Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Reevaluation of systematic evaluation of Tripterygium glycosides in the treatment of diabetic kidney disease / 中国药房

OBJECTIVE To systematically reevaluate （umbrella review） the systematic review/meta-analysis of Tripterygium glycosides （TG） in the treatment of diabetic kidney disease （DKD）， in order to provide a higher quality evidence-based reference for TG in the treatment of DKD. METHODS The systematic reviews/meta-analysis of TG in the treatment of DKD were searched from CNKI， Wanfang， VIP， CBM， PubMed， Cochrane Library and Embase. The PRISMA 2020 statement， the AMSTAR 2 scale and the GRADE tool were used to evaluate the quality of the report， the quality of the methodology， and the quality of the evidence， respectively. The quantitative results of the included systematic review/meta-analysis were analyzed comprehensively. RESULTS A total of 18 systematic reviews/meta-analyses were included. PRISMA 2020 stated that 3 reports were complete， 13 reports had partial information defects， and 2 reports had serious information defects. The results of the AMSTAR 2 scale evaluation showed that 4 literature had low methodological quality， and 14 literature had very low methodological quality. GRADE tool evaluation results showed that there were 106 outcome indicators， including 34 intermediate-quality evidence accounted for 32.1%， 51 poor-quality evidence accounted for 48.1%， 21 very poor-quality evidence accounted for 19.8%， and there was no high- quality evidence. Comprehensive analysis of quantitative results of various outcome indicators showed that TG had definite improvement effects on the total effective rate of DKD， 24-hour urinary protein quantity and serum albumin， and the adverse drug reactions were different in every study. CONCLUSIONS The efficacy of TG in the treatment of DKD is relatively accurate， safety still needs to be paid attention to， and future studies with larger sample size need to be verified.

Clinical classification and histopathological features of connective tissue nevi / 中华皮肤科杂志

Connective tissue nevi (CTN) , a kind of benign skin hamartomas, can be classified into 3 types according to the excessive components predominating in skin lesions, including collagen type, elastin type and proteoglycan type, and each type of CTN includes various inherited and acquired diseases. Therefore, genetic, clinical, and histopathological features should be considered for the confirmation of diagnosis of CTN and its subtypes. According to the latest Chinese and international literature, this review elaborates clinical classification and histopathological characteristics of CTN, aiming to further strengthen the understanding of this disease.

Role of cold-inducible RNA-binding protein in acute renal injury in a mouse model of myocardial ischemia-reperfusion: relationship with NF-κB signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of cold-inducible RNA-binding protein (CIRP) in acute renal injury in a mouse model of myocardial ischemia-reperfusion (I/R) and the relationship with nuclear factor kappa B (NF-κB) signaling pathway.Methods:Twenty-four SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, with body mass index of 24-28 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group) and myocardial I/R + CIRP-derived peptide C23 group (I/R+ C23 group). The model of myocardial I/R was developed by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. CIRP-derived peptide C23 8 mg/kg was intraperitoneally injected before myocardial ischemia and reperfusion in I/R+ C23 group, while Sham group was only threaded without ligation. Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB), lactic dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) concentrations. Renal tissues were obtained for examination of the pathological changes, and the tubular injury score was assessed. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB), Nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β) and IL-18 in renal tissues was detected by Western blot. The expression of Toll-like receptor 4 (TLR4), NLRP3, IL-1β, TNF-α and IL-6 mRNA was determined by real-time polymerase chain reaction. Results:Compared with Sham group, the levels of serum CK-MB, LDH, Cr and BUN and renal tubule injury score were significantly increased, the expression of p-NF-κB, NLRP3, IL-1β and IL-18 was up-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and the pathological injury to renal tissues was aggravated in I/R group. Compared with I/R group, the serum CK-MB, LDH, Cr, BUN and renal tubular injury score were significantly decreased, and the expression of p-NF-κB, NLRP3, IL-1β and and IL-18 was down-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the pathological injury to renal tissues was alleviated in I/R+ C23 group. Conclusions:CIRP is involved in the process of acute renal injury in a mouse model of myocardial I/R, which is associated with activation of NF-κB signaling pathway and promotion of inflammatory responses.

