Electrospun nanofiber scaffolds for soft and hard tissue regeneration / 中国组织工程研究

BACKGROUND:Currently,electrospun nanofibers,which are biomimetic materials of natural extracellular matrix and contain a three-dimensional network of interconnected pores,have been successfully used as scaffolds for various tissue regeneration,but are still faced with the challenge of extending the biomaterials into three-dimensional structures to reproduce the physiological,chemical as well as mechanical properties of the tissue microenvironment. OBJECTIVE:To summarize the process and principles of electrostatic spinning and to explore the applications of the resulting electrospun nanofibers in tissue regeneration of skin,blood vessels,nerves,bone,cartilage and tendons/ligaments. METHODS:With"electrospinning,electrospun nanofibers,electrospun nanofiber scaffolds,tissue regeneration"as the Chinese and English search terms,Google Academic Database,PubMed,and CNKI were searched,and finally 88 articles were included for review. RESULTS AND CONCLUSION:(1)The electrospun nanofibers are a natural fibrous extracellular matrix mimetic material and contain a three-dimensional network of interconnected pores that have been successfully used as scaffolds for a variety of tissue regeneration applications.(2)Several papers have described the great potential of electrospun nanofiber scaffolds applied to the regeneration of skin,blood vessels,nerves,bones,cartilage and tendons/ligaments,providing a solid theoretical basis for its final application in clinical disease treatment,or for its transformation into practical products to enter the market.(3)However,the current research results are mostly based on cell experimental research results in vitro,and whether it can be finally applied to human body still needs clinical verification.(4)At present,many kinds of electrospun products for various clinical needs have been commercialized in and outside China,indicating that the research field of electrospun nanofiber scaffolds for soft and hard tissue regeneration has great research value and application potential.

RAS-selective lethal small molecule 3 inhibits the fibrosis of pathological scar fibroblasts / 中国组织工程研究

BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

A preliminary study of the value of N-terminal pro-B-type natriuretic peptide in patients with end-stage heart failure implanted with magnetic fluid suspended left ventricular assist devices / 中华检验医学杂志

Objective:To investigate the changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its role in predicting major adverse cardiac events (MACEs) in patients with end-stage heart failure (ESHF) before and after implanted a HeartCon left ventricular assist device (LVAD).Methods:The retrospective study included 30 ESHF patients [23 males and 7 females, aged 54.5 (40.8, 60.0) years], who were admitted to TEDA International Cardiovascular Disease Hospital from September 15, 2020 to June 20, 2023 to receive treatment with HeartCon LVAD implantation. Their clinical data were analyzed and NT-proBNP concentrations in their blood samples were measured preoperatively and during the follow-up period. Patients were followed regularly and MACEs, including cardiac death and rehospitalization for right heart failure, were recorded within 6 months of discharge; Logistic regression was used for prognostic analysis, and Receiver Operator Characteristic (ROC) curves were used to assess the adjunctive diagnostic value of NT-proBNP for poor prognosis in LVAD patients. The cut-off values for diagnosing poor prognosis by NT-proBNP were divided into two groups, and survival analysis was performed by Kaplan-Meier and tested by log rank; Cox regression was performed to analyze whether high levels of NT-proBNP at 6 months of follow-up wsa a risk factor for poor prognosis in patients with LVAD.Results:The median preoperative NT-proBNP level in 30 ESHF patients successfully implanted with HeartCon LVADs was 3 251.0 (1 544.5, 6 401.5) pg/ml. It decreased significantly 7 days postoperatively (3 251.0 vs. 1 815.0 pg/ml, P<0.05), and then the decreasing trend slowed. It decreased to 1 182.0 (620.0, 3 385.3) pg/ml on the 90th post-operative day. The preoperative NT-proBNP>3 251.0 pg/ml group had a longer postoperative hospital stay (47 d vs 33 d, Z=-2.138, P=0.032). Multivariate logistic regression analysis, only NT-proBNP at 7 days postoperatively was found to predict poor prognosis in LVAD patients, with an OR of 1.001 ( P=0.01); ROC curves were analyzed for the adjunctive diagnostic value of 7-day postoperative NT-proBNP levels for poor prognosis (cut-off value of 2 083.0 pg/ml), with an AUC of 0.833 ( P=0.002); The Kaplan-Meier survival analysis showed that the time to MACEs within 6 months was significantly shorter in the group with NT-proBNP>2 083.0 pg/mL on postoperative day 7 than in the group with NT-proBNP≤2 083.0 pg/ml (3.538±0.689 vs. 5.471±0.323 months, P=0.004); Cox regression analysis showed that the risk of MACEs was 4.25 times higher in the 7-day postoperative NT-proBNP>2 083.0 pg/ml group than in the NT-proBNP≤2 083.0 pg/ml group ( HR=4.25, P=0.035). Conclusions:The higher the preoperative NT-proBNP level, the longer the postoperative hospital stay in HeartCon LVAD patients. NT-proBNP levels decrease most significantly on postoperative day 7 and is a risk factor for MACEs. It may be used as a prognostic predictor in ESHF patients with implanted LVADs.

