Embryonic stem cell pluripotent factor NANOG mediates the activity and invasion of breast cancer cells via AMPK/mTOR pathway / 中华内分泌外科杂志

Objective:To investigate the role of embryonic stem cell pluripotent factor NANOG in mediating the activity and invasion of breast cancer cells via AMPK/mTOR pathway.Methods:A total of 58 breast cancer patients were collected from Jul. 2019 to Aug. 2020, and the clinical data of each patient at admission were collected for comparative analysis. qRT-PCR was used to detect the expression level of NANOG in adjacent tissues and cancer tissues, and Western blot was used to verify the regulation of AMPK/mTOR pathway by NANOG. Cells were treated with NANOG specific plasmid or AMPK inhibitor Compound C. Cell viability was detected by MTT and invasion ability was detected by Transwell.Results:The expression of NANOG was increased in breast cancer tissues (adjacent to cancer tissue: 1.00±0.31, cancer tissue: 1.45±0.27, t=8.34, P<0.004) and cell lines (MCF-10A: 1.00±0.12, BT474: 2.64±0.25, t=10.24, P=0.001; MCF-7: 1.56±0.13, t=5.48, P=0.005; ZR-75-30:1.84±0.16, t=7.28, P=0.002), which could be used as a specific biomolecule for predicting breast cancer (all P<0.05). The expression level of NANOG may be related to lymph node metastasis, histological grade and pathological type. Compared with patients with non-lymph node metastasis (1.36±0.23) or non-invasive patients (1.35±0.25), patients with lymph node metastasis (1.54±0.27, t=2.61, P=0.012) or invasive patients (1.53±0.26, t=2.60, P=0.012) had higher expression of NANOG. After NANOG knockdown, AMPK protein and phosphorylation levels were increased, while mTOR and p70S6K protein and phosphorylation levels were decreased (all P<0.05). Knockdown of NANOG in cells inhibited the activity and invasion of breast cancer cells (activity: si-RNA: 100±8.65, si-NANOG: 58.36±4.58, t=7.37, P=0.002; invasion: si-RNA: 121.41±10.34, si-NANOG: 58.34±8.41, t=8.20, P=0.001), and the effect of knockdown of NANOG was relieved after AMPK inhibitor was used in cells (all P<0.05) . Conclusions:Embryonic stem cell pluripotent factor NANOG promotes the activity and invasion of breast cancer cells by inhibiting the activation of AMPK/mTOR pathway. NANOG can be used as an effective biomolecule for predicting breast cancer.

Application of body surface markers localization in totally implantable venous access port implantation via internal jugular vein approach / 国际外科学杂志

Objective:To investigate the feasibility of using body surface marker localization method to determine the correct position of catheter tip (lower 1/3 of the superior vena cava or the junction of superior vena cava and right atrium) in totally implantable venous access port (TIVAP) implantation via internal jugular vein approach.Methods:The clinical data of 220 patients who underwent TIVAP implantation in Beijing Tongren Hospital, Capital Medical University from June 2019 to June 2021 were retrospectively analyzed. Among them, 168 patients used the internal jugular vein approach. According to the method implemented for determining the length of central venous catheter (CVC) during the operation, the patients were divided into two groups: 136 patients using the body surface marker localization method were defined as the study group; and the remaining 32 cases treated by the intraoperative X-ray fluoroscopic localization method were defined as the control group. The difference in the excellent or good rate of CVC tip position immediately after implantation and the time of implantation was compared between the two groups. In addition, the correlation between the length of CVC indwelling, height, age, and the distance between the catheter tip and tracheal carina was analyzed for the patients with right and left internal jugular vein catheterization. Kolmogorov-Smirnov test was used for statistical distribution of measurement data. Normal distribution of measurement data was expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups. Chi-square test was used for comparison between counting data. With TIVAP catheter indenture length as dependent variable and height as independent variable, Pearson correlation analysis was performed, the relationship equation between ideal catheter indenture length and patient height was analyzed by unitary linear regression. Results:When the CVC tip was located at the second intercostal space, the third sternocostal joint and the third intercostal space, the corresponding probability of being in the correct position was 34.8%, 83.3% and 95.0% respectively. The third sternocostal joint or the third intercostal space had a higher probability of correct CVC tip location than the second intercostal space, and the difference were statistically significant ( P<0.001). Furthermore, there was no significant difference in the possibility of the CVC tip located in the correct position between the third sternocostal joint and the third intercostal space ( P=0.149). Compared with the control group (before adjusting catheter position), the proportion of excellent or good CVC position in the study group was significantly improved (94.1% vs 46.9%), and the difference was statistically significant ( χ2=41.99, P<0.001); while the total operation time was significantly shortened [(33.04±6.69) min vs (42.50±5.54) min], and the difference was statistically significant ( P<0.05). There was a linear correlation between the length of CVC insertion and height. Indwelling catheter length via right internal jugular vein approach (cm) =0.159× height (cm)-1.284 ( r=0.597, r2=0.356, P<0.001); length of catheter indwelling through the left approach (cm) =0.097× height (cm) + 12.139 ( r=0.322, r2=0.104, P=0.020). Conclusions:The third sternocostal joint or the third intercostal space would be the corresponding correct surface landmark of the CVC tip when the body surface marker localization method was adopted during the TIVAP implantation via the internal jugular vein approach. Compared with the intraoperative X-ray fluoroscopy localization, the operation time is significantly shortened with the application of the body surface marker localization method. This technique is simple and easy to master and has high reliability in determining the length of catheter and the position of CVC tip.

