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 explore the neuroprotective effects of osteocalcin(OCN)on an Alzheimer's disease(AD)cell model and its potential mechanisms,providing a scientific basis for new therapeutic targets for AD.Methods Human neuroblastoma cell line SH-SY5Y was treated with 40 nmol/L okadaic acid(OA)for 24 h to establish an AD cell model.The cells were divided into a normal group(untreated SH-SY5Y cells),a model group(40 nmol/L OA intervention),and an OCN intervention group(intervention with various concentrations of OCN in the AD cell model),and AKT knockout/overexpression groups(AKT-KO group and AKT-OE group),and AKT-KO OCN group and AKT-OE OCN group.CCK-8 assay was used to detect the changes in cell viability.Wright's staining was employed to observe the morphological changes of AD cells.Western blotting was utilized to detect the protein levels of Tau,p-Tau,Bax,Bcl-2,Caspase-3 and their lytic types,as well as the expression of Tau,p-Tau,mTOR,AKT and p-AKT in each group after AKT knockout/overexpression.TUNEL staining and flow cytometry were applied to detect the changes in early and late apoptotic cells and the apoptotic rate in the OCN-treated AD cell model.Results ①Compared to the normal group,the model group exhibited a significant decrease in cell viability,noticeable morphological and structural damage,upregulation of p-Tau and Caspase-3,increased early and late apoptosis,and a significantly higher apoptotic rate(P<0.05).②After treatment of different concentrations of OCN for 24 h,cell viability was increased to varying degrees compared to the AD model group,with the 100 pg/mL OCN group showing a significant increase in cell viability(P<0.01)and marked improvement in cell number and morphology(P<0.01).③ Compared to the AD cell model group,the p-Tau/Tau ratio was decreased in all OCN treatment groups,particularly in the 100 pg/mL OCN intervention group,where the p-Tau/Tau ratio was significantly lower than that of the model group(P<0.01).④ Compared to the model group,a significant concentration-dependent decrease in the Cleaved Caspase-3/Caspase-3 ratio was observed when OCN concentrations ranged from 1 to 100 pg/mL,with a significant reduction in the Bax/Bcl-2 ratio in the 100 pg/mL group(P<0.000 1).⑤ The results of TUNEL staining and flow cytometry showed that,compared to the model group,all concentrations of OCN effectively inhibited the apoptosis in the AD model cells,with a significant reduction in early and late apoptotic cells and apoptotic rate in the 100 pg/mL OCN group.⑥ Compared with the control group and the model group,the P-AKT was significantly increased in the AKT-OE group after AKT overexpression(P<0.05).The expression level of AKT protein was decreased in the AKT-KO group after AKT knockout(P<0.05).When the AKT pathway was inhibited,the expression level of p-Tau was higher in the AKT-KO group than the control group(P<0.05),and when the AKT was overexpressed,the expression level was significantly inhibited(P<0.05).Conclusion OCN may inhibit cell apoptosis and reduce p-tau protein level by regulating the ratio of Caspase-3/Caspase-3 and Bax/Bcl-2,and thereby improve the morphology of AD model cells and effectively protect nerve cells,which may be related to the regulation of the AKT/mTOR pathway.

Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n＝215) and MT (n＝103) significantly increased, and both DNT and DPT were significantly shortened (P＜0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P＝0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Abstract To investigate the curative effects of modified submucosal tunnel endoscopic resection(STER) and endoscopic submucosal resection(ESE) in the treatment of paracardial submucosal tumors. Eighty-four patients with paracardial submucosal tumors diagnosed through digestive endoscopy and endoscopic ultrasonography signed informed consent forms, and they were randomly divided into observation group(n=42) and control group(n=42) with the help of the table of random numbers. Patients in the control group received ESE treatment. Patients in the observation group received modified STER surgery.The operation time, average hospitalization time and treatment cost of patients in STER group were(61.32±32.01) min,(8.11±2.42) d and(21.7±3.4) thousand Chinese Yuan respectively, which were better than those in ESE group(87.63±34.09) min,(10.05±2.84) d and(25.9±3.9) thousand Chinese Yuan. The difference was statistically significant(P<0.05). The average number of titanium clips used in the observation group was(5.00±1.37), and in the control group the average number was(4.68±1.25). The difference was not statistically significant. In the STER group, there were 2 cases of intraoperative perforation and 1 case of delayed bleeding. In the ESE group, there were 4 cases of intraoperative perforation and 3 cases of intraoperative uncontrollable bleeding. The incidence of postoperative complications in the STER group was lower than that in the ESE group. The postoperative pathological examination revealed that in both groups the tumors were mostly stromal tumor and leiomyoma. A few of the patients were suffering from lipomas and schwannomas. There was no significant difference in terms of the pathological composition of the patients between the two groups.

