Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Changes of complement fragment C3a and its receptor in lung injury induced by silica nanoparticles / 环境与职业医学

Background Silica nanoparticles (SiNPs) enter the human body through respiratory tract, digestive tract, and skin, causing body damage. Lung is one of the main damaged organs. Objective To observe the expressions of complement activated fragment C3a and its receptor C3aR in the lungs of mice exposed to SiNPs through respiratory tract, and to explore the involvement of C3a/C3aR in lung injury induced by SiNPs exposure. Methods The ultrastructure of SiNPs (particle size 5-20 nm) was determined under a transmission electron microscope, and the hydrodynamic diameter and surface Zeta potential of SiNPs were determined using a nanoparticle size analyzer. A total of 88 SPF C57BL/6J mice were randomly divided into five groups: a blank control group without any treatment (14 mice), a vehicle control group treated with 50 μL stroke-physiological saline solution by intratracheal instillation (14 mice), and three SiNPs exposure groups (low-dose group, medium-dose group, and high-dose group with 20 mice in each group, who were given 50 μL SiNPs suspension of 7, 21, and 35 mg·kg−1 respectively and exposed once every 3 days for 5 times). The mice were anesthetized on day 1 (1-day model group) and day 15 (15-day model group) after exposure, then sacrificed after extraction of bronchoalveolar lavage fluid (BALF), and lung tissues were retained. The morphological changes of lung tissues were observed by HE staining, the expression level of C3a in BALF was detected by enzyme-linked immunosorbent assay, the deposition of C3a and C3aR in lung tissues were observed by immunohistochemistry, the protein expression level of C3aR was determined by Western blotting, and the localization and semi-quantitative detection of C3a and C3aR in lung tissues was observed by immunofluorescence. Results SiNPs agglomerated in stroke-physiological saline solution. The average hydrodynamic diameter was (185.60±7.39) nm and the absolute value of Zeta potential was (43.33±0.76) mV. The condition of mice in the 1-day model group and the 15-day model group was good, while 2 mice died in the medium-dose group of the 1-day model group due to misoperation. The autopsy results of the two mice showed congestion of the lung tissue, emphysema, and no imperfection of trachea integrity. No death was observed in other dose groups. The HE staining results showed pathological damage to the mouse lung, including alveolar wall thickening and inflammatory cell infiltration after SiNPs exposure. The pathological damage became more serious with the increase of dose. Regarding pathological changes, the 15-day model group was slightly relieved compared with the 1-day model group, but there were still pathological changes. The enzyme-linked immunosorbent assay results showed that there was no difference in the expression level of C3a between the blank control group and the vehicle control group (P＞0.05), the expression levels of C3a in the medium-dose group and the high-dose group were significantly higher than that in the vehicle control group (P<0.05). The immunohistochemistry results showed that C3a deposition was consistent with the enzyme-linked immunosorbent assay results. The Western blotting and the immunohistochemistry results showed that C3aR expression was low in the blank control group and the vehicle control group, while the expression in each dose group tended to increase with the increase of dose. The immunofluorescence results showed that the fluorescence signals of C3a and C3aR were weak in the blank control group and the vehicle control group in the 1-day model group and the 15-day model group, while the fluorescence signals in the lung tissues of mice in the SiNPs exposure groups tended to increase with the increase of dose. Conclusion The increased expressions of C3a and C3aR in complement activation may be related to lung injury induced by intratracheal instillation of SiNPs, suggesting that C3a/C3aR may be involved in lung injury induced by SiNPs exposure.