Practice and effect evaluation of refined setting of evidence-based reference prescription pre-audit rules in anes-thesiology department / 中国药房

OBJECTIVE To optimize the pre-audit rules for anesthesia prescriptions， improve the audit quality and rational drug use. METHODS The inpatient medical orders of anesthesia department from prescription pre-audit system of the Affiliated Hospital of Qingdao University （hereinafter referred to as “our hospital”） were analyzed from April 1 to 30， 2023. The classification statistics and evidence-based inquiry were carried out for irrational drug use issues； combined with our hospital’s current implementation of the Anesthesiology Clinical Pathway Medication Standards， the audit rules were set in details， and audit management and communication feedback processes were established. The total number of monthly audited orders， the number of pre-audit pop ups， system interception rate， physician modification rate after system audit， pharmacist audit rate， and reasonable rate of medical orders after refined setting of rules （May-December in 2023） were compared with before setting （April in 2023）； the average medication cost per anesthesia session after refined setting of rules was also compared with before setting （May- December in 2022）. RESULTS Irrational drug use in the anesthesia department mainly included inappropriate indications， inappropriate administration routes， inappropriate usage and dosage， inappropriate compatibility， medication problems in special populations， and improper medication during the perioperative period. After the refinement of the rules， the number of pre-audit pop ups in the anesthesia department significantly decreased over time， and gradually reached a stable state after continuous improvement. Compared with before setting， the system interception rate after the refinement of rules （P＜0.001）， physician modification rate after system audit （P＜0.001） both increased significantly， while the pharmacist audit rate significantly decreased （P＜0.001）. There was a linear trend between the reasonable rate of medical orders and the month from May to December in 2023 （P＜0.05）. Compared with before the setting， the average medication cost of anesthesia per session decreased from 720.72 yuan to 528.21 yuan， with a decrease of 26.71%. CONCLUSIONS Based on evidence-based reference， refining pre-audit rules for anesthesia prescriptions can significantly improve the quality of prescription examination， promote rational drug use， and save patient’s medical expenses.

Internet of things based early warning model for lung cancer in COPD patients / 中国现代医生

