Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

Objective To evaluate the cost-effectiveness of toripalimab plus axitinib compared to sunitinib in the first-line treatment of advanced renal cell carcinoma patients.Methods Based on the RENOTORCH trial,constructed a partitioned survival model to evaluate the long-term costs and health outcomes of toripalimab plus axitiniband sunitinib in the first-line treatment of advanced renal cell carcinoma(RCC)patients from the Chinese healthcare system perspective.The cycle length of the model was 3weeks,simulating the total cost,quality adjusted life years(QALYs),and incremental cost-effectiveness ratio(ICUR)for patients over 25 years.The costs were derived from the average bidding price of Yaozhi database in 2023 and published literature.The health state utility values were derived from clinical trials.The discount rate was 5%,and the willingness to pay(WTP)threshold was 3 times the per capita gross domestic product(GDP)in 2022.One-way and probability sensitivity analyses were used to test the robustness of the model.Results Based on the progression free survival(PFS)evaluated by the Independent Review Committee(IRC)and Investigator(IA),the ICUR values were 239 436.39 yuan/QALY and 175 440.39 yuan/QALY,respectively,both lower than the WTP threshold.One-way sensitivity analysis showed that the health state utility values of PFS status and the price of axitinib had a significant impact on the model.Probability sensitivity analysis showed that the probability of toripalimab plus axitinib being cost-effective was 63.64%and 98.03%according to the IRC and IA assessments,respectively.Conclusion Toripalimab plus axitinib was cost-effective in the first-line treatment of advanced RCC patients.

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

Objective To evaluate the cost-effectiveness of toripalimab plus axitinib compared to sunitinib in the first-line treatment of advanced renal cell carcinoma patients.Methods Based on the RENOTORCH trial,constructed a partitioned survival model to evaluate the long-term costs and health outcomes of toripalimab plus axitiniband sunitinib in the first-line treatment of advanced renal cell carcinoma(RCC)patients from the Chinese healthcare system perspective.The cycle length of the model was 3weeks,simulating the total cost,quality adjusted life years(QALYs),and incremental cost-effectiveness ratio(ICUR)for patients over 25 years.The costs were derived from the average bidding price of Yaozhi database in 2023 and published literature.The health state utility values were derived from clinical trials.The discount rate was 5%,and the willingness to pay(WTP)threshold was 3 times the per capita gross domestic product(GDP)in 2022.One-way and probability sensitivity analyses were used to test the robustness of the model.Results Based on the progression free survival(PFS)evaluated by the Independent Review Committee(IRC)and Investigator(IA),the ICUR values were 239 436.39 yuan/QALY and 175 440.39 yuan/QALY,respectively,both lower than the WTP threshold.One-way sensitivity analysis showed that the health state utility values of PFS status and the price of axitinib had a significant impact on the model.Probability sensitivity analysis showed that the probability of toripalimab plus axitinib being cost-effective was 63.64%and 98.03%according to the IRC and IA assessments,respectively.Conclusion Toripalimab plus axitinib was cost-effective in the first-line treatment of advanced RCC patients.

OBJECTIVE To review the current research progress on pharmacoeconomics evaluation related to spinal muscular atrophy （SMA）， in order to provide valuable insights for clinical treatment， screening and medical insurance payment decision- making. METHODS A computerized search was conducted across multiple databases including PubMed， Web of Science， Embase， Scopus， Cochrane Library， EBSCOhost， CNKI， VIP， CBM and Wanfang database as well as other important health technology assessment （HTA） websites， such as National Institute for Health and Care Research，International Society of Technology Assessment in Health Care， Agency for Healthcare Research and Quality， etc. The pharmacoeconomics evaluation studies related to SMA were collected from the inception to December 31st， 2023. The literature/reports were rigorously screened based on predefined inclusion and exclusion criteria by two researchers， and the essential information from the included literature/ reports was extracted using Excel 2019. The quality of the included literature/reports was evaluated by Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS Finally， 9 articles and 15 HTA reports were included， with overall good quality of literature， but poor quality of HTA reports. There were a total of 24 studies on the pharmacoeconomics evaluation of SMA， including treatment options such as nusinersen sodium， sovaprevir， risperidone， and best supportive therapy.The review results showed that nusinersen sodium was not cost-effective in the treatment of SMA； there was no consensus on the economic viability of treatment options such as risperidone and sovaprevir； newborn/prenatal screening combined withmedication therapy was cost-effective. CONCLUSIONS newborn/prenatal screening combined with SMA medication therapy demonstrates economic advantages. It is suggested to further investigate the cost-effectiveness of new SMA drugs and SMA screening in China， taking localization parameters and medical insurance prices into account， and gradually incorporate SMA screening into the scope of neonatal genetic disease detection， in order to alleviate the financial burden of patients’ families and healthcare systems.

