Diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules.

OBJECTIVES: To investigate the diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. METHODS: The clinical data, ultrasonic images, C-TIRADS categories and CEUS images of 192 patients with indeterminate FNA cytological thyroid nodules confirmed by the surgical pathology were analyzed retrospectively. The diagnostic efficacy of CEUS, C-TIRADS and CEUS-TIRADS were calculated. RESULTS: The AUCs of CEUS, C-TIRADS and CEUS-TIRADS were 0.905 (95% CI: 0.862∼0.949), 0.881 (95% CI: 0.825∼0.938) and 0.954 (95% CI: 0.922∼0.986), respectively. The sensitivity, specificity, PPV, NPV, accuracy, LR- and LR+ were 84.7% (116/137), 85.5% (47/55), 93.5% (116/124), 69.1% (47/68), 84.9% (163/192), 0.179, 5.82 and 84.7% (116/137), 83.6% (46/55), 92.8% (116/125), 68.7% (46/67), 84.4% (162/192), 0.183, 5.17, 92.7% (127/137), 89.1% (49/55), 95.5% (127/133), 83.1% (49/59), 91.7% (176/192), 0.082, and 8.50, respectively. Compared with CEUS and C-TIRADS, CEUS-TIRADS had improved the AUC, sensitivity and accuracy (all P < 0.05). CONCLUSIONS: CEUS and C-TIRADS had high diagnostic values in indeterminate FNA cytological thyroid nodules. CEUS-TIRADS improved AUC, diagnostic sensitivity and accuracy, and helped to distinguish indeterminate FNA cytological nodules.

Diagnosis and management of benign recurrent intrahepatic cholestasis and psychosocial stressors in an adolescent: A case report.

BACKGROUND: Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive disorder, characterized by episodes of intense pruritus, elevated serum levels of alkaline phosphatase and bilirubin, and near-normal -glutamyl transferase. These episodes may persist for weeks to months before spontaneously resolving, with patients typically remaining asymptomatic between occurrences. Diagnosis entails the evaluation of clinical symptoms and targeted genetic testing. Although BRIC is recognized as a benign genetic disorder, the triggers, particularly psychosocial factors, remain poorly understood. CASE SUMMARY: An 18-year-old Chinese man presented with recurrent jaundice and pruritus after a cold, which was exacerbated by self-medication involving vitamin B and paracetamol. Clinical and laboratory evaluations revealed elevated levels of bilirubin and liver enzymes, in the absence of viral or autoimmune liver disease. Imaging excluded biliary and pancreatic abnormalities, and liver biopsy demonstrated centrilobular cholestasis, culminating in a BRIC diagnosis confirmed by the identification of a novel ATP8B1 gene mutation. Psychological assessment of the patient unveiled stress attributable to academic and familial pressures, regarded as potential triggers for BRIC. Initial relief was observed with ursodeoxycholic acid and cetirizine, followed by an adjustment of the treatment regimen in response to elevated liver enzymes. The patient's condition significantly improved following a stress-related episode, thanks to a comprehensive management approach that included psychosocial support and medical treatment. CONCLUSION: Our research highlights genetic and psychosocial influences on BRIC, emphasizing integrated diagnostic and management strategies.

Construction of a Cancer Stem Cell related Histone Acetylation Regulatory Genes Prognostic Model for Hepatocellular Carcinoma via Bioinformatics Analysis: Implications for Tumor Chemotherapy and Immunity.