Objective To use the Internet of things based early warning model of lung cancer to perform early lung cancer screening among chronic obstructive pulmonary disease(COPD)patients in Lishui City.Methods Patients with COPD diagnosed in our hospital from July 2021 to June 2022 underwent plain chest CT,and the 300 patients who had lung nodules detected and agreed to participate in the study were completed with lung nodule target scan + two-and three-dimensional reconstruction to detect gene polymorphisms of CYP1A1,GST and XRCC1 and mirna130a and mir204-5p in peripheral blood.Asked to wear smart hand ring for 10 hours every day while awake from July 2022 to September 2022 to detect vital signs and exercise volume.Review lung nodule target scan + two three dimensional reconstruction in October 2022.If the nodules were larger than before,the patient was truthfully informed of the results.The patient and the specialist of our hospital discussed whether to carry out lung puncture for pathology.Patients with pathologically confirmed lung cancer were progression group and the rest were stable group.Results Totally 240 patients were in the stable group,48 patients were in the progression group,12 patients continued to follow-up after consultation by physicians.There were significant differences in adiposity,mean oximetry,nadir oximetry,forced vital capacity(FVC)predicted,exercise capacity,and lung nodule diameter between the two groups.The expression levels of peripheral mirna-130a,mirna-204-5p were significantly different between the two groups(P<0.001).There were significant differences in CYP1A1,GST,and XRCC1 genotypes in peripheral blood between stable and progressive patients.The areas under the receiver operating characteristic(ROC)curves were mean oxygen saturation(0.681),lowest oxygen saturation(0.735),FVC predicted(0.781),exercise(0.835),lung nodule length diameter(0.825),peripheral blood mirna-130a(0.796),mirna-204-5p(0.893).Conclusion The Internet of things based early warning model for lung cancer can be used for lung cancer screening among COPD patients.

Intelligent identification of livestock, a source of Schistosoma japonicum infection, based on deep learning of unmanned aerial vehicle images / 中国血吸虫病防治杂志

Objective To develop an intelligent recognition model based on deep learning algorithms of unmanned aerial vehicle (UAV) images, and to preliminarily explore the value of this model for remote identification, monitoring and management of cattle, a source of Schistosoma japonicum infection. Methods Oncomelania hupensis snail-infested marshlands around the Poyang Lake area were selected as the study area. Image datasets of the study area were captured by aerial photography with UAV and subjected to augmentation. Cattle in the sample database were annotated with the annotation software VGG Image Annotator to create the morphological recognition labels for cattle. A model was created for intelligent recognition of livestock based on deep learning-based Mask R-convolutional neural network (CNN) algorithms. The performance of the model for cattle recognition was evaluated with accuracy, precision, recall, F1 score and mean precision. Results A total of 200 original UAV images were obtained, and 410 images were yielded following data augmentation. A total of 2 860 training samples of cattle recognition were labeled. The created deep learning-based Mask R-CNN model converged following 200 iterations, with an accuracy of 88.01%, precision of 92.33%, recall of 94.06%, F1 score of 93.19%, and mean precision of 92.27%, and the model was effective to detect and segment the morphological features of cattle. Conclusion The deep learning-based Mask R-CNN model is highly accurate for recognition of cattle based on UAV images, which is feasible for remote intelligent recognition, monitoring, and management of the source of S. japonicum infection.

Detection of IgG protein in human urine based on vertical flow paper microfluidic chip / 生物工程学报

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.

Physiological regulation of salicylic acid on Helianthus tubeuosus upon copper stress and root FTIR analysis / 生物工程学报

Phytoremediation plays an important role in the treatment of heavy metal pollution in soil. In order to elucidate the mechanism of salicylic acid (SA) on copper absorption, seedlings from Xuzhou (with strong Cu-tolerance) and Weifang Helianthus tuberosus cultivars (with weak Cu-tolerance) were selected for pot culture experiments. 1 mmol/L SA was sprayed upon 300 mg/kg soil copper stress, and the photosynthesis, leaf antioxidant system, several essential mineral nutrients and the changes of root upon copper stress were analyzed to explore the mechanism of copper resistance. The results showed that Pn, Tr, Gs and Ci upon copper stress decreased significantly compared to the control group. Meanwhile, chlorophyll a, chlorophyll b and carotenoid decreased with significant increase in initial fluorescence (F0), maximum photochemical quantum yield of PSⅡ (Fv/Fm), electron transfer rate (ETR) and photochemical quenching coefficient (qP) content all decreased. The ascorbic acid (AsA) content was decreased, the glutathione (GSH) value was increased, the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in the leaves were decreased, and the peroxidase (POD) activity was significantly increased. SA increased the Cu content in the ground and root system, and weakened the nutrient uptake capacity of K, Ca, Mg, and Zn in the root stem and leaves. Spray of exogenous SA can maintain the opening of leaf stomata, improve the adverse effect of copper on photosynthetic pigment and PSⅡ reaction center. Mediating the SOD and APX activity started the AsA-GSH cycle process, effectively regulated the antioxidant enzyme system in chrysanthemum taro, significantly reduced the copper content of all parts of the plant, and improved the ion exchange capacity in the body. External SA increased the content of the negative electric group on the root by changing the proportion of components in the root, promoted the absorption of mineral nutrient elements and the accumulation of osmoregulatory substances, strengthened the fixation effect of the root on metal copper, and avoided its massive accumulation in the H. tuberosus body, so as to alleviate the inhibitory effect of copper on plant growth. The study revealed the physiological regulation of SA upon copper stress, and provided a theoretical basis for planting H. tuberosus to repair soil copper pollution.