Research on a new microtubule technology of reagent bursting for crossmatching test / 中国输血杂志

【Objective】 To develop a quick and accurate crossmatching test technology without the power equipment and additional reagents before blood transfusion, so as to improve the timeliness and safety of blood transfusion treatment in sudden situations as war or natural disasters. 【Methods】 The irregular antibodies quickly promote coagulants (QPC) were used as the reaction medium reagent. The 200 μL QPC were wrapped in the bursts bead and preset within different recess of the detection tubes. The bursts beads were squeezed with the reagent left in the well, then the blood samples were dropped in the main(recipient plasma: 200 μL, donor 3%—5% RBC: 100 μL) and secondary(donor plasma: 200 μL, recipient 3%—5% RBC: 100 μL)reaction grooves. The result interpretated by hand wrestling or 1 500 g centrifugation of 15 seconds. Meanwhile, the comparing experiments with the prior methods were implemented to evaluate the method’s reliability. 【Results】 The results of the bursting reagent, being stored at 37℃ for one week, were consistent with those of the freshly prepared cross-matching reagent, indicating that the bursting reagent was practical in the field and had good stability at normal temperature. No statistical difference between the sensitivity and the results of the microcolumn gel method was noticed by paired data t test (P>0.05). The parallel cross matching tests of 50 clinical samples were performed by microcolumn gel method and coagulant-bursting technique; the Kappa value was 0.973 2, and irregular antibodies were detected in 2 cases, with concordance rate at 100%, showing good consistency. 【Conclusion】 The improved method is simple and fast, and also safe and reliable for compatibility testing before blood transfusion, which is especially suitable for the field rescue of the wounded in wartime and sudden natural disasters, and is worthy of popularization.

Effect of apatinib combined with fluzoparib on proliferation ability of human ovarian cancer cisplatin-resistant cells / 肿瘤研究与临床

Objective:To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods:Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1, 2, 4, 8, 16, 32, 64,128 μg/ml cisplatin at different times; CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration ( IC50) of SKOV3 and SKOV3/DDP cells, and the drug-resistance fold of SKOV3/DDP cell was also calculated. SKOV3/DDP cells were treated with different concentrations of apatinib (4, 8, 16, 32, 64 μmol/L) and fluzoparib (148.15, 222.22, 333.33, 500.00, 750.00 μmol/L) for 24 h, 48 h and 72 h, respectively; the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated. SKOV3/DDP cells were divided into the blank control group (cells untreated with drugs), cisplatin group, cisplatin + apatinib group, cisplatin + fluzoparib group, cisplatin + fluzoparib + apatinib group, and drug intervention was given in each group; the inhibition rate of cells in each group was detected by using CCK8 method. Results:The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 4, 8, 16, 32, 64 μmol/L apatinib was 742.1μmol/L at 24 h, 156.8 μmol/L at 48 h, and 77.5 μmol/L at 72 h. Compared with the control group, the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32 μmol/L was significantly decreased, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 148.15, 222.22, 333.33, 500.00, 750.00 μmol/L fluzoparib was 878.5 μmol/L at 24 h, 406.7 μmol/L at 48 h, and 283.3μmol/L at 72 h. When the effective concentration of fluzoparib was more than 333.33 μmol/L for 24 h, the proliferation rate of SKOV3/DDP cells was lower than that of the control group, and the differences were statistically significant (all P < 0.05). Compared with the control group, the proliferation rate of SKOV3/DDP cells was decreased when the effective concentration was more than 148.15 μmol/L at 48 h and 72 h, and the differences were statistically significant (all P < 0.05). The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib group was lower than that of 5 μg/ml cisplatin group [(40.4±1.4)% vs. (62.7±1.4)%, t = 20.22, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(5.2±0.4)% vs. (62.7±1.4)%, t = 52.04, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(0.3±0.8)% vs. (62.7±1.4)%, t = 53.98, P < 0.001]. The 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group had the lowest proliferation rate of SKOV3/DDP cells, which was lower than that of 5μg/ml cisplatin + 64 μmol/L apatinib group and 5 μg/ml cisplatin + 290 μmol/L fluzoparib group (all P < 0.001). Conclusions:Apatinib and fluzoparib can enhance the sensitivity of human ovarian cancer cisplatin-resistant cells SKOV3/DDP to cisplatin, and the combination of drugs can produce the stronger inhibitory effects and reverse cisplatin resistance of ovarian cancer.

Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway / 中华医学杂志(英文版)

BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Novel coronavirus infection and its vaccination-related ocular disease / 国际眼科杂志(Guoji Yanke Zazhi)

The continuous pandemic coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is a serious threat to human life and health because of high infectious pathogenicity, and it also has posed a new challenge to the current medical model. Many literatures have shown that these changes range from the more common ocular surface diseases such as inflammation of the cornea, conjunctiva, and sclera, to the relatively rare paracentral acute middle maculopathy and acute macular neuroretinopathy. For patients with ocular symptoms as the first or accompanying symptoms of SARS-CoV-2 infection, how to identify the correlation between ocular manifestations and SARS-CoV-2 infection is undoubtedly a serious challenge for ophthalmologists. In this review, the ocular pathology caused by both SARS-CoV-2 infection and vaccination was discussed, covering pathological changes in the ocular surface, uvea, retina and macula, and cranial nerves.

Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway / 中国药房

OBJECTIVE To investigate the effects of salidroside （Sal） on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group， model group and Sal low-dose， medium-dose and high-dose groups， with 10 mice in each group. Except for the control group， the mice in other groups were injected subcutaneously with isoproterenol 5 mg/（kg·d）to prepare the myocardial fibrosis model. Since modeling， mice in the Sal low-dose， medium-dose and high-dose groups were given 10， 30 and 50 mg/kg of Sal by intragastric administration every day； control group and model group were given 10 mL/kg of normal saline by intragastric administration every day， for 14 consecutive days. After the last medication， the mice were sacrificed； hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell； Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction （CVF）； quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ （Col Ⅰ）， α-smooth muscle actin （α-SMA）， Toll-like receptor 4 （TLR4）， NOD-like receptor pyrin domain containing 3 （NLRP3）， caspase-1 andgasdermin D （GSDMD） in myocardial tissues. The total protein expressions of Col Ⅰ， α-SMA， TLR4， NLRP3，caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group， the myocardial cells in the model group were enlarged， the arrangement of myocardial fibers was disordered， the matrix metabolism was significantly increased， the CVF in myocardial tissue was significantly increased， and the mRNA and protein expression levels of Col Ⅰ， α-SMA， TLR4， NLRP3， caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly （P＜0.01）. Compared with model group， the myocardial cell morphology was clearer， myocardial fibrosis was alleviated， and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees， especially in Sal high-dose group（P＜0.05 or P＜0.01）. In addition， the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis， and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.

Influence of the interaction between tumor microenvironment and liver cancer stem cells on the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

In recent years, liver cancer stem cells (LCSC) have been considered one of the main causes of treatment failure and recurrence of hepatocellular carcinoma (HCC). Many studies have shown that LCSC are a small fraction of cells with the abilities of self-renewal, differentiation, and tumorigenesis in HCC tumor, which can initiate the onset of HCC and affect its proliferation, invasion, metastasis, recurrence, and drug resistance. Therapies based on tumor microenvironment (TME) have been developed recently, and a number of studies have found that targeting the relevant elements of TME has a higher therapeutic value than targeting tumor cells themselves. TME is the microenvironment for the growth of LCSC and HCC cells, and it interacts with LCSC and has a synergistic effect, thereby playing a positive role in the development and progression of HCC. This article introduces how various cellular components and non-cellular components in TME interact with LCSC to regulate the development and progression of the HCC. In addition, this article also describes the molecular targets, therapies, and drugs associated with the main components of TME and LCSCs, in order to seek safer and more effective targeted therapies for HCC.

Investigation and influencing factors on pelvic floor muscle strength of 929 adult females in gynecological outpatient department / 中华妇产科杂志

