Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

Objective To analyze the risk factors for postoperative gastroparesis syndrome (PGS) in gastric cancer patients undergoing laparoscopic radical gastrectomy (LRG) and to construct and validate a nomogram prediction model for PGS. Methods The clinical data of 439 gastric cancer patients were retrospectively analyzed. Patients were divided into PGS group and control group based on whether PGS occurred within 2 months after surgery. Logistic regression analysis was used to screen for risk factors of PGS in LRG patients, and a nomogram prediction model was constructed based on the screening results. The discriminative ability of the nomogram was assessed by the receiver operating characteristic (ROC) curve, and its consistency was evaluated by the calibration curve. Results Among 439 patients, 52 developed PGS, with an incidence rate of 11.85%. The proportions of patients aged ≥60 years, complicating with diabetes, having a history of abdominal surgery, complicating with pyloric obstruction, having surgery duration ≥4 hours, and intraoperative anastomosis type of B-Ⅱ were higher in the PGS group than those in the control group (P < 0.05). The results of multivariate Logistic regression analysis showed that diabetes, a history of abdominal surgery, pyloric obstruction, surgery duration ≥4 hours, and intraoperative anastomosis type of B-Ⅱ were risk factors for PGS in LRG patients (P < 0.05). Internal validation results showed that the area under the ROC curve was 0.839 (95%CI, 0.773 to 0.905), the calibration curve fitted well, and the Hosmer-Lemeshow goodness-of-fit test result was good(χ²=9.078, P=0.247). Conclusion Diabetes, a history of abdominal surgery, pyloric obstruction, surgery duration ≥4 hours, and intraoperative anastomosis type of B-Ⅱ are risk factors for PGS in LRG patients. The nomogram constructed based on these factors can effectively predict the risk of PGS in LRG patients.

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
Rats ; Animals ; Chromatography, Liquid ; Gardenia ; Tandem Mass Spectrometry ; Gastrointestinal Microbiome ; alpha-Linolenic Acid ; Metabolomics/methods* ; Arthritis, Rheumatoid/drug therapy* ; Inflammation ; Glycerophospholipids

Objective: To summarize the application experience and the therapeutic effect of Nirmatrelvir-Ritonavir (trade name: Paxlovid) for COVID-19 in children. Methods: A retrospective analysis was performed on the clinical data, including collecting the clinical manifestations and clinical outcomes, dynamically monitoring the blood routine, hepatic and renal function and SARS-CoV-2 nucleic acid results, and observing the related side effects during the treatment, etc, of 3 cases with COVID-19 treated with Paxlovid admitted to Shanghai Children's Hospital (designated referral hospital for SARS-CoV-2 infection in Shanghai) from May 1^st to June 1^st, 2022. Results: The 3 cases were 12, 14, 17 years of age, among which 2 cases were males, 1 case was female. All 3 cases were mild cases with underlying diseases and risk of developing into severe COVID-19, with symptoms of high fever, sore throat and dry cough. The treatment of Paxlovid at 3^rd day of symptom onset contributed to the symptom-free after 1-2 days and negative results of SARS-CoV-2 nucleic acid after 2-4 days. All patients had no adverse manifestations of gastrointestinal tract and nervous system but a case had little skin rashes, which recovered after the withdrawal of Paxlovid. Three cases had normal hepatic and renal function during the Paxlovid treatment. At 3 months after discharge, no clinical manifestations of post-COVID syndrome were found in all 3 cases. Conclusion: Paxlovid was effective and relatively safe in the treatment of 3 children with COVID-19.
Child ; Male ; Humans ; Female ; COVID-19 ; SARS-CoV-2 ; Ritonavir/therapeutic use* ; Retrospective Studies ; China ; Nucleic Acids ; COVID-19 Drug Treatment

Isopentenyl flavonoids are a class of characteristic components in Sophora flavescens Ait. (S. flavescens). They have biological activities such as anti-tumor, anti-bacteria, anti-inflammol/ Lation and anti-oxidation. In this paper, the structural types, toxicology and pharmacological effects of isopentenyl flavonoids from S. flavescens were briefly reviewed. Furthermore, the worth of further study on pharmacokinetics, pharmacodynamics, toxicology, action targets, molecular mechanisms and structure-function relationships of isopentenyl flavonoids were proposed. The deep exploration on functional characterastics of isopentenyl flavonoids of S. flavescens and their application on development of innovative drugs are of great significance to further improve the added value of isopentenyl flavonoids and expand their application fields.

Aortic Valve/surgery* ; Aortic Valve Insufficiency/surgery* ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Humans ; Perioperative Period ; Severity of Illness Index ; Transcatheter Aortic Valve Replacement ; Treatment Outcome

Objective:To establish a candidate reference method for simultaneous determination of whole blood iron and copper based on ICP-MS technology.Methods:Cobalt (Co) was chosen as the internal standard, and was added gravimetrically into the standard solution and the whole blood sample. The whole blood sample was digested by electric heating plate and diluted. The isotopic ratios of 57Fe/ 59Co and 63Cu/ 59Co were measured by ICP-MS in the isotopic analysis mode. The precision, standard recovery and accuracy of the method were verified by measuring EQA materials and certified standard materials, and the performance of the method was further evaluated by method comparison. Results:The detection limit of iron is 0.136 mg/kg and the limit of quantification was 0.454 mg/kg in this method. The detection limit of copper in whole blood was 0.008 mg/kg and the limit of quantification was 0.027 mg/kg. The standard curve of copper ranges from 0.83-3.33 mg/kg, iron ranges from 167-667 mg/kg. The calibration curve of iron and copper was good linearity ( R 2>0.999 90). The precision of the method did well. The total CV range was 0.42%-0.68% for iron and 0.14%-0.94% for copper. The spike recoveries were all around 100%, the range of iron: 99.69%-100.07%; copper: 99.26%-100.51%. The correlation between this method and the existing clinical mass spectrometry methods was good. Conclusions:A candidate reference ICP-MS method for simultaneous determination of whole blood Fe and Cu was established. This is a simple and rapid method with good precision and spike recovery compared to the traditional one.

Objective To use World Health Organization Family International Classifications (WHO-FICs) to explore the framework and approaches of development and research of guidelines of rehabilitation at levels of policies, community and services.Methods The important documents and tools of rehabilitation at international level, including United Nations Convention on the Rights of Persons with Disabilities, WHO World Report on Disability, Community-based Rehabilitation Guideline, Rehabilitation in Health Service System, and International Classification of Diseases (ICD), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHI) of WHO-FICs, had been discussed.Results The framework, classifications, diagnosis and description of diseases and functioning, coding, intervention and functioning evaluation based on ICD-11, ICF and ICHI-β-2 had been established for development and implementation of rehabilitation guidelines and Cochrane rehabilitation.Conclusion The framework and systematic approaches of ontology, classification, terminology, coding, diagnosis and description of diseases and functioning, interventions and evaluations for the development and implementation of rehabilitation guidelines had been developed.