A case of congenital systemic lipodystrophy with exfoliated xanthoma caused by AGPAT2 gene mutation / 基础医学与临床

Objective To analyze the clinical characteristics and genotype of a patient with congenital systemic lip-odystrophy(CGL)type 1 associated with exudative xanthoma caused by AGPAT2 gene mutation,and to provide ev-idence for clinical and genetic diagnosis of the disease.Methods Clinical data of the patient such as medical histo-ry,physical examination and laboratory examination were collected.Peripheral venous blood was collected for whole exome sequencing analysis and Sanger sequencing verification,and treatment was provided to patients according to the changes of condition.Results The clinical manifestations of the patient were subcutaneous fat reduction,fatty liver,spleen enlargement,kidney enlargement,high blood sugar and lipids,severe insulin resistance,scattered yellow rash on limbs,which was confirmed as xanthoma.The results of whole exon sequencing showed that the AGPAT2 gene of the patient had a heterozygous nonsense mutation of c.202C＞T:p.R68?and c.646A＞T:p.K216?,and the former was the pathogenic mutation site.Follow-up therapy covers improvement of lifestyle,low-fat diet and regular exercise.The rashes subsided after active lipid-lowering therapy.Conclusions Apart from typical lipody-strophy,the patient was accompanied by exanthemous xanthoma.No CGL1 patient with exanthemous xanthoma has been reported in the domestic literature database up to now,and the genetic test results showed that there was a c.202C＞T heterozygous mutation of AGPAT2 gene.This gene site has not been reported in the literature,and its functional verification needs to be further studied.

Preparation and verification of dezocine polylactic acid-glycolic acid block copolymer microspheres / 中华麻醉学杂志

Objective:To prepare and preliminary verify dezocine polylactic acid-glycolic acid block copolymer (PLGA) microspheres.Methods:Preparation of dezocine PLGA microspheres Dezocine 120 mg, PLGA 0.1 g and the solubilizing additive poloxamer 0.1 g were dispersed in tetrahydrofuran solvent to form an organic phase solution. Sodium chloride and polyethylene glycol were dissolved in water for injection to form an inner aqueous phase solution and an outer aqueous phase solution. After the organic phase solution 20 ml was mixed with the inner aqueous phase solution 20 ml to form a water/oil colostrum, the water/oil colostrum was added to the outer aqueous phase solution to form a water/oil/water multiple emulsion, which was fully mixed with lyophilized powder protective agent and freeze-dried to prepare dezocine PLGA microspheres. Verification Eighteen clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), dezocine ordinary preparation group (group D 1) and dezocine PLGA microspheres group (group D 2). Normal saline, dezocine injectio (dose 1 mg) and dezocine PLGA microsphere injectio (dose 0.2 μg) 0.2 ml were intramuscularly injected in C, D 1 and D 2 groups, respectively. The concentrations of dezocine in plasma were measured at 30 min and 1, 2, 3, 4, 5, 6, 7 and 8 h after administration, and thermal paw withdrawal latency was measured at T 1-T 3, T 5 and T 9. Tissues from the injection site were obtained on day 7 after intramuscular injection, and the inflammatory response was observed after HE staining. Results:Compared with group C, the thermal paw withdrawal latency was significantly prolonged at T 1-T 3 in group D 1 and at T 1-T 3, T 5 and T 9 in group D 2 ( P<0.05). Compared with group D 1, the thermal paw withdrawal latency was significantly prolonged at T 5 and T 9, and the plasma concentrations of dezocine were increased at T 6-T 9 in group D 2 ( P<0.05). Compared with the values at T 2, the plasma concentrations of dezocine were significantly decreased at T 4-T 9 in group D 1 ( P<0.05), and no significant change was found in the plasma concentrations of dezocine at T 3-T 9 in group D 2 ( P>0.05). On 7 days after injection, no inflammation was found in the local tissues in C, D 1 and D 2 groups, and no significant difference was found among the three groups. Conclusions:The sustained-release formulation of dezocine PLGA microspheres is successfully prepared, and it can maintain stable blood concentrations, effectively prolongs the action time of the drug and has significant sustained-release effect in rats.