Analysis of the molecular typing and clinicopathological features of POLE and POLD1 gene mutations in middle-aged and elderly patients with colorectal cancer / 中华老年医学杂志

Objective:To examine the clinicopathological and molecular pathological characteristics of patients with colorectal cancer(CRC)who have mutations in the POLE and POLD1 genes.Methods:In this study, we retrospectively collected data from 276 middle-aged and elderly patients aged 45 years and over who were diagnosed with colorectal cancer at Beijing Hospital between October 2020 and September 2022.We utilized next generation sequencing and bioinformatics analysis to screen for harmful germline and somatic mutations in the POLE and POLD1 genes.The study involved 276 patients, who were divided into three groups based on their genetic mutations.The deleterious mutation group had 6 cases, the mutation of unknown significance group had 18 cases, and the wild type group had 252 cases.We also collected clinical and pathological features of the patients and analyzed their correlation with other molecular pathological results such as tumor mutation burden(TMB), microsatellite instability(MSI), and gene co-mutation.Results:No germline mutations were detected in the POLE and POLD1 genes across all patients.Out of the 276 patients, 18(6.5%)were found to carry POLE mutations.Among these, 6(2.2%)were classified as deleterious mutations, 12(4.3%)were positive for POLE mutations of unknown significance, and the remaining patients had wild type POLE genes.Out of the 276 patients, POLD1 gene mutations of unknown significance were found in 10 patients(3.6%). Among the 276 patients, 5 cases(1.8%)carried two types of gene mutations.Patients in the deleterious mutation group showed earlier tumor stage( P<0.05)and a higher prevalence of low-grade tumor budding( P<0.05), with 6 patients being affected by this.Compared to the wild type group, colon cancer patients showed a higher frequency of deleterious mutations and variants of unknown significance in the poorly differentiated group( P<0.05). The median TMB in the deleterious mutation group was 257.76 muts/Mb, 74.4 muts/Mb in the mutation of unknown significance group, and 5.81 muts/Mb in the wild type group.The study found significant differences in TMB-H status among the three groups, with all P-values less than 0.01.MSI-H status was detected in 1 case(16.7%, 1/6), 14 cases(77.8%, 14/18), and 18 cases(7.1%, 18/276)in the deleterious mutation group, variant of undetermined significance group, and wild type group, respectively.Notably, patients with variants of undetermined significance had a higher MSI-H status than patients with wild type and POLE deleterious mutations, with all P-values less than 0.01.The frequencies of co-mutations in KRAS, NRAS, BRAF, and PIK3CA were higher in the deleterious mutation group compared to the mutation of undetermined significance group and wild type group(all P<0.05). Conclusions:Colorectal cancer(CRC)patients with harmful mutations and variants of undetermined significance exhibit unique clinicopathological features.Patients with variants of undetermined significance are more likely to develop colon cancer, show poor differentiation, and have higher frequencies of TMB-H(tumor mutational burden)and MSI-H(microsatellite instability-high).

Animal Modeling of Diabetic Nephropathy：A Study Based on Literature / 中国实验方剂学杂志

ObjectiveTo summarize the modeling elements， evaluation indicators， characteristics， and drawbacks of the animal models of diabetic nephropathy， and thus provide guidance for the standardized modeling and rational application of these models. MethodThe articles about the animal experiments of diabetic nephropathy published in the last decade were retrieved from China National Knowledge Infrastructure， Wanfang Data， and PubMed. The data of animal species， sex， modeling techniques， modeling criteria， and evaluation indicators were analyzed in Excel. ResultA total of 287 publications were included in this study. Male SD rats were mainly used for the modeling of diabetic nephropathy. The animal models of type 1 diabetes were mainly established by intraperitoneal injection of streptozotocin （STZ） at 60-69 mg·kg-1 once or 50 mg·kg-1 for 5 continuous days， and those of type 2 diabetes by intraperitoneal injection of STZ at 30-39 mg·kg-1 once or 30 mg·kg-1 for 2 continuous days combined with 4 weeks of high-fat and high-sugar diet. Blood glucose and 24-hour urine protein were mainly used to determine whether the modeling was successful. The evaluation indicators of the animal models mainly included basic indicators， glucose and lipid metabolism indicators， and renal function indicators. ConclusionAnimal models are commonly used in the research on diabetic nephropathy， while there is no unified standards for the preparation or evaluation of the animal models. Moreover， Chinese medicine is rarely considered in the modeling. Through literature review and data analysis， this paper summarizes the modeling elements and standards， key evaluation indicators， characteristics， and shortcomings， aiming to build the animal models of diabetic nephropathy with a high success rate and with the characteristics in line with the clinical pathogenesis and syndromes.