BACKGROUND: Cancer stem cells (CSC) play an important role in the development of Liver Hepatocellular Carcinoma (LIHC). However, the regulatory mechanisms between acetylation- associated genes (HAGs) and liver cancer stem cells remain unclear. OBJECTIVE: To identify a set of histone acetylation genes (HAGs) with close associations to liver cancer stem cells (LCSCs), and to construct a prognostic model that facilitates more accurate prognosis assessments for LIHC patients. METHODS: LIHC expression data were downloaded from the public databases. Using mRNA expression- based stemness indices (mRNAsi) inferred by One-Class Logistic Regression (OCLR), Differentially Expressed Genes (DEGs) (mRNAsi-High VS. mRNAsi-Low groups) were intersected with DEGs (LIHC VS. normal samples), as well as histone acetylation-associated genes (HAGs), to obtain mRNAsi-HAGs. A risk model was constructed employing the prognostic genes, which were acquired through univariate Cox and Least Shrinkage and Selection Operator (LASSO) regression analyses. Subsequently, independent prognostic factors were identified via univariate and multivariate Cox regression analyses and then a nomogram for prediction of LIHC survival was developed. Additionally, immune infiltration and drug sensitivity analysis were performed to explore the relationships between prognostic genes and immune cells. Finally, the expressions of selected mRNAsi-HAGs were validated in the LIHC tumor sphere by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) assay and western blot analysis. RESULTS: Among 13 identified mRNAsi-HAGs, 3 prognostic genes (HDAC1, HDAC11, and HAT1) were selected to construct a risk model (mRNAsi-HAGs risk score = 0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11). T-stage, mRNAsi, and mRNAsi-HAGs risk scores were identified as independent prognostic factors to construct the nomogram, which was proved to predict the survival probability of LIHC patients effectively. We subsequently observed strongly positive correlations between mRNAsi-HAGs risk score and tumor-infiltrating T cells, B cells and macrophages/monocytes. Moreover, we found 8 drugs (Mitomycin C, IPA 3, FTI 277, Bleomycin, Tipifarnib, GSK 650394, AICAR and EHT 1864) had significant correlations with mRNAsi-HAGs risk scores. The expression of HDAC1 and HDAC11 was higher in CSC-like cells in the tumor sphere. CONCLUSION: This study constructed a mRNAsi and HAGs-related prognostic model, which has implications for potential immunotherapy and drug treatment of LIHC.

Stigmasterol: Remodeling gut microbiota and suppressing tumor growth through Treg and CD8+ T cells in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), the most primary malignant liver tumor and is ranked as the fifth most common malignancy worldwide. Despite various therapeutic approaches being used in clinical practice, the overall effectiveness remains insufficient. Stigmasterol, a compound known for its anti-tumor properties and ability to induce apoptosis in tumor cells, has been found to influenced the composition of the intestinal microbiota. However, the mechanism through which stigmasterol influences the intestinal microbial-host crosstalk in HCC remains elusive. PURPOSE: This study was to investigate whether stigmasterol can remodel gut microbiota, and suppress tumor volume by regulating Treg and IFN-γ+ CD8+ cell in the host with HCC. METHOD: Stigmasterol (at dosages of 0, 50, 100, or 200 mg/kg) was orally administered to Balb/c mice with subcutaneous tumor once every 2 days for 3 weeks. RESULTS: We first found that tumors volume in the group treated with 100 mg/kg stigmasterol were significantly decreased compared with those in the control group (P < 0.05), which exhibited a similar effect as the sorafenib treatment in mice with HCC. This resulted in a significant upregulation of Caspase3, Bax, and P53 expressions, as well as a decrease in Cyclin D1 expression, ultimately leading to a reduction in tumor volume. Additionally, stigmasterol can alter the α and ß diversity of the intestinal flora and significantly increase the abundance of Lactobacillus_johnsonii, Lactobacillus_murinus, and Lactobacillus_reuteri (P<0.05), which can lead to a decrease in the ratio of regulatory T cells (Tregs) to CD8+ T cells in the intestinal tract and tumor tissue, and consequently enhance immune response in the tumor microenvironment (TME) in the host with HCC. CONCLUSION: In this study, we initially utilized different dosages of stigmasterol to intervene in mice with HCC and confirmed its inhibitory effects on tumor growth in vivo, and discovered that stigmasterol affected Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri, resulting in an increased proportion of IFN-γ+ CD8+ T cells and Treg cells in both the intestinal mucosa and tumor tissues, and ultimately leading to increased levels of apoptotic proteins and the subsequent death of tumor cells, which shed light on the effect of stigmasterol on host intestinal tissue and intratumoral immune cells by reshaping the intestinal microbiota, and provide a theoretical foundation for the potential clinical application of stigmasterol in the treatment of HCC.

Cause-specific mortality in a population-level cohort of diffuse large B-cell lymphoma following chemotherapy in the early 21st century.

Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed.

NOTCH pathway mutation contributes to inferior prognosis in HBV-infected chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) patients with hepatitis B virus (HBV) infection have a poor prognosis, underlying mechanism remains unclear. NOTCH mutations are frequent in CLL and associated with disease progression and drug resistance. It is also reported to be associated with hepatitis infection in lymphoid malignancies. In order to investigate the relation between the NOTCH pathway and HBV-associated CLL, we studied 98 previously untreated HBV-positive CLL patients and 244 HBV-negative CLL. NOTCH mutations were more frequent in HBV-positive CLL subgroup (p = 0.033). By survival analysis, HBV infection was associated with disease progression and poor survival (p = 0.0099 for overall survival (OS) and p = 0.0446 for time-to-treatment (TTT)). Any lesions of the NOTCH pathway (NOTCH1, NOTCH2, and SPEN) aggravated prognosis. In multivariate analysis, NOTCH mutation retained an independent significance for HBV-infected patients (p = 0.016 for OS and p = 0.023 for TTT). However, HBV positive with NOTCH unmutated had no statistical difference in prognosis compared with HBV-negative patients (p = 0.1706 for OS and p = 0.2387 for TTT), which indicated that NOTCH pathway mutation contributed to inferior prognosis in HBV-infected CLL. In conclusion, a cohort of CLL patients with HBV positive displayed a worse clinical outcome and the status of the NOTCH signaling pathway might play a crucial role.

Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors / 复旦学报（医学版）

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients / 复旦学报（医学版）

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Advances in epigenetics of nonalcoholic fatty liver desease / 复旦学报（医学版）

Nonalcoholic fatty liver disease(NAFLD)is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis(NASH).NASH is characterized by persistent liver damage,inflammation,and fibrosis which significantly increases the risk of end-stage liver diseases,such as liver cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD/NASH is not yet fully understood,but its recent epigenetic advances have provided new insights into the mechanisms of this disease.This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection,diagnosis,and treatment of this disease.

Retest improvement for minipool nucleic acid testing positive samples / 中国输血杂志

【Objective】 To analyze the correlation between the distribution interval of minipool nucleic acid testing(NAT) positive CT value and the resolution rate, so as to improve the retest model and reduce residual risk of blood transfusion. 【Methods】 The resolution testing results by Cobas S201 system of our blood center from January 2017 to December 2021 were retrospective analyzed, and the retest model was developed based on the distribution interval of CT values. For minipool NAT HBV positive samples from March 2022 to March 2023, synchronous detection was conducted by Cobas S201 and Panther detection system, and the detection results were statistically analyzed. 【Results】 From 2017 to 2021, 474 were minipool NAT positive, among which 324 were HBV positive, accounting for 68.35%. From 2017 to 2020, the proportion of HBV positive per year was significantly higher than that of HCV and HIV(P40, with the resolution rate at 95.8%, 56.5% and 14.8% respectively(P40, 36

[Preparation of Bamboo-based N, P Co-doped Activated Carbon and Its Lanthanum Ion Adsorption Performance].

Using diammonium hydrogen phosphate as an activator and N and P source and and bamboo chips as the carbon source, N, P co-doped activated carbon was prepared by one-step pyrolysis and used to efficiently remove La3+ in aqueous solutions. The effects of activation temperature and pH value on the adsorption performance of La3+ were analyzed, and the activation and adsorption mechanisms were explored using TG-IR, SEM-EDX, pore structure, XPS, and hydrophilicity. The results showed that diammonium hydrogen phosphate easily decomposed at a high temperature to produce ammonia and phosphoric acid, which activated the material and promoted the increase in the specific surface area and pore volume of the activated carbon. As an N and P source, the addition of diammonium hydrogen phosphate successfully achieved the N, P co-doping of activated carbon, and the introduction of N- and P-containing functional groups was the key to enhance the adsorption of La3+. Among them, graphitic nitrogen could provide interactions between La3+-π bonds, and C-P=O and C/P-O-P could provide active sites for the adsorption of La3+ through complexation and electrostatic interaction. The adsorption of La3+ on N, P co-doped activated carbons was endothermic and spontaneous, and the adsorption process conformed to the Langmuir isotherm and secondary kinetic model. Under the process conditions of an activation temperature of 900℃ and pH=6, the adsorption capacity of the N, P co-doped activated carbon was as high as 55.18 mg·g-1, which was 2.53 times higher than that of the undoped sample, and its adsorption selectivity for La3+ in the La3+/Na+and La3+/Ca2+ coexistence systems reached 93.49% and 82.49%, respectively. Additionally, the removal efficiency remained above 54% after five successive adsorption-desorption cycle experiments.