Effect of acute sleep fragmentation on cognitive function and hippocampal Homer1a expression in aged rats / 中华行为医学与脑科学杂志

Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.

Role of Homer1a/mGluR5 signaling pathway in cognitive dysfunction induced by sleep deprivation in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.

Correlation of endoscopic evaluation with laboratory indices and clinical disease activity in Crohn disease patients with different intestinal involvement / 中华消化内镜杂志

Objective:To investigate the correlations of endoscopic evaluation results with laboratory indices and clinical disease activity in Crohn disease (CD) patients with different intestinal involvement.Methods:Data of 147 patients diagnosed as having CD who visited the Department of Gastroenterology, Zhongnan Hospital of Wuhan University from July 1, 2017 to June 30, 2022 were collected retrospectively. According to the involvement of intestinal segment, patients were divided into three groups: the group with isolated small intestinal involvement ( n=55), the group with both small intestinal and large intestinal involvement ( n=48), and the group with isolated large intestinal involvement ( n=44). Correlations of endoscopic evaluation (based on CDEIS) with laboratory indices and clinical disease activity (based on Harvey-Bradshaw index) were analyzed. Results:C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) could be used for the prediction of endoscopic disease activity. The areas under curve (AUC) of receiver operator characteristic (ROC) were 0.677 (0.506-0.849) and 0.744 (0.597-0.890), respectively. In terms of determing clinical disease activity, clinical Harvey-Bradshaw index was consistent with endoscopic CDEIS score in 65.3% (96/147) patients, showing a low positive correlation ( r=0.260, P<0.05). In subgroup analysis for patients with isolated small intestinal involvement, CRP showed no predictive value for clinical disease activity [AUC (95% CI): 0.617 (0.461-0.773), P=0.148], while for endoscopic activity neither CRP nor ESR showed predictive value [AUC (95% CI): 0.537 (0.146-0.929), P=0.829; AUC (95% CI): 0.571 (0.153-0.990), P=0.680]. Furthermore, for patients with isolated small intestinal involvement and both small intestinal and large intestinal involvement, no correlation was found between clinical Harvey-Bradshaw index and endoscopic CDEIS score ( r=0.222, P=0.092; r=0.142, P=0.322). Conclusion:For CD patients with small intestinal involvement, especially isolated small intestinal involvement, laboratory indices and clinical disease activity cannot accurately reflect endoscopic disease activity. Great importance should be attached to evaluation of the extent and activity of intestinal lesions by endoscopy, especially enteroscopy.

