This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

Objective:To systematically evaluate the disease experience and inner needs of young and middle-aged patients with end-stage renal disease, so as to provide evidence for medical personnel to pay more attention to the mental health of this population and give personalized care.Methods:The qualitative studies on the real experience, psychological feeling and experience of young and middle-aged patients with end-stage renal disease were searched by PsycInfo, PubMed, Embase, CINAHL, Web of Science, China National Knowledge Network, Wanfang, VIP and China Biomedical Literature Database. The retrieval period was from the establishment of the database to April 20, 2024. Joanna Briggs Institute Evidence-based Health Care Center Evaluation criteria (2016 edition) were used to evaluate the literature quality, and the results were summarized and integrated by aggregative meta-integration method.Results:A total of 10 studies were included, and 47 clear findings were extracted and classified into 10 new categories, which were combined into 4 integrated results: the phased changes of patients′ real experience at all levels of body, mind and society, impairment of their own and family role functions, desire for support and lack of autonomy in decision-making, and reconstruction of positive attitude and future outlook in the face of disease.Conclusions:Nursing staff should pay attention to and understand the psychosocial conditions of young and middle-aged patients with end-stage renal disease, timely provide targeted psychological support and help to enhance their confidence in treatment, better return to work and society, and improve their quality of life.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

To summarize rescuing and nursing experience of 3 ectopic pregnancy patients,suffering from severe toxicity caused by low-dose methotrexate(MTX)treatment.The key points include:constantly monitoring of patients for at least a week after MTX administration,and identifying MTX toxicity related symptoms as soon as possible;promptly establishing a multidisciplinary medical team to establish individualized rescue plans;quickly initiating the rescue therapy and implementing targeted fluid management to accelerate MTX excretion;intensifying protective isolation caring to prevent and control infection;applying refined safety management to prevent spontaneous bleeding;providing intensive caring of skin and mucosal toxicity symptoms to promote healing process;supplying individualized psychological counseling and support in time;strengthening the protection of the damaged organ.After emergent rescuing and intensive nursing,all 3 patients successfully recovered and were discharged from the hospital.

Objective To explore the role and potential mechanisms of plasma-activated solution(PAS)in alleviating dextran sulfate sodium salt(DSS)-induced ulcerative colitis.Methods We constructed a DSS-induced ulcerative colitis mouse model and evaluated the effect of PAS in vivo by observing mouse weight,calculating disease activity indexes,detecting inflammatory factors and oxidative stress indicators through ELISA.We also evaluated the effect of PAS on colon cell proliferation and migration ability through clone formation experiments,scratch experiments,and used Western blotting to determine the expression levels of proliferation-related proteins.Results PAS significantly reversed DSS-induced weight loss and increased disease activity indexes in mice(P＜0.05).The serum inflammatory cytokine levels(TNF-α,IL-6 and IL-1β)in PAS group were significantly reduced compared to those in DSS group(P＜0.05).PAS treatment could improve the imbalance of colonic redox homeostasis including changes of malondialdehyde,catalase and superoxide dismutase caused by DSS(P＜0.05).After the use of endothelial nitric oxide synthase inhibitors,changes in various indicators caused by in vivo PAS disappeared(P＜0.001).The clone formation ability of colon cells was stronger in the group treated with PAS,and the expression of proliferation-related proteins increased.Cell scratch experiments suggested that intervention with PAS could reverse the decrease in cell migration ability caused by lipopolysaccharide(P＜0.001).After the application of endothelial nitric oxide synthase inhibitors,the pro-proliferative and migratory effects of PAS disappeared(P＜0.05).Conclusion PAS alleviate DSS-induced colitis in mice and promote colonic epithelial cell repair through the eNOS pathway.