Oral administration of Bifidobacterium breve improves anti-angiogenic drugs-derived oral mucosal wound healing impairment via upregulation of interleukin-10 / 国际口腔科学杂志·英文版

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study.

OBJECTIVE: To evaluate the clinical effect of transcutaneous auricular vagus nerve nerve stimulation (taVNS) on disorders of consciousness (DOC) patients with Coma Recovery Scale-Revised (CRS-R) and cerebral cortex activity by electroencephalogram (EEG) detection. METHODS: Randomized controlled methods were used to evaluate the clinical effect of taVNS on patients with DOC. Twelve patients with initial CRS-R of 6-10 were randomly divided into the treatment group of taVNS and control group of transcutaneous non-auricular vague nerve stimulation (tnVNS). According to clinical diagnosis, the treatment group was divided into vegetative state (VS) group and minimally conscious state (MCS) group. RESULTS: The energy of delta and beta bands is positively correlated with the brain activity of patients. taVNS has different regulatory effects on patients with different conscious States. In taVNS group, the energy of delta band in local brain regions changed significantly. Significant changes in brain connection activity were limited to local brain regions. While in patients with MCS in the taVNS group, delta and beta band energy significantly changed in multiple brain regions and cross-brain connection activity also changed significantly. CONCLUSION: These findings suggest that taVNS may be a related extra method for arousing patients' awakening by improving brain connection activity. And the effect is remarkable in MCS patients.

Classification and analysis of three types of blood donors based on local resident population / 中国输血杂志

【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.

Study on the age composition of blood donors in some areas of China / 中国输血杂志

【Objective】 To explore the recruitment and retention strategy of blood donors by investigating the age composition of blood donors in some areas of China, so as to promote blood donation and enhance clinical blood supply. 【Methods】 Through the working platform of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions, the average age and age composition of blood donors from 22 blood centers were collected, and statistical analysis was conducted after eliminating invalid data. 【Results】 The median average age of blood donors during the survey year was 30.02.The median age in 2.89% of the blood centers was lower than 25. The average age of different genders was statistically significant only in 2018(P<0.05). Fot first-time blood donors, the median constituent ratio of donors <25 and ≥25 years old was 54.53% and 44.28%, with median retention rate at 10.30% and 9.61%, respectively. The median overall participation rate of blood donors was 2.7%, with median participation rate of blood donors <25 years old at 5.1%. 【Conclusion】 The recruitment and retention of blood donor is crucial to enhance clinical blood supply. Blood donors <25 years old, with a longer period for future donation, should be the main target of blood donation recruitment. Meanwhile, the revision of upper age limit for blood donation is another important initiative to grow the blood donor pool.

Analysis of pyroptosis-related genes of colon cancer cells based on bioinformatics screening and construction of prognostic model / 肿瘤研究与临床