Clinical prospects and research strategies of long non-coding RNA encoding micropeptides / 浙江大学学报·医学版

Long non-coding RNAs (lncRNAs) which are usually thought to have no protein coding ability, are widely involved in cell proliferation, signal transduction and other biological activities. However, recent studies have suggested that short open reading frames (sORFs) of some lncRNAs can encode small functional peptides (micropeptides). These micropeptides appear to play important roles in calcium homeostasis, embryonic development and tumorigenesis, suggesting their potential as therapeutic targets and diagnostic biomarkers. Currently, bioinformatic tools as well as experimental methods such as ribosome mapping and in vitro translation are applied to predict the coding potential of lncRNAs. Furthermore, mass spectrometry, specific antibodies and epitope tags are used for validating the expression of micropeptides. Here, we review the physiological and pathological functions of recently identified micropeptides as well as research strategies for predicting the coding potential of lncRNAs to facilitate the further research of lncRNA encoded micropeptides.

Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel / 药物分析学报

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99％of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

Construction of an entrustable professional activities framework for medical undergraduates / 中华医学教育探索杂志

Objective:To construct an entrustable professional activities (EPAs) assessment framework for undergraduate medical students suited to the national conditions in China.Methods:The Delphi method was used to construct an EPAs assessment framework for medical undergraduates. Twenty-one clinical experts across China were invited to participate in two rounds of Delphi consultation.Results:All the 21 experts completed the two rounds of Delphi consultation. The effective questionnaire response rates of the two rounds of consultation were 100.0% (21/21). For the first-round expert consultation, the W values of importance and feasibility scores of EPAs were 0.182 and 0.173 (both P<0.05), respectively. For the second-round expert consultation, the W values of importance and feasibility scores of EPAs were 0.167 and 0.152 (both P<0.05), respectively. According to the second-round Delphi consultation, the importance and feasibility scores of all 14 EPAs indicators were >3.5 points, with the coefficients of variation <0.25 points. We preliminarily established 12 EPAs indicators and 42 key assessment points and determined the expected entrustment levels of each EPA at different stages for medical undergraduates. Conclusion:This study preliminarily constructed an EPAs assessment framework for medical undergraduates, which provides a new evaluation method for the cultivation of medical undergraduates in China.

Age estimation based on machine learning and thin-layer CT of sternal end of clavicle / 中国法医学杂志

Objective The Kellinghaus grading method was used to manually read and grade the thin-layer CT of sternal end of clavicle,and a variety of traditional statistical methods as well as machine learning methods were used to construct age estimation models for adolescents and adults in early adulthood,to explore the value of the application of machine learning technology in the study of age estimation of the Han Chinese population in Sichuan.Methods Thin-section CT images of the chest were retrospectively collected from 491 individuals aged 10～30 years,and the collected samples were assigned a reading grade with reference to the Kellinghaus grading method.10%of the xases were randomly selected as the test set,and the remaining data were used as the training set to construct a variety of traditional statistical regression models and machine learning models for estimating the age of adolescents and adults in early adulthood,and the performance of the models was evaluated by using the mean absolute error(MAE).Results The statistical regression model with the best efficacy was the cubic regression model,with an MAE value of 1.34 for males and 1.57 for females;of the three machine learning models,the Random Forest model had the best predictive efficacy for males,with an MAE value of 1.39,and the Support Vector model had the best predictive efficacy for females,with an MAE value of 1.51.Conclusion In the construction of age estimation models for sternal end of clavicle,the machine learning model has a certain improvement in the accuracy of age prediction,but there is no obvious advantage compared with the traditional statistical regression model,and the use of the machine learning method in age estimation based on sternal end of clavicle still needs further exploration.

