Cigarette Smoke or Motor Vehicle Exhaust Exposure Induces PD-L1 Upregulation in Lung Epithelial Cells in COPD Model Rats.

A high smoking-independent chronic obstructive pulmonary disease (COPD) prevalence is observed in lung cancer patients. However, the underlying connection between these two diseases still remains unclear. Cigarette smoking and ambient air pollution are common risk factors for COPD and lung cancer. In this study, we established rat COPD model through exposure to cigarette smoke (CS) or motor vehicle exhaust (MVE). The model rats developed COPD-like phenotypes, manifested as lung functions decline, lung inflammation, emphysema-like alveolar enlargement and airway remodeling. The programmed death-ligand 1 (PD-L1), a factor contributing to immune escape of tumor cells, was overexpressed in lungs from COPD model rats, though more severe COPD phenotypes did not bring with further PD-L1 overexpression in lung. The upregulations of proinflammatory cytokines and PD-L1 were also observed in cultured human bronchial epithelial cells BEAS-2B upon treatment with cigarette smoke extract (CSE) or diesel-related particulate matter 2.5 (PM2.5, SEM1650b). The inflammatory cytokines produced in BEAS-2B cells reflected the PD-L1 levels. Furthermore, ERK1/2, a kinase mediating PD-L1 upregulation in premalignant bronchial cells or NSCLC cells, and STAT1/3, which was reportedly associated with PD-L1 expression in lung tumors, were activated in COPD rats' lungs or in BEAS-2B cells treated with CSE or PM2.5. Therefore, we proposed that inflammation associated PD-L1 overexpression in airway epithelial cells could be the underlying factor facilitating lung cancer incidence in COPD.

Clinicopathological characteristics and prognosis of gastrointestinal vascular tumours.

To evaluate the clinicopathological characteristics and prognosis of gastrointestinal vascular tumours. By reviewing the information from the electronic medical record system and pathology database of Hangzhou First People's Hospital affiliated with Zhejiang University School of Medicine and Jiaxing First People's Hospital from June 2008 to December 2019, 31 patients pathologically diagnosed with vascular tumours were included in this study. The age of onset, sex differences, clinical manifestations, imaging and endoscopic characteristic manifestations, pathological characteristics, treatment methods and prognosis were analysed. The pathological classification was haemangiolymphangioma, haemangioma, and lymphangioma in 8, 14, and 9 cases, respectively. The age of onset was 44-66 years, with no significant difference according to sex (P = 0.583); 32.26% (10/31) of patients had no noticeable symptoms, 37.5% (12/31) of patients had gastrointestinal bleeding, and 6.45% (2/31) of patients, all with lymphangioma, had intestinal obstruction. The lesions were located in and below the duodenum. Endoscopy showed colour differences. Both endoscopic and surgical treatments were safe and effective. The mean survival time was 57.06 ± 35.64 months. Regarding vascular tumours without typical symptoms, the main pathological classification is haemangioma. Vascular tumours are often clinically identified because of bleeding or obstruction and can be treated with endoscopy or surgery. Clinical follow-up is recommended because no invasive manifestations or instances of recurrence were observed.

Trans-fatty acid content in edible vegetable oil under different high temperatures / 上海预防医学

ObjectiveAn experimental method was established to determine the level of trans-fatty acids in edible vegetable oil and the changes of trans-fatty acid content during high-temperature simulated cooking. MethodsFour common edible vegetable oils on the market were selected， and three temperature points were set at 180 ℃ （light stir-fry）， 220 ℃ （fry） and 260 ℃ （stir fry）. The samples were taken after the heat treatment of 0， 1， 2， 3， 4， 5， 6 and 7 hours，respectively， to investigate the changes of trans-fatty acid content. ResultsUnder the heat treatment of 180 ℃ and 220 ℃， the content of trans-fatty acids remained basically stable in rapeseed oil， corn oil， soybean oil and olive oil. Under the heating condition of 260 ℃， the content of trans-fatty acids in these four vegetable oils increased significantly， and the absolute content of trans-fatty acids in rapeseed oil was the highest， reaching 6.84%. Soybean oil showed the larger increase， up to 247.90% from the initial content. The content of trans-fatty acids in olive oil increased from 0.26% to 1.69%， although the increase was large， but the absolute content of trans-fatty acids was still low. The content of trans-fatty acids in sesame oil increased significantly under the three temperatures， reaching 4.79% when heated at 260 ℃， and an increase of 369.61% compared with no heating. ConclusionTrans-fatty acid content in edible vegetable oils increases significantly in the cooking process， the higher the temperature and the longer the cooking time， the more significant the increase. It is recommended to avoid high temperature cooking and long time fried food.

