Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

Objective A competing endogenous RNA (ceRNA) regulatory network associated with long non-coding RNA (lncRNA) specific for lung adenocarcinoma (LUAD) was constructed based on bioinformatics methods, and the functional mechanism of actinfilament-associated protein 1-antisense RNA1 (AFAP1-AS1) in LUAD was analyzed, in order to provide a new direction for the study of LUAD therapeutic targets. Methods The gene chip of LUAD was downloaded from the Gene Expression Omnibus (GEO), and lncRNA and mRNA with differential expression between LUAD and normal tissues were screened using GEO2R online software, and their target genes were predicted by online databases to construct ceRNA networks and perform enrichment analysis. In cell experiments, AFAP1-AS1 was genetically knocked down and siRNA was constructed and transfected into LUAD cells A549 by cell transfection. CCK8, transwell, scratch assay and flow cytometry were used to detect the ability of cells to proliferate, invade, migrate and apoptosis. Results A total of 6 differentially expressed lncRNA and 494 differentially expressed mRNA were identified in the microarray of LUAD. The ceRNA network involved a total of 6 lncRNA, 22 miRNA, and 55 mRNA. Enrichment analysis revealed that mRNA was associated with cancer-related pathways. In cell assays, knockdown of AFAP1-AS1 inhibited cell proliferation, invasion, and migration, and AFAP1-AS1 promoted apoptosis. Conclusion In this study, we construct a lncRNA-mediated ceRNA network, which may help to further investigate the mechanism of action of LUAD. In addition, through cellular experiments, AFAP1-AS1 is found to have potential as a therapeutic target for LUAD.

With the development of modern medical standards,autoimmune diseases and their associ-ated successive osteoporosis have received increasing attention in recent years.Patients with autoimmune diseases,due to the characteristics of the disease and the prolonged use of glucocorticoid hormone thera-py,may affect the bone formation and bone absorption of the patient,followed by severe successive osteo-porosis,thereby increasing the risk of osteoporotic vertebral fractures.Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures.Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases.Percutaneous vertebro-plasty(PVP)and percutaneous kyphoplasty(PKP)are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures.However,due to the operation of spinal puncture during the operation,there are serious surgical risks such as bone cement leakage,spinal epidural hemorrhage,subdural hemorrhage,and subarachnoid hemorrhage in both PVP and PKP.As a result,it is necessary to evaluate the patient's body before surgery carefully,especially in the case of blood coagulation.This article reports a case of autoimmune disease patient admitted to Peking University People's Hospital due to lumbar 4 vertebral compression fracture combined with Sj?gren's syn-drome.The patient's preoperative examination showed that the activated partial thromboplastin time(APTT)was significantly prolonged.After completing the APTT extended screening experiment and lu-pus anticoagulant factor testing,the multi-disciplinary team(MDT)of Peking University People's Hospi-tal jointly discussed the conclusion that the patient's test results were caused by an abnormal self-immuni-ty anti-copulant lupus(LAC).Based on the results of the laboratory examination,the patient was con-sidered to be diagnosed with combined antiphospholipid syndrome(APS).For such patients,compared with the patient's tendency to bleed,we should pay more attention to the risk of high blood clotting in the lower limbs of the patient,pulmonary clots and so on.With timely anti-coagulation treatment,the patient safely passed the peripheral period and was successfully discharged from the hospital.Therefore,for pa-tients with autoimmune diseases with prolonged APTT in the perioperative period,doctors need to careful-ly identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

Objective:To gain insights into the cognitive processes and utilization patterns of medical students regarding teaching information platforms and resources,and aims to provide valuable references for the implementation of modern medical information technology in educational reforms.Methods:A survey was conducted among all voluntary medical students of grade 2019 to grade 2022.Questionnaire surveys and semi-open interviews were used to investigate.Results:The findings indicated that medical students possess a comprehensive understanding of various teaching platforms,with a high frequency of accessing course materials through these platforms.However,the browsing rate for case analyses recommended by teachers on these platforms remains relatively low.Students demonstrated awareness and utilization of quality courses,particularly MOOCs and micro-courses,which were more frequently utilized compared to other courses.Conclusion:Medical students have a strong awareness of information technology and the ability to solve academic problems through multiple platforms and channels.The construction of teaching platform resources needs to further optimize and improve its simplicity and affinity,and teachers should selectively push high-quality teaching resources to realize the rational application of medical information technology in teaching.

