Alzheimer's disease(AD)is a degenerative disease of CNS that tends to occur in the elderly.It is characterized by cognitive decline and memory impairment,accompanied by mental symptoms,which seriously affect the daily life of patients.The gut microbiota is a collection of all microorganisms residing in the gastrointestinal tract(GI)and is an integral part of the human body.The gut microbiota can affect the CNS through the brain-gut axis,thereby increasing the risk of the occurrence of AD.The traditional drugs approved for AD are not effective,so a new treatment for AD is urgently needed.This paper will explain the relationship between intestinal flora and AD,and explore new therapies for AD targeting intestinal flora.

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliomet-ric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications(1406).The analysis with VOSviewer showed that the re-search on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolini-um-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mava-camten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective To optimize the extraction process of flavonoids from Plantago asiatica L.rich in plantagoside by response surface methodology,and to explore the protective effect and mechanism of plantain flavonoids on H2O2-damaged L02 cells.Methods The effects of various parameters,including ethanol concentration,extraction temperature and the liquid-solid ratio on the yield of flavonoids from P.asiatica and the transfer rate of plantagoside were studied by single factor experiment.The central composite design(CCD)and response surface methodology(RSM)were employed on this basic to screen the optimized extraction conditions,which yielded the highest extraction rate of flavonoids from P.asiatica and the maximum transfer rate of plantagoside.The protective effect of flavonoids from P.asiatica on H2O2-damaged L02 cells was assessed through the analysis of cell survival rate,apoptosis rate,mitochondrial membrane potential,malondialdehyde(MDA)and glutathione(GSH)levels,oxide dismutase(SOD)concentration,and the expression levels of HO-1,Nrf2,and SOD proteins.Results The results showed that the highest yield of extraction rate of flavonoids from P.asiatica(1.82％)and the maximum transfer rate of plantagoside(35.01％)were achieved under the optimized extraction condition:extraction temperature of 80 ℃,ethanol concentration of 65％and liquid-solid ratio of 15:1.Flavonoids from P.asiatica extracted under these parameters significantly reduced the apoptosis rate(P<0.001)and the degree of mitochondrial membrane potential damage(P<0.001),increased the expressions of SOD and GSH(P<0.001),and reduced the MDA level(P<0.01,P<0.001)in H2O2-damaged L02 cells at concentrations ranging from 25 to 100 μg·mL-1.In addition,100 μg·mL-1 flavonoids from P.asiatica were found to regulate the expressions of HO-1,Nrf2 and SOD in H2O2-damaged L02 cells.These flavonoids decrease the expressions of HO-1 and Nrf2 proteins,while enhance the expression of SOD protein in H2O2-damaged L02 cells(P<0.05,P<0.01).Conclusion The extraction process for flavonoids from P.asiatica,which was optimized using the response surface method,is operationally simple and yields a high transfer rate of the key active component,plantagoside.This approach offers valuable insights for the actual production of flavonoids from P.asiatica.Besides,flavonoids from P.asiatica could reduce oxidative stress level in H2O2-damaged liver cells,which exhibited a certain protective effect on L02 cells against oxidative damage.This study provides a foundational basis for the development and application of flavonoids from P.asiatica as liver-protective health supplements.

Objective:To analyze the clinical effect of real-time virtual sonography (RVS) surgical navigation combined with indocyanine green fluorescence imaging technology in the anatomical liver segmentectomy for hepatocellular carcinoma (HCC).Methods:The clinical data of 35 patients who underwent anatomical liver segmentectomy using RVS surgical navigation combined with indocyanine green fluorescence imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to January 2022 were retrospectively analyzed. There were 22 males and 13 females, aged (60.0±10.0) years. RVS is real-time virtual sonography, which fuses real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images to guide the surgical plane. Methods of operation, time of operation, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. Postoperative complications were graded by Clavien-Dindo system. The 1-year overall survival and tumor-free survival rates of patients were followed up by outpatient or telephone review.Results:Anatomical liver segmentectomy was performed on 36 patients, including 1 patient (2.9%) of segment Ⅱ, 1 patient (2.9%) of segment Ⅲ, 5 patients (14.3%) of segment Ⅳ, 6 patients (17.1%) of segment Ⅴ, 10 patients (28.6%) of segment Ⅵ, 7 patients (20.0%) of segment Ⅶ, 4 patients (11.4%) of segment Ⅷ, and 1 patient (2.9%) of segments Ⅴ+ Ⅷ. The operation time of 35 patients was (310.2±81.6) min, with an intraoperative blood loss of [ M( Q1, Q3)] 390.0(250.0, 500.0) ml. The hospital stay was (11.6±2.1) d. There was no postoperative death. Postoperative complications occurred in 3 cases (8.6%), of which 2 cases (5.7%) were ascites, Clavien-Dindo grade Ⅰ; Postoperative hemorrhage occurred in 1 case (2.9%), Clavien-Dindo grade Ⅱ. HCC was confirmed by pathology in all cases, and the operative margins were negative. The median follow-up time was 14 months (12 to 20 months). The 1-year overall survival rate after surgery was 100.0%(35/35), three patients (8.6%) had tumor recurrence, and the 1-year tumor-free survival rate was 91.4% (32/35). Conclusion:RVS surgical navigation combined with indocyanine green fluorescence imaging technology could be feasible in anatomical segmental hepatectomy for HCC.