Objective:To explore the characteristics of pyroptosis-related genes in colon cancer cells screened by bioinformatics, and to verify the constructed prognostic model of colon cancer based on differentially expressed pyroptosis-related genes.Methods:Genetic data of RNA sequencing and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Fifty-two genes associated with pyroptosis were identified by searching the literature and compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from TCGA database to obtain differentially expressed pyroptosis-related genes in clinical samples. The protein interaction network of differentially expressed pyroptosis-related genes was analyzed by using STRING website and R software. Based on the differential expression of pyroptosis-related genes in clinical samples of TCGA database, colon cancer patients in TCGA database were divided into pyroptosis and non-pyroptosis groups, and genes with significant differential expression between the two groups were screened at P < 0.05 according to gene expression; based on these differentially expressed genes, LASSO Cox regression was used to construct a prognostic model of colon cancer associated with pyroptosis. Patients collected from TCGA database were divided into high risk (≥ median value) and low risk (< median value) groups according to the median value of risk scores calculated by the model, and the overall survival of the two groups was analyzed by Kaplan-Meier survival function. The time ROC package of R software was used to analyze the efficacy of applying risk scores to predict the different survival time of colon cancer patients in TCGA database. Multivariate Cox regression was used to analyze the effects of clinicopathological factors and risk scores calculated by the model on the survival of patients in TCGA database. R software was used to analyze and obtain the differential genes between high and low risk groups of colon cancer patients in TCGA database. R software was used to conduct Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and single sample gene set enrichment analysis of immune cells and immune function (ssGESA) for differentially expressed pyroptosis-related genes. Results:Thirty-eight differentially expressed pyroptosis-related genes between colon cancer tissues and normal tissues of clinical samples were obtained based on data of TCGA database. A prognostic model consisting of 13 pyroptosis-related genes was established by applying LASSO Cox regression, the risk score = 0.118×MID2+0.354×IL20RB+0.083×HOXC11+0.011×TMEM88+0.021×SYNGR3+0.246×UPK3B+0.030×EGFL7+0.109×TMPRSS11E+0.138×IFITM10+0.161×RNF207+0.097×LINGO1+0.202×HEYL+0.025×ROBO3. Survival analysis showed that TCGA database had worse overall survival in the high-risk group than in the low-risk group ( P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve of the prognostic model risk score in predicting the survival of colon cancer patients in TCGA database at 1, 3 and 5 years was all > 0.7. Multivariate Cox regression analysis showed that risk score was an independent influencing factor for survival of colon cancer patients in TCGA database (high risk vs. low risk HR = 3.988, 95% CI 2.865-5.551, P < 0.001). GO and KEGG enrichment analysis showed that the differentially expressed genes between high and low risk groups (SULF1, FBLN2, COL1A1, DES, SFRP2, FNDC1, MYH11, APOE, C3, SPP1, COL1A2, COL10A1, THBS2, AEBP1, CNN1, IGHG1, and SFRP4) were upregulated in the high risk group, which were mainly associated with cellular matrix structural components and extracellular matrix (ECM) receptor interactions. ssGSEA analysis showed that the level of immune cell infiltration was higher in high risk group, especially B cells, macrophages, mast cells, helper T cells, and tumor-infiltrating lymphocytes were higher than those in low risk group; for immune function, chemokine receptors, immune checkpoints, human leukocyte antigens, parainflammation, T cell suppression, T-cell stimulation, and type Ⅱ interferon response in high risk group were higher than those in low risk group. Conclusions:The constructed prognostic model of colon cancer based on pyroptosis-related genes is valuable for predicting the prognosis of colon cancer patients. Pyroptosis-related genes may play an important role in tumor immunity of colon cancer and can be used for prognostic analysis of colon cancer patients.

Role ofdenervation on kidney tubulointerstitial fibrosis induced by ischemia reperfusion injury via Nrf2/TGF-β pathway / 中华器官移植杂志

Objective:To explore the role of denervation on kidney tubulointerstitial fibrosis(TIF)induced by ischemia reperfusion injury(IRI)via NF-E2-related factor-2 (Nrf2)/transforming growth factor-β(TGF-β)pathway in mice.Methods:C57BL/6 mice were randomized into four groups(n=12 each)of sham, kidney ischemia reperfusion(IR), RDN and RDN+ IR(DIR). At Days 1 and 7 post-reperfusion, kidney histology and fibrotic injury are observed after hematoxylin-eosin(HE)and Masson staining.α-SMA protein is detected by immunohistochemistry.The serum levels of blood urea nitrogen(BUN), creatinine(Cr)and neutrophil gelatinase-associated lipocalin(NGAL)are measured.And the contents of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 4(IL-4), interleukin 10(IL-10)and interleukin 13(IL-13)in kidney tissues are detected.Western blot is utilized for observing the expression levels of Nrf2, TGF-β and phospho-Smad3 protein in kidney tissues.Results:Compared with sham group, kidney histologic score, serum levels of BUN, Cr and NGAL and contents of MDA, IL-4, IL-10 and IL-13 in kidney tissues spiked while activity of SOD declined.Protein expressions of Nrf2, TGF-β and phospho-Smad3 rise in IR-1 and DIR-1 groups( P<0.05). Compared with IR-7 group, degree of fibrosis and levels of α-SMA, IL-4, IL-10 and IL-13 drop in DIR-7 group, Nrf2 protein expression increased and protein expressions of TGF-β and phospho-Smad3 decreased( P<0.05). Conclusions:Acute oxidative stress injury induced by IRI becomes aggravated after kidney denervation and initiates TIF.The long-term expression of TGF-β and phosphorylation of Smad3 are suppressed due to a continuous activation of Nrf2 pathway, thereby blunting the long-term TIF degree of kidney.

