ObjectiveTo explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

Objective:To explore a definition of healthy longevity in the Chinese population based on the Delphi method.Methods:Through a comprehensive literature review and expert consultation, the dimensions in the definition of healthy longevity were identified, and a preliminary list of questions was created. Experts in clinical medicine, public health, basic research, and the elderly care service industry, who had been working in the field of geriatric health for at least 5 years, were invited to participate in the Delphi survey from August to December 2022. The survey questionnaires were administered via email in two rounds, and experts were asked to select the optimal options from the provided questions. The active coefficients were expressed by the response rate, and a consensus was reached when the largest number of experts agreed for single-choice questions and more than 70% agreed for multiple-choice questions.Results:In the two rounds, the active coefficients were 96.00% (24/25) and 79.17% (19/24), respectively, and a consensus was finally reached on nine items, including age, physical health, common metabolic indicators, mental health, cognitive function, functional ability, social activity, self-rated health, and subjective well-being. Following discussions among the research team and experts, a final definition of healthy longevity was determined. Healthy longevity could refer to a state of good physical, psychological, cognitive function and social adaptation, as well as subjective well-being, in individuals aged 90 and above. Specifically, individuals with healthy longevity should be free from diseases associated with high disability rates and mortality, such as stroke, cancer, and Parkinson′s disease. They should also maintain reasonable levels of common non-communicable disease indicators, such as blood pressure and blood glucose, and exhibit favorable mental health and cognitive function using validated measurement tools. In addition, individuals with healthy longevity should engage in social interactions with friends and relatives, care for family members, and go out to do things. Meanwhile, with the ability to complete the visual and hearing functions of daily life and communication, and the ability to complete basic activities such as walking, eating, bathing, toileting, dressing, continence of urination, and bowel movement independently, they could rate themselves to be in good health and experience a relatively high level of life satisfaction.Conclusion:A definition of healthy longevity in the Chinese population is established through the two-round Delphi consultation.

Objective:To explore a definition of healthy longevity in the Chinese population based on the Delphi method.Methods:Through a comprehensive literature review and expert consultation, the dimensions in the definition of healthy longevity were identified, and a preliminary list of questions was created. Experts in clinical medicine, public health, basic research, and the elderly care service industry, who had been working in the field of geriatric health for at least 5 years, were invited to participate in the Delphi survey from August to December 2022. The survey questionnaires were administered via email in two rounds, and experts were asked to select the optimal options from the provided questions. The active coefficients were expressed by the response rate, and a consensus was reached when the largest number of experts agreed for single-choice questions and more than 70% agreed for multiple-choice questions.Results:In the two rounds, the active coefficients were 96.00% (24/25) and 79.17% (19/24), respectively, and a consensus was finally reached on nine items, including age, physical health, common metabolic indicators, mental health, cognitive function, functional ability, social activity, self-rated health, and subjective well-being. Following discussions among the research team and experts, a final definition of healthy longevity was determined. Healthy longevity could refer to a state of good physical, psychological, cognitive function and social adaptation, as well as subjective well-being, in individuals aged 90 and above. Specifically, individuals with healthy longevity should be free from diseases associated with high disability rates and mortality, such as stroke, cancer, and Parkinson′s disease. They should also maintain reasonable levels of common non-communicable disease indicators, such as blood pressure and blood glucose, and exhibit favorable mental health and cognitive function using validated measurement tools. In addition, individuals with healthy longevity should engage in social interactions with friends and relatives, care for family members, and go out to do things. Meanwhile, with the ability to complete the visual and hearing functions of daily life and communication, and the ability to complete basic activities such as walking, eating, bathing, toileting, dressing, continence of urination, and bowel movement independently, they could rate themselves to be in good health and experience a relatively high level of life satisfaction.Conclusion:A definition of healthy longevity in the Chinese population is established through the two-round Delphi consultation.

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

BACKGROUND: Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer. METHODS: MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I2 statistic, and publication bias was evaluated using a Deeks' funnel plot and linear regression test. RESULTS: A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies. CONCLUSIONS Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.
Humans ; Adult ; Middle Aged ; Aged ; Lung Neoplasms/diagnostic imaging* ; Early Detection of Cancer ; Sensitivity and Specificity ; Mass Screening ; Tomography, X-Ray Computed

This study has combed and analyzed the characteristics of medical doctoral supervisors and the enrollment status from 2015 to 2018 in Tongji University School of Medicine. The results show that the distribution of doctoral supervisors' age, gender and professional title is relatively balanced. The enrollment situation shows the clustering trend. There are obvious differences in enrollment among clinical medical disciplines, and the scales of doctoral supervisors and doctoral students are not matched and unevenly distributed. It is essential to give an overall consideration in discipline resources and optimize enrollment allocation, for improving the construction of doctoral supervisors and the quality of doctoral training.

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Objective:To explore the criteria of general practice doctoral supervisors.Methods:The expert consultation questionnaire was formed by literature analysis. Experts in the field of general medicine from universities and tertiary hospitals in Shanghai were invited to participate in two rounds of Delphi consultation. The consultation content included the basic requirements and the importance evaluation of the selection criteria for general practice doctoral supervisors. Descriptive analysis and Analytic Hierarchy Process (AHP) were used to analyze the results of the study.Results:A total of 29 experts participated in the consultation, all with senior professional titles and doctoral degrees. The positive coefficient and expert authority coefficient of the two rounds of expert consultation were 1.0 and 0.925, respectively. The Kendall coordination coefficient of indicator importance evaluation were 0.436 and 0.397, respectively. The ethics, age, professional title, educational background and academic degree and diploma were considered to be included in the basic qualifications. The optimal standards for supervisor selection included teaching ability, scientific research ability, student training and team promotion ability that subdivided into 13 evaluation indexes.Conclusion:The basic qualifications and optimal standards for general practice doctoral supervisors have been preliminarily developed, which provides reference for selection of qualified general practice doctoral supervisors.

Patients with non-small cell lung cancer (NSCLC) are treated in a variety of ways. In addition to radiotherapy, chemotherapy and targeted therapy, breakthroughs have been made in immune checkpoint inhibitors, in particular, programmed cell death 1 (PD-1) and its ligand (PD-L1) inhibitors have achieved survival benefits for NSCLC patients, and some of them have been approved as first-line drugs by the US Food and Drug Administration. Currently, commonly used PD-L1 inhibitors are atezolizumab, durvalumab and avelumab. Combination therapies include combination with chemotherapy, anti-vascular endothelial growth factor drugs, molecular targeted therapy and immunotherapy.