Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis.

BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging. AIM: To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EXAD) and exogenous mitochondria (mitoEx) protect the lung from ARDS complicated by SS. METHODS: In vitro study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EXAD), 4 (ARDS-SS + mitoEx), and 5 (ARDS-SS + EXAD + mitoEx), were included in the present study. RESULTS: In vitro study showed an abundance of mitoEx found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (P < 0.001). The protein levels of inflammation [interleukin (IL)-1ß/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EXAD treatment than without EXAD treatment, whereas the protein expressions of cellular junctions [occluding/ß-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all P < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P < 0.0001), whereas arterial oxygen-saturation (SaO2%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO2% among the groups (all P < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1ß/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P < 0.0001). CONCLUSION: Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice / 中国实验方剂学杂志

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg-1·d-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg-1·d-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Reliability of ICF dysfunction combination in rehabilitated inpatients / 中国现代医生

@#Objective To explore the inter-rater and within-rater reliability of the 30 categories of the International Classification of Functioning Disability,and Health(ICF)dysfunction set(ICF generic-30 set)in clinical function assessment,to provide a basis for its clinical application.Methods Ninety patients from the Neurorehabilitation Department of the First People's Hospital of Suqian City were enrolled in this study.All patients were evaluated by the same functional evaluator's ICF dysfunction combination at the two time points of admission and discharge for the internal reliability analysis of the evaluator.Thirty patients in the neurorehabilitation department were randomly selected to be evaluated by two ICF function evaluators at the same time to conduct test-retest reliability analysis among evaluators.The internal consistency of the Cronbach's α coefficient test scale,and the intra-group correlation coefficient(ICC)test inter-rater reliability and within-rater reliability.Results The Cronbach's α coefficients of the combination of ICF dysfunction,physical function and activity,and participation in the two subscales were 0.941,0.717,and 0.942,respectively.The inter-rater reliability analysis showed that the ICC of the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.998,0.971,0.999(P<0.01),and the inter-rater reliability good;the internal reliability analysis of the evaluator showed that the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.988,0.917,0.991(P<0.01),except that b640 sexual function is not applicable,and b130 energy Harmony drive function ICC is 0.558,b280 pain ICC is 0.409,ICC of other combination items is 0.838-0.986(P<0.01),the evaluator's internal reliability is good;90 patients'ICF dysfunction combination scale has 30 categories.The comparison between admission and discharge was statistically significant except that b640 was not applicable for sexual function(P<0.05).Conclusion The combination of ICF dysfunction has good internal consistency and inter-evaluator and intra-evaluator reliability in the functional evaluation of patients in neurorehabilitation department.

Factors affecting laryngeal cancer relapse after postoperative radiotherapy and relationship between relapse with radiotherapy dose / 中国医学物理学杂志

Objective To explore the factors associated with laryngeal cancer relapse after postoperative radiotherapy,discuss the relationship between radiotherapy dose under various surgical procedures and relapse,and analyze their effects on survival rate.Methods The clinical data of 134 patients with laryngeal cancer treated with postoperative radiotherapy in Shijiazhuang People's Hospital were retrospectively analyzed.The risk factors of postoperative relapse were analyzed with univariate analysis,followed by multivariate Logistic regression analysis.The relationships between radiotherapy doses under various surgical procedures and the relapse were discussed.Kaplan-meler method and Log rank test were used to analyze the 2-year survival rate of laryngeal cancer patients.Results Thirty out of the 134 patients relapsed after treatment,and there was no recurrence in the remaining 104 patients.Multivariate Logistic regression analysis identified clinical stage(Ⅲ-Ⅳ),T stage(T3-T4),N stage(N1-N3),radiotherapy dose(low-dose),thyroid cartilage invasion(yes)and surgical margin(positive)as independent risk factors for postoperative laryngeal cancer relapse(OR>1,P<0.05).The relapse rates of patients receiving high-dose radiotherapy after laser vocal cord mass resection/partial laryngectomy and total laryngectomy under self-retaining laryngoscope were lower than those of patients receiving low-dose radiotherapy,with a statistically significant difference in overall relapse rate(P<0.05).As of June 2023,the median follow-up time of 134 patients undergoing postoperative radiotherapy for laryngeal cancer was 14.23 months(1-24 months),and there were 8 deaths in low-dose group and 2 deaths in high-dose group.The estimated median survival times in low-and high-dose groups were 19.13 months and 22.13 months.The survival curves in two groups were different(Log rank P=0.20),with high-dose group outperforming low-dose group.Conclusion The overall therapeutic effect of surgery combined with postoperative radiotherapy for laryngeal cancer is favorable.However,clinical stage,T stage,N stage,low-dose radiotherapy,tumor invasion into thyroid cartilage,positive surgical margin,and>11 weeks from postoperation to radiotherapy completion were risk factors for disease relapse.In clinical practice,the radiotherapy dose should be appropriately increased based on the patient's condition to improve prognosis and extend survival duration.