Microecological characteristics of different types of vaginitis and their correlation with HPV infection / 国际生物医学工程杂志

Objective:To retrospectively analyze the relationship between different types of vaginal infection, vaginal microecology, and human papillomavirus (HPV) infection.Methods:A retrospective analysis of 6056 patients who underwent vaginal microecology examination was performed, and patients with vaginal infection or HPV detection were screened out. The detection rates of various types of vaginal infection, HPV infection, and infection in different age groups were calculated.Results:A total of 2 737(45.2%) vaginal infection patients were screened, with 7 types of vaginal infection covered. The top three detection rates of vaginal infection were bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and aerobic vaginal infection (AV). In 6056 patients, 1843 patients underwent HPV detection, among which the top three positive rates of HPV were BV, mixed infection, and VVC. The first three cases of vaginal infection with high-risk HPV infection were BV, mixed infection, and BV intermediate type. The age distribution of different types of vaginal infection combined with HPV infection was different, and the age at which it occurred and the trend of change with age were obvious.Conclusions:BV is closely related to HPV infection. It is suggested that HPV detection should be performed simultaneously in BV patients with vaginal infection, especially those aged 30 to 40 years, which has important clinical significance for HPV screening and prevention.

Predictive value of mNUTRIC score for chronic critical illness in elderly patients with sepsis / 中华急诊医学杂志

Objective:To explore the predictive value of the modified NUTrition risk in the critically ill (mNUTRIC) score for chronic critical illness (CCI) in elderly sepsis patients.Methods:A prospective observational study was conducted. Elderly sepsis patients admitted to Medical Intensive Care Unit (MICU) of General Hospital of Southern Theatre Command for more than 24 h from August 2019 to January 2021 were enrolled. Age, sex, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, acute gastrointestinal injury (AGI) score, clinical frailty score and mNUTRIC score at admission, length of ICU stay, usage of mechanical ventilation and renal replacement therapy were recorded. According to the occurrence of CCI, patients were divided into the CCI group and rapid recovery (RAP) group, and the differences between the two groups were compared. The risk factor of CCI after sepsis in elderly patients were analyzed by log-binomial regression analysis. Receiver operating characteristic (ROC) analysis was performed for mNUTRIC score. Differences were considered significant at P<0.05. Results:Of the enrolled 91 sepsis patients, 14 (15%) patients died within the first week, 37 (41%) exhibited RAP and 40 (44%) developed CCI. The CCI patients were significantly older and presented a higher APACHE Ⅱ score, CFS score, mNUTRIC score, and usage of mechanical ventilation and renal replacement therapy compared with the RAP patients ( P<0.05). Multivariate regression analysis revealed that mNUTRIC score was an independent risk factor for the development of CCI in elderly sepsis patients, prevalence ratio was 1.503 (95% CI: 1.007-2.244). The area under the curve (AUC) of mNUTRIC score was 0.706 (95% CI: 0.592-0.805). Conclusions:The mNUTRIC score at the time of admission in the intensive care unit can be used to predict CCI after sepsis in elderly sepsis patients.