The predicting value of amplitude integration electroencephalogram to the long-term neurodevelopmental disorders in neonatal congenital heart disease / 中国小儿急救医学

Objective:To analyze the association between the perioperative amplitude-integrated electroencephalogram(aEEG)of neonates with congenital heart disease(CHD) and their neurodevelopmental outcome at 2 years of age.Methods:Neonates with CHD ( n=32) who were admitted to the neonatal intensive care unit at our hospital were included.All patients had undergone cardiac surgery during the neonatal period and preoperative and postoperative aEEG monitoring.The background pattern, sleep-wake cycle(SWC) pattern and seizure activity (including electrographic seizure activity) were used to quantify cerebral activity related to brain function.Infants with CHD were enrolled prospectively to follow up at 2 years old.Participants were assessed at 2 years old via the Bayley Scale of Infant Development. Results:A total of 32 neonates were enrolled in the study.Compared with average of normal population, psychomotor development index(PDI) of participants decreased significantly ( P<0.05). The mental development index(MDI) of patients with abnormal behavior was significantly lower.The longer length of ICU, longer time of ventilation, and the older age of father were risk factors of lower PDI.The MDI (76.29±23.38) of cases with mild abnormal preoperative background pattern were significantly lower than that with normal background pattern (97.37±22.65)( P=0.039). The PDI (74.00±20.09) of cases with abnormal preoperative background pattern was significantly lower than that (92.12±20.42) with normal preoperative background pattern ( P=0.046). The PDI (85.04±20.384) of cases with immature preoperative SWC were significantly lower than that with the normal preoperative SWC(110.00±16.55) ( P=0.027). Conclusion:Abnormal perioperative background pattern and SWC are markers for neurodevelopment disorder.The perioperative aEEG is a useful bedside tool that helps predict outcomes in infants underwent heart surgery.

The history and clinical practicability of the diagnosis of bronchopulmonary dysplasia / 中国小儿急救医学

A clear and well-accepted diagnostic criterion is a prerequisite to evaluate the prevention or treatment effects of bronchopulmonary dysplasia(BPD). With the survival of extremely premature infants, the improvement of neonatal intensive care, the diagnostic criteria of BPD updated for several times.To be familiar with the diagnosis of BPD and the evidence of transition in different periods is of great significance for the research of BPD.This review introduced the history and the clinical practicability of the changing of BPD diagnostic criteria, to help clinicians and health care managers better evaluate existing research findings and guide long-term management policies for extremely premature infants.

Analysis of prognosis for colon cancer patients based on the characteristics of ferroptosis-related long non-coding RNA / 肿瘤研究与临床

Objective:To explore the value of prognostic model based on ferroptosis-related long non-coding RNA (lncRNA) in predicting the prognosis of patients with colon cancer.Methods:Ferroptosis-related genes were downloaded from FerrDb database, and the RNA sequencing gene data and clinical data of colon cancer patients from the establishment of the database to November 2021 were downloaded from the Cancer Genome Atlas (TCGA) database. Through R3.6.3 software, the colon cancer gene expression data obtained from TCGA database and ferroptosis-related genes obtained from FerreDb database were analyzed to obtain differentially expressed ferroptosis-related genes in colon cancer and normal tissues. The expression correlation between ferroptosis-related genes and lncRNA in colon cancer was calculated by using R3.6.3 software to determine ferroptosis-related lncRNA in colon cancer. The survival-related differentially expressed ferroptosis-related lncRNA was screened and included in the multivariate Cox proportional hazards model to construct a colon cancer prognosis model; and the risk score of colon cancer patients was calculated by the prognostic model according to the lncRNA expression. According to the median risk score, the clinical cases collected from TCGA database were divided into high-risk group and low-risk group with 223 cases in each group. Kaplan-Meier survival analysis was performed for the two groups. The receiver operating characteristic (ROC) curve was used to analyze the effect of prognostic model risk score and clinical characteristics on predicting the survival of all patients. GSEA 4.1.0 software was used for gene set enrichment analysis (GSEA) of lncRNA in high-risk and low-risk groups, and ggpubr package of R3.6.3 software was used for single sample GSEA (ssGSEA) of immune cells and immune function of differentially expressed lncRNA between high-risk and low-risk groups.Results:According to the intersection of ferroptosis-related genes and differentially expressed genes obtained from databases, 65 differentially expressed ferroptosis-related genes were obtained, and 24 lncRNA related to the prognosis of colon cancer were analyzed, and then prognostic model was constructed based on lncRNA. Kaplan-Meier survival analysis showed that the survival of low-risk group was better than that of high-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve (AUC) of 1-, 2-, 3-year survival predicted by the prognostic model risk score was more than 0.75, and the AUC of 1-year survival predicted by the risk score for all patients was greater than age, gender, the National Comprehensive Cancer Network (NCCN), T staging, N staging and M staging. GSEA showed that differentially expressed lncRNA in high-risk and low-risk groups concentrated in tumor and immune-related pathways; ssGSEA showed that there were differences in T cells, macrophages, mast cells, neutrophils, immune stimulation, human leukocyte antigen, type Ⅰ and type Ⅱ interferon response between high-risk group and low-risk group (all P < 0.05), and the expression levels of CD200 and TNFRSF14 at the immune checkpoint were significantly different (both P < 0.01). Conclusions:Ferroptosis-related lncRNA may play an important role in tumor immunity of colon cancer, and it can be used for the prognosis analysis of patients with colon cancer.

