Strategy to Guide Revascularization of Non-culprit Lesions in Patients With STEMI:State of Art and Future Prospects / 中国循环杂志

Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

Progress of brain metastasis in common gynecologic malignancies / 肿瘤研究与临床

Brain metastasis is an uncommon complication that occurs in the advanced stage of gynecologic malignancies. Brain metastasis tends to be one of the major factors contributing to the poor prognosis of patients. There have been more reports about brain metastasis in cervical, ovarian and endometrial cancers in recent years due to the growth of large databases and improved diagnostic methods. Great attention has been paid to the selection of appropriate therapeutic options to improve the survival of gynecologic malignancies patients with brain metastasis. This article reviews the research progress of brain metastasis in cervical, ovarian and endometrial cancers, aiming to provide better options for treatment of patients with common advanced gynecologic malignancies.

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Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women / 中华内分泌代谢杂志

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Clinical effects of totally robotic digestive tract reconstruction and modified right iliac auxiliary Trocar hole for specimen extraction in radical proctectomy / 中华消化外科杂志

Objective:To investigate the clinical effects of totally robotic digestive tract reconstruction and modified right iliac auxiliary Trocar hole for specimen extraction in radical proctectomy.Methods:The retrospective and descriptive study was conducted. The clinical data of 139 patients with rectal cancer who were admitted to the Chongqing University Three Gorges Hospital from June 2019 to January 2022 were collected. There were 81 males and 58 females, aged (64±15)years. All patients underwent radical proctectomy with totally robotic alimentary tract reconstruction and modified right iliac auxiliary Trocar hole for specimen extraction. Observation indicators: (1) surgical and postoperative situations; (2) follow-up. Measurement data with normal distribution were represented as Mean± SD, and count data were represented as absolute numbers. Results:(1) Surgical and postoperative situations. All the 139 patients completed radical proctectomy with totally robotic alimentary tract reconstruction and modified right iliac auxiliary Trocar hole for specimen extraction successfully, without conversion to laparotomy, unplanned return to surgery or death. The length of surgical incision was (4.5±1.1)cm, operation time was (157±63)minutes, volume of intraoperative blood loss was (65±22)mL, time to postoperative first out-of-bed activities was (2.36±0.29)days, time to first flatus was (2.27±1.13)days, and time to first liquid diet was (2.90±1.12)days. The pain scores at postoperative day 1, 2, 4 were 2.34±1.07, 1.26±0.36, 0.10±0.06. The hospitalization time was (8.92±2.15)days. Results of postoperative pathological examination: the number of lymph nodes dissected was 18.1±2.3, the distal resection margin distance of tumor was (2.6±0.5)cm, and the proximal resection margin distance of tumor was (13.1±2.6)cm. The mesorectum of all specimens was intact, and the circumferential resection margin was negative. Of 139 patients, 1 case of incision fat liquefaction, 1 case of anastomotic leakage, 1 case of anastomotic bleeding, 1 case of intestinal obstruction after operation were discharged after treatment. There was no complication such as abdominal infection or hemorrhage, chylous leakage, abdominal infection. (2) Follow-up. All the 139 patients were followed up for 1 year after operation. No chronic infection of abdominal incision, incisional hernia, incisional tumor implantation, chronic incision pain, sexual dysfunction, dysuria or fecal incontinence were found during the 1-year follow-up.Conclusion:Totally robotic alimentary tract reconstruction and modified right iliac auxiliary Trocar hole for specimen extraction is safe and feasible in radical proctectomy, which has clinical application value.

Association of Ego-depletion level with glycemic control and quality of life among adolescents with type 1 diabetes / 中国实用护理杂志

Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.