Objective: To investigate the present situation of pelvic floor muscle strength, and to analyze the factors affecting pelvic floor muscle strength. Methods: The data of patients who were admitted into the general outpatient department of gynecology, Peking University People's Hospital from October 2021 to April 2022 were collected, and the patients who met the exclusion criteria were included in this cross sectional study. The patient's age, height, weight, education level, defecation way and defecation time, birth history, maximum newborn birth weight, occupational physical activity, sedentary time, menopause, family history and disease history were recorded by questionnaire. Morphological indexes such as waist circumference, abdomen circumference and hip circumference were measured with tape measure. Handgrip strength level was measured with grip strength instrument. After performing routine gynecological examinations, the pelvic floor muscle strength was evaluated by palpation with modified Oxford grading scale (MOS). MOS grade>3 was taken as normal group and ≤3 as decreased group. Binary logistic regression was used to investigate the related factors of deceased pelvic floor muscle strength. Results: A total of 929 patients were included in the study, and the average MOS grade was 2.8±1.2. By univariate analysis, birth history, menopausal time, defecation time, handgrip strength level, waist circumference and abdominal circumference were related to the decrease of pelvic floor muscle strength (all P<0.05). By binary logistic regression analysis, the level of handgrip strength (OR=0.913, 95%CI: 0.883-0.945; P<0.001) was correlated with normal pelvic floor muscle strength; waist circumference (OR=1.025, 95%CI: 1.005-1.046; P=0.016), birth history (OR=2.224, 95%CI: 1.570-3.149; P<0.001), sedentary time> 8 hours (OR=2.073, 95%CI: 1.198-3.587; P=0.009) were associated with the decrease of pelvic floor muscle strength. Conclusions: The level of handgrip strength is related to the normal pelvic floor muscle strength of females, while the waist circumference, birth history and sedentary time>8 hours are related to the decrease of pelvic floor muscle strength of females. In order to prevent the decrease of pelvic floor muscle strength, it is necessary to carry out relevant health education, enhance exercise, improve the overall strength level, reduce daily sedentary time, maintain symmetry, and carry out comprehensive overall intervention to improve pelvic floor muscle function.

Sedentary behavior, screen time and mental health of college students: a Meta-analysis / 中华流行病学杂志

Objective: To evaluate the effects of sedentary behavior/screen time on mental health of college students by Meta-analysis based on the results of literature retrieval and provide theoretical basis for the improvement of college students' mental health. Methods: The original research literatures about sedentary behavior (including screen time) and college students' mental health published as of 14 July 2022 were retrieved from PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang data. Data were extracted from the included studies and scored by one author in accordance with the proposed programme, and quality score was reviewed by another author. The literature that met the inclusion criteria was systematically reviewed and Meta-analysis was carried out by software Stata 14.2 based on the data from the literatures. Results: A total of 36 studies met the inclusion criteria, including 35 observational studies and 1 interventional study. There are 4 papers about the effects of sedentary behavior and 9 papers about the effects of screening time on depression in college students and 4 papers about the effects of sedentary behavior/screening time on anxiety in college students were used for a Meta-analysis, and the other studies were also analyzed. The Meta-analysis on the effects of sedentary behavior on depression in college students showed that there was a significant positive correlation between higher level sedentary behavior and increased risk for depression (OR=1.07,95%CI:1.05-1.10). Subgroup analysis indicated that there was no significant correlation between higher level sedentary behavior and depression (OR=1.74, 95%CI:0.93-3.25) in the unadjusted confounding factor model, but there was significance positive correlation after adjusting confounding factors (OR=2.15, 95%CI:1.18-3.90). Meta-analysis on the effects of screen time on depression in college students showed that longer screen time were significantly positively correlated with higher depression level (OR=1.03, 95%CI: 1.02-1.05). The results of subgroup analysis showed that in both unadjusted confounding factor model and adjusted confounding factor model, longer screen time was significantly positively correlated with depression (OR=1.27, 95%CI: 1.13-1.42; OR=1.45, 95%CI: 1.18-1.79) , respectively. Meta-analysis on the effects of sedentary behavior on anxiety showed that longer screen time was significantly positively correlated with increased anxiety risk (OR=1.44, 95%CI: 1.31-1.58). The results of subgroup analysis showed that in both unadjusted confounding factor model and adjusted confounding factor model, there was a significant positive correlation between longer screen time and anxiety (OR=1.47, 95%CI: 1.31-1.65; OR=1.38, 95%CI:1.17-1.62). The analysis for the literatures which were not eligible for Meta-analysis found that sedentary behavior/screen time was significantly associated with stress and other mental health in college students. Conclusions: Sedentary behavior or screen time is significantly negatively correlated with college students' mental health, in particular, resulting in depression and anxiety. These effects might be be different between weekdays and weekend days.

