Source analysis and health risk assessment of polycyclic aromatic hydrocarbons in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021 / 环境与职业医学

Background Polycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. Objective To identify the distribution characteristics and sources of PAHs in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. Methods From 2019 to 2021, air PM2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d−1, and the sampling flow rate was 100 L·min−1. PM2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. Results From 2019 to 2021, the annual average concentrations [M (P25, P75)] of ∑PAHs in atmospheric PM2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m−3, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m−3) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P<0.001, P<0.05). The ∑PAHs concentration distribution showed a seasonal variation, with the highest value in winter and the lowest value in summer (P<0.05). Among the atmospheric PM2.5 samples, the proportion of 5-ring PAHs was the highest, the proportion of 2-3-ring PAHs was the lowest; the proportion of 2-4-ring PAHs showed a yearly upward trend, and the proportion of 5-6-ring PAHs showed yearly downward trend (P<0.05). The characteristic ratio and PCA results suggested that the sources of sampled PAHs were mainly mixed sources such as dust, fossil fuel (natural gas), coal combustion, industrial emissions, and motor vehicle exhaust emissions. The ILCR (RILCR) of PAHs by inhalation for men, women, and children were 1.83×10−6, 2.35×10−6, and 2.04×10−6, respectively, and the annual average RILCR was 2.07×10−6, all greater than 1×10−6. Conclusion For the sampled time period, the main sources of PAHs pollution in atmospheric PM2.5 in the target district of Taizhou City are dust, fossil fuel (natural gas), coal combustion, industrial emissions, motor vehicle emissions, etc., and PAHs may have a potential carcinogenic risk to local residents.

Effects of diisononyl phthalate on lipid metabolism in HepG2 cells / 环境与职业医学

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P<0.05). After exposure to 30 mmol·L−1 and 100 mmol·L−1 DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L−1 DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L−1 group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L−1 DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L−1 and 100 mmol·L−1 can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.

Jiedu Tongluo Tiaogan Prescription Protects Pancreatic β Cell by Targeting NLRP3 Inflammasome via TGR5/cAMP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Analysis of clinicopathological features, therapeutic efficacy, prognosis and mutation in 11 patients with cardiac diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.

In Situ Labeling of Erythrocyte Membrane Anion Channel Proteins with Gold Nanoparticles Observed by Cryo-Scanning Electron Microscopy / 分析化学

Band 3 protein is an important channel protein in the erythrocyte membrane which mediates the anion transport process inside and outside the cell membrane,as well as contributes to the maintenance of erythrocyte morphology,and has important physiological functions.However,the distribution state of this protein in the primary cell membrane is not known.Cryo-scanning electron microscopy enables imaging of the surface morphology of biological samples in a near-physiological state.In order to investigate the distribution of band 3 protein on erythrocyte membranes under physiological conditions,the present study utilized 5-nm gold nanoparticles modified with the antibodies to specifically bind to the band 3 protein on human blood erythrocyte membranes and imaged them by cryo-scanning electron microscopy,to obtain distribution of band 3 protein on human blood erythrocyte membranes.The results showed that the membrane proteins on the erythrocyte membranes tended to be clustered and distributed to form ″protein islands″,and band 3 proteins were mainly distributed in these protein islands,which were tightly connected with each other to form several functional microregions to play their respective roles.

Cu0 Modification and Cu2+ Self-intercalation of Ti3C2Tx Two-dimensional Material for Electrocatalytic Reduction of CO2 / 分析化学

The conversion of carbon dioxide into high value-added energy has become a research hotspot.In this study,by using Ti3AlC2 and CuCl2·2H2O as precursors,accordion-like two-dimensional Cu0/Cu2+-Ti3C2Tx catalysts modified with Cu0 nanoparticles and Cu2+ self-intercalation were successfully prepared for electrocatalytic reduction of CO2.The performance of the material was tested,and the results showed that in a CO2-saturated 0.5 mol/L KHCO3 electrolyte solution,compared with the original Ti3AlC2,the initial potential of the electrocatalytic conversion of CO2 to C2H4 over Cu0/Cu2+-Ti3C2Tx catalyst decreased from ?0.65 V(vs RHE)to?0.01 V(vs RHE).The maximum current density increased from 0.19 mA/cm2 to 2.5 mA/cm2,the double layer capacitance(Cdl)value increased from 2.61 mF/cm2 to 55.06 mF/cm2.The material showed higher catalytic activity and faster electron transfer rate(Charge transfer resistance(Rct)value was only 16.9 Ω).Moreover,the material showed high electrochemical active area and excellent stability.This research provided a promising method for designing and preparing elcetrocatalytic reduction(ECR)catalysts in the future.