BACKGROUND:Lingual movable wing is a new type of lingual orthodontic technique and the different stretching lengths of the wring affect the torque control effect of anterior teeth.However,there is yet no related biomechanical research. OBJECTIVE:To investigate the displacement trend of dentition during adduction of mandibular anterior teeth and the effect of different wing stretching lengths on the biomechanical effect of mandibular anterior teeth. METHODS:The data of the mandible and lower dentition were collected by cone-beam CT and reconstructed using Mimics software to establish a three-dimensional finite element model of mandibular anterior teeth adducted by the lingual movable wing.The ANSYS software was used to analyze the initial displacement of the mandibular anterior teeth under the following conditions:A,2 mm stretching length;B,2.5 mm stretching length;C,3 mm stretching length;and D,3.5 mm stretching length. RESULTS AND CONCLUSION:The trend of initial displacement of lower dentition:The central incisors moved lingually with depression,the lateral incisors and canines moved mildly lingually with mesial lingual torsion,the second premolar was tilted distally with a marked lingual inclination and the first molar showed an overall mesial inclination with mesial crown eversion.Therefore,in the adduction cases of mandibular tooth extraction,attention should be paid to the lingual movement of the second premolar,which could be offset by corresponding techniques in clinic.The trend of anterior tooth displacement in all directions:from condition A to condition D,in the sagittal direction,the difference value in crown-root displacement of central incisors changed from-11.891 μm to-5.757 4 μm,indicating that the central incisor changes from oblique movement to overall movement.The difference value in crown-root displacement of lateral incisors changed from-11.828 1 μm to-6.711 45 μm,and that of canines changed from-7.572 3 μm to-4.695 5 μm,indicating that the oblique movement of the lateral incisors and canines is also changing to an overall movement.In the vertical direction,from condition A to condition D,the reduction of incisors was gradually increased,while that of canines was gradually decreased.These findings indicate that the stretching length of the wing can affect the oblique movement trend of the anterior teeth.As the wing continues to stretch,the torque control of the lower anterior teeth will become better.

Objective:To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice.Methods:This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3 rd and 4 th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification ( n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results:The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group ( P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550 ±23, 235 ±9, and 856 ±35, respectively, which were significantly higher than 188 ±14, 97 ±6, and 370 ±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively , P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups ( P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group ( P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group ( P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions:hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