M6A-mediated EGLN3 and FOSL2 enhance radioresistance in nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To screen and verify the key radioresistance genes regulated by m6A methylation in nasopharyngeal carcinoma (NPC) based on the chip data and cell experiments.Methods:The microarray data of NPC radioresistance genes, m6A regulated genes and mRNA expression profiles of NPC genes were downloaded from Gene Expression Omnibus (GEO) database. The differential genes were screened and statistically analyzed by R software. The biological processes, signal pathways and interaction networks of these genes were analyzed by bioinformatics. The m6A regulatory factors were knocked down and the radioresistant strains were constructed. The above m6A differential radioresistant genes of NPC were screened and verified by real-time reverse transcription PCR (qRT-PCR) and Western blot. The m6A modification of screened genes and their direct binding ability with methyltransferase 3 (METTL3) were verified by methylated RNA immunoprecipitation qPCR (MeRIP-qPCR). The siRNA of selected genes was transfected into NPC cells, and after treatment with ionizing radiation, cell proliferation was detected by CCK-8 assay and EdU, apoptosis and cell cycle were detected by flow cytometry, and radiosensitivity was detected by clone formation assay. The trend of differences in the abundance of Fe 2+ and lipid peroxidation between the control and EGLN3 knockdown groups after ionizing radiation treatment was compared by paired t-test. Results:Chip data GSE48501 intersected with GSE200792 and GSE53819 to obtain 6 differential genes, including EGLN3, FOSL2, ADM, JUN, VEGFA and PRDM1. The target genes of EGLN3 and FOSL2 were further screened by TNMplot and KMplot, etc. The mRNA of the target genes directly bound to METTL3 and were subjected to its mediated modification of m6A. The target genes were up-regulated in the parental cells after irradiation in a dose and time gradient manner, which were also significantly up-regulated in radioresistant cells. After EGLN3 and FOSL2 were down regulated, the proliferation activity of NPC cells was more significantly decreased after irradiation, and the radiosensitization ratio was statistically significant compared with that of NPC cells without EGLN3 and FOSL2 down-regulation. After irradiation, EGLN3 down-regulated NPC cells significantly down-regulated glutathione peroxidase 4 (GPX4) expression, increased the abundance of Fe 2+ and lipid peroxidation, which played a role in radiosensitization by inducing ferroptosis. Conclusions:EGLN3 and FOSL2 play a role in radioresistance in NPC through METTL3 mediated m6A methylation. Down-regulation of EGLN3 combined with ionizing radiation can increase the intracellular Fe 2+ abundance and lipid peroxidation and down-reuglate the expression of GPX4 in NPC cells, which can enhance radiosensitization for NPC radiotherapy by the ferroptosis pathway.

Evaluation of molecular point-of-care testing for rapid diagnosis of influenza A virus and influenza B virus / 国际检验医学杂志

