Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective:To explore the effect of hospital-community continuous management based on mobile health and dyadic coping intervention in ileostomy patients and their spouses.Methods:This was a randomized controlled trial. Patients with rectal cancer who underwent ileostomy at Taizhou People′s Hospital between August 2018 and August 2023, along with their spouses, were enrolled. Patient-spouse dyads were randomly assigned to either the intervention group or the control group using a random number table method. Baseline demographic data were collected from both groups. The control group received routine care, whereas the intervention group was given a hospital-community transitional care program based on mHealth (mobile health) and a dyadic coping model. Stoma adaptation, family functioning, and dyadic coping capacity were evaluated at 1 week, 1 month, and 3 months postoperatively. Sedentary behavior time and exercise compliance were also assessed at 1 month and 3 months after surgery.Results:A total of 47 patient-spouse dyads were included in the control group and 48 dyads in the intervention group. There were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). Similarly, no significant differences were found in the age, sex or education level of the spouses (all P>0.05). At 1 week postoperatively, there were no significant differences in family cohesion and adaptability scores between the two groups (all P>0.05). However, at 1 and 3 months postoperatively, the intervention group had significantly higher family cohesion and adaptability scores than the control group (all P<0.05). With regard to dyadic coping capacity, no significant differences were observed in any of the subscale scores of the dyadic coping questionnaire at 1 week postoperatively (all P>0.05). At 1 and 3 months postoperatively, the intervention group scored significantly higher than the control group on stress communication, supportive coping, delegated coping, and joint coping ( P<0.05), but lower on negative coping ( P<0.05). In terms of stoma adaptation, no significant difference was found between the two groups at 1 week postoperatively ( P>0.05). At 1 and 3 months postoperatively, the intervention group showed significantly higher stoma adaptation and exercise compliance scores, as well as shorter sedentary behavior time, compared to the control group (all P<0.05). Conclusions:The hospital-community transitional care program developed by the research team effectively improves family functioning, dyadic coping capacity in ileostomy patient-spouse dyads, and postoperative stoma adaptation and rehabilitation outcomes.

AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)recep-tor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthe-sia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was ter-minated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anes-thesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tis-sues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloid β-protein(Aβ),and p-tau were detected by Western blot.RE-SULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points dur-ing anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+in-creased.The protein levels of GluN1 subunit,Aβ and p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves and δ waves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβ and p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLU-SION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power of δ EEG waves,but has no significant effect on recovery time.Me-mantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA recep-tors,Aβ and p-tau,and attenuating neuroinflammation.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Objective To investigate the impacts of miR-141-3p on the proliferation,migration and epithelial-mesen-chymal transformation of glioma cells by regulating lysophosphatidic acid receptor 3(LPAR3).Methods RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in glioma tissues and cells.Dual luciferase was used to de-tect the targeting relationship between miR-141-3p and LPAR3.The cells were divided into control group,miR-NC group,miR-141-3p mimics group,miR-141-3p mimics+pcDNA3.1 group,and miR-141-3p mimics+pcDNA-LPAR3 group,and then transfected with corresponding plasmids.RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in cells.EdU method was used to detect cell proliferation.The scratch healing experiment was used to detect cell migration.Western blot was used to detect the expression of proteins related to cell proliferation,migration,and epithelial-mesenchymal transformation.Xenograft tumor model in nude mice was used to observe tumor formation.RT-qPCR was used to detect the level of miR-141-3p in tumor tissue.In addition,Western blot was performed to detect the expression of LPAR3,PCNA,and MMP-2.Results miR-141-3p was downregulated,whereas LPAR3 mRNA was upregulated in glioma tissues and U251,T98G,and CHG-5 cell lines(P＜0.05).There was a targeted binding site between miR-141-3p and LPAR3.miR-141-3p mimics significantly increased the ex-pression of miR-141-3p and E-cadherin,but decreased LPAR3 mRNA level,EdU-positive rate,scratch wound healing rate,and the expression of PCNA,cyclin D1,MMP-2,MMP-9,N-cadherin,and vimentin(P＜0.05).pcDNA-LPAR3 reversed effect on expression of these factors(P＜0.05).Tumor transplantation experiments in nude mice showed that miR-141-3p mimics reduced tumor volume,tumor weight,LPAR3,PCNA,and MMP-2 expres-sion,and increased the level of miR-141-3p(P＜0.05).Conclusions miR-141-3p can inhibit proliferation,mi-gration,and epithelial-mesenchymal transformation of glioma cells by down-regulating LPAR3.