Wake up ischemic stroke (WUIS),also known as awakening stroke,refers to patients with no new stroke symptoms during sleep,but after waking up,the patients or witness who found the acute cerebral infarction with stroke performance.The key to the treatment of acute ischernic stroke is to effectively restore reperfusion within the time window.The original intravenous recombinant tissue-type plasminogen activator (rt-PA) thrombolytic therapy,is widely recognized as an effective treatment method of choice for 4.5h onset of acute ischemic stroke reperfusion.Because the exact onset time of WUIS is unclear and limited by current scientific and technical levels,intravenous thrombolysis may lead to an increased risk of intracranial hemorrhage.Therefore,the American Heart Association and the American Stroke Association (AHA/ASA) were included in the "Intravenous Thrombolysis".Intravenous thrombolysis is not recommended in the Standard Scientific Statement.Patients who may be suitable for thrombolytic therapy are not able to obtain thrombolytic therapy,resulting in poor clinical prognosis.In recent years,with the further development of relevant clinical research and the rapid development of imaging technology,the latest research found that multi-mode imaging examination is safe and effective for intravenous thrombolytic therapy in patients with poststroke stroke.Multi-mode imaging studies help screening patients with acute reperfusion therapy,so that part of WUIS patients will benefit from the acute reperfusion therapy.This article reviews and summarizes the literature findings of WUIS in recent years.The pathophysiological changes,clinical features and imaging changes of patients with WUIS and non-WUIS are almost unanimously.Early CT and MRI examinations can help to extend acute stroke treatment to patients with WUIS.At present,for this type of patients,there are great research progress in the formulation and implementation of clinical treatment strategies.This article will briefly summarize the research progress and treatment status of WUIS.

Objective:To assess antimicrobial activity of Fe 3O 4 nanozymes against Candida albicans. Methods:Fe 3O 4 nanozymes were prepared by using a modified hydrothermal synthesis method. Candida albicans suspensions were divided into 4 groups: nanozyme group treated with 0.5 g/L Fe 3O 4 nanozymes, H 2O 2 group treated with 0.1% H 2O 2, combination group treated with 0.5 g/L Fe 3O 4 nanozymes and 0.1% H 2O 2, and control group receiving no treatment. Candida albicans in the above 4 groups was all cultured with Sabouraud liquid medium, the absorbance value at 600 nm was detected every 2 hours, and the growth of Candida albicans was observed. After 2-hour treatment, the morphology of Candida albicans in the 4 groups was observed by scanning electron microscopy; after plate coating, Candida albicans was cultured at 36 ℃ for 48 hours, colonies were observed and counted, and the inhibition rate of colony formation was calculated. One-way analysis of variance was used for comparing means among several groups, and least significant difference (LSD) - t test for multiple comparisons. Results:A relatively stable survival curve of Candida albicans was observed in the control group, while the growth of Candida albicans was inhibited in the nanozyme group, H 2O 2 group and combination group. The colony count significantly differed among the control group, H 2O 2 group, nanozyme group and combination group (124 830 ± 45 170, 86 330 ± 13 960, 91 670 ± 31 370 and 30 330 ± 3010 respectively; F = 9.41, P < 0.05) , and was significantly lower in the combination group than in the control group ( t = 4.63, P < 0.05) . There was a significant difference in the colony-formation inhibition rate among the H 2O 2 group, nanozyme group and combination group (30.84% ± 5.00%, 26.57% ± 11.24%, 75.70% ± 2.42% respectively; F = 9.413, P < 0.01) , and the combination group showed a significantly higher inhibition rate compared with the H 2O 2 group and nanozyme group ( t = 8.08, 4.27 respectively, both P < 0.01) . Scanning electron microscopy showed changes in the morphology of Candida albicans treated with H 2O 2 and nanozymes alone or in combination, including shrinkage, rupture and even collapse. Conclusion:Fe 3O 4 nanozymes combined with H 2O 2 have obvious antimicrobial effect against Candida albicans.