Objective To evaluate the performance of two molecular point-of-care testing(POCT)prod-ucts in the diagnosis of influenza A virus(Flu A)and influenza B virus(Flu B)of clinical samples,and pre-liminarily evaluate the clinical diagnostic value of the changes of infection-related indicators in peripheral blood.Methods A total of 491 oropharyngeal swabs from patients with influenza-like symptoms who were treated in the hospital were recruited into this study from November 1,2019 to June 30,2023.These swabs were collected using reverse transcription real-time quantitative fluorescent polymerase chain reaction(RT-qPCR),and two POCT molecular products,XpertTM Xpress Flu/RSV and EasyNAT? Flu Assay,respectively.The diagnostic performance of two POCT molecular products was analyzed using RT-qPCR reaction as a standard.According to the results of RT-qPCR method,the subjects were divided into Flu A positive group,Flu B positive group and negative group(both Flu A and Flu B were negative).The levels of indicators in pe-ripheral blood of the three groups were compared to evaluate the value of these indicators in the clinical diag-nosis of Flu A and Flu B.Results Among the 491 patient specimens,the XpertTM Xpress Flu/RSV assay showed the sensitivity for Flu A was 96.88%,and the specificity was 99.75%,and the sensitivity for Flu B was 100.00%,and the specificity was 100.00%.EasyNAT? Flu Assay assay showed the sensitivity for Flu A was 94.79%,and the specificity was 96.81%,and the sensitivity for Flu B was 100.00%,and the specificity was 100.00%.And two POCT molecular methods performed well consistency(Kappa value was 0.974).There was no significant difference in the levels of C-reactive protein and serum amyloid A among the negative group,Flu A positive group,and Flu B positive group(P>0.05).But the levels of white blood cell count in the negative group were higher than those in the Flu A positive group and Flu B positive group(P<0.01).Conclusion In this paper,two typical molecular POCT products are studied.Their sensitivity and specificity are highly consistent with the results of RT-qPCR.Molecular POCT products have the advantages of flexibil-ity and rapidity,which are of great value for the improvement of clinical diagnosis and treatment.Molecular detection combined with peripheral blood infection related indicators is helpful for the early diagnosis of influ-enza virus infectious diseases.

Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation.

INTRODUCTION: Intestinal ischemia/reperfusion (II/R) injury is a life-threatening situation accompanied by severe organ injury, especially acute lung injury (ALI). A great body of evidence indicates that II/R injury is usually associated with hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, has been recognized as a regulatory factor in inflammation, but whether it was involved in II/R injury-induced ALI is still unknown. METHODS: To establish the II/R injury model, the superior mesenteric artery of the mice was occluded gently by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the lung injury after II/R. The pulmonary histopathological alteration was evaluated by H&E staining. The concentration of proteins, the number of infiltrated cells, and the level of IL-6 were measured in BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Administration of the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological abnormalities, upregulated the concentration of proteins, the number of infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma. CONCLUSION: After induction of ALI by II/R, the administration of DHBA aggravated ALI through NETs formation in the lung.

Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction.

This study tested whether human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 105/co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1ß/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-ß/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats (n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO2%/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-ß/p-NF-κB/IL-1ß/TNF-α)/fibrotic (p-SMad3/TGF-ß), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO2% among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.

Jagged/Notch proteins promote endothelial-mesenchymal transition-mediated pulmonary arterial hypertension via upregulation of the expression of GATAs.

This study tested the hypothesis that Jagged2/Notches promoted the endothelial-mesenchymal transition (endMT)-mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA-binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly reduced, whereas the endothelial-phenotype markers (CD31/E-cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly upregulated in TGF-ß/monocrotaline-treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right-ventricular systolic-blood-pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham-control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß-MHC)/pressure-overload (BNP)/oxidative-stress (NOX-1/NOX-2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/TGF-ß/α-SMA/p-Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged-Notch-GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU.

An automated workflow on data processing (AutoDP) for semiquantitative analysis of urine organic acids with GC-MS to facilitate diagnosis of inborn errors of metabolism.

Determination of urine organic acids (UOAs) is essential to understand the disease progress of inborn errors of metabolism (IEM) and often relies on GC-MS analysis. However, the efficiency of analytical reports is sometimes restricted by data processing due to labor-intensive work if no proper tool is employed. Herein, we present a simple and rapid workflow with an R-based script for automated data processing (AutoDP) of GC-MS raw files to quantitatively analyze essential UOAs. AutoDP features automatic quality checks, compound identification and confirmation with specific fragment ions, retention time correction from analytical batches, and visualization of abnormal UOAs with age-matched references on chromatograms. Compared with manual processing, AutoDP greatly reduces analytical time and increases the number of identifications. Speeding up data processing is expected to shorten the waiting time for clinical diagnosis, which could greatly benefit clinicians and patients with IEM. In addition, with quantitative results obtained from AutoDP, it would be more feasible to perform retrospective analysis of specific UOAs in IEM and could provide new perspectives for studying IEM.

