Sleep patterns, physical activity, genetic susceptibility, and incident rheumatoid arthritis: a prospective cohort study.

BACKGROUND: Sleep and physical activity (PA) are thought to be interconnected with the development of rheumatoid arthritis (RA). However, the precise nature and extent of these relationships have yet to be fully quantified. This study aimed to quantify the longitudinal effects of sleep behaviors, PA, and genetic susceptibility on the incidence of RA and to estimate the combined effects and interactions among these exposures. METHODS: A total of 363,211 adults were derived from a large European cohort. We incorporated five sleep behaviors (sleep duration, insomnia, snoring, chronotype, and daytime sleepiness) to generate sleep patterns, which were defined based on healthy sleep scores. Multivariate-adjusted Cox proportional hazard models were conducted to assess the individual and combined associations of sleep patterns, PA, and genetic susceptibility with the risk of RA occurrence. Multiplicative and additive interactions were estimated by Pinteraction and relative excess risk due to interaction (RERI) between each of the two exposures. RESULTS: During a follow-up of 12.5 years, 4262 RA cases were ascertained. A healthy sleep pattern was associated with a decreased risk of RA in a dose-response manner, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.75-0.84), independent of traditional risk factors and genetic predisposition. Under the restricted cubic splines model, a non-linear association was detected for PA and RA risk. Participants in the intermediate quintile 3 showed the lowest risk for developing RA, with a HR 95% CI of 0.84 (0.76-0.92). Moreover, there was an additive interaction effect of intermediate sleep pattern and PA, with a 0.45 (95% CI = 0.02-0.87) RERI of developing RA. Additionally, individuals at high genetic risk had the greatest 10-year absolute risk reduction (10.58 per 1000 person-years) when adopting both favorable behaviors. CONCLUSIONS: A healthy sleep pattern and moderate PA were associated with a reduced risk of developing RA, which can offset the deleterious effects of predisposing genetic components. Implementing these modifiable lifestyle factors into public health practices is beneficial for RA prevention.

The epidemic characteristics of Mycoplasma pneumoniae infection among children in Anhui, China, 2015-2023.

The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021-2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children. IMPORTANCE: The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

Routine blood parameters as auxiliary diagnostic tools for Mycoplasma pneumoniae infection in children.

Introduction. Recently, the incidence of Mycoplasma pneumoniae (M. pneumoniae) infection in children has been increasing annually. Early differential diagnosis of M. pneumoniae infection can not only avoid the abuse of antibiotics, but also is essential for early treatment and reduction of transmission.Gap statement. The change of routine blood parameters may have important clinical significance for the diagnosis of M. pneumoniae infection, but it has not been reported so far.Aim. This study aims to establish a predictive model for M. pneumoniae infection and explore the changes and clinical value of routine blood parameters in children with M. pneumoniae infection, serving as auxiliary indicators for the diagnosis and differentiation of clinical M. pneumoniae infection.Methodology. A total of 770 paediatric patients with respiratory tract infections were enrolled in this study, including 360 in the M. pneumoniae group, 40 in the SARS-CoV-2 group, 200 in the influenza A virus group, and 170 in the control group. The differences of routine blood parameters among all groups were compared, and risk factors were analysed using multivariate logistics analysis, and the diagnostic efficacy of differential indicators using ROC curves.Results. This study revealed that Mono% (OR: 3.411; 95% CI: 1.638-7.102; P=0.001) was independent risk factor associated with M. pneumoniae infection, and Mono% (AUC=0.786, the optimal cutoff at 7.8%) had a good discriminative ability between patients with M. pneumoniae infection and healthy individuals. Additionally, Mono% (OR: 0.424; 95% CI: 0.231-0.781; P=0.006) and Lymp% (OR: 0.430; 95% CI: 0.246-0.753; P=0.003) were independent risk factors for distinguishing M. pneumoniae infection from influenza A virus infection, and the Lymp% (AUC=0.786, the optimal cutoff at 22.1%) and Net% (AUC=0.761, the optimal cutoff at 65.2%) had good discriminative abilities between M. pneumoniae infection and influenza A infection. Furthermore, platelet distribution width (OR: 0.680; 95% CI: 0.538-0.858; P=0.001) was independent risk factor for distinguishing M. pneumoniae infection from SARS-CoV-2 infection. Meanwhile, the ROC curve demonstrated that PDW (AUC=0.786, the optimal cutoff at 15%) has a good ability to differentiate between M. pneumoniae infection and SARS-CoV-2 infection.Conclusion. This study demonstrates that routine blood parameters can be used as auxiliary diagnostic indicators for M. pneumoniae infection and provide reference for the diagnosis and differentiation of clinical M. pneumoniae infection.