Gut microbiota and cerebral vessel diseases / 国际脑血管病杂志

Gut microbiota is involved in maintaining intestinal homeostasis. The bidirectional communication between intestinal flora and brain can also be conducted through the neuro-immune-endocrine network, namely, the "microbiota-gut-brain axis". A number of studies have shown that the "microbiota-gut-brain axis" disorder plays an important role in the occurrence, development and prognosis of some cerebrovascular diseases, such as cerebral small vessel disease and stroke. This article introduces the latest research progress of the relationship between gut microbiota and cerebrovascular diseases, so as to provide more ideas and options for the treatment of cerebrovascular diseases.

The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition / 中华内科杂志

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

Epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China / 中华流行病学杂志

Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.

Deepening the Action on Salt Reduction in China-suggestions on strategy and implementation plan / 中华预防医学杂志

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.

18F-FDG PET/CT Prognostic Role in Diffuse Large B-cell Lymphoma Following Chemotherapy / 中山大学学报(医学科学版)

ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

Research of the mechanism of Huganning tablet in the treatment of nonalcoholic fatty liver disease based on network pharmacology and computer-aided drug design / 药学学报

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Influence of baseline cognitive function on risk of prodromal Parkinson's disease in Chinese adults aged 55 and older: A prospective cohort study / 环境与职业医学

Background Changes in cognitive function exist before the onset of clinical Parkinson's disease. However, studies on association between cognitive function and prodromal Parkinson's disease (pPD) are limited. Objective To estimate probability of pPD and assess its association with global and domain cognitive function in Chinese elders. Methods Data were drawn from the Community-based Cohort Study on Nervous System Disease 2018 (baseline) and 2020 (follow-up). We selected 3911 residents aged 55 and above who participated the two waves, without Alzheimer's disease and Parkinson's disease, and with completed information on demographics, disease history, cognitive function test, and risk factors of Parkinson's disease. Cognitive function was assessed using the Chinese version of Montreal Cognitive Assessment Scale. Calculation of probability of pPD and assessment of possible (probability between 30% and <80%) or probable (probability ≥80%) pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multiple linear regression model was employed to analyze the association between baseline cognitive function and follow-up probability of pPD. Results The medians of scores of baseline global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention, and orientation were 23, 12, 9, 6, 5, 14, and 6, respectively. The median of follow-up probability of pPD was 0.87%, and the proportion of participants with possible or probable pPD was 0.4%. The differences in the distribution of follow-up probability of pPD were significant in groups by baseline global cognitive score quartiles (χ2=21.68, P<0.001). A higher baseline global cognitive score was considerably related to a lower follow-up probability of pPD, b(95%CI)=0.994(0.988~0.999), P=0.040. After adjusting for selected confounders, the results of multiple linear regression analyses showed that the probability of pPD in the highest quartile group was decreased by 10.7% (b=0.893, 95%CI: 0.794-0.992, P=0.034) relative to the lowest quartile group, and the trend was significant (trend P=0.031). Higher baseline index scores of execution, attention, and orientation were highly related to a lower follow-up probability of pPD (all P<0.05). Conclusion Declines in global cognitive function and cognitive domains of execution, attention, and orientation may associate with a higher probability of pPD in middle-aged and elderly population, which suggests the significance of cognitive intervention in early stage for pPD prevention.