Efficacy of intravascular ultrasound versus coronary angiographic guided drug-eluting stent implantation in the treatment of left main coronary artery disease: a meta-analysis / 中华心血管病杂志

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss. Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo.@*METHODS@#For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot.@*RESULTS@#EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05).@*CONCLUSIONS@#EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.

Preliminary establishment and evaluation of a model for early diagnosis of acute aortic dissection / 中国综合临床

Objective:An early diagnosis model of acute aortic dissection (AAD) was established based on chest pain center database.Methods:The clinical data of patients who attended Chest Pain Center of Department of Emergency in Affiliated Hospital of Jining Medical University of Shandong Province from January 2020 to December 2020 were retrospectively collected. Patients were divided into AAD and non-AAD groups according to whether or not AAD was diagnosed. The clinical related indicators of the two groups were compared. The research indicators with statistical differences between the two groups were included in multivariate Logistic regression analysis, and the early diagnosis of AAD nomogram model was established. The receiver operating characteristic (ROC) curve of the model was used to evaluate the prediction accuracy, and the Homser-Lemeshow statistics were used to test the goodness of fit for the model. A total of 630 patients with chest pain who visited the hospital from January 2021 to March 2021 were also collected for external validation of the model. The t-test of independent samples was used to compare the measurement data of normal distribution, nonparametric test was used to compare the measurement data of skewness distribution, and χ 2 test was used to compare the counting data between groups. Results:A total of 2 738 patients were included, of which 4.09% (112/2 738) were AAD patients. Univariate analysis showed that in AAD group, male morbidity (74.11%(83/112)), hypertension history (70.54%(79/112)), aortic disease history (10.71%(12/112)), family history of aortic disease (4.46%(5/112)), sudden onset of symptoms (76.79%(86/112)), percentage of patients with laceration pain (38.39%(43/112)), patients with back pain (66.07%(74/112)), patients with abdominal pain (16.96%(19/112)), systolic blood pressure ((159.44±30.94) mmHg), bilateral blood pressure/pulse asymmetry (23.21% (26/112)), incidence of complicated neurological signs (7.14%(8/112)) and D-dimer (3.57(2.10, 6.62) mg/L) were significantly higher than those in non-AAD group (59.56%(1 564/2 626), 46.23%(1 214/2 626), 0.23%(6/2 626), 0.08%(2/2 626), 35.99%(945/2 626), 0.08%(2/2 626), 3.08%(81/2 626), 3.81%(100/2 626), (142.46±27.90) mmHg, 0.15%(4/2 626), 0.27%(7/2 626), 0.31(0.20, 0.50) mg/L). Age ((57.95±14.35) years old) and CK-MB (1.50(0.90, 3.25) μg/L) were significantly lower than those in the non-AAD group ((61.94±15.77) years, 2.50(1.24, 4.81) μg/L). The differences were statistically significant (the statistical values were χ 2=9.47, χ 2=25.46, χ 2=180.80, χ 2=81.11, χ 2=76.17, χ 2=975.60, χ 2=798.00, χ 2=44.72, t=6.28, χ 2=527.20, χ 2=93.22, Z=14.09, t=2.61, and Z=3.51, respectively; P values were 0.002, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, 0.009, and <0.001, respectively). Multivariate analysis showed that history of hypertension ( OR=3.088, 95% CI:1.294-7.374), history of aortic disease ( OR=20.771, 95% CI:2.132-202.361), family history of aortic disease ( OR=266.425, 95% CI:17.610-4 030.851), sudden onset of symptoms ( OR=3.538, 95% CI:1.643-7.619), laceration pain ( OR=1 771.971, 95% CI:204.048-15 387.935), back pain ( OR=61.550,95% CI:27.987-135.367), abdominal pain ( OR=12.325, 95% CI:4.201-36.161), systolic blood pressure ( OR=1.026, 95% CI:1.013-1.039), bilateral blood pressure/pulse asymmetry ( OR=338.357, 95% CI:60.704-1 885.949) and D-dimer ( OR=1.241, 95% CI:1.176-1.309) were independent factors for the diagnosis of AAD in patients with chest pain (P values were 0.011, 0.009, <0.001, 0.001, <0.001, <0.001, <0.001, <0.001, <0.001, and <0.001, respectively). Furthermore, the nomogram model was constructed. ROC curve analysis showed that the area under the curve was 0.976 ( P<0.01), the specificity was 94.52%, and the sensitivity was 91.96%. The statistics of Homser-lemeshow was used to test the goodness of fit, which shows that the model can be fitted well (χ 2=2.928, P=0.939). The prediction model was verified by external validation data, and the area under the ROC curve was 0.934 ( P<0.01), indicating that the model had good prediction performance. Conclusions:History of hypertension, history of aortic disease, family history of aortic disease, sudden onset of symptoms, laceration pain, back pain, abdominal pain, systolic blood pressure, bilateral blood pressure/pulse asymmetry and D-dimer were independent factors for the diagnosis of AAD in patients with acute chest pain. The AAD early diagnosis nomogram model based on the above factors has good predictive performance.