Value of the biomarkers derived from cerebrospinal fluid in the diagnosis of Alzheimer disease / 中华检验医学杂志

Alzheimer disease (AD) is a neurodegenerative disease in the elderly. Early intervention is the only reliable means to delay the progress of the disease. Referring to the diagnostic criteria of AD, this paper summarizes and analyzes the representative literatures of various AD biomarkers derived from cerebrospinal fluid in recent years, and reviews the efficacy of various cerebrospinal fluid biomarkers in the diagnosis and differential diagnosis of AD. Results show that CSF Aβ42, Aβ42/Aβ40, T-tau, p-tau, Aβ42/p-tau, growth-associated protein 43, synaptosomal-associated protein 25, neurogranin and visinin-like protein-1 are of great value in the diagnosis and differential diagnosis of AD. The above CSF biomarkers can be used in the diagnosis and differential diagnosis of AD. The laboratory should select appropriate AD CSF biomarkers according to its own conditions in daily laboratory works.

Increased expression of Cyclin F in liver cancer predicts poor prognosis: A study based on TCGA database.

BACKGROUND: Cyclin F (CCNF) dysfunction has been implicated in various forms of cancer, offering a new avenue for understanding the pathogenic mechanisms underlying hepatocellular carcinoma (HCC). We aimed to evaluate the role of CCNF in HCC using publicly available data from The Cancer Genome Atlas (TCGA). METHOD: We used TCGA data and Gene Expression Omnibus (GEO) data to analyze the differential expression of CCNF between tumor and adjacent tissues and the relationship between CCNF and clinical characteristics. We compared prognosis of patients with HCC with high and low CCNF expression and constructed receiver operating characteristic (ROC) curves. In addition, we also explored the types of gene mutations in relevant groups and conducted Gene Set Enrichment Analysis (GSEA). RESULTS: The expression of CCNF in liver cancer tissues was significantly increased compared with that in adjacent tissues, and patients with high CCNF expression had a worse prognosis than those with low CCNF expression. Patients with high CCNF expression also had more somatic mutations. High expression of CCNF hampers the prognosis independently. The GSEA showed that the "http://www.gsea-msigdb.org/gsea/msigdb/cards/BIOCARTA_WNT_PATHWAY" Wnt pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/BIOCARTA_P53_PATHWAY" P53 pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/HALLMARK_PI3K_AKT_MTOR_SIGNALING" PI3K/Akt/mTOR pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/HALLMARK_NOTCH_SIGNALING" Notch pathway were enriched in patients with the high CCNF expression phenotype. CONCLUSION: High CCNF expression can be seen as an independent risk factor for poor survival in HCC. Its expression may serve as a target for the diagnosis and treatment of liver cancer.