Correlation analysis of serum miR-939 and miR-15b expression and microvascular injury in diabetic retinopathy patients / 国际检验医学杂志

Objective To analyze the correlation between serum miR-939 and miR-15b expression and mi-crovascular injury in patients with diabetic retinopathy(DR).Methods A total of 176 patients with type 2 di-abetes diagnosed and treated in the Baoding Second Hospital from January 2021 to October 2022 were selected as the study objects.The subjects were divided into 74 patients without DR(NDR group),62 patients with non-proliferative DR(NPDR group)and 40 patients with proliferative DR(PDR group)according to whether or not DR occurred and the degree of lesions.Real-time fluorescent quantitative PCR was used to detect the relative expression levels of miR-939 and miR-15b in serum of all groups,the level of vascular endothelial growth factor(VEGF)was detected by enzyme-linked immunosorbent assay,and the count percentage of en-dothelial cells(ECs),endothelial progenitor cells(EPCs)and circulating progenitor cells(CPCs)was detected by flow cytometry.Serum levels of miR-939,miR-15b,VEGF and ECs,EPCs and CPCs were compared in 3 groups.Pearson correlation was used to analyze the correlation between serum miR-939 and miR-15b and VEGF,ECs,EPCs and CPCs.Multivariate Logistic regression was used to analyze the factors affecting the oc-currence of DR in patients with type 2 diabetes.Results The relative expression levels of miR-939 and miR-15b in PDR group and NPDR group were lower than those in NDR group,while the serum VEGF levels were higher than those in NDR group,with statistical significance(P＜0.05).ECs in PDR group and NPDR group were higher than those in NDR group,while EPCs and CPCs were lower than those in NDR group,the differ-ence was statistically significant(P＜0.05).Serum miR-939 was negatively correlated with VEGF and ECs(r=-0.407,-0.613,P＜0.05),and positively correlated with EPCs and CPCs(r=0.481,0.486,P＜0.05).Serum miR-15b was negatively correlated with VEGF and ECs(r=-0.539,-0.625,P＜0.05),and positively correlated with EPCs and CPCs(r=0.451,0.483,P＜0.05).Multivariate Logistic regression anal-ysis showed that the duration of type 2 diabetes,hemoglobin A1c,2-hour postprandial blood glucose,VEGF,miR-939 and miR-15b were the influencing factors for the occurrence of DR in type 2 diabetes patients(P＜0.05).Conclusion The expression of miR-939 and miR-15b in serum of DR patients is closely related to VEGF,ECs,EPCs and CPCs,and the expression of miR-939 and miR-15b in serum of DR patients can provide a certain reference for early judgment and evaluation of the degree of microvascular injury.

Anti-fibrosis Action of Therapy of Tonifying Kidney and Removing Stasis on Moderate-to-Severe Intrauterine Adhesions and Its Influence on Extracellular Matrix Degradation Related Factors in Menstrual Blood / 广州中医药大学学报

