Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

Narrative is the cornerstone of interpersonal relationships and life safety. However， its important value in daily life， school education， health management， personal happiness， career development， and other aspects has been ignored. The narrative ecology of families， schools， hospitals， workplaces， and elderly care institutions is worrying， the narrative connection between parent-child and intergenerational is broken， the narrative nature of adolescents is ignored， the narrative demands of patients are neglected， narrative relationships in the workplace are indifferent， and the narrative capital of the elderly is idle. These issues have resulted in serious social problems， such as depression and suicide among adolescents， conflicts between doctors and patients， workplace and life burnout among middle-aged people， and the inability of the elderly to achieve healthy aging， which have become a “stumbling block” to the realization of holistic health. Advocating the construction of narrative ecology and interpersonal narrative connections is an important measure of achieving holistic health. Taking the “narrative concept” as the overall framework， and based on the research， education， and practice carried out by the Alliance of Narrative Medicine in Higher Education Institutions， this paper proposed that actively build China’s narrative system of life and health， to enable narrative play an active and dynamic role in the construction of narrative ecology in different spaces， such as the families， the schools， the hospitals， the workplaces， and the elderly care institutions， as well as practically improve the quality of life of the people.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

Accurate prediction of drug responses in cancer cell lines (CCLs) and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine. Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response (CDR) prediction, challenges remain regarding the generalization of new drugs that are unseen in the training set. Herein, we propose a multimodal fusion deep learning (DL) model called drug-target and single-cell language based CDR (DTLCDR) to predict preclinical and clinical CDRs. The model integrates chemical descriptors, molecular graph representations, predicted protein target profiles of drugs, and cell line expression profiles with general knowledge from single cells. Among these features, a well-trained drug-target interaction (DTI) prediction model is used to generate target profiles of drugs, and a pretrained single-cell language model is integrated to provide general genomic knowledge. Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods. Further ablation studies verified the effectiveness of each component of our model, highlighting the significant contribution of target information to generalizability. Subsequently, the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments, demonstrating its potential for real-world applications. Moreover, DTLCDR was transferred to the clinical datasets, demonstrating satisfactory performance in the clinical data, regardless of whether the drugs were included in the cell line dataset. Overall, our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Objective To study the death status of pancreatic cancer among residents in Xuhui district, Shanghai, from 1992 to 2021, and analyze its trends of change, so as to provide evidence for the prevention and treatment of pancreatic cancer. Methods Based on the database of Shanghai death registration system from 1992 to 2021, the crude mortality rate, standardized mortality rate, age-specific mortality rate and other indicators of pancreatic cancer among registered residents in Xuhui district were calculated. The Joinpoint software was used to analyze the trends of average annual percent change (AAPC) of pancreatic cancer mortality rate, and the age-period-cohort model was used to analyze the age effect, period effect and birth cohort effect pairs significant changes in pancreatic cancer mortality. Results In 2021, the mortality rate of pancreatic cancer in Xuhui district, Shanghai, ranked fourth among malignant tumors, and the winning rate and world standard rate of the whole population, males and females were 8.34/100 000 (8.81/100 000, 7.98/100 000) and 7.28/100 000 (7.69/100 000, 6.96/100 000), respectively, with males higher than females. AAPC of crude mortality rate and the standardized (6) mortality rate were higher in males than that in females. The age-specific mortality rate increased with the increase of age, and the highest mortality rate was found in 60-84 years old group. The age-period-cohort model showed that from 1992 to 2021, the annual net shift of pancreatic cancer mortality among the whole population, male and female residents in Xuhui district, Shanghai, was 1.22%, 1.58%, 1.15% (P=0.20, 0.19, 0.45) respectively, and the time trend was not significant. From the perspective of age effect, the risk of death from pancreatic cancer in the whole population and with age deviation in males had an obvious trend with increasing age (P<0.05), while the age effect in females had no obvious trend. From the perspective of period effect, no period deviation was significant in the whole population, males and females (P>0.05). In terms of cohort effects, there were significant differences in the whole population and the male cohort deviations(P<0.05). No significant cohort effect was observed in the female population. Conclusions The mortality rate of pancreatic cancer among registered residents in Xuhui district, Shanghai from 1992 to 2021, was on the rise, especially in the 60-84 years old group and male. The prevention and control of pancreatic cancer needs to develop effective epidemic prevention measures for corresponding populations.

