Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

In the development of flap surgery, the groin flap was one of the earliest flaps used in repair of soft tissue defect. However, due to its unstable anatomical position and many variations, small vessels and great difficulty in vascular anastomosis, the application of this flap reduced gradually. With the development of microsurgical techniques and the increasing demand of patients for aesthetics in donor site, the groin flap has been still widely used in the repair of soft tissue defect in limb maxillofacial region, and perineal partsin in recent 10 years, due to its advantages of concealed donor site and large area of flap. This article review the historical development of the groin flap, summarize the clinical application of perforator flap, and special types of groin flaps in repair of soft tissue defect in extremities. Hoping to further promote the application and development of groin flap in soft tissue repair.

OBJECTIVE： To establish antibiotics use rationality evaluation model in type Ⅰ incision surgery patients， and to provide reference for prescription review of clinical pharmacists. METHODS： Totally 432 inpatients underwent type Ⅰ surgical incision in a hospital from Jan. 1st- Dec. 31st， 2017 were selected as the research objects. The information of diagnosis and treatment including age， nosocomial infection， the number of kinds of antibiotics used were extracted. Based on the results of clinical pharmacists’ comments on the antibiotics use rationality in patients’ prevention and treatment， non-conditional Logistic regression and support vector machine （SVM） in machine learning method were used to convert clinical pharmacists’ comments into objective index that can be recognized by the machine learning model， using categories of antibiotics （preventive or therapeutic use） as dependent variables and the patient’s diagnosis and treatment information as independent variables. Classification and identification model was established for antibiotics use rationality in type Ⅰ incision surgery patients. Using sensitivity， specificity and Youden index as indexes， established mode was validated on the other 61 samples of type Ⅰ incision surgery patients. The rationality of antibiotics prescriptions in type Ⅰ incision surgery patients before （by manual review， Jan.-Dec. 2017） and after （Jan.-Oct. 2018） using the model were collected， and the effects of the model were evaluated. RESULTS： The sensitivity， specificity and Youden index of non-conditional Logistic regression model were 65.63％， 75.00％ and 40.63％， respectively. Main parameters of the model established by SVM included gamma 0.01， cost 10， sensitivity 92.19％， specificity 87.50％， Youden index 79.69％. The model established by SVM was better than non-conditional Logistic regression. SVM was used to validate established mode， and sensitivity， specificity and Youden index were 100％， 88.57％ and 88.57％， respectively. Compared with before using the model， the evaluation ratio increased from 69.44％ to 100％， the rate of prophylactic use of antibiotics decreased from 23.84％ to 16.43％， the rate of rational drug type selection increased from 37.86％ to 54.39％， and treatment course shortened from 5.01 days to 3.26 days after using the model. CONCLUSIONS： Established antibiotics use rationality evaluation model in typeⅠincision surgery patients by SVM in machine learning method fully covers all the patients， promotes rational use of antibiotics in typeⅠincision surgery patients， and provides a new idea for pharmacist prescription comment.

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.
Aging ; genetics ; Animals ; Astrocytes ; cytology ; metabolism ; Brain ; cytology ; metabolism ; Cell Differentiation ; genetics ; Cell Division ; genetics ; Cell Proliferation ; genetics ; Gene Expression Regulation ; genetics ; Mice ; Neural Stem Cells ; metabolism ; Single-Cell Analysis ; Stem Cells ; cytology ; metabolism ; Transcriptome ; genetics