Objective:To evaluate the efficacy and safety of clip-with-endoloop method during endoscopic submucosal dissection (ESD) in treatment of early gastric angle cancer and precancerous lesions.Methods:A total of 59 patients with early gastric angle cancer or precancerous lesions underwent ESD from January 2018 to December 2018 were randomly divided into the routine ESD group ( n=28) and the clip-with-endoloop group ( n=31). The frequency of supplementary submucosal injection, ESD procedure time, area of the resected specimen, dissection time, submucosal dissection speed, complete resection rate and complications were compared between the two groups. Results:The frequency of supplementary submucosal injection in the clip-with-endoloop group was less than that in the routine ESD group (2.3±1.1 VS 3.7±1.4, t=4.557, P<0.001). There was no significant difference in the area of the resected specimen between the two groups (12.7±2.6 cm 2 VS 11.7±2.7 cm 2,t=1.485, P=0.143). The ESD procedure time (72.4±24.7 min VS 93.6±28.9 min, t=3.043, P=0.004) and dissection time (67.7±23.3 min VS 88.2±28.3 min, t=3.054, P=0.003) in the clip-with-endoloop group were significantly shorter compared with those in the routine ESD group. The submucosal dissection speed in the clip-with-endoloop group was higher than that in the routine ESD group (20.2±3.2 mm 2/min VS 14.3±3.4 mm 2/min, t=6.879, P<0.001). The complete resection rate was 100.0% in the both groups. No perforation or postoperative bleeding occurred in the two groups. The incidence of intraoperative bleeding in the clip-with-endoloop group was lower than that in the routine ESD group [19.4% (6/31) VS 35.7% (10/28), χ2=1.992, P=0.158]. Conclusion:Clip-with-endoloop method makes ESD procedures easier and faster, with a lower possibility of intraoperative bleeding in treatment of early gastric angle cancer.

Objective:To evaluate the diagnostic value of HPV detection in squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site.Methods:Clinical data of 6 patients who were initially diagnosed with squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site and eventually diagnosed with HPV-related oropharyngeal squamous cell carcinoma were collected, and the process of diagnosis was analyzed.Results:Upon the initial admission, all patients were diagnosed with squamous cell carcinoma of the cervical lymph node metastasis with positive p16 expression, positive HPV-16 subtype and negative EBER expression. No obvious primary lesion was found after comprehensive examination. Subsequently, four of them underwent ipsilateral tonsollar blind biopsy ( n=2) and ipsilateral tonsillectomy ( n=2). All these four patients were pathologically diagnosed with tonsillar squamous cell carcinoma. For the other two cases, MRI detected the thickening complicated with enhancement of ipsilateral wall of oropharynx and tongue root after follow-up for D149 and D545 , respectively. Biopsy confirmed the diagnosis of squamous cell carcinoma of the tonsil and tongue root, respectively. Conclusion:For patients with HPV-positive squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site, the possibility that the primary lesion originates from the oropharyngeal site, especially the tonsil and tongue root, should be highly suspected.

Objective To investigate the diagnostic value of IL-27, ADA and TB-Ab in TB pleurisy. Methods The data of 74 TB pleurisy cases and 45 non-TB pleurisy cases were screened randomly from June 2017 to July 2018 in Dalian Tuberculosis Hospital. Value of IL-27, ADA and TB-Ab in blood and pleural fluid of the two groups of cases was detected, and diagnostic value of these biomarkers in TB pleurisy was compared. Results The value of IL-27, ADA and TB-Ab in blood and pleural effusion of patients with TB pleurisy were higher than those of control group (P < 0.05). ROC curve analysis showed that areas under the blood IL-27, ADA and TB-Ab curves were 0.820, 0.744 and 0.589 (P<0.05) respectively, while those under the pleural effusion curves were 0.921, 0.876 and 0.708 (P<0.05) respectively. The area under the curve of IL-27 and ADA ROC curve was 0.921 (P<0.05), but 95% CI was higher than that of pleural effusion ADA (0.804-0.930) and IL-27(0.857-0.962). Conclusions Detection of IL-27 and ADA in pleural effusion is of great value in the diagnosis of TB pleurisy. The combined detection of IL-27 and ADA in pleural effusion would improve the diagnostic value.