OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Formaldehyde is a prevalent organic solvent in industrial and indoor environment,which can seriously harm human health,so it is of great significance to develop highly sensitive formaldehyde sensors with fast response,low detection limit and long life.In this study,the NiO-In2O3 composite structure was prepared using indium-based metal organic framework(In-MOF)as the precursor,and the formaldehyde gas sensor was constructed with In2O3 and NiO-In2O3 composite structure as the sensitive material.The results demonstrated that the In2O3 material had a microflower-like structure,while the NiO-In2O3 composite structure was composed of NiO nanoparticles attached to the surface of In2O3.The sensor exhibited excellent detection performance for formaldehyde in the environment of relative humidity of 33%and 75%,especially the response characteristic of the NiO-In2O3 composite structure sensor to formaldehyde was considerably better than that of the In2O3 sensor under the same test conditions,which was closely related to the catalytic effect of NiO and the heterogeneous structure formed between NiO and In2O3.The NiO-In2O3 composite structure sensor had a response value of 21.3 and 12.6 to 10 μL/L formaldehyde when the relative humidity was 33%and 75%at 200℃.The response/recovery time was 4/6 s and 7/10 s,and the limit of detection(LOD)was 1.2×10-7 μL/L and 4.1×10-5 μL/L respectively.Meanwhile,the sensor had excellent selectivity and long-term stability.This sensor showed a wide application prospect in the field of high-performance detection of low concentration of formaldehyde gas.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

Objective To investigate the safety and efficacy of interventional therapy in patients with secondary atrial septal defect(ASD)with complete aortic rim deficiency.Methods 402 patients with ASD who underwent transcatheter closure and followed up in outpatient at both 6-month and 1-year in the Department of Cardiology,Zhongshan Hospital,Fudan University from January 2018 to June 2020 were enrolled.They were divided into complete aortic rim deficiency group and normal aortic rim group.The clinical features,interventional parameters,and complications were compared between the two groups.Echocardiographic were used to evaluate the outcome.Results The occluder size was larger in the aortic rim deficiency group([26.4±6.9]mm,n=128)than that in normal aortic rim group([23.4±7.7]mm,P＜0.001;n=274).Both groups exhibited no major postoperative complications,and significant improvements were observed in right heart remodeling following the operation,including pulmonary artery pressure decreasing,the diameters of the right atrium and right ventricle reducing,and the degree of tricuspid regurgitation reducing(P＜0.001).There was no significant change in left ventricular ejection fraction in all patients.Conclusion Transcatheter closure of ASD with complete aortic rim deficiency is safe and feasible.

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.
COVID-19/prevention & control* ; China/epidemiology* ; Humans ; Machine Learning ; Pandemics/prevention & control* ; Policy ; Reproducibility of Results ; SARS-CoV-2

Cardiac Catheterization ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Treatment Outcome ; Tricuspid Valve/surgery* ; Tricuspid Valve Insufficiency/surgery*

ObjectiveTo predict the potential targets and mechanism of Jingfang mixture in the treatment of H1N1 influenza and provide references for clinical application of Jingfang mixture. MethodThe active components and targets of Jingfang mixture against H1N1 influenza were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），SwissTargetPrediction， and TargetNet. The targets of H1N1 influenza were obtained from GeneCards，Online Mendelian Inheritance in Man （OMIM）， and DisGeNET and standardized by UniProt KB. The intersection targets were obtained by Venny 2.1.0. The "drug-component-target" network was constructed with Cytoscape 3.2.1 and analyzed for the topological attributes. The intersection targets were uploaded to STRING 11.5 to obtain the protein-protein interaction （PPI） network. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis were carried out by Metascape. Finally，the top active components ranked by degree were docked to the core targets by Autodock vina and visually analyzed by PyMOL. Balb/c female rats were used for experimental verification. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in lung tissues. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of tumor necrosis factor-α（TNF-α），interleukin-10（IL-10）， and interleukin-17（IL-17）. Real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels in lung tissues. ResultThere were 144 active components in Jingfang mixture. A total of 421 target genes of Jingfang mixture and 2 956 targets of H1N1 influenza were identified，including 199 common targets. Topological analysis showed that the core components of Jingfang mixture against H1N1 influenza included quercetin，luteolin， and kaempferol，and the core targets included prostaglandin-endoperoxide synthase 2（PTGS2），estrogen receptor alpha（ESR1），inducible nitric oxide synthase 2（iNOS2），peroxisome proliferator-activated receptorγ（PPARγ），and cyclooxygenase-1（PTGS1）. GO enrichment yielded 697 items in biological process （BP） （P<0.01）， 59 items in molecular function （MF）（P<0.01）， and 21 items in cellular component （CC） （P<0.01）. A total of 132 signaling pathways （P<0.01） were obtained by KEGG enrichment analysis， including phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway，most of which were related to the regulation of immune inflammation. Molecular docking showed that the binding energy of the active components of Jingfang mixture to the core targets was less than -5.0 kcal·mol^-1，indicating good binding activity. HE staining showed that the lung tissues were significantly improved after drug intervention，and Real-time PCR and Western blot showed that Jingfang mixture could reduce the mRNA and protein expression of PI3K and Akt in lung tissues. ConclusionJingfang mixture can play an anti-viral effect against the influenza A virus through multiple components，multiple targets， and multiple pathways. The active components quercetin，luteolin， and kaempferol may control the inflammation and regulate immunity on the PI3K/Akt，MAPK， and other signaling pathways by acting on targets such as PTGS2，ESR1，iNOS2，PPARγ， and PTGS1.

Objective: To evaluate the efficacy of surgical treatment of papillary thyroid carcinoma (PTC) involving larynx and trachea. Methods: A total of 1 436 cases of thyroid malignant tumors were admitted to the Department of Otolaryngology, Qilu Hospital of Shandong University from 2004 to 2019, including 110 cases of PTC involving larynx and trachea, and of which 105 cases with complete follow-up data were retrospectively analyzed. There were 42 males and 63 females, with a male/female ratio of 1∶1.5, aged from 28 to 81 years. All lesions involved trachea, including 11 cases involving both trachea and larynx. Of those 83 cases underwent laryngeal and airway wall tumor excision, and 22 cases underwent radical tumor excision plus laryngeal and trachea repair. Extubation rate was analyzed and the postoperative survival curve of patients was analyzed by Kaplan-Meier method. Results: Among 105 cases, 16 cases underwent tracheotomy and 12 cases were successfully extubated. The overall 3- 5- and 10-year survival rates were 100.0%, 86.4% and 72.5%, and the disease-free survival rates were 93.1%, 81.6% and 57.7%, respectively. There was significant difference in survival curve between the two groups (χ²=4.21, P=0.040). The 5-year and 10-year survival rates were 94.6% and 77.3% in laryngeal and tracheal tumor exclusion group, and 85.7% and 51.4% in the radical tumor resection group. There was no significant difference in the survival curves between the two groups (χ²=3.50, P=0.061). Conclusion: PTC patients with laryngeal and tracheal involvement can achieve long survival and good quality of life through reasonable surgical treatment.
Female ; Humans ; Larynx/surgery* ; Male ; Neoplasm Invasiveness ; Quality of Life ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/pathology* ; Trachea/surgery*