Objective To explore the application of plasma-activated solution(PAS)in the treatment of peritoneal metastasis in mice.Methods A mice model of peritoneal tumor transplantation was established,and PAS was prepared for intervention in the mice.The growth of the peritoneally transplanted tumor was assessed using in vivo imaging technology,while the apoptosis level was evaluated through flow cytometry,immunofluorescence,and Western blotting.Results At the in vitro level,there was no significant impact on tumor cell apoptosis level under adherent conditions observed when utilizing PAS(P＞0.05).Under non-adherent condition,PAS significantly augmented tumor cell apoptosis level(P＜0.05),substantially increased the proportion of deceased cells(P＜0.05),and markedly elevated intracellular total and mitochondrial reactive oxygen species levels(P＜0.05).In vivo level,using PAS following peritoneal transplanted tumor formation exhibited no noteworthy influence on peritoneal transplanted tumor growth(P＞0.05),while immediate utilization of PAS during model conducting effectively reduced abdominal tumor spread(P＜0.05).Conclusion PAS inhibits tumor peritoneal dissemination in mice by promoting tumor cell anoikis.

Objective By exploring the establishment of a follow-up and pre-visit model,this study aims to facilitate the development of a modernized Chinese medical service model for public hospitals,characterized by optimized workflows,continu-ous care models,efficient services,comfortable environments,and patient-centered attitudes,thereby improving patient experi-ence and enhancing the quality of outpatient follow-up visits.Methods Under the value co-creation framework,with both healthcare providers and patients as core value stakeholders,this program introduced a self-service examination appointment plat-form,established a follow-up and pre-visit process,and implemented time-slot-based appointments for diagnosis and treatment.These steps aim to promote the equitable allocation of medical resources and refine the follow-up and pre-visit model in public hospitals.Results Implementation at Hospital P demonstrated that after process reengineering,patients'average in-hospital time reduced by nearly 135 minutes,significantly enhancing treatment efficiency,satisfaction levels among both medical staff and patients,and accessibility of medical services.Conclusion Grounded in value co-creation theory,the follow-up and pre-visit model of Hospital P is divided into three stages:mutual value positioning of both doctors and patients,collaborative value crea-tion,and sustained value continuation for both.This alignment between process reengineering goals and value co-creation out-comes helps improve the quality of medical services,better meet the medical needs of patients,and achieve a win-win scenario for both doctors and patients.

Objective:To analyze the genomic characteristics and antibiotic resistance of Listeria monocytogenes isolated from food sources in Beijing City in 2022. Methods:A total of 83 strains of Listeria monocytogenes were isolated from three major categories of food, namely raw poultry, raw livestock meat and ready-to-eat foods, in Beijing′s food safety risk monitoring in 2022. Whole-genome sequencing (WGS) was performed to determine serogroups, multilocus sequence typing (ST) and core genome multilocus sequence typing (cgMLST). Virulence genes and antibiotic resistance genes were identified using the VFDB and ResFinder 3.0 databases. Antimicrobial susceptibility to eight antibiotics was tested via the broth microdilution method. Results:The predominant serogroup was 1/2a, 3a (61.2%). All the isolates were divided into 14 STs, with ST121 (21.7%), ST8 (20.5%), ST9 (13.3%), and ST87 (13.3%) as the dominant types. All 83 isolates were classified into 75 cgMLST types, with six clusters showing identical profiles, indicating potential clonal transmission. Comparative genomic analysis revealed that strains of the same ST clustered together regardless of geographic origin, and some Beijing isolates differed by fewer than 10 alleles from strains isolated in other countries. All the isolates in the study carried virulence islands 1(LIPI-1) and LIPI-2. LIPI-3 was detected in ST1, ST11 and ST3 isolates, while LIPI-4 was found in ST87 isolates. About 42 isolates (50.6%, including ST1, ST11, ST5, ST307, ST8, ST9, ST155, and ST3) harbored SSI-1, and 18 ST121 isolates carried SSI-2. Only 3.61% (three strains) and 4.82% (four strains) of isolates exhibited resistance to tetracycline and erythromycin, respectively. No resistance to other tested antibiotics was observed.Conclusion:Foodborne Listeria monocytogenes in Beijing exhibits high genomic diversity but is dominated by specific STs, some of which are associated with hypervirulence. Some Beijing isolates have homology with food-derived isolates from other countries.