Visual analysis of Chinese medicine nursing of coronary heart disease research based on CiteSpace / 中国实用护理杂志

Objective:To provide a reference for in-depth application and research in the field of coronary heart disease traditional Chinese medicine (TCM) nursing. Based on the CiteSpace software, the development trend and research hotspots of the literature are displayed and analyzed in this field.Methods:The China Knowledge Network (CNKI) database was used to retrieve the literature related to the research in this field published in the past 20 years from January 1st 2001 to October 5th 2021, and CiteSpace was used to visually analyze the number of articles, research institutions, authors and keywords, and to interpret its meaning in combination with the content of the atlas.Results:The amount of research literature in this field was generally on the rise, but the cooperation between various research institutions and authors needs to be strengthened. Research hotspots mainly focused on five areas: coronary heart disease-related symptom care, the application of characteristic TCM nursing techniques, the outcome indicators of the research, the TCM health management of patients with coronary heart disease, and the application model of TCM nursing.Conclusions:It is recommended to strengthen multidisciplinary and teamwork in this field, carry out high-quality randomized controlled studies, and focus on related research on multiple nursing models, evaluation tools, and symptom management.

The efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer / 中华泌尿外科杂志

Objective:To summarize the efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer.Methods:The clinical data of 28 patients with bladder cancer who were admitted in Zhengzhou People's Hospital from July 2020 to October 2021 were analyzed retrospectively. There were 22 males and 6 females, with the average age of (68.8±8.9) years old. Twenty cases were with single bladder tumor, and 8 cases were with multiple bladder tumors. The diameter of single bladder tumor measured by CT was less than 4 cm, with a median tumor diameter of 2.3(0.9, 2.8)cm. All 28 patients underwent transurethral partial cystectomy combined with intravesical suturation for the first time. Intraoperative intravesical instillation was conducted with 1 g gemcitabine. Bladder hot reperfusion treatment was performed with gemcitabine 2 g at 45℃ immediately after operation. The patients underwent reexamination with cystoscopy every 3 months after operation.Results:All the 28 patients successfully completed the operation. The average operation time was (128.3±16.3)min. No obturator nerve reflection was induced during operation. Muscularis tissue was found in all tumor pathological specimens after operation, among which 4 cases showed muscularis infiltration. Pathology of tumor basal and peripheral tissues showed tumor cell infiltration in 3 cases (1 case full-thickness infiltration, namely the incision margin was positive). The median continuous irrigation time of bladder after operation was 24.0(20.9, 25.0)h. The median time of indwelling catheter after operation was 6.5(6.0, 7.0)days, and one case developed severe bladder spasm. All patients were followed up, with a median follow-up of 7.5(4.0, 10.8) months.Postoperative recurrence occurred in 3 cases, all of which were ectopic recurrence in bladder.The 1-year recurrence rate was 10.7% (3/28).Conclusions:In the first surgical treatment of bladder cancer, transurethral partial cystectomy combined with intravesical suturation can provide accurate pathological staging, and low positive surgical margin rate. Immediate suturation of bladder wound during operation and immediate bladder perfusion chemotherapy can provide short bladder irrigation time, with few adverse reactions and low incidence of complications.

Photoelectric therapy for rosacea / 中华皮肤科杂志

Rosacea is a chronic inflammatory dermatosis mostly occurring on the central face, and its pathogenesis is still unclear. Currently, drug treatment is the first-line therapy for rosacea. In recent years, photoelectric therapy has showed a favorable therapeutic effect on rosacea by selective photothermolysis. This review summarizes latest advances in photoelectric therapy for rosacea.

Application of education picture of standardized position in patients undergoing gastroscopy in awake state / 中华消化内镜杂志

To explore the effect of education picture of standardized position in patients undergoing gastroscopy in awake state, 80 patients who underwent gastroscopy in Beijing Friendship Hospital from April 2022 to May 2022 were prospectively selected and divided into two groups by random number method, with 40 cases in experimental group and 40 cases in control group. Patients in control group received traditional conduction before gastroscopy, while patients in experimental group received picture education with standardized position based on the traditional method. The time of position placement, the time of gastroscopy, patient satisfaction, operator satisfaction and the occurrence of related adverse reactions between the two groups were recorded and compared. The results showed that the time of body position placement was 38.70±3.09 seconds in the experimental group and 50.25±3.12 seconds in the control group with statistical difference ( t=-16.637, P<0.001). The time of gastroscopy in the experimental group was 11.63±1.51 min, while that in the control group was 15.53±1.69 min, with statistical difference ( t=-10.856, P<0.001). Patient satisfaction was 92.5% (37/40) in the experimental group and 65.0% (26/40) in the control group, and operator satisfaction was 90.0% (36/40) and 67.5% (27/40) in the experimental group and the control group, respectively. The differences were both statistically significant ( P=0.005, P=0.027). Postoperative nausea occurred in 1 case in the experimental group, while 9 cases in the control group ( P=0.014). Using education picture of standardized position in patients before undergoing gastroscopy can shorten the time of position placement and gastroscopy, improve the satisfaction of patients and physicians, and reduce the occurrence of adverse events.