Objective:To develop an intelligent surveillance system for identifying upper gastrointestinal high-risk patients and assigning surveillance intervals, and to verify its efficacy.Methods:The endoscopic and pathological reports of 23 035 patients undergoing endoscopy at Renmin Hospital of Wuhan University from January to October 2021 were collected retrospectively. A training set of 17 934 patients (January to August) and a test set of 5 101 patients (September to October) were established. Keywords in the endoscopic and pathological reports were extracted by the intelligent surveillance system, and high-risk patients were automatically identified and classified into 7 risk levels. Then the standardized surveillance intervals were assigned based on the guideline. Guideline-based surveillance intervals assigned by expert endoscopists based on endoscopic and pathological reports were used as the golden standard. The accuracy of the intelligent surveillance system was calculated. Of the patients within the test set, 189 were hospitalized and the surveillance intervals given by physicians could be obtained from the electronic health records. The accuracy of the intelligent surveillance system with that of physicians from different departments was compared. Then 67 patients were randomly selected from 189 patients by simple random sampling to evaluate the adjunctive effect of the system in assigning surveillance intervals among 3 endoscopists.Results:The overall accuracy of the intelligent surveillance system in identifying upper gastrointestinal high-risk patients was 99.94% (5 098/5 101), and that of assigning surveillance intervals to correctly included patients was 100.00% (534/534). The intelligent surveillance system achieved significantly higher accuracy compared with all physicians from different departments [98.94% (187/189) VS 35.45% (67/189), χ2=118.01, P<0.001] as well as physicians from department of gastroenterology [100.00% (117/117) VS 24.79% (29/117), χ2=86.01, P<0.001]. With the assistance of the intelligent surveillance system, the endoscopists' accuracy of assigning surveillance intervals to 67 patients was significantly improved [55.22% (111/201) VS 22.39% (45/201), χ2=58.68, P<0.001]. Conclusion:The intelligent surveillance system can accurately identify upper gastrointestinal high-risk patients and assign surveillance intervals according to risk levels, which can alleviate the workload of doctors and improve the follow-up rate of patients.

Objective:To develop an artificial intelligence (AI) calculation system for the effective withdrawal time of colonoscopy and to evaluate its clinical application value.Methods:First, 17 118 colonoscopy pictures from Renmin Hospital of Wuhan University were used for training and testing to establish a deep convolutional neural network model to recognize various colonoscopy fields. Then this model was integrated with the internal and external recognition model and cecum recognition model developed by the research group to create an AI system for automatic calculation of the effective withdrawal time. Finally, 944 colonoscopy videos from the Endoscopy Center of Renmin Hospital of Wuhan University from July 1, 2020 to October 10, 2020 were included in a retrospective analysis. AI automatic computing system was used to calculate the effective withdrawal time, and 89 of them were manually calculated to evaluate the accuracy of the AI automatic computing system. The remaining 855 cases were divided into two groups according to AI calculations, namely, the effective withdrawal time <6 min group ( n=615) and the effective withdrawal time ≥6 min group ( n=240), and the differences in the overall detection rate of adenoma and polyp were compared and analyzed. Results:The accuracy of AI automatic calculation system for effective withdrawal time reached 92.1% (82/89). The overall adenoma detection rate in the group with effective withdrawal time ≥6 min was 37.5% (90/240), that in the group with effective withdrawal time <6 min was 19.0% (117/615), and the difference was statistically significant ( χ2=32.11, P<0.001). The overall polyp detection rate in the group with effective withdrawal time ≥6 min was 75.0% (180/240), and that in the group with effective withdrawal time <6 min was 45.2% (278/615), with statistical significance ( χ2=61.62, P<0.001). Conclusion:AI automatic computing system can accurately calculate the effective withdrawal time of colonoscopy, and can be used to monitor the effective withdrawal time of clinical colonoscopy. In addition, effective withdrawal time ≥6 min can effectively improve the detection rate of adenoma and polyps.

Objective:To explore status and influencing factors of surveillance in colorectal post-polypectomy patients.Methods:Patients who underwent colorectal polypectomy in Renmin Hospital of Wuhan University between April 1, 2019 and June 30, 2019 were retrospectively studied. The surveillance information was obtained through electronic health record and telephone call. Status and influencing factors of surveillance in colorectal post-polypectomy patients were evaluated. Logistic regression model was used for multivariate analysis to determine independent risk factors influencing surveillance.Results:A total of 268 colorectal post-polypectomy patients and their surveillance information were reviewed, of whom 153 (57.09%) patients received surveillance colonoscopy, and 115 (42.91%) patients did not. Univariate analysis showed that the source of patients (outpatients VS inpatients, χ 2=5.68, P=0.017), department (others VS department of gastroenterology, χ 2=6.64, P=0.010), and the number of polyps (1/(2~4)/≥5, χ2=7.32, P=0.026) influenced the outcome of surveillance. Logistic regression model indicated that department of gastroenterology ( P=0.039, OR=2.12, 95% CI:1.04-4.34), risk level 3 ( P=0.040, OR=1.92, 95% CI:1.03-3.58) and the number of polyps ≥5 ( P=0.016, OR=2.89, 95% CI:1.22-6.83) were independent risk factors influencing surveillance. Conclusion:Patients visit the department of gastroenterology or had a risk level 3 or ≥5 polyps are more likely to opt for surveillance following the procedure.