Normoalbuminuric diabetic kidney disease and hyperuricaemia in elderly type 2 diabetic patients / 中华内分泌代谢杂志

Objective:To assess the correlation between hyperuricaemia and normoalbuminuric diabetic kidney disease(NADKD) in elderly type 2 diabetic patients.Methods:This retrospective case-control study enrolled 910 patients with type 2 diabetes mellitus who were hospitalized in the Geriatric Department of Nanjing Drum Tower Hospital from 2015 to 2020. The patients were divided into NADKD group [urinary albumin/creatinine(UACR)<30 mg/g and estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, n=169)], albuminuria DKD group [UACR ≥30 mg/g and eGFR <60 mL·min -1·(1.73 m 2) -1, n=234], and control group [UACR <30 mg/g and eGFR≥60 mL·min -1·(1.73 m 2) -1, n=507]. Medical history, physical examination, and laboratory tests were collected. Results:The proportion of women in the NADKD group was significantly higher than that in the albuminuric DKD group(50.89% vs 40.60%, P<0.05). Duration of diabetes, HbA 1C, fasting plasma glucose(FPG), the prevalences of hypertension and hyperuricaemia, blood urea nitrogen, blood creatinine, and blood uric acid were significantly lower in the NADKD group than those in the albuminuric DKD group(all P<0.05). Blood urea nitrogen, serum creatinine, triglycerides, serum uric acid and the prevalence of hyperuricemia were significantly higher in the NADKD group compared the control group(all P<0.001) while the proportion of hypertension, systolic blood pressure, LDL-C, HbA 1C, and FPG were lower(all P<0.05). Multivariate linear regression analysis showed that eGFR was negatively associated with urea nitrogen and serum uric acid while positively associated with HbA 1C in normoalbuminuric elderly type 2 diabetic patients(all P<0.001). Logistic regression analysis revealed that hyperuricaemia was a risk factor for NADKD in elderly type 2 diabetic patients after adjusting for BMI, blood pressure, lipids, and glucose( OR=1.963, 95% CI 1.157-3.332, P=0.012). Conclusion:Hyperuricaemia is significantly associated with NADKD in elderly patients with type 2 diabetes.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer / 中国结合医学杂志

OBJECTIVE@#To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment.@*METHODS@#HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied.@*RESULTS@#HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01).@*CONCLUSIONS@#HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

Clinical Efficiency of Rituximab Combined with Autologous Hematopoietic Blood Stem Cell Transplantation for Treatment of CD20 / 中国实验血液学杂志

METHODS@#From January 2005 to December 2013, 83 patients with refractory/recurrent CD20@*RESULTS@#All the patient achieved complete response. The median follow.up time was 39 months. Both the two groups collected peripheral blood stem cells successfully, and had no difference in hematopoietic reconstitution time. Three patients in treatment group and six patients in control group relapsed and the three year overall survival and EFS in treatment group was significantly higher than that in control group, that is（93.0% vs 73.1%, P=0.037） and （89.5% vs 65.4%, P=0.034）, respectively. Subgroup analysis showed that: compared with the treatment group in which using R in the whole courses(before and after transplantation, and collection of stem cells) was superior to the control group in both OS and EFS, with the OS 97% vs 87.5% (P>0.05) and EFS 97% vs 76.2% (P=0.05) respectively. While stratified by the different courses of rituximab, the OS was 88.9% (1-2 courses, 9 cases), 93.1% (3-4 courses, 29 cases), 94.7%(more than 5 courses,19 cases), and EFS was 77.8%, 89.7% and 94.7%, respectively.@*CONCLUSION@#For the patients with refractory/recurrent CD20