[Ecological Toxic Effect of Perfluorinated Compounds on Fish Based on Meta-analysis].

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are refractory organic pollutants, which are characterized by ubiquity, bioaccumulation, and biological toxicity. To explore the biotoxic effects of PFAS on fish, this study reviewed 64 publications. The toxicity of PFAS on functional traits of fish exposed to PFAS was analyzed based on Meta-analysis combined with effect sizes, which provided reference for the toxicity assessment of PFAS and was conducive to the priority control and management of PFAS pollution. The results showed that:① of the 12 functional traits studied, seven were found to be vulnerable in fish; the order of toxicity response was malformation (lnRR=-2.5599), development (lnRR=-0.4103), cell damage (lnRR=-0.3962), reproduction (lnRR=-0.3724), thyroid response (lnRR=-0.2492), growth (lnRR=-0.2194), and survival (lnRR=-0.2192). ② The aquatic toxicity of PFAS was significantly affected by the sex and developmental stage of fish. PFAS tended to have adverse effects on female fish (lnRR=-0.1628), and the physiological function of embryos was most significantly affected by PFAS (lnRR=-0.3553). ③ A total of 13 PFAS were involved in the study, among which PFAS with sulfonate groups and long-chains were more likely to have significant toxicity to the functional traits of fish (P<0.05).④ Existing data revealed that PFAS tended to produce acute toxicity to fish at medium and low concentrations (0.01-10 mg·L-1, P<0.05).

Personalized smart voice-based electronic prescription for remote at-home feedback management in cardiovascular disease rehabilitation: a multi-center randomized controlled trial.

Objective: To investigate the quality and efficacy of remote at-home rehabilitation for patients with cardiovascular disease (CVD) using personalized smart voice-based electronic prescription, and further explore the standardized health management mode of remote family cardiac rehabilitation. Trial design: A multicenter, randomized (1:1), non-blind, parallel controlled study. Methods: A total of 171 patients with CVD who were admitted to 18 medical institutions in China from April 2021 to October 2022 were randomly divided into a treatment group (86 cases) and a control group (85 cases) in a non-blinded experiment, based on the sequence of enrollment. The control group received routine at-home rehabilitation training, and the treatment group received remote feedback-based at-home cardiac rehabilitation management based on routine at-home rehabilitation training. The primary outcome was the difference in VO2peak (mL/min/kg) after 12 weeks. A linear mixed model was developed with follow-up as the dependent variable. Age and baseline data were utilized as covariates, whereas hospital and patient characteristics were adjusted as random-effect variables. As the linear mixed model can accommodate missing data under the assumption of random missing data, there was no substitute missing value for quantitative data. Results: A total of 171 participants, with 86 in the experimental group and 85 in the control group, were included in the main analysis. The analysis, which used linear mixing model, revealed significant differences in cardiopulmonary function indexes (VO2/kg peak, VO2peak, AT, METs, and maximum resistance) at different follow-up time (0, 4, and 12 weeks) in the experimental group (p < 0.05). In the control group, there was no significant difference in cardiopulmonary values at different follow-up time (0, 4, and 12 weeks; p > 0.05). VO2/kg peak (LS mean 1.49, 95%CI 0.09-2.89, p = 0.037) and other indicators of cardiopulmonary function (p < 0.05) were significantly different between the experimental group and the control group at week 12. The results were comparable in the complete case analysis. Conclusion: The remote home cardiac rehabilitation management mode using personalized smart voice-based electronic prescription provides several benefits to patients, including improvements in muscle strength, endurance, cardiopulmonary function, and aerobic metabolism. It also helps reduce risk factors for cardiovascular disease and enhances patients' self-management abilities and treatment compliance.Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2100044063.