NAT10-mediated ac4C modification promotes stemness and chemoresistance of colon cancer by stabilizing NANOGP8.

Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.

Randomized Controlled Trial and Correlation Analysis of Gandouling Tablet in Treatment of Abnormal Lipid Metabolism of Wilson's Disease with Turbid Phlegm and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Gandouling tablet （GDL） on abnormal lipid metabolism in Wilson's disease （WD） and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD. MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， serum triglyceride （TG）， total cholesterol （TC）， apolipoprotein B （ApoB）， low density lipoprotein cholesterol （LDL-C）， bile acid （BA）， γ-glutamyl transferase （GGT）， prediction model of hepatic steatosis ［hepatic steatosis index （HSI） and Zhejiang University index （ZJU index）］， ultrasonic attenuation coefficient imaging （ATT）， and traditional Chinese medicine （TCM） syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG， TC， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome score， ATT， and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method， with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate （DMPS）， while the control group was only treated with DMPS as a control. After six courses of treatment， 24-hour urine copper， TC， TG， LDL-C， ApoB， HSI， ZJU， ATT， TCM syndrome score， and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC， TG， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome scores， and ATT was analyzed. ResultPearson correlation analysis showed that serum TC （r = 0.811）， TG （r = 0.826）， LDL-C （r = 0.802）， ApoB （r = 0.820）， ALT （r = 0.497）， ALT/AST （r = 0.826）， TCM syndrome score （r = 0.716）， and ATT （r = 0.736） were positively correlated with HSI （P<0.01）， while AST， BA， and GGT had no significant correlation with HSI. TC （r = 0.718）， TG （r = 0.765）， LDL-C （r = 0.667）， ApoB （r = 0.699）， ALT/AST （r = 0.403）， TCM syndrome score （r = 0.666）， and ATT （r = 0.684） were positively correlated with ZJU （P<0.01）. ALT， AST， BA， and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 （37/43）， and that of the control group was 72.09% （31/43）. The total effective rate of the observation group was higher than that of the control group （Z = -2.301， P<0.05）. After treatment， the 24-hour urine copper of the two groups increased significantly. The levels of TC， TG， LDL-C， and ApoB were significantly decreased， and the HSI， ZJU， and ATT were significantly decreased （P<0.01）. Compared with those in the control group after treatment， the above indexes improved better in the observation group （P<0.05， P<0.01）. ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD， with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.

Prognostic factor and its predictive value of patients with Wilson's disease-related acute-on-chronic liver failure / 解放军医学杂志

Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.

Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.

OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.

Comparison of immune responses in children with infectious mononucleosis caused by Epstein-Barr virus at different infection stages.

INTRODUCTION: Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein-Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages. METHODS: This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM). RESULTS: The results revealed that the absolute numbers of leukocytes and CD8+ T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4+ T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α-HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection. CONCLUSION: There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection.

Construction and optimization of a novel plasma membrane model for membrane affinity assay based on polydiacetylene vesicles / 药学学报

Most drugs need to interact with cell membrane to reach the biological target, so that membrane affinity assay is an important early screening step in drug discovery. However, at present, the traditional oil-water distribution method is still used, a new, simple and accurate method for membrane affinity assay is urgently needed. In this study, according to the colorimetric principle, a new assay model based on polydiacetylene vesicles was optimized through a series of experiments including different concentrations of vesicle solution, temperature, or pH reaction environment. On this basis, tetracaine hydrochloride, 2-methylimidazole and histamine were used as model drugs to measure the membrane affinity constants and verify the between-batch precision of the optimized assay model (relative standard deviation less than 5%). In addition, polydiacetylene vesicles were stable for up to 180 days, demonstrating the potential application of the assay model. This strategy is simple, stable, reliable, with high reproducibility, low cost and easy to promote, which provided a new tool and a new direction for the high-throughput assay of membrane affinity.

Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles / 中华妇产科杂志

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Metabolomics study of corn silk on renal tissue and urine of diabetic nephropathy rats / 中国药理学通报

Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy (DN) rats using metabolomics technology. Methods DN rat model was established by feeding with high-sugar and high-fat diet, combined with intraperitoneal injection of low dose streptozotocin. Renal organ index, fasting blood glucose, albumin creatinine ratio, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol indexes were measured, and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats. Further, UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine, combined with principal component analysis (PC A) and orthogonal partial least squares discriminant analysis (OPLS-DA). After identification by HM-DB and KEGG database, the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis. Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk, indicating that corn silk had a good intervention effect on DN. Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk, and it involved 18 metabolic pathways mainly including phenylalanine, tyrosine and tryptophan biosynthesis, riboflavin metabolism, arachidonic acid metabolism, and tyrosine metabolism. Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism, riboflavin metabolism, and arachidonic acid metabolism.

Development and validation of models to predict serosal invasion in advanced gastric cancer using the enhanced CT imaging-based radiomics features and clinical features / 中国医学物理学杂志

Objective To explore the predictive value of the enhanced CT imaging-based radiomics model and the clinical model for the serosal invasion in advanced gastric cancer.Methods The data were collected from 351 patients with advanced gastric cancer who underwent abdominal enhanced CT examination within 2 weeks before surgery,and the patients were randomly divided into a training group(n=247)and a validation group(n=104)in a ratio of 7:3.The 3190 radiomics features which were extracted from the arterial and venous phase CT images using A.K software were dimensionally reduced for constructing a radiomics model.The pathological features between serosal invasion positive and negative groups were compared,and the significant features were used to establish a clinical model.The model's performance was evaluated using receiver operating characteristic curve.Results In the training and validation groups,N staging and M staging were different in serosal invasion positive and negative groups(P<0.05).A total of 14 radiomic features were ultimately selected from the arterial and venous phase images.In the validation group,the diagnostic efficacy of the radiomic model for predicting serosal invasion in advanced gastric cancer was higher than that of the clinical model based on the combination of N staging and M staging(AUC:0.854 vs 0.793).Conclusion Both the radiomics model based on the enhanced CT imaging and the clinical model based on the combination of N staging and M staging can successfully predict serosal invasion in advanced gastric cancer,but the former performs better.

Establishment of mouse models of lymphoma with dual-labeled EBV-immortalized lymphoblastoid cell lines by intravenous versus subcutaneous injection / 中国肿瘤临床

Objective:To establish a green fluorescent protein(GFP)and firefly luciferase(Luc)double-labeled Epstein-Barr virus(EBV)infec-ted B lymphoblastoid cell lines(B-LCL)and apply them to mouse models,then compare the advantages and disadvantages of models inocu-lated by intravenous(IV)or subcutaneous(SC).Methods:B lymphoblastoid cell lines double-tagged with GFP/Luc(B-LCL-GL)were con-structed through lentivirus transduction,puromycin intervention.Subcutaneous xenograft and hematogenous metastasis models were re-spectively established by subcutaneous or intravenous injection of B-LCL-GL cells at three concentrations in(NOD)/Prkdcscid/IL-2Rγnull(NPG)mice for in vivo bioluminescence imaging.Results:In the B-LCL-GL group,the ratio of the GFP-positive cell population was 92.5%,and the average luminescence intensity was as high as 4.80E+08 Photons/s,which was considerably higher than that of untreated B-LCLs.In the hematogenous metastasis models,tumor bioluminescence was initially located in the peritoneal area and then spread throughout the en-tire body between 7 and 28 days.In the subcutaneous xenograft models,strong central and weak peripheral tumor-related biolumines-cence signal was detected on day 7 in the three groups,which then spread throughout the body on day 28 in the high-dose group.Taken to-gether,there was no significant difference in tumor progression between the two routes of administration when using the same dose of B-LCL-GL cells.However,the survival analysis indicated that the IV injection group,in which all the mice ultimately died,had a shorter time frame for testing than that of the SC injection group,in which the mice survived until day 100 in the low-dose and medium-dose groups,thus allowing for long-term testing.Conclusions:GFP and Luc dual-positive B-LCLs were successfully established to generate hematogenous metastasis and subcutaneous xenograft models,which allow the monitoring of the location and size of lymphomas in vivo.It provide plat-form for the study of tumor characteristics and selecting anti-tumor drugs.