Construction of training system for first aid ability of nurses in Head and Neck Oncology Department / 中国实用护理杂志

Objective:To develop a training system for head and neck oncology nurses to improve the emergency response competency to recognize and response to acute and critical medical conditions.Methods:Based on literature review and semi-structured interviews with 12 nurses, two rounds of consultation with 15 head and neck cancer care specialists from 6 Tertiary hospitals using Delphi method were conducted to establish the training system for head and neck oncology nurses.Results:The authority coefficients of experts were 0.87 and 0.89, respectively. The coefficient of variation of each item ranged from 0 to 0.167. The coefficients of concordance ranged from 0.243 to 0.403 ( P<0.01). There was statistical significance after Chi-square test ( χ2 values were 14.60-436.64, all P<0.01). In the final training system, training aims included 5 first-level indicators and 16 second-level indicators; training contents included 5 first-level indicators, 16 second-level indicators, and 60 third-level indicators. Conclusions:The authority coefficients and the coefficients of concordance of the experts for the training system were both high. The training system can be applied to improve the emergency response competency of head and neck oncology nurses.

Externalizing Behavior Problems Among Hui Ethnicity Left-Behind Children in Rural China: A Cross-Sectional Study

Objective@#This study aimed to investigate the prevalence of externalizing behavior problems (EBPs) and its influencing factors among Hui left-behind children (LBC) in rural China. @*Methods@#A cross-sectional study was conducted among school students from the southern rural areas in Ningxia, China (2012–2013). The general self-made questionnaire, Egma Minnen av Bardndosna Uppforstran, Eysenck Personality Questionnaire (for Children), Piers-Harris Children’s Self-Concept Scale, and Achenbach’s Child Behavior Checklist (for parents) were used to investigate the related information. Binary logistic regressions were conducted. @*Results@#The prevalence of EBPs in boys Hui LBC was significantly higher than that of non-LBC (12.37% vs. 6.84%, χ2=4.09, and p=0.04). Multivariate logistic regression analysis showed that low self-awareness of behavior (odds ratio [OR]=29.78), introversion (OR=21.67) and intermediate personality (OR=15.83), poor academic performance (OR=11.65) and both parent migrating (OR=2.73) were the risk factors for the EBPs of Hui LBC, while middle and high father refusal and denial (OR=0.11, OR=0.09) were their protective factors. @*Conclusion@#Our findings suggest that both parent migrating is a potential risk factor for EBPs among Hui LBC. Hui boys LBC should be paid more attention when formulating relevant policies.

Nodal marginal zone lymphoma with elevated monoclonal IgM: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features, diagnosis, differential diagnosis and treatment of nodal marginal zone lymphoma (NMZL) with elevated monoclonal IgM.Methods:The clinical data of one NMZL patient with elevated monoclonal IgM treated at Yancheng No.1 People's Hospital in July 2020 were retrospectively analyzed, and the related literature was analyzed.Results:The patient was a 57-year-old female and the main clinical manifestations were fatigue and bone pain in left rib. Serum immunofixation electrophoresis showed IgM-κ type M proteinemia, bone marrow cytology showed a few plasmacytoid lymphocytes, bone marrow biopsy and immunohistochemistry showed B-cell non-Hodgkin lymphoma, bone marrow genetic testing showed MYD88 L265p and CXCR4 were both negative, postoperative pathology result of retroperitoneal lymph node biopsy was marginal zone lymphoma (mature small B type, prone to NMZL),and immunohistochemistry results: CD3, CD5, CD138, κ, λ, CD10, Cyclin D1 were negative, CD20, Pax-5, CD23 (FDC), bcl-2 were positive; Ki-67 positive index < 5%. The final diagnosis was NMZL with elevated monoclonal IgM. Partial remission was achieved after 8 cycles of reduced-dose CHOP regimen; thalidomide was used in the maintenance treatment, the disease condition was stable until August in 2021 and the follow-up was continuing.Conclusions:NMZL with elevated monoclonal IgM is relatively rare. Its diagnosis should be differentiated from Waldenstr?m macroglobulinemia and other inert B-cell lymphomas. Currently, there is no standard treatment and following the principle of individualized treatment can improve the prognosis of patients.

