Objective:To explore the characteristics of key ferroptosis-related genes as therapeutic targets for sepsis based on bioinformatics analysis, and describe their immune characteristics.Methods:The transcriptome datasets GSE57065, GSE9960, GSE28750, and GSE137340 were downloaded from the Gene Expression Omnibus (GEO) database, immune-related gene (IRG) were obtained from ImmPort and InnateDB databases, and ferroptosis-related gene (FRG) were downloaded from the FerrDb database. The datasets GSE57065, GSE9960, and GSE28750 were integrated into an analysis dataset by the surrogate variable analysis (SVA) package and analyzed this analysis dataset by using the "limma" package to obtain differentially expressed gene (DEG), then the intersection set of DEG, FRG, and IRG were considered as ferroptosis and immune-related DEG (FImDEG). Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using "ClusterProfiler" to understand the biological function of FImDEG. The key genes were screened by protein-protein interaction (PPI) network, least absolute shrinkage and selection operator (LASSO) regression algorithms, and support vector machine (SVM) analyses, and Logistic regression model was built based on above key genes. Receiver operator characteristics curve (ROC curve) was plotted to evaluate the diagnostic efficacy of the key genes alone or combinative. The degree of infiltration of 22 immune cells was assessed using the "CIBERSORT" package, and the correlation between the expressions of key genes and infiltration degree of immune cells was analyzed. Dataset GSE137340 was used to verify these key genes.Results:A dataset consisting of 146 sepsis samples and 61 healthy control samples was obtained by processing the database and removing batch effect. A total of 4?537 DEG were obtained, including 2?066 up-regulated genes and 2?471 down-regulated genes. 2?519 IRG and 855 FRG were obtained from the relevant database. Using the intersection of DEG, IRG and FRG, 34 FImDEG were obtained, including 20 up-regulated genes and 14 down-regulated genes. GO functional annotation showed that the biological functions of 34 FImDEG were mainly inhibition of transferase activity, regulation of DNA-binding transcription factor activity and cell response to stimulation. In terms of molecular function, it was mainly related to RNA polymerase Ⅱ-specific DNA-binding transcription factor binding and various protein ligase binding. Changes in cell composition occurred mainly in promyelocytic leukemia protein and chromatin silencing complexes. Enrichment analysis of KEGG pathway showed that the major pathways involved in 34 FImDEG included cell aging, expression of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) checkpoint pathways in cancer, interleukin-17 (IL-17) signaling pathway, lipid and atherosclerosis, and NOD-like receptor signaling pathway. Four key genes, including cytochrome b-245 β chain (CYBB), mitogen-activated protein kinase 14 (MAPK14), prostaglandin-endoperoxide synthase 2 (PTGS2) and V-relreticuloendotheliosis viral oncogene homology A (RELA), were screened through PPI network and LASSO and SVM machine learning. ROC curve analysis showed that the area under ROC curve (AUC) of the four key genes for diagnosing sepsis was all greater than 0.65, and the AUC of MAPK14 was 0.911. Logistic regression model was constructed based on four key genes, and the AUC was 0.956. Immunoinfiltration analysis showed that compared with healthy control samples, the infiltration degree of neutrophils and macrophages M0 was significantly increased in sepsis samples, while the infiltration degree of resting natural killer cell (NK cell), naive CD4 + T cell and CD8 + T cell was significantly lowered. Correlation analysis showed that the positive correlation between MAPK14 expression and the infiltration degree of neutrophils was the highest. Validation results in the GSE137340 dataset showed that compared with healthy control samples, the expressions of CYBB and MAPK14 in sepsis samples were significantly up-regulated, however, the expressions of PTGS2 and RELA were significantly down-regulated, similar to the expression trend in the above analysis dataset. Conclusion:Four key genes, including CYBB, MAPK14, PTGS2, and RELA, in the development of sepsis were identified through bioinformatics analysis, which play an important role in the immune process, and MAPK14 may be an important target for immune intervention.