Efficacy and safety of fractional radiofrequency in treatment of acne scar / 中华医学美学美容杂志

Objective:To observe the efficacy and adverse reactions of fractional radiofrequency (FRF) in the treatment of facial acne scars.Methods:Fifty-seven patients with facial acne depressed scars were enrolled with the nature of Dreno scars as the diagnostic criteria. They were treated with lattice radiofrequency. The treatment heads were arranged in a matrix with a treatment area of 1.2 cm ×1.2 cm, an energy density of 80-100 mJ/pin, and an interval of five-seven once a week. And they were followed up and evaluated for the clinical efficacy and adverse reactions 6 months after the last treatment. Scoring was carried out according to the ECCA weight scores, and the efficacy judged according to complete improvement, significant improvement, moderate improvement, and mild improvement.Results:After 3 times of fractional radiofrequency treatment of 57 patients, the effective rate was 44 cases, accounting for 77.2%; the ECCA weight scores before and after treatment were 65.9±25.0 and 47.7±20.2, respectively; the difference was statistically significant ( t=13.92, P<0.001); At the same time of improvement, 32 cases of patients' complexion, fineness of pores, and skin elasticity had been improved to varying degrees, and patient satisfaction was high. Adverse reactions were mainly mild burning sensation, erythema and edema, and some patients had pale yellow exudate, etc, which could be relieved in 5-7 days. Conclusions:Fractional radiofrequency treatment of facial acne scars is safe and effective, with short recovery period, few adverse reactions and high patient satisfaction.

Chr9∶52042693|52047844⁃miR⁃351⁃5p⁃Pten Is Involved in the Development and Progression of Obstructive Sleep Apnea Syndrome through a ceRNA Mechanism / 中国生物化学与分子生物学报

Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.

Research progress of fibroblast growth factor in nervous system diseases / 浙江大学学报·医学版

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.

Comparison of effects of manual and mechanical chest compression during extracorporeal cardiopulmonary resuscitation / 中华急诊医学杂志

Objectives:To compare the effects of manual and mechanical chest compression on patients receiving extracorporeal cardiopulmonary resuscitation (ECPR).Methods:Patients who underwent extracorporeal cardiopulmonary resuscitation admitted to Jinhua Municipal Central Hospital, Hangzhou First People's Hospital and the First Hospital of Jiaxing from September 2014 to July 2022 were enrolled in the study. The patients were divided into the manual group and mechanical group according to the compression method, and the clinical data of the two groups were compared. To explore the effects of the two compression method on the ECPR implementation, proportion of return of spontaneous circulation (ROSC) and hospital survival.Results:A total of 108 patients who underwent ECPR were included in the study, 50 patients in the manual group and 58 patients in the mechanical group. There were no significant differences in sex, age, laboratory tests before ECPR, ROSC proportion (90.0% vs. 86.2%) and survival (34.0% vs. 39.7%) between the two groups (all P>0.05). The puncture time in the mechanical group was shorter than that in the manual group [12 (9,15) min vs. 13 (11,16) min, P<0.05]. Conclusions:Compared with manual compression, mechanical compression during ECPR neither increase the probability of ROSC nor reduce in-hospital mortality in patients with cardiac arrest. However, mechanical compression may help to shorten the puncture time.

Mechanism of action of long non-coding RNAs in cutaneous squamous cell carcinoma / 中华皮肤科杂志

Long non-coding RNAs (lncRNAs) participate in the occurrence and development of cutaneous squamous cell carcinoma (cSCC) mainly through epigenetic modification, mRNA alternative splicing, and binding to microRNAs. This review focuses on recent research progress in regulatory role of lncRNAs in cSCC, and discusses their mechanisms of action, aiming to seek potential therapeutic targets and biomarkers for cSCC.