens were randomly divided into three groups:intact group,fusion group and non-fusion group.The anatomical parameters of L2 vertebral body and adjacent intervertebral discs were collected by software (Mimics 16.0,Materialise Company,USA) and the new prosthesis was personalized by 3D printing and mechanical processing.All specimens in fusion group and in non-fusion group were implanted with titanium cage,titanium plate and MALV respectively after partial resection of L2 vertebra and adjacent intervertebral disc.No other intervention was conducted on physiological specimens.All specimens were examined by imaging to determine the position of the prosthesis and the condition of the spinal cord.Specimens in all groups were subjected to a 7.5 N · m load biomechanical test in flexion,extension,left and right lateral bending,left and right rotation aiming to evaluate the mobility of operative site and adjacent discs.Results The new prosthesis consists of three parts,vertebral body,intervertebral disc and composite material ball.All 15 cadavers were free of spinal deformity,fracture and osteoporosis.Postoperative radiographic examination indicated no prosthesis displacement and spinal compression without adverse phenomena.The results in vitro mechanical test were as followed.There was no statistical difference in ROM of the T12L1 intervertebral in non-fusion group (3.68°±0.86°,3.52°± 0.86°,2.64°±0.93°,2.58°±0.76° respectively) and in intact group (3.98°±0.90°,3.74°±0.91°,2.94°±1.10°,2.96°±0.86° respectively) in flexion,extension,left and right lateral bending (P＞0.05).The ROM of the T12L1 intervertebral in fusion group (5.28°±0.83°,5.32°±0.42°,4.72°±1.10°,4.94°±1.17° respectively) was significantly larger than that in intact group and non-fusion group (P＜0.05).There was no statistically significant difference between the ROM of L1.2 and L2.3 intervertebral in flexion,extension and left and rightlateral bending in the non-fusion group (ROM of L1.2 were 4.62°±0.51 °,4.34°±0.67°,3.16°±0.55°,3.28°±0.41 ° respectively;ROM of L2.3 were 4.54°±0.58°,4.36°±0.65°,3.26°±0.21°,3.42°±0.37° respectively) and the intact group (ROM of L1.2 were 4.10°±0.53°,3.72°±0.42°,2.74°±0.50°,3.04°±0.40° respectively;ROM of L2.3 were 4.26°±0.72°,4.08°±0.77°,3.00°±0.36°,3.20°±0.31° respectively) (P＞0.05).The ROM of L1.2 and L2.3 in intact group and in non-fusion group were significantly greater than those in the fusion group (ROM of L1.2 were 1.10°± 0.35°,1.28°±0.31°,0.84°±0.34°,0.80°± 0.43° respectively;ROM of L2.3 were 1.14°±0.30°,1.18°±0.28°,0.94°± 0.36°,1.06°±0.32°) (P＜0.05).There was no statistically significant difference in the ROM of the T12-L3 full segment in the left and right rotation of the three groups (Intact group:4.47°± 0.99°,4.40°±0.70°;Non-fusion group:4.60°±0.90°,4.50°±0.77°;Fusion group:3.85°±0.50°,3.72°±0.70°)(P＞0.05).Conclusion The MALV can retain the mobility of the operative site in flexion,extension,lateral bending and rotation.Furthermore,it can effectively avoid the increased mobility of adjacent segment intervertebral.After implantation,the prosthesis can obtain satisfied immediate stability.

Objective To investigate the effects of virtual reality prism adaptation on visuospatial neglect in stroke patients.Methods Thirty stroke patients with visuospatial neglect were studied.The subjects were divided into atreatment group and a control group.The subjects in the treatment group were treated with virtual reality prism adaptation and routine rehabilitation interventions for 2 weeks,while those in the control group were treated with routine rehabilitation interventions only.All the patients performed a battery of spatial attention tests including line bisection,letter cancellation,clock drawing and the Attention Network Test at the beginning and after 2 weeks of treatment.Results The virtual reality prism adaptation training had significant positive effects on all the measures of visuospatial neglect.Pair-wise comparisons confirmed significant differences between the treatment and control groups after 2 weeks of treatment with regard to all of the measures.Conclusions Virtual reality prism adaptation treatzment combined with routine rehabilitation can be more effective than conventional measures alone in improving the visuospatial performance of stroke survivors.

