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 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 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.

OBJECTIVE: To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis. METHODS: We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed. RESULTS: A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS). CONCLUSIONS Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.
Antibodies ; metabolism ; Humans ; Myositis ; classification ; physiopathology ; Retrospective Studies

OBJECTIVE: To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis. METHODS: We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed. RESULTS: A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS). CONCLUSIONS Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.
Antibodies ; Autoantibodies ; Dermatomyositis ; Humans ; Lung Diseases, Interstitial ; Myositis ; Retrospective Studies

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development.Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations.To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia,we examined patterns of dysmorphology caused by Hh signalling inhibition.Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 or 150 mg·kg-1 body weight at preselected time points between embryonic days (E)8.5 and 12.5.The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg·kg-1.Exposure between E9.5 and E10.5 induced frontal bone dysplasia,micrognathia and limb defects,with administration at E10.5 producing the most pronounced effects.This model showed decreased ossification of the frontal bone with downregulation of Hh signalling.The osteoid thickness of the frontal bone was significantly reduced.The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.

Objective: To analysis teratogenic effect of GDC-0449 to fetus and set up the animal model of GDC-0449 induced oromandibular limb hypogenesis in mouse for further research of its pathogenesis. Methods: Twenty-seven pregnant Institute of Cancer Research (ICR) mice were randomly divided into: control group, embryonic day 8.5 (E8.5) exposed groups, E9.5 exposed groups, E10.5 exposed groups, E11.5 exposed groups, E12.5 exposed groups, E13.5 exposed groups, E14.5 exposed groups and E15.5 exposed groups. Each group had 3 mice. Exposed groups were treated with the Hedgehog pathway antagonist GDC-0449 at a single dose 150 mg/kg by oral gavage from E8.5 to E15.5. At E16.5, embryonic phenotypes were analyzed in detail by stereo microscope and histology. After establish an optimal dysmorphogenic concentration, 6 pregnant ICR mice were randomly divided into control group and the optimal group, embryonic phenotypes were analyzed by whole-mount skeletal staining and micro-computed tomography at E18.5. Results: The mice were exposed to GDC-0449 on E11.5 and E12.5 had a high incidence of cleft palate. GDC-0449 exposed between E9.5 and E10.5 caused craniofacial and limb dysmorphology, including micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. Most interestingly, these are extremely similar to oromandibular limb hypogenesis syndrome. Conclusions The results of this study indicate that GDC-0449 can be used to induce micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. This work established a novel mouse model for oromandibular limb hypogenesis.

Objective Based on the medical records and follow-up records of hospitalized patients who received anti-tuberculosis therapy in the Third People' s Hospital of Zhenjiang in Jiangsu province from 2006 to 2012,we investigated the incidence and outcome of anti-tuberculosis drug induced hepatotoxicity (ATDH) and provided evidence for the prevention of ATDH.Methods According to tuberculosis patients' medical information and liver function test records,ATDH patients were diagnosed according to the criteria of International Consensus Meeting and American Thoracic Society respectively,then the related factors and outcomes were analyzed.Results A total of 1 967 hospitalized tuberculosis patients were reviewed retrospectively,in which 1 403 (71.3％) were men,1 790 (91.0％) were pulmonary tuberculosis patients,1 528 (77.8％) were patients receiving initiative treatment,979 (49.8％) were sputum smear-positive patients,and 1 297 (65.9％) had other complicated diseases.According to the criterion of International Consensus Meeting,the incidence of ATDH was 16.5％,the median time of onset was 25 days.According to the criterion of American Thoracic Society,the incidence of ATDH was 8.3％,the median time of onset was 23 days.The incidence of ATDH was significantly higher in males and HRZE therapy group (P＜0.05).Under the two liver criteria,69.5％ and 70.1％ of the patients changed primary therapy respectively after ATDH occurred.89.8％ and 88.4％ patients' liver function returned to normal range after changing or stopping therapy.Conclusion According to two liver injury criteria,the incidences of ATDH were 16.5％ and 8.3％ in hospitalized tuberculosis patients respectively,and ATDH mainly occurred in the furst month of anti-tuberculosis treatment.The monitoring of liver function should be strengthened in males and HRZE therapy group to reduce the incidence of ATDH.