Segmentation of ground glass pulmonary nodules using full convolution residual network based on atrous spatial pyramid pooling structure and attention mechanism / 生物医学工程学杂志

Accurate segmentation of ground glass nodule (GGN) is important in clinical. But it is a tough work to segment the GGN, as the GGN in the computed tomography images show blur boundary, irregular shape, and uneven intensity. This paper aims to segment GGN by proposing a fully convolutional residual network, i.e., residual network based on atrous spatial pyramid pooling structure and attention mechanism (ResAANet). The network uses atrous spatial pyramid pooling (ASPP) structure to expand the feature map receptive field and extract more sufficient features, and utilizes attention mechanism, residual connection, long skip connection to fully retain sensitive features, which is extracted by the convolutional layer. First, we employ 565 GGN provided by Shanghai Chest Hospital to train and validate ResAANet, so as to obtain a stable model. Then, two groups of data selected from clinical examinations (84 GGN) and lung image database consortium (LIDC) dataset (145 GGN) were employed to validate and evaluate the performance of the proposed method. Finally, we apply the best threshold method to remove false positive regions and obtain optimized results. The average dice similarity coefficient (DSC) of the proposed algorithm on the clinical dataset and LIDC dataset reached 83.46%, 83.26% respectively, the average Jaccard index (IoU) reached 72.39%, 71.56% respectively, and the speed of segmentation reached 0.1 seconds per image. Comparing with other reported methods, our new method could segment GGN accurately, quickly and robustly. It could provide doctors with important information such as nodule size or density, which assist doctors in subsequent diagnosis and treatment.

Clinical Efficacy of Gandou Fumu Granules on Wilson Disease with Liver-kidney Deficiency and Phlegm-blood Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandou Fumu granules （GDFM） in the treatment of Wilson disease （WD） with liver-kidney deficiency and phlegm-blood stasis. MethodNinety WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly divided into a control group （45 cases） and a treatment group （45 cases）. All patients were treated with sodium 2，3-dimercaptopropane-1-sulfonate （DMPS）， while those in the treatment group received additional GDFM. All patients were treated for four courses （32 days）. The traditional Chinese medicine （TCM） syndrome scores，clinical effective rate，24 h urinary copper，ceruloplasmin （CER），tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），interleukin-6 （IL-6），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） levels of the two groups before and after treatment were observed. ResultAfter treatment， the TCM syndrome scores of the two groups decreased （P<0.01），and the score of TCM syndrome in the treatment group was lower than that of the control group （P<0.01）. The total effective rate of the treatment group was 82.22% （37/45）， higher than 57.78% （26/45） of the control group （χ2=6.402，P<0.05）. There was no significant difference in CER before and after treatment in both groups. The post-treatment 24 hour urinary copper increased （P<0.01）， which was higher in the treatment group than that in the control group （P<0.05）. The TNF-α，IL-1β， and IL-6 levels were significantly reduced in both groups after treatment（P<0.01），and the above indicators in the treatment group were significantly lower than those in the control group （P<0.01）. After treatment，the SOD level increased and the MDA level decreased in the control group （P<0.01）， while no significant difference in GSH-Px level was observed. The SOD and GSH-Px levels increased and the MDA level decreased in the treatment group （P<0.01）. After treatment， SOD and GSH-Px levels of the treatment group were higher than those in the control group， while the MDA level was lower than that in the control group（P<0.05，P<0.01）. ConclusionGDFM can improve the TCM syndrome score and clinical efficacy，enhance the copper removing effect，and inhibit the inflammatory response and antioxidative stress in the treatment of WD with liver and kidney deficiency and phlegm-blood stasis.

Exploration of discipline construction at university-affiliated hospitals in building " first-class universities and disciplines" / 中华医院管理杂志

Discipline construction is the core of hospital development. Under the initiative to build " first-class universities and disciplines" , in order to speed up the construction of first-class hospitals, a university-affiliated hospital carried out discipline construction management by optimizing top-level design, discipline differentiation development, evaluation index system construction and strengthening its application, and carrying out process management in the form of project system.In 2018, the hospital levelled its individual disciplines as leading ones, advantageous ones, backbone ones, backbone promising ones and potential ones, each granted with corresponding funding support. Medians of the disciplinary construction scoring of disciplines at various levels from 2015 to 2018 were used as the standard scoring in examinations in the next two years(2019 and 2020), guiding the disciplines to upgrade their design for discipline construction index system. The appraisal of discipline construction in 2019 and 2020 found 38 disciplines up to the standard scoring, including 16 twice higher than the scoring, while only 7 scored lower than the standard one. The hospital has made stage-based progress in discipline reputation, faculty, science research and social contribution, initially achieving effective guidance of disciplines of the hospital.