Two new ursane triterpenoids from Agastache rugosa (Fisch. et.Mey.) O. Kuntze / 药学学报

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC50 as 4.77, 1.59, 11.11 and 25.87 μmol·L-1, resepectively.

Analysis of the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022 / 中华预防医学杂志

Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.

Evaluation of early renal function changes in patients with type 2 diabetes mellitus using BOLD and ASL / 中华放射学杂志

Objective:To noninvasively evaluate the clinical value of early renal function changes in patients with type 2 diabetes mellitus (T2DM) using blood oxygenation level dependent (BOLD) and arterial spin labeling (ASL) MRI.Methods:A total of 63 T2DM patients from Tianjin First Central Hospital from September 2019 to May 2022 were prospectively collected, 30 healthy volunteers (control group) were collected during the same period. According to albumin creatinine ratio (ACR), patients with T2DM were divided into normal albuminuria (NAU, ACR<30 mg/g) group and microalbuminuria (MAU, 30 mg/g≤ACR≤300 mg/g) group, there were 35 and 28 cases respectively. All subjects underwent abdominal BOLD and ASL scans. The values of renal cortical and medullary apparent relaxation rate (R 2*) and renal cortical renal blood flow (RBF) were measured. One-way ANOVA was used to compare the differences in R 2* and RBF among the three groups. Receiver operating characteristic curve was used to analyze relevant parameters to identify the diagnostic effectiveness of each group, and area under the curve (AUC) was compared by Z-test. Results:There were significant differences in renal medullary R 2* and renal cortical RBF among the control group, NAU group and MAU group ( F=45.83, 34.15, P<0.001). There was no significant difference in renal cortical R 2* ( F=2.98, P=0.056). In differentiating the control group from the NAU group, the AUC of renal medullary R 2*, renal cortical RBF and their combined parameters were 0.921 (95%CI 0.827-0.973), 0.704 (95%CI 0.578-0.811), 0.964 (95%CI 0.885-0.994), respectively. The AUC of combined parameters was significantly different from renal cortical RBF ( Z=4.07, P<0.001), but not from renal medullary R 2* ( Z=1.57, P=0.117). In differentiating the NAU from the MAU group, the AUC were 0.898 (95%CI 0.796-0.960), 0.919 (95%CI 0.823-0.973), 0.985 (95%CI 0.881-0.994), respectively. The AUC of combined parameters was significantly different from renal medullary R 2* and renal cortical RBF ( Z=2.39, P=0.017; Z=2.20, P=0.028). Conclusions:The changes of renal oxygenation level and blood flow in early stage of T2DM patients can be evaluated noninvasively and quantitatively using BOLD and ASL. Renal medullary R 2* combined with renal cortex RBF shows better diagnostic efficacy for early renal function changes in diabetes than each single index.

m6A recognition protein YTHDF1 ameliorates Duchenne muscular dystrophy and its mechanism / 解放军医学杂志