State-level COVID-19 Trend Forecasting Using Mobility and Policy Data

AO_SCPLOWBSTRACTC_SCPLOWThe importance of pandemic forecast cannot be overemphasized. We propose an interpretable machine learning approach for forecasting pandemic transmission rates by utilizing local mobility statistics and government policies. A calibration step is introduced to deal with time-varying relationships between transmission rates and predictors. Experimental results demonstrate that our approach is able to make accurate two-week ahead predictions of the state-level COVID-19 infection trends in the US. Moreover, the models trained by our approach offer insights into the spread of COVID-19, such as the association between the baseline transmission rate and the state-level demographics, the effectiveness of local policies in reducing COVID-19 infections, and so on. This work provides a good understanding of COVID-19 evolution with respect to state-level characteristics and can potentially inform local policymakers in devising customized response strategies.

Clinicopathological analysis of ten cases of mucinous nevi / 中华皮肤科杂志

Objective:To investigate clinical and histopathological features of mucinous nevi.Methods:Clinical and pathological data were collected from 10 patients with clinically and histopathologically confirmed mucinous nevi in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2014 to December 2019, and retrospectively analyzed.Results:All cases developed mucinous nevi in childhood, with an average age of onset being 6.5 years. Of the 10 patients, 7 had lesions on the trunk, among whom 4 had lesions on the back; the remaining 2 had lesions on the limbs, and 1 had generalized lesions on the trunk and limbs. The skin lesions were locally arranged in lines, bands or clusters, and skin-colored, reddish or yellow in color, with the texture varying from soft to hard. Histopathological examination showed that 10 patients presented with disordered arrangement of collagen fiber bundles in the dermis and mucin deposition at varying locations and to different degrees among them, 6 with thickened and red-stained collagen fibers in the deposition area, and the remaining 4 with sparse and decreased collagen; focal liquefaction degeneration of the basal layer was observed in 2 cases, and different amounts of mature adipose tissue in the dermis were seen in 3 cases.Conclusions:Mucinous nevus pathologically manifests as mucin deposition of varying degrees among disorderedly arrangd collagen fiber bundles in the dermis, which is similar to some other diseases, and is easily misdiagnosed. Close combination of clinical and pathological features facilitates confirmed diagnosis.

Analysis of psychological status and influencing factors of medical workers amid COVID-19 pandemic; analysis of influencing factors / 中华健康管理学杂志

Objective:The study seeks to explore the factors influencing the psychological status and sleep quality of medical workers amid the ongoing COVID-19 pandemic, in order to provide data sources and theoretical basis for the development of relevant psychological intervention programs.Methods:Employing the convenience sampling method, general information questionnaire (age, gender, marital status, educational background, job status, etc.), Generalized Anxiety Disorder-7 and Patient Health Questionnaire, epidemic stress index scale, and sleep quality questionnaire were distributed to medical staff between February 18 and April 3, 2020, using the PEM mental health care platform of by ZhongShengKaiXin for medical staff issued. Descriptive, single factor, and correlation analyses, as well as multiple linear regression analysis were used to analyze the data.Results:Overall, 24, 845 questionnaires were collected from 23 provinces, of which 24, 687 were valid, with a recovery rate of 99.36%. The findings showed that the proportion of medical personnel with symptoms of anxiety and depression was 50.58% and 51.37%, respectively; 16.11% had poor or very poor anti-stress ability; and 71.78% reported poor or very poor sleep quality. There was a positive correlation between anxiety, depression, anti-stress ability, and sleep quality ( P<0.05). Anxiety was positively correlated with depression, stress tolerance, and sleep quality( r=0.787, 0.667, and 0.486, all P<0.001); depression was positively correlated with stress tolerance and sleep quality ( r=0.709 and 0.586, both P<0.001); and stress tolerance was positively correlated with sleep quality ( r=0.452, P<0.001). Multiple linear regression analysis results showed that age, gender, marital status, educational background, professional title, job status, and participation influenced the anxiety levels of medical personnel in the backdrop of the pandemic ( P<0.001). Depression levels of medical staff were influenced by gender, educational background, job position, and participation ( P<0.001), while gender, marital status, educational background, job position, and participation influenced the stress tolerance levels ( P<0.001). The sleep quality of medical workers was influenced by age, gender, job position, participation in the fight against the pandemic, and professional title ( P<0.001). Conclusions:Amid the ongoing COVID-19 pandemic, medical staff reported poor mental health status and sleep quality, which can be attributed to diverse factors. The research findings can be useful for assisting medical staff to strengthen their self-cognition, while also providing certain psychological counseling data and theoretical basis for management departments.