Objective To investigate the anti-fibrosis action of the therapy of tonifying kidney and removing stasis(shortened to Bushen Quyu method)on moderate-to-severe intrauterine adhesion and its influence on extracellular matrix degradation related factors in menstrual blood.Methods A total of 124 patients with moderate-to-severe intrauterine adhesions of kidney deficiency and blood stasis syndrome who were to undergo transcervical resection of adhesion(TCRA)were randomly divided into a study group and a control group,with 62 patients in each group.Both groups were given TCRA treatment.After the operation,the control group was treated with Progesterone + Estradiol Valerate Tablets,and the study group was treated with the combination of the Bushen Quyu method by using modified Guishen Decoction based on the treatment of the control group.The treatment covered 3 menstrual cycles.The changes in menstrual status,transvaginal color Doppler sonography parameters,scores of kidney deficiency and blood stasis syndrome,and scores of uterine adhesion in the two groups were observed before and after the treatment.Moreover,the two groups were observed before and after treatment in the changes of vascular endothelial growth factor(VEGF),transforming growth factor β1(TGF-β1),platelet-derived growth factor(PDGF),and connective tissue growth factor(CTGF)as well as the mRNA expression levels of matrix metalloproteinase 9(MMP-9),matrix metalloproteinase inhibitory factor 1(TIMP-1),phosphatidylinositol-3-hydroxykinase(PI3K)and collagen type I A1 protein(COL1A1).After treatment,the clinical efficacy and safety of the two groups were assessed.Results(1)After 3 menstrual cycles of treatment,the total effective rate in the study group was 93.55%(58/62),and that in the control group was 80.65%(50/62).The intergroup comparison showed that the therapeutic effect of the study group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the menstrual flow,menstrual cycle and menstrual period of the two groups were significantly improved compared with those before treatment(P＜0.05),and the recovery of menstrual flow,menstrual cycle and menstrual period in the study group was significantly superior to that in the control group after treatment(P＜0.05).(3)After treatment,the transvaginal color Doppler sonography parameters of uterine blood flow index(FI),pulsatility index(PI),resistance index(RI),uterine cavity volume,and endometrial thickness in the two groups were significantly improved compared with those before treatment(P＜0.05).And the study group had significantly higher FI,uterine cavity volume,and endometrial thickness and had lower PI and RI than the control group(P＜0.05 or P＜0.01).(4)After treatment,the scores of uterine adhesion and the scores of kidney deficiency and blood stasis syndrome in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the above scores in the study group were significantly lower than those of the control group after treatment(P＜0.01).(5)After treatment,the levels of VEGF,TGF-β1,PDGF,and CTGF in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of the above cytokines in the study group were significantly lower than those in the control group after treatment(P＜0.01).(6)After treatment,the relative mRNA expression levels of MMP-9 and PI3K in the menstrual blood of the two groups were significantly higher and the mRNA expression level of COL1A1 was significantly lower than that before treatment(P＜0.05).And the study group had higher mRNA expression levels of MMP-9 and PI3K in the menstrual blood than the control group after treatment(P＜0.05 or P＜0.01).(7)The total incidence of adverse reactions in the control group was 25.81%(16/62)and that in the study group was 16.13%(10/62).The intergroup comparison showed that the difference between the two groups was not statistically significant(P＞0.05).The symptoms of adverse reactions in the two groups disappeared after symptomatic treatment,and there were no adverse reactions related to the medication of Chinese medicine during the study.Conclusion The combination of Bushen Quyu formula combined with western medicine is more effective than western medicine alone for the treatment of patients with uterine adhesions after TCRA.The application of Bushen Quyu formula can further promote the recovery of menstruation in the patients,improve the circulation of blood flow in the endometrium,increase the endometrial thickness,regulate the expression of fibrosis factors,up-regulate the mRNA expressions of PI3K and MMP-9,restore the balance of the extracellular matrix(ECM),and prevent the reoccurrence of intrauterine adhesions.And its clinical medication is safe.

Analysis of Vitamin D in Children with Henoch-Schonlein Purpura / 昆明医科大学学报

Objective To analyze the changes of vitamin D in children with Henoch-Schonlein purpura(HSP).Methods 130 children with HSP from Kunming Children's Hospital between July 2022-July 2023 were selected as the study subjects and 100 healthy children were selected during the same period as the control group.The blood samples were collected from the children with HSP and the healthy children.The content of vitamin D was measured by Kunming Kingmed Institute for Clinical Laboratory.Results The content of 25(OH)D in children with HSP was lower than that in healthy children,and the difference was statistically significant(P<0.01).The proportion of vitamin D insufficiency in children with HSP was higher than that in healthy children,and the difference was statistically significant(P<0.01).Conclusion The children with HSP are prone to vitamin D insufficiency.Vitamin D supplementation may provide a new method for the treatment of HSP.

Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma / 上海交通大学学报（医学版）

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

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.