Clinical application of clot waveform analysis / 中华检验医学杂志

Bleeding and thrombotic diseases are closely related to various clinical departments. Laboratory-related tests play an important role in disease diagnosis and differential diagnosis, risk assessment, cause finding, and efficacy monitoring. Clot waveform analysis (CWA), as an automated coagulation detection technology, can provide more valuable information about the entire coagulation process of a plasma sample. A large number of studies have showed that CWA has certain value in the evaluation of coagulation status of COVID-19 patients, the judgment of clinical phenotype of hemophilia A (HA) patients, and the monitoring of direct oral anticoagulant drugs (DOAC). In-depth interpretation and application of CWA in different clinical settings can provide more laboratory information for diagnosis and treatment of bleeding and thrombotic diseases.

Predictive value of neutrophil to lymphocyte ratio in the progression of sepsis to chronic critical illness in elderly patients / 中华危重病急救医学

Objective:To explore the predictive value of neutrophil to lymphocyte ratio (NLR) in the progression of sepsis to chronic critical illness (CCI) in elderly patients.Methods:Patients with sepsis who were hospitalized more than 24 hours and older than 60 years old admitted to the department of medical intensive care unit (MICU) of General Hospital of Southern Theatre Command from August 2019 to April 2021 were enrolled. The neutrophil count (NEU), lymphocyte count (LYM) and NLR of peripheral blood cells were recorded on the 1st, 4th and 7th day after admission. Patients were divided into the CCI group and the non-CCI group according to whether they progressed to CCI, and differences between the two groups were compared. The CCI was defined as a MICU length of stay (LOS) ≥ 14 days and persistent organ dysfunction [sequential organ failure assessment (SOFA) score ≥ 2]. Logistic regression analysis was performed to evaluate the risk factors for predicting CCI. The receiver operator characteristic curve (ROC curve) was plotted for evaluating the predictive value of NLR in the progression of sepsis to CCI in elderly patients.Results:① Among 103 sepsis patients enrolled, 16 (15.5%) died within 2 weeks of admission to the MICU, 46 (44.7%) developed CCI, and 41 (39.8%) were non-CCI. ② Compared between the two groups, the NEU of CCI group on day 7 was significantly higher than that of non-CCI group [×10 9/L: 9.80 (6.72, 16.80) vs. 6.66 (5.14, 9.29), P < 0.01], LYM was significantly lower than that of non-CCI group [×10 9/L: 0.77 (0.46, 1.20) vs. 1.00 (0.86, 1.48), P < 0.05], and NLR on day 4 and day 7 were significantly higher than those of non-CCI group [12.85 (6.56, 17.56) vs. 8.26 (5.34, 13.17), 13.76 (6.97, 23.66) vs. 6.14 (4.04, 8.84), both P < 0.05]. Compared with different time points in the same group, NEU and NLR decreased gradually and LYM increased gradually in non-CCI group (χ 2 values were 10.216, 28.343, 7.189, respectively, all P < 0.05), which tended to be normal. There were no significant differences in NEU, LYM and NLR of CCI group at each time point (χ 2 values were 0.798, 4.478, 5.783, respectively, all P > 0.05). ③ Multivariate Logistic regression analysis showed that NLR on day 7 was an independent risk factor for sepsis progression to CCI [odds ratio ( OR) = 1.155, P = 0.005]. ④ ROC curve analysis showed that the area under the curve (AUC) of NLR predicting the sepsis progression to CCI on day 7 was 0.775, and the 95% confidence interval (95% CI) was 0.670-0.860, P < 0.01; when the cut-off value was 9.25, the sensitivity was 69.57% and the specificity was 80.56%. Conclusion:Dynamic monitoring of NLR is helpful to determine the progress of sepsis in elderly patients, NLR on day 7 has a certain predictive value for the occurrence of CCI.