Impact of insulin injection induced lipohypertrophy on multidimensional glucose variability in patients with type 1 diabetes mellitus / 中华内分泌代谢杂志

Objective:This study aimed to investigate the effect of lipohypertrophy induced by insulin injection on blood glucose fluctuation in patients with type 1 diabetes mellitus.Methods:A total of 80 patients with type 1 diabetes mellitus were recruited between June 2021 and December 2021 from the First Affiliated Hospital of Nanjing Medical University. And these patients all received insulin injection more than six months. Lipohypertrophy was assessed by ultrasound scanning, and blood glucose fluctuation was evaluated using the flash glucose monitoring system(FGM). Univariate analysis and multivariate linear regression were used to analyze the relationship of lipohypertrophy and and core indicators of blood glucose fluctuation.Results:Compared with patients without lipohypertrophy, patients with lipohypertrophy had higher mean amplitude of glycemic excursions(MAGE), coefficient of variation(CV), mean of daily differences(MODD), standard deviation(SD) of blood glucose, time above range(TAR), and high blood glucose index(HBGI; all P<0.05), while time in range(TIR) of glucose markedly become lower( P<0.01). Moreover, multivariate linear regression analysis showed that lipohypertrophy detected by ultrasound was an independent influencing factor of TIR( β=-9.423, P=0.032), MAGE( β=1.114, P=0.039), CV( β=4.304, P=0.041), MODD( β=0.717, P=0.046) after adjusting for age at diagnosis, duration of insulin injection, fasting C-peptide, and daily dose of insulin per unit weight. Conclusion:Lipohypertrophy increases glycemic variability and imposes negative impact on glycemic control rate in patients type 1 diabetes mellitus.

Bone turnover markers, hip bone geometry parameters and metabolic syndrome in community overweight postmenopausal women / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.

Progress of relationship between body mass index and gynecological malignancies / 肿瘤研究与临床

Body mass index (BMI) is an index closely related to the total body fat. It is often used to measure the degree of obesity and reflect the nutritional status of the human body to a certain extent. The incidence rate and mortality rate of gynecological malignancies remain high. Some studies have found that BMI has certain value in the incidence and prognosis evaluation of gynecological malignancies, and is crucial to prolong the survival of patients. This review summarizes the recent research progress on the correlation between BMI and common gynecological malignancies and the mechanism of BMI on its occurrence and development.

Five-year outcomes of biodegradable versus second-generation durable polymer drug-eluting stents used in complex percutaneous coronary intervention / 中华医学杂志(英文版)

BACKGROUND@#There are few data comparing clinical outcomes of complex percutaneous coronary intervention (CPCI) when using biodegradable polymer drug-eluting stents (BP-DES) or second-generation durable polymer drug-eluting stents (DP-DES). The purpose of this study was to investigate the safety and efficacy of BP-DES and compare that with DP-DES in patients with and without CPCI during a 5-year follow-up.@*METHODS@#Patients who exclusively underwent BP-DES or DP-DES implantation in 2013 at Fuwai Hospital were consecutively enrolled and stratified into two categories based on CPCI presence or absence. CPCI included at least one of the following features: unprotected left main lesion, ≥2 lesions treated, ≥2 stents implanted, total stent length >40 mm, moderate-to-severe calcified lesion, chronic total occlusion, or bifurcated target lesion. The primary endpoint was major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction, and total coronary revascularization (target lesion revascularization, target vessel revascularization [TVR], and non-TVR) during the 5-year follow-up. The secondary endpoint was total coronary revascularization.@*RESULTS@#Among the 7712 patients included, 4882 (63.3%) underwent CPCI. Compared with non-CPCI patients, CPCI patients had higher 2- and 5-year incidences of MACE and total coronary revascularization. Following multivariable adjustment including stent type, CPCI was an independent predictor of MACE (adjusted hazard ratio [aHR]: 1.151; 95% confidence interval [CI]: 1.017-1.303, P  = 0.026) and total coronary revascularization (aHR: 1.199; 95% CI: 1.037-1.388, P  = 0.014) at 5 years. The results were consistent at the 2-year endpoints. In patients with CPCI, BP-DES use was associated with significantly higher MACE rates at 5 years (aHR: 1.256; 95% CI: 1.078-1.462, P  = 0.003) and total coronary revascularization (aHR: 1.257; 95% CI: 1.052-1.502, P  = 0.012) compared with that of DP-DES, but there was a similar risk at 2 years. However, BP-DES had comparable safety and efficacy profiles including MACE and total coronary revascularization compared with DP-DES in patients with non-CPCI at 2 and 5 years.@*CONCLUSIONS@#Patients underwent CPCI remained at a higher risk of mid- to long-term adverse events regardless of the stent type. The effect of BP-DES compared with DP-DES on outcomes was similar in CPCI and non-CPCI patients at 2 years but had inconsistent effects at the 5-year clinical endpoints.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine

The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.