Objective: The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment. Methods: We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed. Results: A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and β2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05). Conclusions Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, β2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB) on the kidney injury of the diabetic rats, and to discuss its mechanism preliminarily.Methods:The male Wistar rats were intraperitoneally injected with STZ (65 mg·kg-1) to establish the diabetes models, then the model rats were randomly divided into model (M)group, and metformin (MMet, 105 mg·kg-1) group , low dose of combined administration (ML,105 mg·k-1 metformin+94.5 mg·kg-1 ,DECB) group, medium dose of combined administration(MM, 105 mg·kg-1 metformin+ 189 mg·kg-1 DECB) group, high dose of combined administration(MH, 105 mg·kg-1 metformin +378 mg·kg-1,DECB) group, another ten Wistar rats were selected as normal control(NC)group.The rats were intragastrically administed with metformin and intraperitoneally injected with DECB, once a day, total of 8 weeks.The rats in NC group and M group were given normal saline solution.The weights and blood glucose levels of the rats in various groups were determined;the levels of serum high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), blood urea nitrogen (BUN), urinary albumin (UAlb), urine creatinine (UCR), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG), uric acid (UA), glutathione (GSH), and malondialdehyde (MDA) were detected;the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined.The pathological changes of kidney tissue of the rats in various groups were detected by HE staining.Results:Compared with NC group, the weight of the rats in M group was reduced(P<0.05),and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG,and MDA were increased(P<0.05);the levels of HDL-C and GSH were obviously reduced(P<0.05),and the activities of SOD adn GSH-Px were obviously reduced(P<0.05).Compared with M group,the weights of the rats in MM and MH groups were increased (P<0.05), and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG, and MDA were decreased (P< 0.05);the levels of HDL-C and GSH were increased (P<0.05),and the activities of SOD and GSH-Px were increased (P<0.05).The pathological observation of kidney tissue showed that the rats in M group had obvios kidney tissue lesions with glomerular congestion and renal tubular edema compared with NC group;compared with M group,the pathological changes of the kidney tissue of the rats in drug administration groups were significantly improved, the renal tubular vacuoles were reduced, and the interstitial hyperplasia was not obvious.Conclusion:DECB combined with metformin can reduce the blood glucose level, regulate blood lipid, improve the pathological changes of kidney tissue in the diabetic rats, reduce the renal damage, and enhance the antioxidant capacity of the body.

Objective:To explore the mechanism of the embolism and sclerotherapy of fibrin glue combined with bleomycin (FG/BLM) for the treatment of cervicofacial vascular malformations by color doppler ultrasound.Methods:10 patients with venous malformation(VM) and 10 patients with arterio-venous malformation(AVM) were included.All patients underwent embolism and sclerotherapy of FG/BLM guided by ultrasound.Color doppler ultrasound was used to record the real-time two-dimensional ultrasonography and color doppler image.The flow and distribution of FG/BLM after injection into the lesions were observed.Results:Two-dimensional ultrasonography showed clumps or flake strong echo after immediate injection of FG/BLM into the cavity of VMs,then floated in the abnormal venous lumen and diffused throughout the cavity.At the later stage the lesions were filled by a large number of flocculent and netted low echo,and patchy strong echo.The volume of VMs cavity expanded dramaticlly,and the blood flow signal was significantly decreased.After injection of FG/BLM into the lumen of AVMs,clumps or flake strong echo were observed,then most of the snowflake strong echo rapidly filled or scattered along with blood stream to the distal part of the vessels.The color doppler showed significantly decrease of blood flow signal.Conclusion:FG/BLM injection can embolize and block the draining vein of VM,and play a role on the storage of sclerozing agent.FG/BLM injection can embolize both the dilated blood vessels and capillary network of AVM.

OBJECTIVETo identify the risk factors associated with lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy (CRT).

METHODSFrom January 2005 to December 2013, the clinical data of 178 patients with advanced rectal cancer undergoing radical excision after neoadjuvant CRT in our department were reviewed retrospectively. A total of 11 clinicopathologic factors relating to lymph node metastasis were studied using univariate and multivariate Logistic regression analyses.

RESULTSThere were 74(41.6%) cases with lymph node metastasis, while 104 cases without lymph node metastasis. Univariate analysis showed that age(P=0.000 2), post-CRT CEA level(P=0.011 2), ypT stage(P=0.000 0), pathologic type(P=0.004 0), and tumor regression grade(TRG)(P=0.033 8) were significantly associated with lymph node metastasis. Multivariate analysis showed that age(OR=2.385, 95% CI:1.372 ~ 4.147, P=0.002 1), post-CRT CEA level(OR=2.310, 95% CI:1.005 ~ 5.307, P=0.048 6) and ypT stage(OR=2.592, 95% CI:1.236 ~ 5.432, P=0.011 7) were independent risk factors. However, 15.8% of the patients who achieved TRG1 had lymph node metastasis and TRG failed to independently correlate with lymph node metastasis in rectal cancer after neoadjuvant CRT.

CONCLUSIONSThere was a higher ratio of lymph node metastasis in rectal cancer patients who were young, CEA≥5 μg/L or deep invasion after neoadjuvant CRT. Therefore, neoadjuvant CRT should be carefully considered in these patients.

Age Factors ; Carcinoembryonic Antigen ; blood ; Chemoradiotherapy ; Female ; Humans ; Lymphatic Metastasis ; diagnosis ; Male ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Rectal Neoplasms ; complications ; epidemiology ; therapy ; Remission Induction ; Retrospective Studies ; Risk Factors ; Treatment Outcome