Meta-analysis of the effect of psychological nursing on the functional recovery of patients with dysphagia after stroke / 中国实用护理杂志

Objective:To evaluate the influence of psychological nursing on the functional recovery of patients with dysphagia after stroke using the method of Meta analysis.Methods:A computer search of PubMed, Cochrane Library, Web of Science, VIP, Wanfang Data, China Knowledge Infrastructure Engineering and China Biomedical Literature Database was used to collect the psychological nursing on the function of patients with dysphagia after stroke. The data were collected from June 1956 to August 2020. The literature of randomized controlled studies using Revman 5.3 for Meta analysis.Results:A total of 7 controlled studies on the impact of the use of the core quality of life scale (QLQ-C30) and the treatment efficacy survey on the functional recovery of patients with dysphagia after stroke and the impact of quality of life were included, with a total of 660 samples. The results of Meta analysis showed that the average difference of mental function after psychological nursing intervention was statistically significant [weight mean difference( WMD)=-16.66, 95% CI -18.09--15.22, P<0.001]; in the physical function score, the intervention group performed relatively significant difference compared with the control group ( WMD=-14.10, 95% CI -16.26--11.95, P<0.001); the average difference in social function after psychological nursing intervention was statistically significant ( WMD=-13.52, 95% CI -15.64--11.41, P<0.001); in the quality of life score, the control group performed worse than the intervention group ( WMD=-14.58, 95% CI -15.86--13.31, P<0.001); the treatment effect of the intervention group was better than that of the control group, and the difference was statistically significant [odds ratio ( OR=0.16, 95% CI 0.08-0.32, P<0.001]. Conclusions:Through the intervention of psychological care, the swallowing disorder of stroke patients is relieved and the quality of life is improved.

Nutrition support in the chronic critically ill patients / 中华危重病急救医学

Over the last decade, chronic critically ill (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and implementation of care bundles has significantly decreased early deaths of critically ill patients, and have allowed them to survive previously lethal multiple organ failure (MOF). However, more and more survivors leave persistent low grade organ dysfunctions, depend on continues organ support, need to stay in ICU, and become CCI patients. These patients experience a persistent immune dysregulation with persistent inflammation, immunosuppression, and catabolic syndrome. Therefore, malnutrition is an important feature of patients with CCI, and nutritional support is a crucial part of their treatment. The main strategies of nutritional support are as follows: providing sufficient calories and proteins with appropriate anabolic agents to promote anabolic metabolism, using immunomodulators to improve immune suppression and inflammatory responses, and supplementing micronutrients to enhance metabolic support. In this review, the nutritional assessment, calorie assessment, protein assessment and other nutrient supplementation (such as β blocker, testosterone and oxandrolone, immunonutrition, vitamins) of CCI patients were reviewed, so as to provide reference for the treatment of CCI.

Progress of clinicopathological features, diagnosis and treatment and screening of early-onset colorectal cancer / 肿瘤研究与临床

The incidence of early-onset colorectal cancer is increasing year by year, and it occupies an important position in colorectal cancer. Most of the characteristics of patients with early-onset colorectal cancer are different from those with late-onset colorectal cancer, the patients are diagnosed in a late stage, and their pathological manifestations show a type of poor prognosis. At present, there is a lack of consensus and guideline for the diagnosis, treatment and screening of early-onset colorectal cancer. A full understanding of the characteristics of early-onset colorectal cancer helps to understand its pathogenesis and guide screening and treatment to reduce the incidence and mortality of colorectal cancer. This article reviews the clinicopathological characteristics, molecular pathological mechanisms, diagnosis and treatment, and prognosis of early-onset colorectal cancer, in order to provide references for elucidating its etiology and formulating scientific and standardized screening strategies.

A 180-day mortality predictive score based on frailty syndrome in elderly patients with sepsis: a Logistic regression analysis model / 中华危重病急救医学