The difference of gray matter volume and its correlation with clinical characteristics in patients with anxious depression / 中华行为医学与脑科学杂志

Objective:To explore the difference of gray matter volume between anxious depression(AD)and non anxious depression(NAD) patients, and its correlation with clinical characteristics.Methods:One hundred and fifty patients with depression were included from September 2014 to October 2018, meanwhile 62 healthy controls with matching demographic characteristic were recruited. The severity of the patients was assessed by Hamilton depression scale-17(HAMD-17). Patients were divided into anxious depression group(AD group, n=80)and non-anxious depression group (NAD group, n=70) according to whether anxiety/somatization factor scored 7. All subjects were scanned with 3.0 T underwent structural MRI scan. The structural magnetic resonance data were preprocessed by voxel-based morphometry (VBM). The rest toolkit was used to calculate the difference of gray matter volume among the three groups. By SPSS 19.0, post-hoc t test was used for pairwise comparison and Pearson correlation analysis was performed between gray matter volume and clinical factors in patients with anxious depression. Results:Compared to the NAD group, the gray matter volume of the right middle frontal gyrus(MNI: x=28.5, y=21.0, z=48.0, t=-4.83, Bonferroni multiple comparison adjustment, P<0.05/3) and left dorsolateral superior frontal gyrus(MNI: x=-18.0, y=27.0, z=43.5, t=-6.08, Bonferroni multiple comparison correction, P<0.05/3)were significantly decreased in AD group. Correlation analysis found that the gray matter volume of the right middle frontal gyrus in patients with anxious depression was negatively correlated with the insight of anxiety/somatization factor score ( r=-0.36, P=0.001). Conclusion:The volume of prefrontal lobe in patients with anxiety depression is lower than that in patients with non anxiety depression, which may be related to the serious clinical symptoms in patients with anxiety depression.The decrease of right middle frontal gyrus volume can be used as a potential biological marker for the severity of impaired insight.

The Prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease / 预防医学

Objective@#To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data.@*Methods@#The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period.@*Results@#The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July.@*Conclusion@#The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.

Epidemiological characteristics of notifiable infectious diseasesin Zhejiang Province, 2021 / 预防医学

Objective@#To investigate the epidemiological features of notifiable infectious diseases in Zhejiang Province in 2021, so as to provide the evidence for formulating infectious disease control measures.@*Methods@#The data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2021 were retrieved from the Infectious Disease Surveillance System of China Information System for Disease Control and Prevention. The incidence and mortality of notifiable infectious diseases in Zhejiang Province in 2021 were descriptively analyzed.@*Results@#Totally 29 types of notifiable infectious diseases with 396 623 cases and 391 deaths were reported in Zhejiang Province in 2021, with a reported incidence of 614.28/105 and a reported mortality of 0.605 6/105, respectively. There were 93 204 cases with class B notifiable infectious diseases, with a reported incidence rate of 144.35/105 and 303 419 cases with class C notifiable infectious diseases, with a reported incidence rate of 469.92/105; while no cases with class A notifiable infectious diseases were reported. Syphilis (39.45/105), tuberculosis (37.12/105), viral hepatitis (31.90/105) and gonorrhea (26.34/105) were the four most common class B notifiable infectious diseases, and AIDS (0.477 0/105) and pulmonary tuberculosis (0.116 2/105) were the two most deadly class B notifiable infectious diseases, while hand, foot and mouth disease (192.00/105), other infectious diarrhea (184.24/105) and influenza (86.45/105) were the three most common class C notifiable infectious diseases. According to the transmission route, intestinal and respiratory infectious diseases were the two most common infectious diseases, with reported incidence rates of 384.10/105 and 133.73/105, respectively; and according to the reported region, the highest incidence of class B notifiable infectious diseases was reported in Zhoushan and Ningbo cities, and the highest incidence of class C notifiable infectious diseases was reported in Ningbo City. Totally 1 101 COVID-19 cases were reported in Zhejiang Province in 2021, including 712 confirmed cases and 389 asymptomatic cases, and no deaths occurred.@*Conclusions@#The reported incidence of notifiable infectious diseases declined in Zhejiang Province in 2021 as compared to that prior to COVID-19 epidemics, with remarkable reductions in the incidence of respiratory and intestinal infectious diseases. The management of pulmonary tuberculosis, viral hepatitis and AIDS requires to be reinforced during the containment of COVID-19, to prevent the seasonable epidemic of influenza, hand, foot and mouth disease and other infectious diarrhea in Zhejiang Province.