Objective:To analyze the influencing factors on the occurrence of acute kidney injury (AKI) in hospitalized patients treated with esomeprazole and to construct a risk prediction model to predict the occurrence of esomeprazole-associated AKI.Methods:The study was designed as a retrospective study. The subjects were selected from patients who were hospitalized in the First Affiliated Hospital of Shandong First Medical University from January 2018 to December 2020 and received treatment with esomeprazole. The clinical data of patients, including basic information, operations, intervention measures, medication, and laboratory test results, was collected through the hospital′s electronic medical record system. Patients were divided into AKI and non-AKI groups according to the occurrence of esomeprazole-associated AKI, and the clinical characteristics between the 2 groups were compared. The least absolute shrinkage and selection operator (LASSO regression) was used to analyze the influencing factors of esomeprazole-associated AKI. Patients were randomly divided into the training set and the test set at a 8∶2 ratio. Based on data in the training set, 5 machine learning algorithms were used to build esomeprazole-associated AKI prediction models, including logistic regression, random forest, gradient boosting machine (GBM), extreme gradient boosting, and light gradient boosting machine. Based on data in the test set, the performance of 5 models was validated through the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.Results:A total of 5 436 patients were enrolled in the study, including 3 231 males and 2 205 females, with an age of 61(51, 70) years. Esomeprazole-associated AKI occurred in 393 patients, with an incidence of 7.23%. The results of LASSO regression analysis identified 24 variables closely related to esomeprazole-associated, such as hepatic insufficiency, chronic renal insufficiency, hypoproteinemia. Based on data in the training set (4 349 patients), the esomeprazole-associated AKI risk prediction models were constructed and their predictive performance was good (all AUC>0.900). The predictive performance validation was conducted using the data in the test set (1 087 patients), and the results showed that the GBM model has the highest AUC (0.922) and relatively stable performance, with small differences in various indicators between the training and the test sets.Conclusions:The use of esomeprazole is significantly associated with AKI, and the risk is influenced by factors such as baseline renal function, comorbidities, and combined medications. The risk prediction model based on GBM algorithm is helpful for early assessment of the risk of esomeprazole-related AKI in clinical practice.

Objective:To analyze the influencing factors on the occurrence of acute kidney injury (AKI) in hospitalized patients treated with esomeprazole and to construct a risk prediction model to predict the occurrence of esomeprazole-associated AKI.Methods:The study was designed as a retrospective study. The subjects were selected from patients who were hospitalized in the First Affiliated Hospital of Shandong First Medical University from January 2018 to December 2020 and received treatment with esomeprazole. The clinical data of patients, including basic information, operations, intervention measures, medication, and laboratory test results, was collected through the hospital′s electronic medical record system. Patients were divided into AKI and non-AKI groups according to the occurrence of esomeprazole-associated AKI, and the clinical characteristics between the 2 groups were compared. The least absolute shrinkage and selection operator (LASSO regression) was used to analyze the influencing factors of esomeprazole-associated AKI. Patients were randomly divided into the training set and the test set at a 8∶2 ratio. Based on data in the training set, 5 machine learning algorithms were used to build esomeprazole-associated AKI prediction models, including logistic regression, random forest, gradient boosting machine (GBM), extreme gradient boosting, and light gradient boosting machine. Based on data in the test set, the performance of 5 models was validated through the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.Results:A total of 5 436 patients were enrolled in the study, including 3 231 males and 2 205 females, with an age of 61(51, 70) years. Esomeprazole-associated AKI occurred in 393 patients, with an incidence of 7.23%. The results of LASSO regression analysis identified 24 variables closely related to esomeprazole-associated, such as hepatic insufficiency, chronic renal insufficiency, hypoproteinemia. Based on data in the training set (4 349 patients), the esomeprazole-associated AKI risk prediction models were constructed and their predictive performance was good (all AUC>0.900). The predictive performance validation was conducted using the data in the test set (1 087 patients), and the results showed that the GBM model has the highest AUC (0.922) and relatively stable performance, with small differences in various indicators between the training and the test sets.Conclusions:The use of esomeprazole is significantly associated with AKI, and the risk is influenced by factors such as baseline renal function, comorbidities, and combined medications. The risk prediction model based on GBM algorithm is helpful for early assessment of the risk of esomeprazole-related AKI in clinical practice.