CT findings of non-tuberculous mycobacteria pulmonary disease and the differential diagnosis with tuberculosis / 实用放射学杂志

Objective To explore the CT imaging characteristics of non-tuberculous mycobacteria(NTM)pulmonary disease and image differences from tuberculosis(TB).Methods The imaging data of 46 with NTM pulmonary disease(NTM pulmonary disease group)and 64 with TB(TB group)confirmed by flora identification or transbronchial biopsy were analyzed retrospectively.Results The mean age of NTM pulmonary disease group was greater than that of TB group(t=2.561,P<0.05).Clinical manifestations:TB group had more cough and expectoration than NTM pulmonary disease group,and yet NTM pulmonary disease group had more basic lung diseases than TB group(P<0.05).Imaging manifestations:bronchiectasis,subpleural thin-walled cavity,and consolidation(≥3 cm)with bronchiectasis were more common in NTM pulmonary disease group than TB group(P<0.05).In TB group,centrilobular nod-ules,large nodules(≥0.8 cm),and mediastinal/hilus of lung lymph node enlargement were more common than in NTM pulmonary dis-ease group(P<0.05).In multivariate binary logistic regression analysis,bronchiectasis,and subpleural thin-walled cavity were independent risk factors for NTM pulmonary disease(P<0.05),and large nodules(≥0.8 cm)was risk factor for TB(P<0.05).Conclusion Bronchiectasis,subpleural thin-walled cavity,and consolidation(≥3 cm)with bronchiectasis are the characteristic CT manifesta-tions of NTM pulmonary disease,which has important clinical significance for the diagnosis of NTM pulmonary disease.

Different reaction patterns and influencing factors among family caregivers of patients with advanced gynecological malignancies: a latent profile analysis / 中国实用护理杂志

Objective:To explore the different reaction patterns among family caregivers of patients with advanced gynecological malignancies, and to analyze the influencing factors of different profiles.Methods:A cross-sectional study was conducted with 210 family caregivers of patients with advanced gynecological malignancies from Obstetrics and Gynecology Hospital in Shanghai from January 2022 to December 2022. Data were collected by Caregiver Reaction Assessment, Mishel's Uncertainty in Illness Scale-Family Member Form and Perceived Social Support Scale. Latent profile analysis was used to explore the different reaction patterns among family caregivers of patients with advanced gynecological malignancies. The influencing factors of caregiver reaction were identified by multivariate Logistic regression.Results:Totally 208 questionnaires were effectively collected. The family caregivers among patients with advanced gynecological malignancies included 163 males and 45 females, aged (53.89 ± 12.61) years old. The reaction characteristics of 208 family caregivers among patients with advanced gynecological malignancies were divided into three categories: low burden and high benefit group (24.5%, 51/208), moderate burden and benefit group (30.8%, 64/208), and high burden and low benefit group (44.7%, 93/208). Compared to the low burden and high benefit group, caregivers with lower levels of social support were more likely to be classified as moderate burden and benefit group, high burden and low benefit group ( OR = 0.563, 0.407, both P<0.01). Caregivers with moderate burden and benefit group, high burden and low benefit group had higher levels of disease uncertainty ( OR = 1.328, 2.064, both P<0.01). The caregiver′s age, monthly family income, education level, and co-caregivers were also influencing factors regarding to care reaction among family caregivers of patients with advanced gynecological malignancies ( OR values were 0.207-6.422, all P<0.05). Conclusions:The care reaction of family caregivers among patients with advanced gynecological malignancies has obvious categorical features. Healthcare professionals should implement targeted nursing interventions according to their reaction characteristics, so as to reduce the care burden of family caregivers and improve the quality of care for patients with advanced gynecological malignancies.