Effects of dairy products intake on prodromal Parkinson's disease in Chinese adults aged 55 and above: A prospective cohort study / 环境与职业医学

Background It has been reported that a high intake of dairy products might be associated with an increased risk of Parkinson's disease (PD) in foreign studies, but no such study has yet been conducted on prodromal Parkinson's disease (pPD) and the Chinese population. Objective To investigate the prospective relationship between the intake of dairy products and pPD among people aged 55 and above in four provinces of China. Methods The research data were obtained from the baseline 2018 and follow-up 2020 surveys of Community-based Cohort Study on Nervous System Disease. A total of 9984 residents were selected who participated in both waves of surveys and had complete data on demographics, dietary products intake, and risk factors for PD. We evaluated the risk level and the numbers of related risk/prodromal markers of pPD in the participants based on a criteria recommended by the International Parkinson and Movement Disorder Society (MDS). Food Frequency Questionnaire was used to obtain food consumption data in the past 12 months, and the intake of dairy products was calculated and divided into non-consumption and tertiles of consumption (T1, T2, and T3 from low to high). Multiple linear regression was used to analyze the association between baseline dairy intake and risk level of follow-up pPD. Poisson regression and multinomial logit regression models were used to analyze the relationship of baseline dairy products and the number of risk/prodromal markers of follow-up pPD in the population, and multiple logistic regression was used to analyze each risk/prodromal marker of follow-up pPD according to baseline levels of dairy products intake. Results The percentage of residents without dairy products consumption was 58.02% in 2018, and the dairy products intakes were relatively high among residents being female, aged 55 to 74 years, with an education level of middle school and above, with a per capita monthly household income ≥ 1000 yuan, living in urban areas, and without active employment (P<0.05). The median risk level of pPD was 0.74% in 2020, and the proportion of residents with 3 to 5 markers was 66.74%. The multiple linear regression analysis results suggested no association between baseline dairy intake and follow-up risk level of pPD. The Poisson regression model showed that the high dairy products intake group at baseline (T3, median=250.00 g·d−1) was found to be 1.159 (95%CI: 1.065~1.261, Ptrend<0.001) times more likely to have the risk/prodromal markers of pPD at follow-up than non-consumers. When the number of markers was grouped, no statistically significant association was found by multiple logistic regression analysis. Conclusion Although high dairy products intake levels might be associated with pPD risk/prodromal markers among people aged 55 and above in four provinces of China, no direct association is found between dairy products intake and pPD risk levels in this study.

Effects of red meat and processed meat intake on prodromal Parkinson's disease in Chinese adults aged 55 and above: A prospective cohort study / 环境与职业医学

Background Gastrointestinal microbiota plays an important role in the development of Parkinson's disease (PD), and dietary factors have a great impact on intestinal micro ecology. At present, few studies focus on red meat and PD, especially prodromal PD (pPD). Objective To understand the relationships of the intake of red meat and processed meat products with pPD and the number of risk/prodromal markers, and to explore the association of dietary factors with pPD. Methods Based on the data of Community-based Cohort Study on Nervous System Disease in 2018 and 2020, adults aged 55 years and older with complete demographic information, dietary survey information, and information on risk factors related to PD were selected from four provinces of China. After excluding those reporting abnormal total energy intake or those reporting alcohol drinking or abused drugs for a long period of time, and confirmed mental diseases with prescribed drugs, a total of 10003 subjects were included. Food frequency questionnaire was used to calculate the intake of red meat and processed meat products. The pPD-related risk/prodromal markers were selected following the International Parkinson and Movement Disorder Society criteria for pPD, and the risk level and the number of markers of pPD were then calculated. The relationship between the intake of red meat and processed meat and the risk level of pPD was analyzed by multiple linear regression. The relationship between the intake of red meat and processed meat and the pPD marker number groups was analyzed by multinomial logit regression model. Results In 2018, the intake of red meat and processed meat was 28.57 g·d−1 in the target population. In 2020, the median of the number of risk/prodromal markers was 3, and the median M (P25, P75) of the posterior probability of pPD was 0.74% (0.42%, 1.49%). The multiple linear regression analysis showed that the higher the intake of red meat and processed meat, the higher the risk level of pPD in follow-up (b=0.021, P<0.05). The multiple logit regression model showed that compared with the lowest quartile (Q1), the highest quartile (Q4) group of red meat and processed meat intake were more likely reporting 3−5 risk/prodromal markers than ≤ 2 risk/prodromal markers (OR=1.185, 95%CI: 1.015−1.382). Conclusion The intake level of red meat and processed meat is related to the risk level of pPD, and a higher intake of red meat and processed meat may be a potential risk factor of pPD.

