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.

Objective:To investigate the application effect of production-oriented approach (POA) for consulting ability teaching in general practice standardized residency training.Methods:Eighteen third-year general practice residents in the Second Affiliated Hospital of Harbin Medical University received a special training course on the consulting ability based on POA with the situational simulation teaching from September 2021 to March 2022. The consulting ability of residents was evaluated with Objective Structured Clinical Examination (OSCE) and Leichester Assessment Package (LAP) before and after the training, and the results were compared. Meanwhile, a questionnaire survey and semi-structured interviews were conducted to assess residents′ satisfaction with the course.Results:All 18 resident trainees (11 females and 7 males) aged 25 to 34 (27.3±2.4) years successfully completed the training. Both OSCE scores and LAP scores after the training were significantly higher than those before training (66.25±5.84 vs. 44.44±12.80, t=8.46, P<0.001; 65.78±7.05 vs. 38.33±14.2, t=1.47, P<0.001, respectively). The ability of medical history collection, physical examination, patient management, problem solving, doctor-patient relationship, preventive care and medical record writing were all significantly improved after the training compared with those before training ( t=2.464, 4.278, 8.997, 2.385, 10.35, 5.212, 7.578, all P<0.05). The questionnaire survey showed that all the 18 residents were satisfied with the reasonableness of the teaching content, the class time arrangement, the teaching progress arrangement and the instructors. In the dimension of training effectiveness, 18 participants all believed that the course was helpful to improve their humanistic quality and confidence in reception. In terms of self-promotion, all respondents believed that this course was able to promote their reflection ability and stimulate their learning interest. By coding and analyzing the contents of the semi-structured interviews with the residents, nine main themes were constructed, namely course deficiencies, course characteristics, course advantages, course suggestions, trainees′ deficiencies, trainees′ gains, trainees′ goals, previous teaching deficiencies, and instructor′s role. The results showed that all residents had a high degree of satisfaction with the course, and they thought the course was vivid and interesting and it is able to mobilize the enthusiasm of learning, promote learner to reflect. The residents also suggested to increase the teaching hours and to enrich teaching cases. Conclusion:The consulting ability training of general practice based on POA can effectively improve consulting ability, stimulate learning interest and improve independent learning ability of residents, which gains recognition from both faculty and trainees.

Objective: To investigate the exposure to television advertising of sugar sweetened beverages and the use of persuasive marketing techniques among children and adolescents in Beijing, so as to provide evidence for reduing childrens intake of sugar sweetened beverages. Methods: From October 19, 2020 to November 16, 2021, 32 days were randomly selected. The top four popular channels of children and adolescents aged 3-18 years were defined. Each channel was monitored from 6:00:00 to 23:59:59 for each date. A total of 2 304 h was recorded. Advertisements involving sugar sweetened beverages broadcast before, during or after the program were included. The frequency and the use of persuasive marketing techniques were analyzed. Results: A total of 1 237 advertisements for sugar sweetened beverages were included, of which 50.93% were dairy beverages, 28.38% were teabased beverages, and 19.48% were vegetable protein beverages. The average frequency of sugar sweetened beverages advertisements on every channel was (0.62±1.29)piece/h. The frequency of sugar sweetened beverages advertisements on every local channel [(1.04±1.35)piece/h] and childrens channel [(1.11±1.61)piece/h] was separately higher than every national channel [(0.48±1.24)piece/h] and general channel [(0.12±0.48)piece/h] (t=-14.05, 31.64, P<0.01). There were seasonal differences in television advertising of sugar sweetened beverages, and were more frequent during lunch and dinner times. The most frequently used persuasive marketing techniques were "images of children" (74.54%), "nutritional message" (61.76%), "product composition details" (58.61%), "nutrition claim" (57.24%), and "nutrition function claim or other function claim" (53.11%). Conclusions Children and adolescents are often exposed to television advertisement of sugar sweetened beverages on childrens channels and during meal times. There is an urgent need to formulate relevant policies to regulate the marketing of sugar sweetened beverages advertisement and reduce children and adolescents intake.

Objective:To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. Methods:Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c. 16472_16473del, c. 858dup, c. 11899C>T, and c. 12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. Conclusion:For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

OBJECTIVE To explore the mechanism of action of epigallocatechin-3-gallate(EGCG) in inhibiting laryngeal cancer cells. METHODS The expression of epidermal growth factor receptor(EGFR) in laryngeal cancer cell lines AMC-HN-8, TU686 and TU212 was detected by Western blotting, and the inhibitory effects of cetuximab and EGCG on three laryngeal cancer cells were detected by CCK-8 assay. A lentiviral vector containing EGFR promoter and Luc reporter gene was constructed to generate a TU686-EGFR-Luc cell line that could steadily express Luc activity. Luciferase assay was performed to evaluate the effect of EGCG on the transcription activity of EGFR promoter. Cell cycle and apoptosis of EGCG-treated laryngeal carcinoma cells were analyzed by flow cytometry, and changes of the levels of EGFR and downstream ERK1/2, cell cycle-associated proteins P53 and P27, apoptosis-associated proteins BCL2 and PART, and autophagy marker LC3A/B were further examined. RESULTS The laryngeal carcinoma cell lines were insensitive to cetuximab but could be effectively suppressed by EGCG. EGCG effectively inhibited the transcription activity of EGFR promoter. Treatment of TU686 cells at sub-IC50 dose EGCG resulted in significant cell cycle arrest at S phase with partial apoptosis. Significant inhibition of expression and activation of EGFR and downstream signaling pathway were observed. CONCLUSION EGCG can effectively downregulate EGFR and suppress laryngeal carcinoma cells, further investigation on in vivo effect and mechanisms are anticipated.