Objective:To investigate the clinical characteristics and short-term follow-up outcomes of primary nephrotic syndrome (PNS) children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron variant outbreak in Shanghai, and to provide a reliable reference for clinicians in the diagnosis and treatment.Methods:It was a case-control study. The clinical data of children with PNS (PNS group) who were diagnosed and followed-up up to 1 year in the nephrology department of four children's medical centers in Shanghai, and the children (control group) who had no underlying diseases and were infected with SARS-CoV-2 in Shanghai Jinshan Public Health Center, including the data when they were infected with SARS-CoV-2, were retrospectively analyzed.Results:(1) From March 30th to April 13th, 2022, 6 PNS children in Shanghai were infected with SARS-CoV-2, including 5 boys and 1 girl. The median age was 4.5 (2.0, 11.0) years old. And 30 children were matched by sex, age and disease type as control group, including 20 males and 10 females. The median age was 4.5 (2.0, 9.0) years. There were no significant differences between the PNS group and the control group in clinical symptoms (including fever duration), treatment regimens, vaccine doses and virus clearance time (all P>0.05). (2) The 6 children with PNS included 3 cases of steroid-sensitive type, 3 cases of steroid-resistant type, 2 cases of minimal change disease, 2 cases of focal segmental glomerulosclerosis and 2 cases with no renal biopsy. Before SARS-CoV-2 infection, their primary disease-PNS were stable, and urine protein was negative, four of them were under maintenance treatment with oral steroids or immunosuppressive drugs. At the time of SARS-CoV-2 infection, the symptoms of all of the 6 cases were mild, no severe, critical or fatal cases, and they were all cured and discharged from hospital through medical isolation observation or symptomatic treatment of infections. (3) Five cases of them still had discomfort symptoms such as cough, anorexia, and fatigue after being discharged from the hospital, which lasted for about 1 week. Within 1 year of follow-up, none of the children have suffered from "recurrent positive PCR results" or "secondary infection" of the SARS-CoV-2. (4) Among them, 4 cases of PNS relapsed after SARS-CoV-2 infection, timely addition of steroids was effective, their urine protein quickly turned negative, and there was no recurrence after 1 year of follow-up. (5) Before infection with SARS-CoV-2, the levels of immunoglobulin IgG were lower than the normal reference value in the 4 cases with PNS recurrence. Conclusions:During the Omicron variant outbreak in Shanghai, the infection of SARS-CoV-2 in children with PNS are resulted in high transmission among household contacts. Most of them have mild symptoms and good prognosis. PNS is prone to relapse after SARS-CoV-2 infection, and steroid therapy is effective and safe for these relapse. IgG may be a potential marker for the prognosis of PNS children infected with SARS-CoV-2.

Objective:To analyze the effects of infectious complications [infected pancreatic necrosis (IPN) and extra-pancreatic infection (EPI)] on the outcomes of patients with severe acute pancreatitis (SAP), and evaluate the differences in infection time, infection site and infecting species between SAP patients with infections complications.Methods:The clinical data of 66 SAP patients with combined infectious complications admitted to Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed, and SAP patients were divided into IPN group ( n=7), EPI group ( n=14) and co-infection (EPI+ IPN) group ( n=45) according to the type of infection. Whether the study data conformed to a normal distribution was assessed by the Shapiro-Wilk test, normally distributed measures were expressed as mean ± standard deviation ( ± s), and ANOVA was used for comparison between groups; skewed measures were expressed as median (interquartile range) [ M ( Q1, Q3)], and the rank-sum test was used for comparison between groups. Bonferroni correction was used for multiple group comparisons ( P value significance level reduced to 0.017). Quantitative data were compared between groups using the χ2 test or Fisher's exact probability method. Results:There were no statistical differences between the three groups in terms of baseline data at admission (gender, age, etiology, modified CTSI score, degree of pancreatic necrosis, and number of organ failure) ( P>0.05), patients in the EPI group were referred earlier than the other two groups ( P<0.05). In clinical treatment, patients in the IPN group and co-infection group required multiple minimally invasive interventions compared with those in the EPI group ( P<0.05), and the number of patients requiring combined nutritional support, length of intensive care unit stay, and total length of hospital stay were higher in the co-infection group than in the other two groups ( P<0.05). In addition, 360 strains of pathogenic bacteria were cultured in this study, with Gram-negative bacteria being the most common, and patients with SAP were more likely to have EPI in the early stage of disease onset, with bacteremia and respiratory tract infections in the early stage (≤14 d), and bacteremia, urinary tract infections, and catheter-associated infections in the late stage (>14 d). Conclusions:Among patients with SAP, patients in the co-infection group had higher surgical intervention, nutritional support and length of hospital stay than those in the single infection group. It is advisable to prioritize EPI in SAP patients with suspected infections, and the common infectious strains in SAP patients are still predominantly Gram-negative bacteria, and clinicians need to adjust the treatment plan in a timely manner according to the changes in patients′ conditions.