Objective:To establish a 180-day mortality predictive score based on frailty syndrome in elderly sepsis patients [elderly sepsis score (ESS)].Methods:A prospective study for sepsis patients aged 60 years and above who were admitted to a medical intensive care unit of the General Hospital of Southern Theatre Command from January 1st, 2018 to December 31st, 2018 was conducted. Univariate analysis was performed on 19 independent variables including gender, age, body mass index (BMI), tumor, charlson comorbidity index (CCI), activity of daily living (ADL), instrumental activity of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), clinical frail scale (CFS), sequential organ failure assessment (SOFA), Glasgow coma scale (GCS), acute physiology and chronic health evaluation (APACHEⅡ, APACHEⅣ), modified NUTRIC score (MNS), multiple drug resistance (MDR), mechanical ventilation (MV), continuous renal replacement therapy (CRRT) and palliative care. Continuous independent variables were converted into classified variables. Multivariate binary regression analysis of risk factors was conducted to screen independent risk factors which affecting 180-day mortality in elderly sepsis patients. Then a 180-day mortality predictive score was established, and the discrimination of the mortality of patients using CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS scores were compared.Results:A total of 257 patients were enrolled, with a 180-day mortality of 60.7%. Univariate analysis showed that age, tumor, CCI, ADL, IADL, MMSE, CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS, MDR, MV, CRRT, palliative care were risk factors of 180-day mortality in elderly sepsis patients [age: odds ratio ( OR) = 1.027, 95% confidence interval (95% CI) was 1.005-1.050, P = 0.018; tumor: OR =2.001, 95% CI was 1.022-3.920, P = 0.043; CCI: OR = 1.193, 95% CI was 1.064-1.339, P = 0.003; ADL: OR = 0.851, 95% CI was 0.772-0.940, P = 0.001; IADL: OR = 0.894, 95% CI was 0.826-0.967, P = 0.005; MMSE: OR = 0.962, 95% CI was 0.937-0.988, P = 0.004; CFS: OR = 1.303, 95% CI was 1.089-1.558, P = 0.004; SOFA: OR = 1.112, 95% CI was 1.038-1.191, P = 0.003; GCS: OR = 0.918, 95% CI was 0.863-0.977, P = 0.007; APACHEⅡ: OR = 1.098, 95% CI was 1.053-1.145, P < 0.001; APACHEⅣ: OR = 1.032, 95% CI was 1.020-1.044, P < 0.001; MNS: OR = 1.315, 95% CI was 1.159-1.493, P < 0.001; MDR: OR = 2.029, 95% CI was 1.197-3.437, P = 0.009; MV: OR = 6.408, 95% CI was 3.480-11.798, P < 0.001, CRRT: OR = 2.744, 95% CI was 1.529-4.923, P = 0.001, palliative care: OR = 5.760, 95% CI was 2.177-15.245, P < 0.001]. By binary regression analysis, CFS stratification ( OR = 1.934, 95% CI was 1.267-2.953, P = 0.002), MV ( OR = 4.531, 95% CI was 2.376-8.644, P < 0.001), CRRT ( OR = 2.471, 95% CI was 1.285-4.752, P = 0.007), palliative care ( OR = 6.169, 95% CI was 2.173-17.515, P = 0.001) were independent risk factors of 180-day mortality in elderly patients with sepsis. The model of "ESS = 0.660×CFS stratification+1.511×MV+0.905×CRRT+1.820×palliative care" was established. Receiver operating characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) for predicting 180-day mortality by ESS was 0.785 (95% CI was 0.730-0.834, P < 0.001). When the best cut-off value was 2.2 points, its sensitivity was 78.9%, specificity was 70.3%, the positive predictive value was 80.4%, and the negative predictive value was 68.3%. Simplified ESS was defined as "0.5×CFS stratification+1.5×MV+1×CRRT+2×palliative care". ROC curve analysis showed that AUC for predicting 180-day mortality by simplified ESS was 0.784 (95% CI was 0.729-0.833, P < 0.001). When the best cut-off value was 2.0 points, sensitivity was 76.9%, specificity was 70.3%, the positive predictive value was 80.0%, and the negative predictive value was 66.4%. Compared with CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ and MNS, ESS had a significant difference in discriminating 180-day mortality in elderly patients with sepsis (AUC was 0.785 vs. 0.607, 0.607, 0.600, 0.664, 0.702, 0.657, 95% CI: 0.730-0.734 vs. 0.537-0.678, 0.537-0.677, 0.529-0.671, 0.598-0.730, 0.638-0.766, 0.590-0.725, all P < 0.05). Conclusions:CFS, MV, CRRT, and palliative care are independent risk factors of 180-day mortality in elderly patients with sepsis. We established ESS based on these risk factors. The ESS model has good discrimination and can be used as a reference and assessment tool for prediction and treatment guidance in elderly patients with sepsis.

