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 effect of light music therapy on delirium in intensive care unit (ICU) patients undergoing invasive mechanical ventilation, and provide evidence-based support for clinical prevention of delirium. METHODS: A prospective randomized controlled trial was conducted. 140 patients with invasive mechanical ventilation admitted to the department of respiratory and critical care medicine of First Affiliated Hospital of Guangxi Medical University from January 2024 to January 2025 were enrolled. The patients were divided into intervention group and control group using a random number table method. The control group received routine treatment and nursing care, while the intervention group received light music therapy three times a day for 30 minutes each time for 7 consecutive days. The confusion assessment method-ICU (CAM-ICU) was used to evaluate delirium, and the incidence of delirium within 7 days was statistically analyzed. Richmond agitation-sedation score (RASS), critical care pain observation tool (CPOT) score, mechanical ventilation duration, the length of ICU stay, and ICU stay expenses were record. RESULTS: 129 cases were ultimately included, including 64 cases in the control group and 65 cases in the intervention group. There was no statistically significant difference in baseline data between the two groups, indicating comparability. The incidence of delirium in the intervention group was significantly lower than that in the control group (27.7% vs. 51.6%, χ ² = 7.687, P = 0.006). There was no significantly difference in RASS score between the two groups before enrollment (P = 0.840). After intervention, the RASS score in the intervention group significantly decreased, from 2.00 points on the 1st day of enrollment to 0.00 points on the 7th day, while the control group only decreased from 2.00 points to 1.50 points. The decreasing trend of the intervention group was more pronounced, especially on the 3rd day (P = 0.047) and the 7th day (P =0.005), with significant differences between the groups. The time effect (F = 18.929, P < 0.001), group effect (F = 6.655, P = 0.011), and time group interaction effect (F = 7.372, P < 0.001) of the two groups of RASS score were significant, suggesting that light music therapy has better timeliness and sustainability in improving patients' sedation status. There was no significantly difference in CPOT score between the two groups before enrollment (P = 0.902). After intervention, the CPOT score in the intervention group rapidly decreased from 3.00 points before enrollment to 1.00 points on the 1st day, and continued until the 7th day, while the control group showed a slower decrease from 2.50 points to 2.00 points and only dropped to 1.00 points on the 7th day. There were significant differences on 1st day and 3rd day between two groups (both P < 0.05). The time effect (F = 28.125, P < 0.001), group effect (F = 11.580, P = 0.001), and time group interaction effect (F = 4.048, P = 0.020) of the two groups of CPOT score were significant, indicating that light music therapy has better pain control, but the interaction effect is low, indicating that the impact of the intervention on the CPOT score was mainly concentrated in the early stage (1-3 days), and the long-term effect may be influenced by other factors. Compared with the control group, the intervention group showed a significant reduction in mechanical ventilation time (days: 10.57±2.94 vs. 11.95±3.74, P = 0.021) and the length of ICU stay (days: 14.91±4.37 vs. 17.53±4.83, P = 0.002). The ICU hospitalization expenses of the intervention group was slightly lower than that of the control group [ten thousand yuan: 22.431 (12.473, 28.489) vs. 29.362 (11.996, 41.389)], but the difference was not statistically significant (P = 0.086). CONCLUSIONS Light music therapy can effectively reduce the incidence of delirium in patients undergoing invasive mechanical ventilation, improve consciousness and pain perception, shorten mechanical ventilation time and hospital stay, and has significant clinical promotion value high-quality studies.
Humans ; Delirium/prevention & control* ; Intensive Care Units ; Respiration, Artificial ; Music Therapy ; Prospective Studies ; Male ; Female ; Middle Aged ; Critical Care ; Aged

Objective To investigate the effect of a three-tier delirium care management process in patients with acute stroke in neurology intensive care unit(NICU).Methods A total of 50 patients with acute stroke admitted to the NICU of the Fourth Hospital of Changsha from May to September 2021 were assigned to the control group.The patients in the control group received routine NICU nursing care to prevent delirium.Another 50 patients with acute stroke admitted to the NICU from December 2021 to April 2022 were assigned to the trial group.They were managed with the three-tier delirium nursing management process on top of the routine NICU nursing care for the control group.The incidence of ICU delirium(DICU),duration of DICU,length of stay in NICU and the incidence of delirium-related adverse events were compared between the two groups.The degree of delirium and cognitive function before and after the intervention were compared between the two groups as well.Results The trial group had significantly shorter duration of DICU and NICU stay(both P<0.05)and lower incidence rate of delirium-related adverse events(P<0.05)compared to the control group.After the intervention,the trial group showed significantly lower scores on the intensive care delirium screening checklist(ICDSC)and significantly higher scores of cognitive function compared to those of the control group(both P<0.05).Conclusion The three-tier delirium nursing management process can lower the occurrence of delirium in NICU patients with acute stroke,shorten the NICU stay,reduce the safety risk in nursing,and improve the cognitive function.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.

Objective:To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation.Methods:This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children′s Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children′s Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized.Results:Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy.Conclusions:BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice.Methods A total of 20 C57BL/6 male mice(6～8 weeks old)were randomly divided into 4 groups(n=5).The mice from the control group and heat stress(HS)group were intraperitoneally injected with 10 mL/(kg·d)0.9％normal saline for 14 d,while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d)for 14 d,and then on the 7th day after administration,the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4％chloral hydrate.Mouse spermatocytes GC-2spd(ts)were divided into control group(routine culture for 48 h),HS group(placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture,and cultured till the end of 48 h),HS+Rg1 group(50 μmol/L Rg1 treatment followed by heat stress injury),and Rg1 group(no heat stress injury).In 1 d after modeling,the eyeball blood samples were collected to detect serum testosterone with ELISA,and the testicles were extracted to observe the morphology and weighed to calculate the testicular index.HE staining was used to observe the histopathology of testis,and corresponding reagents and kits was employed to detect the content of malondialdehyde(MDA)and activities of catalase(CAT)and superoxide dismutase(SOD)in testis tissue.After the epididymal sperm were collected,the sperm concentration and motility were analyzed by computer-assisted sperm analysis(CASA)system.In in vitro experiments,cell apoptosis was detected with TUNEL staining,the protein levels of Nrf2,Keap1,HO-1,Bax,Bcl-2 and Caspase3 were detected with Western blotting,and the mRNA levels of GCLC,GCLM and NQO1 were detected by RT-qPCR.Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress,reduced the damage of testicular tissue structure,prevented the decrease of sperm concentration and vitality,antagonized the decreasd number of Leydig cells and serum testosterone level,reduced the accumulation of MDA in testicular tissue,and enhanced the activities of CAT and SOD.Rg1 treatment alleviated the apoptosis of GC-2spd(ts)cells,down-regulated the expression of Bax,Caspase3 and Keap1 proteins,enhanced the expression of Bcl-2,Nrf2 and HO-1 proteins,and increased the transcriptional levels of Nrf2 target genes GCLC,GCLM and NQO1.Conclusion Rg1 has no significant effect on the structure and function of mouse testes,but it can effectively improve the ability of mouse testes to resist heat stress injury,which may be related to the activation of Nrf2 signaling pathway,the improvement of antioxidant enzyme activity,and the reduction of apoptosis of spermatogenic cells.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.