Therapeutic silencing miR-146b-5p improves cardiac remodeling in a porcine model of myocardial infarction by modulating the wound reparative phenotype

Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction (MI). MicroRNA-146b (miR-146b) is an active regulator of immunomodulation, but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following MI remain largely unknown. Herein, miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients. Gain- and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells. Overexpression of miR-146b-5p activated fibroblast proliferation, migration, and fibroblast-to-myofibroblast transition, impaired endothelial cell function and stress survival, and disturbed macrophage paracrine signaling. Interestingly, the opposite effects were observed when miR-146b-5p expression was inhibited. Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1 (IRAK1) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death, and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine MI models. Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following MI.

Relationships between perioperative depression, anxiety symptoms and fear of cancer recurrence in breast cancer patients / 中国实用护理杂志

Objective:To investigate the predictive effect of perioperative depression and anxiety symptoms in breast cancer patients on the fear of cancer recurrence.Methods:A total of 194 patients with breast cancer during perioperative period from May 2019 to May 2020 in Qilu Hospital of Shandong University were selected. The depression, anxiety and fear of cancer recurrence were investigated by the general information questionnaire, the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9) and the Fear of Progression Questionnaire-Short Form (FOR-Q-SF) at admission and two weeks after surgery, respectively.Results:Perioperative depression and anxiety symptoms of breast cancer patients were significant predictors of fear of cancer recurrence ( B value was 2.325, OR value was 10.22, P<0.05; B value was 2.570, OR value was 13.07, P<0.05), and patients with depression and anxiety symptoms after surgery were at higher risk of fear of cancer recurrence ( OR values were 7.653-25.403, P<0.01). Conclusions:For breast cancer patients with negative emotions and fear of disease progression, it is necessary to help them improve their psychological coping ability, encouraging patients to actively cooperate with follow-up treatment, improving the prognosis, and improving their overall quality of life.

Effect of Enpagliflozin on left ventricular function, blood glucose and lipid level in T2DM patients / 国际生物医学工程杂志

Objective:To study the effects of Empagliflozin on left ventricular function and the level of blood glucose and lipid in type 2 diabetes mellitus (T2DM) patients.Methods:A total of 120 patients with T2DM complicated with cardiac function impairment were selected from Chu Hsien-I Memorial Hospital, Tianjin Medical University from December 2020 to May 2021. The diabetic patients were randomly divided into the observation group (60 cases) and control group (60 cases) by random number table method. Patients in the observation group were treated with Empagliflozin, while the control group underwent original hypoglycemic treatment. After the treatment, 6 cases were eliminated and 114 cases were completed, with 57 cases in each group. The changes of echocardiographic left ventricular function related indexes such as E/ e', left atrial volume index (LAVI), tricuspid regurgitation speed, left ventricular ejection fraction (LVEF) and laboratory indexes in the two groups were observed before and after treatment. The laboratory indexes checked include fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and how density lipoprotein (HDL). Results:The E/ e', LAVI of the observation groups was significantly lower than that of the control group, and the differences were statistically significant (all P<0.05). There were no significant changes in tricuspid regurgitation speed, LVEF, TG, TC, LDL and HDL levels between the two groups after the treatment (all P>0.05). After the treatment, the levels of FBG and HbA1c in the two groups decreased, but there was no significant difference between the two groups (all P>0.05). Conclusions:Empagliflozin can effectively control the E/ e', LAVI of T2DM patients, and can early significant improvement of left ventricula diastolic function, which is very favorable for the patients. Along with good safety, Empagliflozin is suitable for clinical recommendation.