Objective:To explore the changes in entero-insular axis function and its role in mice with severe burns.Methods:This study was an experimental study. Ninety C57BL/6J male mice aged 8-10 weeks were divided into sham injury group and burn group (with 45 mice in each group) according to the random number table. A full-thickness scald (hereinafter referred to as burn) wound of 30% of the total body surface area was created on the back of mice in burn group, and the mice in sham injury group were simulated to cause a sham injury. Twenty-four hours after injury, the fasting blood glucose was measured ( n=12), followed by intraperitoneal glucose tolerance test and oral glucose tolerance test; the curve of blood glucose concentration changes over time was plotted, and the area under the curve was calculated ( n=6); the blood was taken from the heart before intraperitoneal injection or gavage of glucose solution and at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution for measuring the plasma insulin and glucagon like peptide-1 (GLP-1) levels using enzyme-linked immunosorbent assay (ELISA), with a sample number of 3; the ileal tissue was taken from 3 mice in each group for detecting the GLP-1 expression and apoptosis levels of intestinal L cells by immunofluorescence staining and TdT-mediated dUTP nick-end labeling staining; the pancreatic islets were collected from 6 mice in each group for glucose-stimulated insulin secretion experiments. After incubation with low glucose (2.8 mmol/L glucose) and high glucose (16.7 mmol/L glucose), the supernatant was taken and the insulin level was detected using ELISA. Thirty-six C57BL/6J male mice aged 8-10 weeks were divided into sham injury group, burn group, and burn+exendin-4 (Ex-4) group (with 12 mice in each group) according to the random number table. The mice in sham injury group and burn group were subjected to the same corresponding treatment as before. The mice in burn+Ex-4 group were injured in the same way as the burn group mice followed by treatment with GLP-1 receptor agonist Ex-4. Twenty-four hours after injury, mouse pancreatic islets were collected, the protein expressions of heavy-chain binding protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected using Western blotting, and the p-PERK/PERK and p-eIF2α/eIF2α ratios were calculated ( n=3), the apoptosis rate of pancreatic islet cells was detected using flow cytometry ( n=3), the glucose stimulated insulin secretion experiment was conducted as before to detect insulin levels in the supernatant ( n=6). Results:Twenty-four hours after injury, the fasting blood glucose of mice in burn group was (7.3±1.0) mmol/L, which was significantly higher than (5.1±0.6) mmol/L in sham injury group ( t=6.36, P<0.05). Twenty-four hours after injury, in the intraperitoneal glucose tolerance test and oral glucose tolerance test, the areas under the curve of blood glucose concentration changes over time of mice in burn group were significantly larger than those in sham injury group (with t values of 4.32 and 6.03, respectively, P<0.05); compared with those in sham injury group, the plasma insulin levels of mice before intraperitoneal injection of glucose solution and the plasma GLP-1 levels of mice before intraperitoneal injection or gavage of glucose solution in burn group were significantly decreased ( P<0.05), and the plasma levels of insulin of mice at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution, as well as the plasma levels of GLP-1 of mice at 30 and 60 minutes after gavage of glucose solution were significantly decreased in burn group ( P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the GLP-1 expression level of intestinal L cells of mice in burn group was significantly decreased ( t=7.74, P<0.05), and the apoptosis level was significantly increased ( t=14.28, P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was (8.5±0.4) ng/mg, which was significantly lower than (15.7±0.3) ng/mg in sham injury group ( t=18.68, P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn group were significantly increased ( P<0.05); compared with those in burn group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn+Ex-4 group were significantly decreased ( P<0.05). Twenty-four hours after injury, the apoptosis rate of pancreatic islet cells of mice in burn group was (32.0±3.0)%, which was significantly higher than (10.3±2.5)% in sham injury group ( P<0.05); the apoptosis rate of pancreatic islet cells of mice in burn+Ex-4 group was (20.0±3.6)%, which was significantly lower than that in burn group ( P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was significantly lower than that in sham injury group ( P<0.05), while the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn+Ex-4 group was significantly higher than that in burn group ( P<0.05). Conclusions:After severe burns, the mice display dysfunction of the entero-insular axis, increased apoptosis of intestinal L cells, decreased synthesis and secretion of GLP-1, endoplasmic reticulum stress and increased apoptosis in pancreatic islet cells and a decrease in glucose-stimulated insulin secretion. The GLP-1 receptor agonist Ex-4 can protect the function of pancreatic islet cells of mice with severe burns, reducing the apoptosis level of pancreatic islet cells and promoting insulin secretion possibly via the alleviation of endoplasmic reticulum stress.