Objective:To analyze the types and characteristics of post-operative complications in colorectal cancer patients aged over 85 years undergoing laparoscopic surgery, and to summarize peri-operative management strategies.Methods:This was an observational study. Inclusion criteria: pathologically confirmed adenocarcinoma; tumor located in ileocecum, ascending colon, transverse colon, descending colon, sigmoid colon, or rectum; undergoing laparoscopic radical resection for colorectal cancer; complete clinical data. Exclusion criteria included distant metastasis, synchronous resection of multiple primary cancers, simultaneous liver metastasis surgery, and follow-up duration <1 month. A retrospective analysis was conducted on 191 patients of colorectal cancer patients aged over 85 years who underwent laparoscopic radical surgery in the General Surgery Department at Peking Union Medical College Hospital from January 2019 to January 2024. Among 191 patients, 107 patients (56.0%) had colon cancer and 84 (44.0%) rectal cancer. All patients received "home-based prehabilitation" and post-operative "enhanced recovery after surgery" protocols. Patient characteristics, peri-operative complication types, treatments, and outcomes were analyzed.Results:Post-operative complications occurred in 97 patients (50.8%), including 53 colon cancer patients (54.6%) and 44 rectal cancer patients (45.4%). Comorbidities existed in 88 patients (90.7%), with 93 patients (95.9%) classified as ASA II-III pre-operatively and 86 (88.7%) having nutritional risks. Surgical procedures included Dixon procedure (38 patients, 39.2%), right hemicolectomy (33 patients, 34.0%), sigmoidectomy (10 patients, 10.3%), and 17 patients (17.5%) received prophylactic stomas. Complication types comprised non-anastomotic infections (38 patients, 19.9%), intestinal flora disorder (26 patients, 13.6%), anastomotic/wound/stoma-related complications (16 patients, 8.4%), thrombotic/hemorrhagic events (6 patients, 3.1%), and others (11 patients, 5.8%). By Clavien-Dindo classification: Grade I (12 patients, 6.3%), Grade II (69 patients, 36.1%), Grade III (12 patients, 6.3%), and Grade IV (4 patients, 2.1%). Except for 5 patients (2.6%) requiring unplanned re-operation, all complications resolved with conservative treatment. The median duration of post-operative hospitalization was 9.5 days (7–13).Conclusion:Non-anastomotic infections and intestinal flora disorder constitute predominant complications after laparoscopic surgery in colorectal cancer patients aged over 85 years, mostly manageable with conservative treatment. Strengthened peri-operative management incorporating pre-operative prehabilitation and post-operative enhanced recovery after surgery protocols is crucial for patients aged over 85 years.

Objective:To explore the application of the camera inversion technique in laparoscopic sphincter-preserving surgery for mid to low rectal cancer.Methods:A retrospective study with historical controls was conducted on patients with non-metastatic mid to low rectal cancer which received laparoscopic total mesorectal excision at Peking Union Medical College Hospital from January 2019 to June 2024. The experimental group (2021.7-2024.6) utilized the camera inversion technique (rotating the lens 180° to position the bevel upward and switching the system to reverse display mode for improved visualization and operative angles) during key surgical steps (such as intraoperative mobilization of the mid-to-lower rectum and anastomosis), while the control group (2019.1-2021.6) did not. Clinical data and surgical videos were collected to analyze indicators like operative time, blood loss, mesorectal integrity, surgical complications, and postoperative hospital stay.Results:A total of 624 patients with non-metastatic mid to low rectal cancer were included, including 412 males and 212 females, with an average age of 59.8 years and an average tumor distance of 5.6 cm from the anal verge. The experimental group comprised 301 patients, while the control group had 323 patients.The proportion of abdominal ISR (intersphincteric resection) was significantly higher in the experimental group [19.3% (58/301) vs. 10.2%(33/323), χ 2=10.140, P=0.001], with a reduction in operative time [(161.8±67.8) minutes vs. (150.2±68.5) minutes, t=2.134, P=0.033] and a decrease in postoperative hospital stay [(7.8±2.1) days vs. (8.3±3.4) days, t=2.003, P=0.046]. The experimental group also demonstrated advantages in intraoperative blood loss, mesorectal integrity rate, and postoperative complications such as urinary retention, though these differences were not statistically significant (all P>0.05). Conclusion:In laparoscopic surgery for mid to low rectal cancer, using camera inversion technique during distal rectum dissection and transanal anastomosis can provide better surgical field exposure, facilitate precise operations within the correct anatomical plane, and minimize collateral damage. The camera inversion technique is safe and effective.