Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

Alzheimer's disease(AD)is a highly destructive neurodegenerative disorder,and due to its complex pathology and insuffi-cient treatment,it is urgent to explore new targets that can directly address the root cause of the disease.In recent years,numerous stud-ies have shown that triggering receptor expressed on myeloid cells 2(TREM2)in microglial cells has the function of delaying the pro-gression of AD,and its abnormality plays a key role in the development and progression of AD,with a potential of being used as a target for the treatment of AD.This article reviews the biological characteristics of TREM2 and discusses its important role in the three major pathological features of AD and its potential as a target for AD treatment,in order to deepen the understanding of the role of TREM2 in AD and provide a theoretical reference for exploring new targets for AD treatment in the future.

The standardized workflow of computer-aided static guided implant surgery includes preoperative exami-nation,data acquisition,guide design,guide fabrication and surgery.Errors may occur at each step,leading to irrevers-ible cumulative effects and thus impacting the accuracy of implant placement.However,clinicians tend to focus on fac-tors causing errors in surgical operations,ignoring the possibility of irreversible errors in nonstandard guided surgery.Based on the clinical practice of domestic experts and research progress at home and abroad,this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection,data collection,guide de-signing and manufacturing and describes strategies to resolve errors so as to gain expert consensus.Consensus recom-mendation:1.Preoperative considerations:the appropriate implant guide type should be selected according to the pa-tient's oral condition before surgery,and a retaining screw-assisted support guide should be selected if necessary.2.Da-ta acquisition should be standardized as much as possible,including beam CT and extraoral scanning.CBCT performed with the patient's head fixed and with a small field of view is recommended.For patients with metal prostheses inside the mouth,a registration marker guide should be used,and the ambient temperature and light of the external oral scan-ner should be reasonably controlled.3.Optimization of computer-aided design:it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers.Properly designing the retaining screws,extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors.4.Improving computer-aided production:it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postpro-cessing procedures.

Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.

Objective:To evaluate modified Lanza score (MLS) of gastric mucosa for predicting the prognosis of geriatric patients with sepsis.Methods:Data of 50 patients with sepsis, who were over 60 years old and underwent gastroscopy for suspected gastrointestinal bleeding in the Department of Geriatric Critical Care Medicine of Guangdong Provincial People's Hospital from January 2019 to April 2022, were retrospectively analyzed. Patients were divided into the death group ( n=32) and the survival group ( n=18) according to their regression within 28 days after gastroscopy. Their gastric mucosa was scored by using MLS system, and the mortality of patients with MLS≥1 was calculated, then the patients were further divided into 2 groups, MLS=0-2 ( n=23, less than 2 regions of lesions ) and MLS=3-5 ( n=27, two or more regions of lesions). The relationship between MLS and acute physiology and chronic health status evaluation (APACHE) Ⅱ score, risk factor of death and mortality in each group were compared. The correlation between MLS and mortality was analyzed. The influence of geriatric sepsis risk factors affecting the prognosis of patients within 28 days were analyzed by using logistic regression. Results:Among the 50 geriatric patients with sepsis, those with gastric mucosal lesions, i.e., MLS ≥1, accounted for 68.00% (34/50), including 84.38% (27/32) patients with MLS≥1 in the death group, which was significantly higher than the 38.89% (7/18) patients with MLS≥1 in the survival group ( χ 2=10.593, P<0.001). Patients with MLS=3-5 had significantly higher APACHE Ⅱ scores (26.09±6.47 VS 18.57±7.66, t=3.527, P=0.001) and higher mortality [85.19% (23/27) VS 39.13% (9/23), χ 2=11.434, P=0.001] compared with MLS=0-2. Correlation analysis showed a significant correlation between MLS and mortality ( r=0.886, P=0.019). Multivariate logistic regression analysis showed that MLS=4-5 was an independent risk factor for death in geriatric patients with sepsis ( OR=17.055, 95% CI: 1.387-209.744, P=0.027). Conclusion:MLS presents high sensitivity in predicting 28-day outcomes for geriatric patients with sepsis. Two or more than 2 regions of gastric mucosal lesions can significantly increase the risk of death in geriatric patients with sepsis.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of malignant endometrial lesions.Methods:A total of 142 patients with endometrial lesions who underwent contrast-enhanced ultrasound examination in Beijing Tiantan Hospital, Capital Medical University from January 2019 to September 2021 were selected. The endometrial lesions were divided into benign group (including endometrial hyperplasia and endometrial polyps) and malignant group (endometrial cancer) according to the pathological results of surgery, and the differences of contrast enhancement patterns between benign group and malignant group were compared. The sensitivity, specificity of CEUS in the diagnosis of endometrial cancer were calculated, and the Kappa value was calculated with the initial enhancement time earlier than or equal to the muscularity or the peak time earlier than the muscularity as the diagnostic index for the diagnosis of endometrial malignant lesions. The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer and endometrial cancer with thickness ≥10 mm were calculated.Results:A total of 108 patients underwent surgery with clear pathological results, including 66 patients in the benign lesion group and 42 patients in the malignant lesion group. The thickness of malignant lesions was significantly larger than that of benign lesions, and the difference was statistically significant( t=4.039, P<0.05), but there was no significant difference of hemodynamic parameters between the two groups ( P>0.05). The initial enhancement time, peak time and peak intensity of benign lesions were significantly different from those of malignant lesions(all P<0.05). The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer were 64.3%, 100% and 0.668, respectively. The sensitivity, specificity and Kappa value of CEUS in the diagnosis of endometrial carcinoma with lesion thickness ≥10 mm were 75.0%, 100% and 0.795, respectively. Conclusions:For the diagnosis of endometrial lesions, especially the malignant endometrial lesions with thickness and diameter greater than or equal to 10mm, there is a high diagnostic coincidence rate between CEUS and pathological diagnosis, and endometrial malignant lesions have more specific CEUS manifestations.