Objective To investigate the improvement effect and potential mechanism of m6A recognition protein YTHDF1 on Duchenne muscular dystrophy(DMD).Methods(1)We collected muscle tissue and peripheral blood from DMD patients(38 confirmed patients with surgery at Xi'an Children's Hospital from September 2016 to June 2017,DMD group)and non-DMD patients with orthopedic surgery(33 age-matched patients,2-3 years old,control group).The expression levels of YTHDF1 and dystrophin in the muscle tissues were quantified by RT-qPCR and Western blotting.The serum creatine phosphokinase(CPK)content was determined using ELISA.(2)Take SkMC from skeletal muscle myoblasts and set up empty vector group(transfected with scrambled negative control),AAV-YTHDF1 group transfected with YTHDF1 overexpression vector and scrambled group(transfected with NC siRNA)and si-YTHDF1 group(transfected with YTHDF1 siRNA).Cell proliferation was analyzed using an EdU assay.The expressions of dystrophin,myogenin(MyoG),and myosin heavy chain(MHC)proteins were measured by Western blotting.A RIP assay was used to verify the interaction between YTHDF1 and YES-associated protein 1(YAP1)mRNA and investigate the modification level of the m6A site on YAP1 mRNA.(3)Thirty Mdx mice were randomly divided into:the empty vector group(n=15,intraperitoneal injection of empty adenoviral empty vector)and the AAV-YTHDF1 group(n=15,intraperitoneal injection of YTHDF1 overexpression adenovirus vector).We profiled the body weights,muscle and organ wet weights,fiber diameter,and fiber type of the mice.The protein levels of YTHDF1 and dystrophin were detected using Western blotting.We used HE staining to observe the pathological changes in the gastrocnemius and quadriceps femoris muscles.Results(1)Compared with control group,the expression of YTHDF1 and dystrophin was significantly lower in DMD patients(P<0.01),and the serum CPK content was significantly increased(P<0.0001).(2)Compared with empty vector group,the EdU positive rate and the expression of dystrophin,MyoG,and MHC proteins significantly increased(P<0.01).In addition,overexpression of YTHDF1 prolonged the half-life and improved the stability of YAP1 mRNA.Compared with Scramble group,the EdU-positive rate and the expression of dystrophin,MyoG,and MHC proteins significantly decreased(P<0.05 or P<0.01).(3)Compared with empty vector group,the mice in AAV-YTHDF1 group developed more rapidly with higher muscle mass in the gastrocnemius muscle,quadriceps muscle,and triceps(P<0.05).We observed no difference in the weights of inguinal,gonadal,or retroperitoneal fat pads and a significant increase in the fiber areas of gastrocnemius and quadriceps femoris(P>0.05).Conclusion YTHDF1 regulates the stability of YAP1 mRNA by recognizing the m6A modification of YAP1 mRNA and thus promotes YAP1/dystrophin-mediated myocyte proliferation to inhibit DMD progression.

Multi-link Linkage Research on Medical Humanistic Education by Integrating Narrative Medical Materials / 中国医学伦理学

Taking the current situation and problems of medical humanities education as the background, the concept of narrative medicine was used to sort out and integrate various course materials of medical humanities, explore the multi-link linkage mode of medical humanities education, and organically integrate medical humanities courses scattered in medical education activities such as medical ethics, health law, doctor-patient communication, and health policy science with teaching stages, teaching resources, and teaching methods, forming vivid narrative medical materials throughout the entire process of medical humanities education, and improving teaching efficiency by sharing and optimizing resources. Through questionnaire analysis, it was found that there are many unsatisfactory aspects of medical humanities education. Further analysis of the issues focuses on the contradiction between learning willingness and time allocation, the lack of synchronization between teaching and social development, the lack of integration between courses, and insufficient innovation in teaching methods. Based on these, countermeasures were put forward to integrate narrative medical materials of medical humanities courses and build a platform for the application and communication of narrative medical materials.

Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens / 中华儿科杂志

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Spatial distribution and prediction analysis of the national AIDS epidemic in 2009 - 2020 / 公共卫生与预防医学

Objective Tto analyze the spatial distribution and characteristics of the national AIDS/HIV epidemics from 2009 to 2020 to discover its distribution, aggregation, and hot spots, and provide corresponding suggestions for AIDS prevention and control. Methods Spatial autocorrelation analysis, hot spot analysis, and Kriging interpolation prediction were used to describe, analyze, and predicting the spatial distribution of AIDS epidemics across the country. Results The national AIDS incidence and mortality rate increased yearly, but the growth rate shows a downward tendency with uneven spatial distribution,focusing on the southwest and northwest regions; the average annual incidence rate of AIDS ( Moran's I> 0, P 0, P “high-high” clusters of AIDS incidence; Sichuan, Yunnan, Guangxi,Hunan,Xinjiang and Guizhou were the areas with “high-high” clusters of average annual mortality. The “hot spot” areas were mainly concentrated in the southwestern part of China, and the “cold spot” areas were mainly concentrated in the eastern coastal and northern parts of China; Kriging interpolation predicted that Xinjiang would be the new hot spot area for future epidemics. Conclusion The spatial distribution of AIDS in China is uneven, showing spatial aggregation, hot spots and cold spots coexist, and the high-risk areas will continue to expand in the future.So the prevention and control work should be carried out in a targeted and localized manner.