OBJECTIVE To reevaluate systematic reviews/meta-analysis of efficacy and safety of tolvaptan for hyponatremia. METHODS Retrieved from CNKI， Wanfang Data， VIP， CBM， PubMed， Embase and the Cochrane Library database， systematic reviews/meta-analysis about tolvaptan for the treatment of hyponatremia were included from the inception to June 15， 2022. After screening literature and extracting data， the PRISMA statement， AMSTAR 2 scale and GRADE method were used to evaluate the reporting quality， methodological quality and evidence quality of the included literature， respectively. RESULTS A total of 6 articles were included， of which 1 was systematic review and 5 were meta-analysis， including 56 outcome indicators. All of the 6 studies had PRISMA scores ranging from 15.0 to 20.5， and the quality of them was moderate. Results of the AMSTAR 2 scale showed that the methodological quality of 5 literatures were very low， and the quality of 1 literature was low. The quality of GRADE evidence showed that there were 6 moderate-quality indicators， 13 low-quality indicators， 35 very low-quality indicators， and 2 indicators that could not be assessed due to missing data. The main factors causing degradation were limitations， inconsistency， imprecision and publication bias. In terms of efficacy， tolvaptan could effectively increase the level of serum sodium， increase urine volume， reduce body weight， reduce abdominal circumference， relieve edema， and reduce alaninetransaminase level. In terms of safety， the incidence of total adverse drug reaction induced by tolvaptan was controversial； it may increase the risk of dry mouth， thirst， frequent urination or excessive correction of serum sodium. CONCLUSIONS Tolvaptan has great efficacy in the treatment of hyponatremia， but serum sodium overcorrection should be avoided in terms of safety. Relevant systematic reviews/meta-analysis have shortcomings of low reporting quality， methodological quality and evidence quality， which may reduce the reliability of the results， so the results should be treated with caution.

Objective:To report the experience of the application of internal carotid artery stent in skull base surgery, and to clarify the important role of internal carotid artery stent in skull base surgery.Methods:A retrospective study of 22 cases with skull base neoplasms implanted with internal carotid artery stents in the Department of ENT Head and Neck Surgery at the Sixth People′s Hospital affiliated with Shanghai Jiao Tong University between July 2019 and January 2021 was conducted. Among them, 17 were male and 5 were female, aged between 33 and 75 years. There were 5 cases on the left, 16 cases on the right, and 1 case on both sides. Of these, there were 4 cases of jugular paraganglioma, 1 case of chondrosarcoma in the jugular foramen, 1 case of carotid body paraganglioma, and 16 cases of nasopharyngeal carcinoma after radiotherapy.Results:The degree of internal carotid artery erosion was assessed by computed tomography angiography (CTA), magnetic resonance imaging and digital subtraction angiography (DSA) images in 22 patients before surgery. It was found that the internal carotid artery was involved to varying degrees in all patients, so internal carotid artery stents were implanted before surgery. Tumor tissue was found to surround the internal carotid artery to varying degrees. Total or subtotal tumor resection was performed in all patients, and no intraoperative and postoperative complications occurred. The postoperative follow-up was 5 months to 2 years, and all patients had no complications such as spontaneous bleeding and pseudo aneurysm. There were no signs of stenosis or occlusion of the internal carotid artery stent segment in all cases.Conclusions:For patients with skull base tumors, preoperative imaging indicates the limited involvement of the internal carotid artery, and internal carotid artery stent implantation before surgery is a safe and effective treatment.