Research on the integration of curriculum ideology and politics into the teaching of Nutrition and Food Hygiene under the background of new medical science / 沈阳医学院学报

Objective:To investigate how to integrate the ideological and political elements into the teaching of Nutrition and Food Hygiene under the background of new medical science.Methods:Through literature review and teaching discussion,suitable ideological and political elements and cases were selected to be integrated into the teaching of Nutrition and Food Hygiene,and feasible strategies were initially explored,which were implemented and evaluated in the grade 2018 students majoring in preventive medicine in Bengbu Medical College.Results:About 94.65% (124/131)of the students were satisfied with the ideological and political content design of the course,97.71% (128/131)of the students thought that it would be helpful to expand their professional knowledge,93.13% (122/131)thought that it would be helpful to establish morality and cultivate talents,and the overall feedback was good.The ideological and political teaching was generally recognized.Conclusions:It is feasible to integrate ideological and political elements into professional core courses,and to a certain extent.It can enrich the content of professional courses,improve students'interest,and make"foster virtue through education"truly implemented in the cultivation of professional quality.

Correlation analysis of serum Chemerin with disease activity and Th17/Treg in patients with rheumatoid arthritis / 天津医药

Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells(Th17/Treg)in patients with rheumatoid arthritis(RA).Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group.According to the DAS28 score,the observation group was divided into the high activity group(60 cases),the moderate activity group(60 cases)and the low activity group(60 cases).Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of Chemerin,interleukin-9(IL-9),interleukin-10(IL-10)and interleukin-17(IL-17).Flow cytometry was used to detect the Th17/Treg ratio.Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score.Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17,Treg cell percentage and Th17/Treg ratio.Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group(P＜0.05).The serum Chemerin level was positively correlated with DAS28 score(P＜0.05).Serum Chemerin levels and DAS28 scores decreased in turn in the high,moderate and low activity groups(P＜0.05).The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group,and the percentage of Treg cells was lower in the observation group than that in the control group(P＜0.05).The level of IL-10 was lower in the observation group than that in the control group,while levels of IL-17 and IL-9 were higher in the observation group than those in the control group(P＜0.05).The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg,and negatively correlated with the percentage of Treg cells(P＜0.05).Conclusion Serum Chemerin level is elevated in patients with RA,which is closely related to disease activity and Th17/Treg ratio.

Mechanical analysis and finite element modeling of rabbit patellar tendon and tendon insertion under different mechanical conditions / 中国组织工程研究

BACKGROUND:The patella-patellar tendon junction is a high-incidence area of injury in patellar tendinopathy.The rabbit patella-patellar tendon injury model is a commonly used animal experimental research object.At present,the stress analysis of the injury mechanism and modeling method is not comprehensive. OBJECTIVE:Based on the previous histological and mechanical measurements,this study used micro CT to scan and model the whole patella,the patella-patellar tendon junction and the tendon quadriceps junction,to analyze the characteristics of changes in stress,and explore the potential impact of different forms of exercise on patellar tendon degeneration so as to provide a theoretical basis for injury prevention and animal model establishment. METHODS:Female healthy adult New Zealand rabbits were selected to study the patella and tendons at both ends of the left knee joint.After the material was taken,the samples were scanned and saved with micro CT.Mimics,Geomagic Studio and SolidWorks were used to establish a three-dimensional model.Finite element analysis was carried out with Ansys Workbench.The equivalent displacement,stress and strain of the target region were analyzed under different loading conditions(load size and direction changes,different action modes). RESULTS AND CONCLUSION:(1)Load direction change affected trend and value change;load size change affected value change.(2)Compared with other areas,the stress concentration was more obvious at the insertion point of the patellar tendon,and the strain value was the lowest.(3)At the insertion point of the patellar tendon,the stress concentration was greater in valgus than in varus and pronation than in extorsion.(4)The stress concentration effect and stress shielding during knee flexion and extension are the main causes of patellar tendon insertion injury.The stress in pronation and valgus states is also a potential factor leading to damage,which needs further study.The animal model established by jumping and running is more in line with the characteristics of sports injury.

Application of MRI-based image navigation and target selection in transcranial magnetic stimulation treatment / 中国组织工程研究