Objective To analyze the clinical characteristics of childhood systemic lupus erythematosus (SLE) patients with severe gastrointestinal manifestations,especially cases with acute and severe abdominal pain,so as to improve the recognition of severe and acute gastrointestinal manifestations of SLE during pediatric diagnosis and treatment.Methods Medical records of 119 patients with SLE under the age 16 years old in Peking Union Medical College Hospital from Jan.2010 to Mar.2013 were reviewed and gastrointestinal manifestations were retrospectively analyzed.All patients were diagnosed as SLE according to 1997 American College of Rheumatology (ACR) revised classification criteria.Results Gastrointestinal involvement was recorded in 24 children (20.2％).The median (range) age at the time of initial gastrointestinal manifestations was (13.5 ± 2.0) years (6-15 years).The ratio of female to male was 1.0 ∶ 2.4.And in 4 cases,gastrointestinal manifestations occurred as the initial symptoms.Abdominal pain was the most frequent symptom,present in 13 patients (54.2％),11 cases (45.8％) had nausea and vomiting,4 cases (16.6％) had abdominal distension,and 3 cases (12.5％) had diarrhea.Abnormal liver function was found by lab test in 8 cases,without obvious symptoms or the proofs of any virus infection.Acute and severe abdominal pain was found in 9 cases,of whom 6 patients were diagnosed as intestinal pseudo-obstruction (2 cases with bilateral ureterohydronephrosis),1 case had acute peritonitis with surgery,1 case was diagnosed as protein losing enteropathy and 1 case had acute pancreatitis.Liver impairment also occurred in SLE.All cases got alleviated with the treatment of steroids and immunosuppressive drugs.Significant difference was found in the occurrence of hydroureter and hydronephrosis and albumin concentrations between SLE digestive and non-digestive system involvement children.However,there was no remarkable difference in the erythrocyte sedimentation rate,or the involvement of kidney and blood system and central nervous system between the 2 groups.Conclusions SLE is a common autoimmune disease in children involving multiple systems.The severity of gastrointestinal involvement is underestimated.Gastrointestinal manifestations can be initial symptoms of SLE.Intestinal pseudo-obstruction,protein losing enteropathy,and acute pancreatitis are uncommon but severe gastrointestinal manifestations of SLE patients should be fully recognized.It is vital for pediatric physicians to make early diagnosis and begin timely treatment on SLE with Corticosteroid and cyclophosphamide.

Objective To explore the role of left frontoparietal pathway in controlling spatial attentional function. Methods 60 healthy, right-handed humans (30 males and 30 females) aged 18~22 years were recruited. They were divided into frontal group (n=30) and parietal group (n=30) in accordance with sex for either the left dorsolateral prefrontal cortex or the left posterior parietal cortex stimuli study, respectively. They were measured with the Attention Network Test following the continuous theta burst stimulation to the left frontoparietal pathway. Results During the Attention Network Test, the efficiencies of alerting network improved in participants after both the left dorsolateral prefrontal cortex and left posterior parietal cortex stimuli. However, the efficiency of orienting network was deficit after the left dorsolateral prefrontal cortex stimuli. Conclusion Inhibition of the left frontoparietal pathway may improve the alerting function of spatial attention network.

To illustrate the complex fermentation process of submerged culture of Antrodia camphorata ATCC 200183, we observed the morphology change of this filamentous fungus. Then we used two optimization models namely response surface methodology (RSM) and artificial neural network (ANN) to model the fermentation process of Antrodia camphorata. By genetic algorithm (GA), we optimized the inoculum size and medium components for Antrodia camphorata production. The results show that fitness and prediction accuracy of ANN model was higher when compared to those of RSM model. Using GA, we optimized the input space of ANN model, and obtained maximum biomass of 6.2 g/L at the GA-optimized concentrations of spore (1.76x 10(5) /mL) and medium components (glucose, 29.1 g/L; peptone, 9.3 g/L; and soybean flour, 2.8 g/L). The biomass obtained using the ANN-GA designed medium was (6.1+/-0.2) g/L which was in good agreement with the predicted value. The same optimization process may be used to improve the production of mycelia and bioactive metabolites from potent medicinal fungi by changing the fermentation parameters.
Algorithms ; Antrodia ; genetics ; metabolism ; Culture Media ; chemistry ; metabolism ; Fermentation ; Mycelium ; metabolism ; Neural Networks (Computer)

Objective The abnormal proliferation of renal cells underlies the pathology of progressive glomerulosclerosis.Cell proliferation is regulated by cell regulatory proteins.This study aims to investigate the expression of cyclin-dependent kinase inhibitor P16INK4a in renal tissue of patients with primary mesangial proliferative glomemlonephritis(MsPGN)and its clinical significance.Methods Paraffinembedded renal biopsy renal tissue sections from 36 patients with MsPGN were detected by immunohistochemical staining.Normal renal ti8.Sue sections from 6 nephrectomized patients with trauma were used as controls.Possible correlation between p16 positive area and sclerotic and crescentic glomeruli,blood pressure,serum creatinine,endogenous creatinine clearance rate,and total proteinuria were evaluated.Resuits There were very few expression of P16INK4a in normal glomemli and renal tubular-interstitial.Compared to the normal comrol group,the expression of P16INK4a in 36 renal biopsy specimens with MsPG'N was significantly higher(P<0.01),especially in sclerotic and crescentic glomeruli,and it had wild expression of the same components in no sclerotic and crescentic glomeruli.There was a statistic difference(P<0.01).No statistic difference was found between the expression of P16 INK4a in renal tubular-interstitial of two groups(P>0.05).Therewag positive correlation among P16 INK4a of glomeruli without use of glucocorticoid/immunoinlfibitors and ACEI/ARB(r=0.774,0.497,P<0.01),also blood pressure and 8ul～m creatinine(r=0.64,0.473,P<0.01).It was negstively correlated with endogenous creatinine clearance rate and total proteinuria(r=-0.487,-0.694,P<0.01).There is no correlation between P16INK4s and clinical data in renal tubular-interstitial.Conclusion This study demonstrated that overexpression of P16INK4a in renal tissue with MsPGN may promote the regression ofabnormal proliferation and senescence cells,and induce sclerotic and crescentic glomeruli.The expression level of P16 INK4a not only reflected the degree of renal function,but also hypertension and proteinuria.In brief,expression of P16INK4a may be an important marker in renal sclerotic or crescentic glomeruli of MsPGN.Some drugs may prevent the expression of P16INKa.