Pancreatic neuroendocrine carcinoma in a pregnant woman: A case report and review of the literature.

BACKGROUND: Portal venous thromboembolism caused by malignant pancreatic neuroendocrine tumor metastasis, as the initial presentation of portal hypertension and upper gastrointestinal bleeding, is a rare entity. To our knowledge, there are no reports of this entity in pregnant women. We describe a case of pancreatic neuroendocrine carcinoma during pregnancy with hematemesis and hematochezia as the initial presentation and review the literature to analyze the demographic, clinical, and pathological features to provide a reference for clinical diagnosis and treatment. CASE SUMMARY: A 40-year-old woman presented with hematemesis and hematochezia at 26-wk gestation; she had no other remarkable medical history. The physical examination revealed normal vital signs, an anemic appearance, and lower abdominal distension. Abdominal color Doppler ultrasonography showed portal vein thrombosis, splenomegaly, intrauterine pregnancy, and intrauterine fetal death. Esophagogastroduodenoscopy revealed esophageal and gastric varicose veins and portal hypertensive gastropathy. Contrast-enhanced computed tomography demonstrated multiple emboli formation in the portal and splenic veins, multiple round shadows in the liver with a slightly lower density, portal vein broadening, varicose veins in the lower esophagus and gastric fundus, splenomegaly, bilateral pleural effusion, ascites and pelvic effusion, broadening of the common bile duct, and increased uterine volume. According to the results of Positron emission tomography-computed tomography and immunohistochemical staining, the final diagnoses were that the primary lesion was a pancreatic neuroendocrine tumor and that there were secondary intrahepatic metastases and venous cancer thrombogenesis. CONCLUSION: Upper gastrointestinal bleeding in a pregnant woman may be caused by portal hypertension due to a malignant pancreatic neuroendocrine tumor.

SOX4 as biomarker in hepatitis B virus-associated hepatocellular carcinoma.

Background: Hepatitis B virus infection is associated with liver disease, including cancers. In this study, we assessed the power of sex-determining region Y (SRY)-related high-mobility group (HMG)-box 4(SOX4) gene to predict the clinical course of hepatocellular carcinoma (HCC). Methods: To evaluate the differential expression of SOX4 and its diagnostic and prognostic potential in HCC, we analyzed the GSE14520 dataset. Stratified analysis and joint-effect analysis were done using SOX4 and clinical factor. We then designed a nomogram for predicting the clinical course of HCC. Differential SOX4 expression and its correlation with tumor stage as well as its diagnostic and prognostic value were analyzed on the oncomine and GEPIA websites. Gene set enrichment analysis was explored as well as candidate gene ontology and metabolic pathways modulated by in SOX4 HCC. Results: Our analysis revealed that the level of SOX4 was significantly upregulated in tumor issue (P <0.001). This observation was validated through oncomine dataset and MERAV analysis (all P <0.05). Diagnostic receiver operating characteristic (ROC) analysis of SOX4 suggested it has diagnostic potential in HCC (GSE14520 dataset: P <0.001, area under curve (AUC) = 0.782; Oncomine: (Wurmbach dataset) P = 0.002, AUC = 0.831 and (Mas dataset) P <0.001, AUC = 0.947). In addition, SOX4 exhibited high correlation with overall survival of HBV-associated HCC (adjusted P = 0.004, hazard ratio (HR) (95% confidence interval (CI)) = 2.055 (1.261-3.349) and recurrence-free survival (adjusted P = 0.008, HR (95% CI) = 1.721 (1.151-2.574). These observations which were verified by GEPIA analysis for overall survival (P = 0.007) and recurrence-free survival (P= 0.096). Gene enrichment analysis revealed that affected processes included lymphocyte differentiation, pancreatic endocrine pathways, and insulin signaling pathway. SOX4 prognostic value was evaluated using nomogram analysis for HCC 1, 3, and 5-year, survival. Conclusion: Differential SOX4 expression presents an avenue of diagnosing and predicting clinical course of HCC. In HCC, SOX4 may affect TP53 metabolic processes, lymphocyte differentiation and the insulin signaling pathway.