Objective:To analyze the clinical phenotype and the associated pathogenic genes in a family exhibiting autosomal dominant inherited optic atrophy (ADOA).Methods:A pedigree analysis was conducted on a Han Chinese family with ADOA comprising two generations and four individuals from Henan Province.The family with two ADOA patients was recruited at Henan Eye Hospital between July and October 2023.Detailed medical histories were collected for the proband and family members.Comprehensive ophthalmologic evaluations were performed, including assessments of visual acuity, visual field, fundus photography, electroretinogram (ERG), visual evoked potential (VEP), and optical coherence tomography.Additionally, hearing, electromyography, and magnetic resonance imaging were performed on the proband to assess the presence of systemic symptoms.Peripheral blood samples were collected from four family members, and whole exome sequencing (WES) was performed on the proband, with subsequent validation via Sanger sequencing for the other family members.The pathogenicity and protein struture of the novel variant were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]).Written informed consent was obtained from each subject.Results:The proband was a 15-year-old female with a 4-year history of vision loss in the left eye and optic atrophy, mild thinning of central macular foveal thickness, locally mild thinning of ganglion cell complex layer thickness, low VEP amplitude, and partial visual field defects in both eyes, and no significant hearing impairment or dystonia on systemic examination.The proband's mother had partial optic nerve atrophy and slightly decreased central macular foveal thickness in both eyes, and mild ERG abnormalities, but no significant VEP abnormalities.WES identified a heterozygous nonsense variant c. 676C>T (p.Gln226Ter) in exon 6 of the OPA1 gene of the proband and her mother.This variant has not been previously reported in the literature, nor is it listed in the Human Gene Mutation Database, the Thousand Genomes Project, or the Genome Aggregation Database, which results in a premature termination codon at glutamine position 226.Protein structure analysis showed that p. Gln226Ter of the OPA1 protein induces alterations in the hydrogen bonding of the protein binding to surrounding residues, which in turn leads to protein function alterations.The variant was classified as potentially pathogenic according to the ACMG standards and guidelines. Conclusions:Patients in this ADOA family present with adolescent-onset optic atrophy in both eyes, with a predominance in the left eye.The c. 676C>T variant in OPA1 gene might be the causative variant in this ADOA family.Notably, this is the first report of this specific variant.

The release of the "Guiding Opinions on Establishing a Standardized Training System for Resident Physicians" in 2013 marked the beginning of the establishment of a standardized training system for general practice (GP) resident physicians in China. The standardized GP residency training program (hereafter GP residency training) has now been in place for a decade. Over the past decade, GP residency training has gone through stages of exploratory development and substantive development, and is currently in the early stages of high-quality development. This review discusses the establishment, developmental trajectory, and future directions of GP residency training.

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 the implementation strategies for promoting healthy longevity among the elderly population in China based on the Delphi method.Methods:Through literature review and expert discussion, a framework for implementation strategies to achieve healthy longevity among the elderly was determined, and a preliminary checklist of implementation strategies was developed. The Delphi method was employed from August to December 2022, inviting 25 experts from various disciplines such as clinical medicine, public health, basic research, and the elderly care services industry. Experts were sent consultation questionnaires via email to assess the importance, feasibility, judgment basis and familiarity of each implementation strategy. Active coefficient, authority coefficient, and harmony coefficient were analyzed to ultimately determine the important and feasible implementation strategies for healthy longevity that were suitable for the Chinese elderly population.Results:The expert active coefficients of the two rounds were 96.00% (24/25) and 79.17% (19/24). The authority coefficients were (0.76±0.19) and (0.77±0.17). The average scores of importance were (4.32±0.84) and (4.36±0.82), and the corresponding scores of feasibility were (3.72±1.04) and (3.80±0.92). The harmony coefficients for the importance score were 0.269 ( χ 2=594.084, P<0.001) and 0.159 ( χ 2=193.624, P<0.001). The harmony coefficients for feasibility scores were 0.205 ( χ 2=452.008, P<0.001) and 0.167 ( χ 2=202.878, P<0.001). The final eight implementation strategies were identified after two rounds of consultation. Conclusion:Through two rounds of Delphi consultations, eight important and feasible implementation strategies for promoting healthy longevity that are suitable for the Chinese context have been proposed.