Objective:To investigate the difference in left ventricular dysfunction between type 2 diabetes mellitus (T2DM) patients with hyperlipidemia and those without hyperlipidemia, and analyze the application value of three-dimensional speckle tracking technology.Methods:The clinical data of 70 patients with T2DM admitted to Heji Hospital Affiliated to Changzhi Medical College from January 2020 to June 2021 were retrospectively analyzed. Among these patients, 35 patients had hyperlipidemia and 35 patients had no hyperlipidemia. At the same time, 40 healthy subjects who concurrently underwent health checkups in the same hospital were included as healthy controls. All subjects underwent routine cardiac ultrasound and 3D-STE examinations. General clinical information and left ventricular function-related parameters, including global longitudinal strain, global circumferential strain, global area strain, and global radial strain were compared between healthy controls and T2DM patients with hyperlipidemia and those without hyperlipidemia.Results:The proportion of left ventricular remodeling increased in T2DM patients without hyperlipidemia, and the proportion of left ventricular hypertrophy was the highest in T2DM patients with hyperlipidemia. Global longitudinal strain and global circumferential strain in T2DM patients without hyperlipidemia were (-16.97 ± 2.59)% and (-17.41 ± 2.50)%, respectively, which were significantly higher than (-18.86 ± 2.46)% and (-18.71 ± 2.92)% in healthy controls ( t = 0.95, 0.57, both P < 0.05). Global longitudinal strain, global circumferential strain, and global area strain in T2DM patients with hyperlipidemia were (-14.98 ± 3.15)%, (-15.80 ± 3.16)%, (-27.17 ± 4.54)%, respectively, which were significantly higher than (-18.86 ± 2.46)%, (-18.71 ± 2.92)%, (-30.62 ± 4.02)% in healthy controls ( t = 0.46, 1.37, 0.98, all P < 0.05) and (-16.97 ± 2.59)%, (-17.41 ± 2.50)%, (-30.06 ± 3.59)% in T2DM patients without hyperlipidemia ( t = 0.37, 1.02, 0.77, all P < 0.05). Global radial strain in T2DM patients with hyperlipidemia was significantly higher than [(51.49 ± 8.94)%, t = 1.35, P < 0.05] in healthy controls and [(47.71± 8.46)%, t = 0.98, P < 0.05] in T2DM patients without hyperlipidemia. In patients with T2DM, fasting blood glucose and hyperlipidemia were independently correlated with all strain-related parameters. Conclusion:Hyperlipidemia can aggravate left ventricular remodeling and dysfunction in patients with T2DM and 3D-STE is one of the examination methods for subclinical left ventricular remodeling and dysfunction in T2DM patients with or without hyperlipidemia.

Objective:To observe any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

Objective:To explore the safety and feasibility of optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation(DKT)and evaluate its effectiveness to provide more alternative protocols for kidney transplantation from extended criteria donors.Methods:DKT was performed in 10 recipients using the same protocol from June 2019 to May 2021.And retrospective reviewing was performed for clinical data, including characteristics of donors and recipients, optimized pathological evaluation system, modified surgery, treatment regimens, complications and follow-ups.Results:There were 8 male and 2 female donors with an age of(57.9±12.8)years and BMI(24.1±4.1)kg/m 2.The percentage of DCD was 70% and DBD 30%.The serum creatinine before procurement was 107.6(93.3-163.5)μmol/l.Zero-point puncture biopsy was performed for both kidneys and optimized pathological evaluation system was implemented(Banff criteria & Remuzzi score). The pathological results indicated that glomerular sclerosis for left and right kidneys were 2.0(1.5-2.0)and 1.5(1.0-2.0). And Remuzzi score for left and right kidneys were(4.4±1.2)and(3.6±1.5)points respectively.All recipients were male with an age of(43.1±9.0)years and BMI(22.2±1.9)kg/m 2.All PRAs were negative pre-operation.Modified surgery was performed in all recipients(two kidneys were implanted outside iliac vessels without patch and artery of superior kidney was anastomosed to internal iliac artery). Operative duration was(195±54.3)min and serum creatinine before discharge 125.0(102.0-199.0)μmol/L.Renal dynamic scintigraphy indicated that glomerular filtration rate was(30.0±8.2)ml/min for left kidney and(29.2±13.9)ml/min for right kidney.MRA results indicated that morphologies of renal arteries and veins were regular.The time between operation and discharge was(22.4±4.7)days.Compared with SKT, serum creatinine before discharge of DKT was lower and DGF incidence of DKT was higher without statistical significance.The time between operation and discharge was longer for DKT than that for SKT( P<0.05). The complications consisted of 20% donor derived infection(DDI)and 50% DGF.And there was no surgical complication associated with vessels and ureter.Renal function remained stable during 6-month follow-ups. Conclusions:Optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation are both safe and feasible.The postoperative function of transplanted dual kidney is successfully restored.However, long-term follow-ups are required for evaluating its effectiveness.

Objective:To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

To evaluate the efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over 75 years. A total of 82 patients with AF who underwent LAAO successfully in Beijing Anzhen Hospital from March 2014 to March 2019 were divided into two groups according to age: the elderly group (aged>75 years) and the young group (aged ≤75 years). Risk of perioperative complications and incidence of ischemic stroke and major bleeding during follow-up were retrospectively analyzed. The results showed that there were no significant differences in procedure-related ischemic stroke(0 vs.1.6%, P=0.768) and major bleeding (0 vs.1.6%, P=0.768) during perioperative period between the two groups. No complications as death or pericardial tamponade occurred in the two group. During a (25.9±15.9) months period of followed up, ischemic stroke event rate was 3.6/100 person-years in the elderly group and 4.9/100 person-years in the young group, respectively. Major bleeding event rate was 2.5/100 person-years in the elderly group and 0/100 person-years in the young group, respectively. Compared with the expected ones, the relative risk reduction (RRR) of stroke in the elderly group was more profound than that in the young group (32.0% vs. 25.0%), while the risk of major bleeding in the young group was significantly lower than that in the elderly group (RRR 100% vs. 56.9%). Therefore, LAAO might be suitable for stroke prevention in the elderly AF patients.