Activated PKB/GSK-3β synergizes with PKC-δ signaling in attenuating myocardial ischemia/reperfusion injury via potentiation of NRF2 activity: Therapeutic efficacy of dihydrotanshinone-I

@#Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract

Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells

Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic embryos, presumably attributable to their aberrant imprinting. We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring. Moreover, normal expression of imprinted genes is found in the germ cells and the mice. pESCs exhibited imprinting consistent with exclusively maternal lineage, and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background. pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function. The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs, consistent with efficient reprogramming of methylation and genomic imprinting. These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting, offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.

Clinicopathological analysis of desmoplastic small round cell tumor / 中国肿瘤临床

Objective: We aimed to investigate the clinicopathological features of desmoplastic small round cell tumor (DSRCT). Methods: We conducted a retrospective analysis of the clinical characteristics of 7 DSRCT specimens collected from January 2012 to November 2019 in Beijing Shijitan Hospital, Capital Medical University. Pathological slides were further studied. Immunohistochemistry and fluorescence in situ hybridization (FISH) were carried out to study the pathological characteristics. Results: The patients were all male with the median age of 29 years. All tumors were located in the abdominal cavity. The clinical symptoms were abdominal distension, abdominal pain, altered bowel habits, and dysuria. Gross pathology showed multiple grey nodules scattered on the omentum and mesentery. Histopathology showed well-defined nests of small round blue tumor cells separated by abundant desmoplastic stroma. Immunohistochemistry showed distinctive expression of paranuclear dot-like pattern of Desmin and Vimentin; expression of EWSR1-WT1 fusion gene was detected by FISH. At the median follow-up period of 15 months, six patients were alive. Conclusions: DSRCT is highly malignant, with distinctive pathological features of paranuclear dot-like expression of Desmin and Vimentin by immunohistochemistry, and the expression of EWSR1-WT1 fusion gene. Keywords: desmoplastic small round cell tumor, clinical pathology, immunohistochemistry, fluorescence in situ hybridization

The application of S.T.O.N.E. nephrolithometry in pediatric patients with upper urinary tract calculi treated with mini-percutaneous nephrolithotomy.

The purpose of this study is to verify the applicability of S.T.O.N.E. nephrolithometry in pediatric patients. 103 cases of pediatric patients younger than 4 years old with upper urinary tract calculi treated with mini-percutaneous nephrolithotomy from January 2012 to March 2014 were retrospectively reviewed and evaluated using this scoring system. All procedures were performed under general anesthesia, using a 14-French nephroscope through a 16-French working access. All patients were divided into two groups according to the stages of the operations, Group A for one-stage operation and Group B for two-stage operation. 87 cases were male and 16 cases were female with the mean age of 26.5 months. The total operation time of group A was 45.89±5.43 min, and 54.62±5.58 min of group B (p=0.000). The hospitalization for group A and group B was 6.63±1.34 and 7.23±1.24 days, respectively (p=0.134). The total S.T.O.N.E. score was 5.93±0.67 for Group A, and 7.92±1.04 for Group B (p=0.000). On further dividing each group into low/moderate/high complexity according to the total score, more cases of low/moderate complexity in group A and more cases of moderate/high complexity in group B (χ2=38.096, p=0.000) were reported. Our data suggest that S.T.O.N.E. nephrolithometry is applicable in pediatric upper urinary tract calculi assessment and predictive for the complexity of the operation, hospitalization, and even complications after the operation. Yet modification may be necessary to make this scoring system more distinguishable for pediatric cases.

Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats

Background@#Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity. @*Methods@#We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol. @*Results@#We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 μg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW. @*Conclusion@#Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.

Correction to: Characterization of oogonia stem cells in mice by Fragilis

In the original publication the labelling of Figure 1D, Y-axis is incorrectly published. The correct labeling should be read as Fragilis+/SSEA1+ and the correct figure is provided in this correction.