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.

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.

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.

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.

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 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 evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym^®) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym^® group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym^® group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym^® group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym^® group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym^® group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym^® group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

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.

Objective To evaluate the therapeutic effect of biofeedbackand thecharacteristics of pelvic floor surface electromyography in elderly patients with functional constipation. Methods Analysis 258 cases of functional constipation patients with 12 index of five steps of the pelvic floor surface electromyographic. Of these, 74 patients(50 older age-group and 24 control group)with functional constipation were treated with biofeedback. Use constipation patient symptomself-assessment scale,before and after treatment,compared two groups with the scord and clinical effect,analysis 12 index of the pelvic floor surface electromyographic in older age-group. Results Compared to control group,the older age-group had a lower amplitude during pre-baseline step,flick step,tonic step,endurance step and pos-baseline step.The older age-group had a higher CV(coefficient of vari-ance)during pre-baseline step and endurance step,median frequency during tonic step and endurance step. Onset time during flick step,CV during tonic step andpos-baseline step in the older age-group is as well as control group. The maximal contraction amplitude,continuous contraction and prolonged contraction amplitude were all increased in the elderly group after biofeedback treatment. The variation coefficient of the prebaseline and the duration of the endurance contraction was decreased. The value frequency of the durable contraction decreases. Conclusion The characteristics of pelvic floor surface electromyography in elderly patients:had a lower ampli-tude duringpre-baseline step,flick step,tonic step,endurance step and pos-baseline step,had a higher CV during pre-baseline step and endurance step,median frequency during tonic step and endurance step.Biofeedback therapy can improve pelvic floor muscle tension and the coordination of sports.