Prodromal Parkinson's disease and its socio-demographic characteristics among people aged 55 and above in four provinces of China / 环境与职业医学

Background China is witnessing an accelerated aging process and an increasingly serious situation of Parkinson's disease. Research on the pre-disease stage and its related influencing factors has gained more and more attention. Objective To analyze the current situation of prodromal Parkinson's disease (pPD) of people aged 55 years and above in four provinces of China, and to explore its influencing demographic and socio-economic characteristics. Methods Using the data of Community-based Cohort Study on Nervous System Disease in 2020, a total of 10724 participants with complete data on demographic and socio-economic factors and risk factors on Parkinson's disease were selected. Based on the criteria recommended by the International Parkinson and Movement Disorder Society (MDS), we evaluated risk level (i.e., post-test probability) of pPd, prevalence of possible or probable pPD, and number of pPD-related risk/prodromal markers in the participants. Multiple linear regression and multiple logistic regression models were used to analyze the influencing socio-demographic factors of risk level of pPd and prevalence of possible or probable pPD, and Poisson regression and multinomial logit regression models were used to analyze the influencing socio-demographic factors of the number of pPD-related risk/prodromal markers in the total sample, men, and women, respectively. Results The median (P25, P75) of post-test probability of pPD in 2020 was 0.78% (0.42%, 1.66%), the prevalence rate of possible or probable pPD was 0.34%, and 69.03% of the participants reported 3-5 pPD-related risk/prodromal markers. The post-test probabilities of men, those with older age, lower education level, per capita monthly household income < 1000 yuan, urban residency, or without active employment were higher (P<0.05). Men and being aged ≥ 75 years had a higher prevalence of possible or probable pPD (P<0.05). The OR of possible or probable pPD was 8.404 (95%CI: 2.839−24.879) in subjects aged ≥ 75 years versus those aged 55−64 years. Males, those without active employment, being less educated, with older age, and urban residents were more likely to report pPD-related risk/prodromal markers than those of the opposite groups (P<0.05). Conclusion Men, subjects aged ≥75 years, those with lower education level, urban residents, and those without active employment have higher risk levels of pPD and are more likely to report pPD-related risk/prodromal markers among people aged 55 years and above in the four provinces of China, poor economic situation is also associated with higher risk levels of pPD.

Concern for nutrition and prodromal Parkinson's disease and actively respond to aging challenge / 环境与职业医学

Parkinson's disease (PD) is a chronic neurodegenerative disease commonly seen in middle-aged and elderly people, and aging is the largest risk factor for PD. With acceleration of the aging process in China, the wellbeing and life quality of the elderly are expected to be disturbed by increasing prevalence of PD. The Community-based Cohort Study on Nervous System Diseases (CCSNSD) has established community population-based cohorts of epilepsy, Alzheimer's disease, and PD, respectively; baseline survey and one round of follow-up have finished so far. The CCSNSD collected data on demographics, community environment, diet, lifestyle, cognition, history of chronic diseases, and PD-related risk factors and facilitated exploration of the relationship between dietary nutrition and PD-related outcomes. This special column described status on prodromal Parkinson's disease (pPD) risk and its demographic & economic differences among people aged 55 and above in four provinces of China, and investigated the associations of red meat and processed meat products intake , dairy products intake, and cognitive function with pPD risk, respectively. Furthermore, one paper reviewed previous studies on dietary nutrition, lifestyle, and PD risks. However, the follow-up time of CCSNSD was relatively short as of the publishing of this column, longer follow-ups are required to allow studying potential factors and risk of incident PD combined with clinical examination and diagnosis of PD.

Tracking analysis of viral nucleic acid Ct value in patients with re-positive SARS-CoV-2 infection / 中华危重病急救医学