BACKGROUND:In clinical application,the therapeutic effect of transcranial magnetic stimulation depends on the ability to accurately target the areas of the brain that need to be stimulated.In recent years,with the development of neuronavigation systems,mobile augmented reality technology,and the new methods of processing magnetic resonance imaging(MRI)data,the accuracy of stimulus target localization and the optimization of target selection are expected to improve further. OBJECTIVE:To review the principle of MRI-based image navigation and its application in transcranial magnetic stimulation and summarize the roles of different modal MRI data analyses in guiding the selection of target areas for transcranial magnetic stimulation. METHODS:An online computer search for relevant literature was performed in PubMed,CNKI database and WanFang database,with the keywords"transcranial magnetic stimulation,coil positioning,neuronavigation,augmented reality,magnetic resonance,theory."Finally,63 documents were included for review. RESULTS AND CONCLUSION:Among the traditional methods of positioning transcranial magnetic stimulation coils,the"5 cm rule"and the international electroencephalogram 10-20 positioning method are the most commonly used.These methods have the advantages of simplicity and economy,but they rely too much on the operator's experience and there were technical differences between operators.The neuronavigation system,which is based on stereotactic technology,is the guiding method for positioning transcranial magnetic stimulation coils with the highest visual degree and accuracy.It achieves visual positioning through MRI data acquisition,3D brain reconstruction,head model registration and stereogeometric positioning.It has high application value in clinical treatment and scientific research,but it cannot be promoted in medical institutions due to its high cost.For various medical institutions,mobile augmented reality is a cost-effective and efficient alternative to the neuronavigation system,which achieves visual positioning of brain tissue under the scalp through MRI data acquisition,2D/3D image construction,virtual image and real brain image superposition.It has the advantages of directly visualization and low cost,and is expected to be popularized and applied in primary medical units.Although the superiority of clinical efficacy of visual coil positioning over the electroencephalogram 10-20 localization strategy has not yet been fully demonstrated,with the progress of brain MRI data analysis,visual positioning is expected to further optimize the target selection strategy of transcranial magnetic stimulation therapy and to improve the response rate and individuation degree of transcranial magnetic stimulation treatment.This is a promising and challenging research direction in the future.

Regulatory mechanism of ferroptosis on pressure ulcers:bioinformatics analysis and experimental validation / 中国组织工程研究

BACKGROUND:Ferroptosis-mediated ischemia-reperfusion injury plays a crucial role in the occurrence and progression in pressure ulcers,and there may be pressure ulcer-associated ferroptosis biomarkers,but the mechanism has not been elucidated. OBJECTIVE:To investigate the molecular mechanisms underlying pressure ulcers using bioinformatic analysis,with a focus on identifying differentially expressed genes associated with ferroptosis during the process of pressure ulcer formation,thereby providing novel insights into the clinical treatment of pressure ulcers. METHODS:The single-cell transcriptome sequencing dataset and ferroptosis-related genes were obtained and preprocessed from the Gene Expression Omnibus(GEO)and FerrDb databases.We performed clustering and proportion analyses,metabolic activity and pseudotime analysis,cell communication analysis,ferroptosis gene set cell population identification,and enrichment analysis to determine differentially expressed genes related to ferroptosis.Animal experiments were then conducted for further validation,with 20 Sprague-Dawley rats randomly assigned into a control group and a model group(n=10 per group).The control group received no treatment,while the model group underwent a cycle of ischemia-reperfusion to establish pressure ulcer models.Changes in differentially expressed genes and proteins in the wound tissues of pressure ulcer rats were detected using fluorescent quantitative PCR and western blot,respectively. RESULTS AND CONCLUSION:The single-cell transcriptome sequencing data were clustered into six cell types,with a higher proportion of type 2 and type 3 keratinocytes observed in the pressure ulcer group.There was evident metabolic heterogeneity and evolutionary trajectory among cell populations.Type 2 and type 3 keratinocytes exhibited stronger cell communication,while type 2 keratinocytes demonstrating optimal ligand-receptor interactions.Type 2 keratinocytes demonstrated higher scores for ferroptosis,accompanied by significant upregulation or downregulation of specific genes.A total of 27 Gene Ontology enrichments,20 Kyoto Encyclopedia of Genes and Genomes enrichments,and 24 ferroptosis-related differentially expressed genes,including glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long chain family member 4(ACSL4),were identified.Animal experiments further confirmed the downregulation of GPX4,the ferroptosis-inhibiting protein,and the upregulation of ACSL4,the ferroptosis-promoting protein,in the model group.Overall,these findings indicate the presence of ferroptosis in pressure ulcer tissue.GPX4 and ACSL4 are important genes regulating ferroptosis in pressure ulcer tissues.