Objective:To investigate the characteristics of three-dimensional high resolution anorectal manometry and the effect of biological feedback therapy on the improvement of clinical symptoms in very elderly patients with chronic functional constipation.Methods:A total of 68 cases with chronic functional constipation were divided into very elderly group(≥80 years old, n=36)and the elderly group(60-79 years old, n=32)in the retrospective analysis.Patients underwent the three-dimensional high resolution anorectal manometry before and after biological feedback therapy, and the related parameters and scores of constipation symptoms before and after treatment were compared between the two groups.Results:The results of 3D high-resolution anorectal manometry showed that the anus relaxation rate in the simulated defecation test was lower and the bowel threshold in the rectal sensory threshold test was higher in the very elderly group than in the elderly group(2.44±33.81% vs.16.34±16.99%, 103.44±42.01 ml vs.77.22±41.85 ml, t=-2.047 and 2.655, P=0.049 and 0.012). In the very elderly group, the post-biological feedback therapy versus pre-biological feedback therapy showed that anal residual pressure during simulated defecation was decreased, the absolute value of negative anorectal pressure difference was reduced and the anal relaxation rate was increased [57.50±18.88 mmHg(1 mmHg=0.133 kPa) vs.64.84±25.82 mmHg, -29.64±15.98 mmHg vs.-39.47±19.45 mmHg, 10.53±29.35% vs.2.44±33.81%, t=3.342, -4.902 and -3.209, P=0.002, 0.000 and 0.003]. The scores of clinical symptom scale showed that there was no significant difference in the effective rate between the very elderly and elderly groups(66.67% or 24/36 vs.71.88% or 23/32, χ2=0.760, P=0.860). Conclusions:The elderly functional constipation patients with defecation disorder often have rectal propulsive insufficiency and dyscoordination of pelvic floor muscle contraction.The main cause of defecation disorder in very elderly patients is the decrease of anal relaxation rate during simulated defecation.Biological feedback therapy can improve the symptoms of defecation disorder in very elderly patients by reducing the anal residual pressure during simulated defecation, increasing the anal relaxation rate and reducing the absolute value of negative anorectal pressure difference.

Objective:To retrospectively analyze the clinical characteristics of elderly patients who received colonoscopy and to explore the clinical value of regular colonoscopy for the elderly.Methods:This was a retrospective cohort study.A total of 1 154 patients aged 75 years and over undergone colonoscopy in Guangdong General Hospital from January 2015 to March 2018 were enrolled and divided into three groups, including 605 cases aged 75-79 years, 527 cases aged 80-89 years and 22 cases aged 90 years and over.Detection rates of colorectal lesions by colonoscopy were recorded.The clinical value of annual colonoscopy on the detection of colorectal lesions in elderly patients 75 years and older were analyzed to assess the necessity for regular monitoring.Results:Overall, 569 cases(49.3%)underwent colonoscopy with sedation and 585 cases(50.7%)underwent colonoscopy without sedation.The total positive detection rate was 83.4%(962/1 154), and the main lesions were polyps(858 cases, 74.4%), including 605(52.4%)cases of adenomas.Among the three groups, gastrointestinal bleeding was the main cause for colonoscopy in the group aged 90 years and over, while abdominal discomfort, elevated immunological tumor markers and history of non-colon cancer were the main reasons for colonoscopy in the group aged 75-79 years( P<0.05). A total of 153 cases underwent annual colonoscopy.The detection rate of polyps and adenomas decreased in the second exam, but still higher than 40.0%. Conclusions:Colonoscopy is a safe and effective method for the elderly population aged 75 years and over.Polyps and adenomas are the most common lesions.Recurrence of polyps after colorectal cancer and polypectomy is common and it is necessary to receive colonoscopy regularly.