Reflections on the evaluation and management of SCI papers based on the category normalized citation impact: Taking a university hospital as an example / 中华医学科研管理杂志

Objective:Analyze the basic information and characteristics of SCI papers published by an institution in 2015-2019 based on the Category Normalized Citation Impact (CNCI), to provide a reference basis for SCI paper management policy improvement.Methods:Retrieve SCI papers completed by the first or correspondent unit from 2015 to 2019 from the scientific research management system of the institution. Obtain index data including journal information, impact factors, and CNCI of this group of papers from Web of science and InCites databases, and use SPSS21.0 statistical software to perform descriptive and chi-square tests.Results:The university-affiliated hospital published 3201 SCI papers from 2015-2019, with a growing trend. These papers were most frequently published in the 1<IF<3 zone, accounted for 44.92%, followed by the 3<IF<5 zone, accounted for 32.27%. These papers are mainly in Q2 journals, accounted for 31.52%, while Q1 and Q3 journals each account for 25%. From the perspective of CNCI, the average CNCI of papers in 2015-2017 was less than 1, and the average CNCI of papers in 2018-2019 was greater than 1, with no statistical difference in CNCI values between years. The proportion of high CNCIs was higher for papers with high IF. The average CNCI per page for papers in Q1 and Q2 was greater than 1, and the average CNCI per page for papers in Q3 and Q4 was less than 1. The proportion of high CNCIs was higher for papers in Q1.Conclusions:The evaluation conclusions reached under different research management perspectives are in-consistent. A comprehensive evaluation of papers based on journal divisions and CNCI is more reasonable. In a new era where indicators such as number of papers and impact factor are not the only thing that matters, it is relevant to select the top journals in the discipline and to apply comprehensive evaluation indicators such as CNCI to the evaluation of papers.

Prevalence of chronic kidney disease and its comorbidity analysis among the elderly in community of Suzhou / 中华老年医学杂志

Objective:To investigate the prevalence of chronic kidney disease(CKD)in community of Suzhou and explore the comorbid health conditions.Methods:The population over 60 years old undergoing health physical examination in community of Suzhou were selected as screening subjects for CKD.Examination data were collected, and other health data were obtained through residents' health records and chronic disease management systems.A total of 7 387 participants were enrolled.Results:In the population of 7 387 individuals, detected cases with CKD were 2 771, with detection rate of 37.5%, awareness rate of 13.9%.The 2 521 patients(91.0%=2 521/2 771 of total CKD patients)with CKD 1-2 stage, and 2222 patients(80.2%=2 222/2 771)with low and medium risk were detected out.The detection rates of CKD were significantly higher in group with hypertension, diabetes, hyperuricemia, hyperlipidemia, obesity and stroke than in the group without those diseases(all P<0.05). With the increase of the number of comorbidity in patients with CKD, the detection rate of CKD was increased( χ2=74.658, P<0.001). In a total of 2771 CKD patients, 33.6% had 1 comorbid condition, 23.4% had two comorbid conditions, and 19.8% had 3 or more comorbid conditions.In the declined-eGFR group, patients with three or more comorbid conditions accounted for 34.0%, which was significantly higher than that in the normal-eGFR group(18.4%)( χ2=35.042, P<0.001). Multivariate Logistic regression analysis revealed that women, advanced age, hypertension and having 3 or more comorbid conditions were independent influencing factors for the CKD detection rate.People with three or more comorbid conditions had a 1.58-fold increased risk for developing CKD as compared with those without comorbid condition(95% CI: 1.30-1.91, P<0.001). Conclusions:The prevalence of CKD in Suzhou community elderly population is high, but the awareness rate is low.A large number of early and low-and moderate-risk of CKD patients have been detected out.Comorbid conditions are prevalent in older patients with CKD.With the decrease of renal function, the number of comorbidity in CKD patients significantly increased.Early screening for CKD in the elderly population is very necessary, especially in those with hypertension and 3 or more comorbid conditions.