Objective To study the changes in peripheral blood T lymphocytes in patients with ankylosing spondylitis and their correlation with the disease's severity and prognosis.Methods We selected 120 patients with ankylosing spondylitis treated between January 2020 and March 2023 as the research group and 120 healthy people who had medical examinations in the same period as the health group.We detected the changes in CD4+,CD8+and CD4+/CD8+values of peripheral blood T lymphocyte subsets with flow cytometry,compared the differences in T lymphocyte subsets between the two groups,and analyzed the correlation with the disease severity of the patients.All the 120 patients with ankylosing spondylitis were followed up for 6 months after treatment to assess their prognosis.General information and T lymphocyte sub-groups CD4+,CD8+level,CD4+/CD8+value changes were compared among patients with different prognosis.We analyzed the value of T lymphocyte sub-groups in predicting the prognosis of patients with ankylosing spondylitis.Results In the research group CD4+and CD4+/CD8+were lower but CD8 1 was higher than those in the healthy group(P＜0.05).CD4+and CD4+/CD8 were lower but CD8+was higher in patients with advanced ankylosing spondylitis than in early and mid-term patients(P＜0.05).The ROC curve analysis showed that the AUC of CD4+,CD8+,and CD4+/CD8+combined diagnosis of ankylosing spondylitis patients was 0.878,with higher diagnostic sensitivity than that of the single diagnosis(P＜0.05).In the poor prognosis group,CD8+was higher than that in the excellent prognosis group,but CD4+and CD4+/CD8 value were lower than the latter(P＜0.05).The results of Pearson test showed that CD4+and CD4+/CD8+were negatively correlated with the prognosis of patients with ankylosing spondylitis(r=-0.568,-0.656,P＜0.001).CD8+was positively correlated with the prognosis of patients with ankylosing spondylitis(r=0.623,P＜0.001).ROC curve analysis showed that the AUC of the combined diagnosis of CD4+,CD8+and CD4+/CD8+for ankylosing spondylitis patients was 0.910,and the diagnostic sensitivity was higher than that of single diagnosis(P＜0.05).Conclusion The abnormal levels of peripheral blood T lymphocyte subsets in patients with ankylosing spondylitis are closely related to the severity and prognosis of the disease,and can be used as a reference indicator for diagnosing the severity and prognosis of ankylosing spondylitis.

With the development of artificial intelligence(AI),AI ethics has become one of the core topics of discussion and research.Starting from the ethical issues and human crises that may be triggered by AI in the process of medical application,this paper discussed the significance of the interpersonal narrative connection between doctors and patients advocated by narrative medicine.It was proposed that to ensure the ethicality,deep humanity,and deep emotional connection of AI applications,AI should create a"life narrative database"based on the"human life database"in the process of basic database modelling.Meanwhile,it also revealed that Chinese narrative medicine helped to improve the professional narrative ability of medical doctors and realise deeply humanized medicine,while actively promoting human-machine value symbiosis and contributing narrative power to the deep humanisation of AI.Combining the concept of narrative medicine in China with the future development and application prospects of medical AI,on the one hand,aims to raise awareness among more people about the importance of interpersonal narrative connection and narrative data for medical quality,on the other hand,calls for active cultivation of clinical narrative thinking by both real doctors and future intelligent doctors to better realize the bioethical and humanistic values emphasized by big health.

Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

BACKGROUND:The landing error scoring system test is a standard for assessing the risk of non-contact injuries and has not yet been developed for Chinese college soccer programs. OBJECTIVE:To establish a test evaluation standard for the landing error scoring system to provide a basis for evaluating the risk of non-contact injuries in college soccer students. METHODS:A prospective cohort study was designed in which 219 athletes from 10 college soccer teams were tested with the standard landing error scoring system,and the subjects were followed up by questionnaires and medical examinations for non-contact injuries of the lower extremities and trunk for 1 year after testing to determine sex differences and assessment criteria for the landing error scoring system test indicators. RESULTS AND CONCLUSION:The total score of the landing error scoring system was(8.22±1.65)points for 219 subjects,(8.29±1.74)for males and(8.07±1.44)for females,with no significant difference between males and females(P>0.05).Within 1 year after the test,the overall injury rate of 219 subjects was 10.05%and the morbidity rate was 15.98%;the injury rate of male subjects with non-contact injury of the lower limbs and trunk was 12.75%and the morbidity rate was 20.13%;the injury rate of female subjects with non-contact injury of the lower limbs and trunk was 4.29%and the morbidity rate was 7.14%.There were no significant differences in the injury rate between men and women(P<0.05).The total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.50±1.14)vs.(8.08±1.64),P<0.01];for male subjects,the total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.63±1.12)vs.(8.09±1.73),P<0.01].The area under the curve for the total score of the landing error scoring system was 0.773(P=0.000),which had a diagnostic value for the risk of non-contact injury of the lower extremities and trunk in male subjects,with a best cut-off point of 8.5,sensitivity of 0.842,specificity of 0.623,positive likelihood ratio of 2.233,negative likelihood ratio of 0.254,relative risk factor of 8.400,and odds ratio of 8.816;the total score of the landing error scoring system was not applicable for assessing the risk of non-contact injury of the lower extremities and trunk in female subjects.To conclude,the landing error scoring system test can be used as a criterion to assess the risk of non-contact injury to the lower extremity and trunk in Chinese college male soccer players,with an optimal cut-off point of 8.5.The risk of non-contact injury to the lower extremity and trunk is 8.40 times higher in male athletes with a landing error scoring system test score of≥8.5 than in male athletes with a score of<8.5.

BACKGROUND:Heart rate variability biofeedback is a respiratory training method that uses slow and deep breathing at the resonant frequency to induce rhythmic,high-amplitude oscillations in the cardiovascular system,thereby stimulating and exercising the autonomic and baroreflex.However,current studies have not systematically reviewed how heart rate variability biofeedback modulates the autonomic function and produces effects.There is a lack of public understanding of the mechanism of heart rate variability biofeedback,and its application progress and scheme are not fully understood. OBJECTIVE:To review the existing experimental studies on the effects of heart rate variability biofeedback on symptoms in different populations at home and abroad and to introduce the mechanisms and advances in the application of heart rate variability biofeedback to modulate the autonomic nervous system. METHODS:"Heart rate variability biofeedback,resonance breathing,heart rate variability,autonomic nerve,breathing training,chronic diseases,mental illness,biofeedback"were used as Chinese or English keywords to search in CNKI,WanFang Database,PubMed,and Web of Science.A total of 72 core related papers were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The body's oscillation system and resonance system are essential for the effectiveness of heart rate variability biofeedback.Oscillations reflect the response to external stimuli and self-regulating reflex systems,while resonances involve synchronous oscillations that result in higher amplitude operations.The balance between sympathetic and parasympathetic nerves is crucial for maintaining a stable internal environment.Autonomic nervous system disorders are associated with reduced heart rate variability and are closely linked to the progression of related diseases.Heart rate variability biofeedback utilizes the resonance characteristics of the cardiovascular system,inducing rhythmic high-amplitude oscillations by employing deep slow breathing at the resonance frequency.This method improves the regulatory function of the sympathetic and parasympathetic system reflexes and enhances the balance regulation between the two systems.Two major mechanisms of cardiovascular system resonance are the baroreflex closed-loop pathway and respiratory sinus arrhythmia.These mechanisms,along with the unique delay of baroreflex,result in a 0° phase angle oscillation between heart rate and respiration and a 180° phase angle oscillation between blood pressure and respiration during breathing at the resonant frequency rhythm.Periodically stimulating the human cardiovascular oscillation system through this method is an easy-to-operate and effective training approach.Currently,heart rate variability biofeedback is mainly applied in the fields of mental illness,chronic disease,and sports.However,the intervention mechanism and efficacy are unclear,the intervention content,frequency and duration are varied,and there are limited review studies on the intervention methods tailored to different types of individuals.As a non-drug and non-invasive intervention,heart rate variability biofeedback can significantly increase heart rate variability,regulate the balance between sympathetic and parasympathetic nerves,and improve the stability and adaptability of the autonomic nervous system.In the future,it is suggested to investigate the mechanisms and potential applications of the pathways of the heart rate variability biofeedback that induce cardiovascular resonance.It is also recommended to incorporate long-term follow-ups to assess the sustained value of heart rate variability biofeedback in various fields.This would provide new directions and strategies for the comprehensive treatment of complex diseases.