OBJECTIVE@#To track analysis of viral nucleic acid test results in patients with re-positive SARS-CoV-2 infection, and provide clinical reference for nucleic acid test of re-positive cases.@*METHODS@#A retrospective study was conducted. The multiple nucleic acid results of 96 cases with SARS-CoV-2 infection tested by medical laboratory of Shenzhen Luohu Hospital Group from January to September in 2022 were analyzed. The test dates and cycle threshold (Ct) values of detectable positive virus nucleic acid in the 96 cases were summarized and analyzed.@*RESULTS@#A total of 96 patients with SARS-CoV-2 infection were retested re-sampled for nucleic acid testing at least 12 days after the initial positive screening. Among them, 54 cases (56.25%) had Ct value of < 35 for nucleocapsid protein gene (N) and/or open reading frame 1ab gene (ORF 1ab), 42 cases (43.75%) had Ct value ≥ 35. In the re-sampling of infected patients, N gene titers were 25.08 to 39.98 Ct cycles, and ORF 1ab gene titers were 23.16 to 39.56 Ct cycles. Compared with the positive results of the initial screening, the Ct values of N gene and/or ORF 1ab gene positive were increased in 90 cases (93.75%). Among them, the patients with the longest duration of nucleic acid positive could still be positive for double targets (the Ct value of N gene was 38.60, and the Ct value of ORF 1ab gene was 38.11) at an interval of 178 days after the initial positive screening.@*CONCLUSIONS@#Patients infected with SARS-CoV-2 can be sustained or repeatedly tested positive for nucleic acid for a long period of time, and most of them had Ct values < 35. But whether it is infectious needs to be comprehensively evaluated by combining epidemiology, variant type, samples with the alive virus, and clinical symptoms and signs.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants.@*METHODS@#China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP).@*RESULTS@#A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05).@*CONCLUSIONS@#Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

Research progress of anti-fibrotic drugs that inhibit epithelial-mesenchymal transition in pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is the end-stage pathological change of lung diseases, which seriously affects the respiratory function of human body. A large number of studies at home and abroad have confirmed that epithelial-mesenchymal transition (EMT) is an important intermediate stage in the development of pulmonary fibrosis. Inhibition of multiple pathways upstream and downstream of EMT, such as the classical Smads pathway and non-Smads pathway of TGF-1 can effectively inhibit the process of EMT and alleviate pulmonary fibrosis. This article will review the main conclusions of the mechanism of action of EMT as a target to improve the pathology of pulmonary fibrosis so far, and provide a theoretical basis and research direction for further research and development of anti-pulmonary fibrosis drugs.

Application of volume replacement techniques in breast conserving surgery for breast cancer treatment / 中华外科杂志

Objective: To examine the application of volume replacement techniques in breast conserving surgery for breast cancer. Methods: The clinic data of 76 breast cancer patients underwent a breast conserving surgery with volume replacement techniques at the Breast Center, Beijing Tongren Hospital, from June 2019 to June 2021 were analyzed retrospectively. All patients were female, aged (42.6±6.4) years (range: 32 to 56 years). Tumor staging inlcuded stage ⅡA in 36 cases, stage ⅡB in 24 cases, stage ⅢA in 12 cases, stage ⅢB in 4 cases. Three types of techniques included the lateral thoracic adipofascial flaps in 47 cases, the upper abdominal wall adipofascial flaps in 22 cases and the latissimus dorsi myocutaneous flap in 7 cases. The specimen volume of tumor expansion resection in breast conserving surgery was measured, while the operative time used for volume replacement techniques, postoperative drainage retention time, postoperative complications and patients' satisfaction with the breast shape were recorded. Results: The specimen volume of tumor was (100.9±24.2) ml (range: 55 to 157 ml) in lateral thoracic adipofascial flap group, (88.4±14.5) ml (67 to 118 ml) in upper abdominal wall adipofascial flap group, (179.7±22.9) ml (range: 155 to 220 ml) in latissimus dorsi myocutaneous flap group. The operative time used to restore the breast shape of the three groups were (52.9±9.0) minutes (range: 45 to 70 minutes), (63.2±8.8) minutes (range: 50 to 70 minutes) and (99.3±3.4) minutes (range: 95 to 105 minutes), respectively. The postoperative drainage retention times of the three groups were (8.6±1.2) days (range: 7 to 10 days), (9.4±0.9) days (range: 8 to 10 days) and (11.4±1.3) days (range: 10 to 13 days), respectively. All the 76 patients were evaluated for their satisfaction with the cosmetic outcomes, 64 patients (84.2%) were strongly satisfied and 12 patients (15.8%) were generally satisfied. The postoperative complications included fat liquefaction in 6 cases (2 cases in the lateral thoracic adipofascial flap group and 4 cases in the upper abdominal adipofascial flap group) and seroma in 4 cases (each 2 cases in the lateral thoracic adipofascial flap group and the latissimus dorsi myocutaneous flap group). Conclusions: For patients with large tissue loss during breast conserving surgery, the corresponding volume replacement techniques, including lateral thoracic adipofascial flaps, upper abdominal wall adpofascial flaps and latissimus dorsi myocutaneous flaps, should be reasonably selected for repair according to the tumor site and the size of the intraoperative breast loss, which can ensure the original volume and shape of the breast, with controllable postoperative complications.

Impacts of cadmium on mouse neural stem cells based on dose-response metabomics / 环境与职业医学

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.