Effects of the S1PR3 specific agonist peptide GPS-725.017 on acute lung injury in mice / 中华急诊医学杂志

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

Long-term prognosis effects of single and staged percutaneous coronary intervention in patients with multi-vessel coronary artery disease / 中国医师进修杂志

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Influence factors of the peak time in computed tomography portal venography / 中国医师杂志

Objective:To evaluate the influence factors of the peak time in computed tomography (CT) portal venography.Methods:Twenty-eight patients who underwent CT perfusion (CTP) examination in Minhang Hospital Affiliated to Fudan University from October 2020 to December 2021 were retrospectively collected. The CT enhancement time-density curves of the main portal vein trunk and abdominal aorta were obtained at the cross section of the left and right branches of portal vein. The peak time of portal vein and abdominal aorta, the enhanced CT attenuation of the liver and spleen parenchyma enhancement at the peak value of portal vein were measured. Pearson correlation and regression analysis were performed.Results:The peak time of abdominal aorta was (16.39±2.68)s, and portal vein was (27.12±4.65)s. The enhanced CT attenuation of liver and spleen parenchyma were (84.64±20.21)HU and (142.28±25.15)HU, respectively. The peak time of portal vein was positively correlated with the peak time of abdominal aorta ( r=0.825, P<0.001), and there was no statistical correlation with the enhanced CT values of liver and spleen. Multiple linear regression analysis showed that the peak time of abdominal aorta was an independent factor affecting the peak time of portal vein ( b=1.326, t=5.874, P<0.001). The regression equation was the peak time of portal vein=4.185+ 1.451× the peak time of abdominal aorta. The peak time of portal vein in cirrhosis group was (27.78±4.48)s, and that in noncirrhosis group was (26.8±4.81)s, with no significant difference between the two groups ( P=0.614). Conclusions:There was a linear correlation between the peak time of portal vein and the abdominal aorta, and the results could be helpful to optimize the setting of delay time before CT portal venography.

A study on the composite indices of femoral neck strength in non-low-weight postmenopausal women with type 2 diabetes mellitus in community / 中华内分泌代谢杂志

Objective:To explore the risk of hip fracture, changes of composite indices of femoral neck strength and its influential factors in non-low-weight postmenopausal women with type 2 diabetes mellitus(T2DM).Methods:A total of 626 non-low-weight postmenopausal women were selected and divided into type 2 diabetes group, pre-diabetic group, and non-diabetic group according to the diagnostic criteria of the American Diabetes Association in 2010. Each participant completed the questionnaire, physical examination, laboratory examination, and Dual-energy X-ray absorptiometry(DXA) examination.Results:Hip fracture rate in T2DM group was significantly higher than that in non-diabetic group(3.4% vs 0.7%, P<0.05), while no significant difference was observed between pre-diabetic group and non-diabetic group(1.1% vs 0.7%, P>0.05). Bone mineral density(BMD) of lumbar spine 1-4, femoral neck, and total hip was comparable between T2DM group and non-diabetic group or pre-diabetic group and non-diabetic group, respectively( P>0.05). The composite indices of femoral neck strength in T2DM group was significantly lower than that in non-diabetic group( P<0.05), but there was no significant difference between pre-diabetic group and non-diabetic group( P>0.05). Regression analysis showed that age and body mass index were the main influential factors of the femoral neck bone mineral density and the composite indices of femoral neck strength( P<0.05). Conclusion:The composite indices of femoral neck strength could be used as one of the markers to evaluate the risk of hip fracture in type 2 diabetic patients.