ObjectiveTo investigate the effect of different cytopathological grading standards on the efficiency of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of pancreatic cancer. MethodsRelated clinical data and pancreatic cytopathological results were collected from 256 patients with pancreatic space-occupying lesions who underwent EUS-FNA in The First Affiliated Hospital of Anhui Medical University from May 2011 to March 2019, and the influencing factors for the diagnostic efficiency of EUS-FNA were analyzed based on surgical pathology and follow-up results. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of different cytopathological grading standards in the diagnosis of pancreatic cancer. ResultsA total of 67 patients who were lost to follow-up were excluded, and a total of 189 patients were included in the study. According to the Papanicolaou cytopathological standard, there were 47 cases of heterotypic cells, 25 cases of suspected cancer cells, 20 cases of cancer cells, and 97 cases without tumor cells based on EUS-FNA. A total of 133 patients were confirmed to have pancreatic cancer by postoperative pathology and follow-up results, among whom 52 had no tumor cells, 36 had heterotypic cells, 25 had suspected cancer cells, and 20 had cancer cells based on cytopathological results. EUS-FNA had a true positive rate of 6090% (81 patients) and a false negative rate of 39.10% (52 patients) in the diagnosis of pancreatic cancer; for the 56 patients without pancreatic cancer, EUS-FNA had a false positive rate of 19.64% (11 patients) and a true negative rate of 80.36% (45 patients). EUS-FNA had an area under the ROC curve of 0.643 (95% confidence interval: 0.561-0.724) in the diagnosis of pancreatic cancer. In combination with different cytopathological grading standards and with the diagnostic criteria of “the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive”, “the identification of suspected cancer cells or cancer cells was considered positive”, and “the identification of cancer cells was considered positive”, the results showed that the diagnostic criteria of “the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive” improved the efficiency of EUS-FNA in the diagnosis of pancreatic cancer, with a sensitivity of 50.38% and a specificity of 75.00%. Among the 189 patients, 13 (6.88%) experienced complications after EUS-FNA, which included hyperamylasemia and abdominal pain. ConclusionThe combination of different cytopathological grading standards can help improve the efficiency of EUS-FNA in the diagnosis of pancreatic cancer.

Malignant tumors usually have no obvious clinical symptoms in the early stage. Most patients are already in the advanced stage when they are diagnosed. Some patients have lost the opportunity for operation, resulting in poor prognosis. Therefore, how to find the best therapeutic target for such patients and improve the prognosis of patients has gradually become the focus of scholar′s attention. Recently, Kruppel-like factor (KLF) is a transcriptional regulator that can bind to the target DNA, and its family plays an important role in the occurrence and development of malignant tumors. It has also been confirmed that the KLF family affects the proliferation, differentiation and migration of tumor cells, but the specific mechanism is still not fully elucidate. Consequently, in order to further explored the effect of the KLF family on tumors, this study intends to briefly review the roles and regulatory mechanisms of the KLF family in the cell proliferation, differentiation and migration of malignant tumors, hoping to provide new target for the biological treatment of tumors.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Its pathogenesis is not only related to abnormal activation of trypsinogen, but also related to calcium overload, mitochondrial dysfunction, impaired autophagy and endoplasmic reticulum stress. However, the mechanism has not been fully elucidated and needs to be further studied. Currently, there is no effective treatment for AP. It is difficult to prevent the loss of pancreatic function. An in-depth understanding of the pathophysiological mechanisms of AP may help to identify the potential therapeutic targets. Therefore, the purpose of this study is to review recent advances in the mechanism of AP in order to provide more research direction for treatment.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective? To investigate the status of caregiver preparedness and adult attachment among the spouse of young and middle-aged stroke patients,and to analyze the correlation between them. Methods? From January 2017 to May 2018,110 spouses of stroke patients who were treated in Affiliated Hangzhou First People＇s Hospital, Zhejiang University School of Medicine were selected as subjects by convenience sampling. The General Information Questionnaire,Care Preparedness Scale (CPS),and Experience in Close Relationship Scale (ECR) were used in the survey. Totally 110 questionnaires were distributed, and 102 valid ones were retrieved, yielding an effective recovery rate of 92.73%. Results? The total CPS score of 102 young and middle-aged stroke patients was (12.87±5.39). The scores of attachment anxiety and attachment avoidance in ECR were (57.96 ±11.69) and (48.06 ±12.10). There were statistically significant differences in the scores of preparedness of caregivers among spouse caregivers of different ages, self reported health status and nursing experience (P＜ 0.05). Attachment anxiety dimension was negatively correlated with caregiver preparedness score (r=-0.318,P＜0.01), and attachment avoidance dimension was negatively correlated with caregiver preparedness score (r=-0.233,P＜ 0.01). Conclusions? The preparedness status of the spouses caregivers of young and middle-aged stroke patients are at a low level. Medical workers can improve their care preparedness by giving them home care knowledge guidance,reducing their attachment avoidance and attachment anxiety so as to improve their preparedness.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

OBJECTIVETo analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO.

METHODSThe clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve.

RESULTSUnivariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg.

CONCLUSIONThe relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.