Objective:Using bioinformatics methods to study the immune infiltration mechanism of lupus nephritis(LN)and to explore potential target Chinese medicines,which can provide new directions for clinical treatment of LN.Methods:Gene expres-sion profile microarray dataset of LN was downloaded from GEO database,differential expressed genes(DEGs)were screened using R software,and GO and KEGG enrichment analysis were performed on these DEGs.Protein interaction network analysis of DEGs was performed by applying STRING database,key genes were screened by using Cytoscape,core gene expression was validated by Nephro-seq database,and the infiltration and correlation of 22 kinds of immune cells in LN were calculated by CIBERSORT deconvolution algorithm.Finally,herbal prediction of significantly enriched immune-related biological processes and key target genes were performed by Coremine Medical database.Results:A total of 367 LN-related DEGs were obtained,of which 253 were up-regulated and 114 were down-regulated.GO was mainly enriched in response to viruses,defense response to viruses,regulation of viral life cycle,regulation of viral processes,etc;KEGG was mainly enriched in S.aureus infection,COVID-19,influenza A,complement and coagulation cascade,pertussis,etc.Ten key genes were screened:IFIT3,OAS2,MX1,OAS1,RSAD2,XAF1,ISG15,IFIT1,ITGAM and PTPRC.Immune infiltration by CIBERSORT deconvolution algorithm showed that monocytes and initial B cells were highly expressed in LN,while memory B cells,naive CD4+T cells,follicular helper T cells and resting natural killer cells were lowly expressed in LN.Immune cell correlation analysis showed a positive correlation between initial B cells and plasma cells,a positive correlation between resting natural killer cells and resting dendritic cells,a negative correlation between monocytes and regulatory T cells,and a negative correlation between resting CD4+memory T cells and monocytes.Coremine Medical predicted that Salvia miltiorrhiza,Panax notogin-seng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony were found to be most closely related to immunity in LN.Conclusion:The development and progression of LN are results of the combined involvement of multiple genes and pathways.Mono-cytes,memory B cells,initial CD4+T cells and initial B cells are most closely associated with LN.The predicted Salvia miltiorrhiza,Panax notoginseng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony may be used as target herbs for the poten-tial treatment of LN.

Objective To study the key genes and immune biomarkers of gout and to explore potential target Chinese medicine,which can provide new directions for the clinical treatment of gout.Methods The gout microarray dataset was downloaded from the GEO database,the differential genes were screened using R software,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on these differential genes.The STRING database was applied to analyze the protein interaction network of the differential genes,and the Cytoscape was used to screen the key genes.The protein expression levels of key genes were validated using the ELISA method.Furthermore,the xCell was used to estimate the relative expression and correlation of immune cells in gout.Finally,the significantly enriched immune-related biological processes and key target genes of Chinese medicine were predicted by Coremine Medical database.Results A total of 852 differential gout genes were screened.GO enrichment analysis was mainly enriched in the leukocyte chemotaxis,interleukin-2 production,and regulation of vasculature development;KEGG pathway was mainly enriched in IL-17 signaling pathway,Chemokine signaling pathway,and TNF signaling pathway.Ten key genes,including TNF,IL-6,IL-1β,CXCL8,FOS,and VEGFA etc,were selected.The experimental validation showed that the protein expression levels of key genes were consistent with the expression trends of the chip data.Immune infiltration showed that monocytes,memory B cells,CD8+T-cells and IDC were closely associated with gout.Herbal predictions had identified Ginseng,Panax notoginseng,Scutellaria,Baicalensis,Saururus chinensis,and Salvia miltiorrhiza as potential drugs for the treatment of gout.Conclusion This study identified possible key genes and immune mechanisms contributing to the pathogenesis of gout,and discovered potential targetable traditional Chinese medicine.These key genes and herbs are expected to offer new insights and methods for the treatment of gout.

Objective:To assess the risk of venous thromboembolism (VTE) and anticoagulation-related bleeding of acute critical emergency patients staying in the emergency department at least 72 h, so as to improve the ability of emergency physicians to identify risk factors of VTE and their awareness of safety prevention in these patients.Methods:Multicenter emergency internal medicine patients meeting the inclusion criteria at the same time were collected. Padua and Caprini scores were used to evaluate the risk of VTE and the HAS-BLED score was used to assess the risk of anticoagulation-related bleeding.Results:A total of 930 emergency patients from 7 medical centers were enrolled in our study from January 15, 2021 to March 15, 2021. The proportion of high-risk population with VTE was 50.22% with Padua score and 78.49% with Caprini score, respectively. The proportion of high-risk bleeding (HAS-BLED score) was 40.43%.Conclusions:More than half of the acute critical ill patients who stay in emergency department for more than 72 h are at high risk of VTE. This group of patients have a relatively low risk of anticoagulation-related bleeding.