A preliminary study of radiomics in predicting WHO/ISUP grading of clear cell renal cell carcinoma based on unenhanced CT texture analysis / 中华放射学杂志

Objective:To investigate the value of radiomics based on unenhanced CT texture analysis in predicting the WHO/International Society of Urological Pathology (ISUP) grading of clear cell renal cell carcinoma (ccRCC).Methods:Postoperative pathology-confirmed ccRCC subjects ( n=90) who received CT scanning and had a definite pathological grading in Cancer Hospital of the University of Chinese Academy of Sciences were collected retrospectively from December 2016 to May 2019. The cases were randomly divided into training group ( n=63) and test group ( n=27) as a ratio of 7∶3. All cases were classified into low grade (grades Ⅰ and Ⅱ, n=57) and high grade (grades Ⅲ and Ⅳ, n=37) according to the new pathological grading (WHO/ISUP grading, version 2016) of renal carcinoma. 3D-ROI segmentation was performed on unenhanced CT images and 93 texture features were extracted. The least absolute shrinkage and selection operator (LASSO) regression was used to reduct dimension of texture parameters and then the radiomics score (Rad-score) was established. The logistic regression was used to develop the prediction model with the pathological grading as the gold standard. The ROC curve and calibration curve were used to evaluate the predictive performance of the model, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Hosmer-Lemeshow test was used to evaluate calibration degree of the model. Results:The 10 non-zero coefficient texture features were screened out through dimension reduction steps. The Rad-score was formed according to the linear combination of these ten features and corresponding coefficients, and then the prediction model was developed. The AUC of the model in training group was 0.933 (95%CI 0.862-1.000), the sensitivity was 92.3%, the specificity was 89.2%, and the model accuracy was 90.5%. The calibration curve showed the good calibration ( P=0.257). The AUC value in test group was 0.875 (95%CI 0.734-1.000), the sensitivity, specificity and accuracy were 72.7%, 87.5% and 81.5%. The calibration curve showed the good calibration ( P=0.125). Conclusion:The radiomics prediction model based on unenhanced CT texture analysis have application potential for the evaluation of WHO/ISUP grading of ccRCC.

Impact of the depth of lipohypertrophy assessed by ultrasound on glycemic control in diabetic patients / 中华内分泌代谢杂志

To evaluate the impact of the depth of lipohypertrophy on glycemic control in diabetic patients, 498 diabetic patients were recruited from July 2017 to July 2020 in the First Affiliated Hospital of Nanjing Medical University. Their demographic and clinical data were collected. Lipohypertrophy was assessed with ultrasound. 85.1%(424/498) of patients had lipohypertrophy. The average depth of lipohypertrophy was(5.62±2.49) mm. Compared with HbA 1C≤7%, patients with HbA 1C>7% had significantly higher proportion of lipohypertrophy with depth >5 mm(69.7% vs 81.3%, P<0.05). After adjusting potential confounders, the level of HbA 1C in patients with the depth of lipohypertrophy>5 mm was still significantly higher than those with the depth of lipohypertrophy≤5 mm( OR=1.716, 95% CI 1.104-2.668, P<0.05). The depth of lipohypertrophy may be an independent risk factor for suboptimal HbA 1C. However, prospective studies are still needed to confirm.

Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

Robust neutralization assay based on SARS-CoV-2 S-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressed BHK21 cells

The global pandemic of Coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable in vitro neutralization assay is very important for the development of neutralizing antibodies, vaccines and other inhibitors. In this study, G protein-deficient vesicular stomatitis virus (VSVdG) bearing full-length and truncated spike (S) protein of SARS-CoV-2 were evaluated. The virus packaging efficiency of VSV-SARS-CoV-2-Sdel18 (S with C-terminal 18 amino acid truncation) is much higher than VSV-SARS-CoV-2-S. A neutralization assay for antibody screening and serum neutralizing titer quantification was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and human angiotensin-converting enzyme 2 (ACE2) overexpressed BHK21 cell (BHK21-hACE2). The experimental results can be obtained by automatically counting EGFP positive cell number at 12 hours after infection, making the assay convenient and high-throughput. The serum neutralizing titer of COVID-19 convalescent patients measured by VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with live SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting receptor binding domain (RBD) of SARS-CoV-2-S were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.