Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L⁻¹. The average concentration of total NAms was 21.30 ng·L⁻¹, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10⁻⁶ to 1.11×10⁻⁵, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10⁻⁵) was higher than that for children and adolescents (1.38×10⁻⁶ to 2.61×10⁻⁶). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10⁻⁴) recommended by the U.S. Environmental Protection Agency (EPA).

Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L⁻¹. The average concentration of total NAms was 21.30 ng·L⁻¹, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10⁻⁶ to 1.11×10⁻⁵, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10⁻⁵) was higher than that for children and adolescents (1.38×10⁻⁶ to 2.61×10⁻⁶). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10⁻⁴) recommended by the U.S. Environmental Protection Agency (EPA).

Objective To explore the psychological experiences of operating room nurses participating in organ transplant surgeries, providing a basis for medical institutions to develop targeted psychological support programs. Methods Using a phenomenological research method, semi-structured, in-depth, face-to-face interviews were conducted from January to March 2026 with 17 operating room nurses who had participated in organ transplant surgeries at a tertiary hospital in Shanghai. Interviews were recorded, and observations were made. The interview data were analyzed, summarized, and themes were refined using Colaizzi’s seven-step analysis method. Results The psychological experiences of operating room nurses participating in organ transplant surgeries were identified as 5 main themes and 14 sub-themes: emotional impact and empathy load (shock and grief confronting life and death, deep empathy for patients and families, awe and gratitude towards organ donors); pressure experience and physical-mental exhaustion (urgency under time pressure, load of operational precision requirements, excessive consumption of physical and mental resources); cognitive appraisal and meaning construction (reappraisal of professional value, deep reflection on the meaning of life, positioning and identification of one’s role); coping strategies and adjustment process (active learning and experiential reflection, self-emotional regulation and social support); growth experience and psychological transformation (enhancement of psychological resilience, establishment of professional confidence, deepening of professional mission). Conclusions Operating room nurses undergo complex and profound psychological experiences while participating in organ transplant surgeries, enduring strong emotional impact and physical-mental stress while also achieving psychological growth and deepening professional identity through practice. Nursing managers should pay attention to the mental health of this group and construct a multi-level support system to promote their physical and psychological well-being.

Cardiac surgery is associated with high risks, significant trauma, and long recovery periods. With advances in cardiac surgery techniques, the mortality rate and incidence of complications have been steadily decreasing. Patient-reported outcomes have gradually become an important area of research in postoperative recovery of cardiac surgery. The use of patient-reported outcome measures (PROMs) in this field helps to reflect patients' physiological, psychological, and social functioning during recovery, and provides scientific evidence for clinical interventions, which may further improve prognosis and enhance patient recovery experience. This paper reviews the dimensions of PROMs in the field of cardiac surgery recovery, the current status of existing PROMs scales, and the progress of their application, while also identifies the limitations of the existing tools. Finally, it explores future research directions for PROMs in cardiac surgery patients.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P＜0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P＜0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P＜0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P＜0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P＜0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P＜0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.

[Objective]To summarize Professor LIN Xianming's clinical experience in treating tic disorders(TD)based on the"promoting Yang to relieve stagnation"approach.[Methods]Through clinical observation,literature review,and analysis of Professor LIN's theoretical discussions and medical case records,this study systematically elaborates the etiology and pathogenesis of TD,and further explores the unique diagnostic and therapeutic approach of"promoting Yang to relieve stagnation"by supporting clinical case.[Results]Professor LIN believes that TD often arises from the gradual stagnation of Yang Qi,leading to internal Yang stasis,which further exacerbates the condition.Manifestations arise either from Yang Qi failing to nourish the mind and sinews,or from the offensive surge of constrained Yang.The traditional"calming the liver and extinguishing wind"method may hinder the development of Yang Qi in children.Therefore,he proposes the"promoting Yang to relieve stagnation"method,combining Cinnamomi Ramulus-based formulas with acupuncture at back-Shu points,which facilitates the dispersal of Yang Qi and restores proper function,thereby nourishing the mind and tendons and alleviating the tics.The differentiated application of various Cinnamomi Ramulus-based formulas,combined with the"quick and slow needling technique"applied to back-Shu points,can effectively treat TD.The attached TD case presents a pattern of depressed Yang Qi failing to flowing smoothly,accompanied with offensive surge of constrained Yang Qi,along with Yang Qi deficiency.The treatment employed Guizhi Gegen Decoction combined with stimulation of the back-Shu acupoints to disperse stagnation and activate Yang,elevate Yang and restore Yin balance,resulting in favorable therapeutic outcomes.[Conclusion]Professor LIN's approach of treating TD through"promoting Yang to relieve stagnation"has shown remarkable efficacy and is worth promoting in clinical practice.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

OBJECTIVES: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure. METHODS: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified via PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested. RESULTS: A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells. CONCLUSIONS Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.
Quercetin/pharmacology* ; Myocytes, Cardiac/drug effects* ; Heart Failure/metabolism* ; Apoptosis/drug effects* ; MAP Kinase Signaling System/drug effects* ; Rats ; Animals ; Isoproterenol