NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To investigate the water quality and sanitary conditions of rural self-provided wells water in Haidian District, Beijing, and to provide reference for strengthening water supply management of self-provided wells. Methods The water quality monitoring data of rural self-provided wells in Haidian District from 2018 to 2022 were analyzed. Results A total of 1 568 water samples were tested in 2018-2022 , of which 1 486 were qualified, with a qualified rate of 94.77%. The qualified rate in each year was 86.75% , 92.86% , 97.48% , 98.06% , and 99.34% , respectively , and the difference was statistically significant ( χ²= 75.296 , P＜0.05). The qualified rates of sensory traits and general chemical indexes, toxicological indexes and microbial indexes were 97.70%, 97.58% and 98.28%, respectively. There were statistically significant differences in the qualified rates among the three indexes in 2018, 2019 and 2021 (P < 0.05). The unqualified indicators included total hardness, total number of colonies, total coliform, fluoride, nitrate and turbidity, with a qualified rate of 97.96%, 98.41%, 99.17%, 99.11%, 98.47% and 99.94%, respectively. Conclusion The water quality of self-provided wells in rural Haidian District is good. Relevant departments should continue to strengthen the supervision of self-provided wells, such as the supervision of self-provided wells disinfection devices and water treatment equipment, to ensure the safety of drinking water for residents.

Objective To explore the impact of high glucose(HG)intervention on immune escape of pancreatic cancer cells and its molecular mechanisms.Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L)for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC)were transfected into PANC-1 cells,which were divided into control group,HG group,HG+mimics NC group,HG+mimics group,HG+mimics+oe-NC group,and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells;Western blot was used to detect the ex-pression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system,and CCK-8 was used to assess cell proliferation activity;apoptosis levels of cells were measured using flow cytometry;lactate dehydrogenase(LDH)release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells;dual-luciferase reporter system was used to validate the target-regulatory relationship between mi R-429 and ZEB1.Results HG could promote the expression of cell surface mole-cules PD-L1 and ZEB1 in PANC-1 cells(P＜0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells,while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 over-expression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells,compared with the control group,the proliferation activity of PANC-1 cells in the HG group sig-nificantly increased,and the apoptosis rate and cytotoxicity significantly decreased(P＜0.05).Compared with the HG+mimics NC group,the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased,and the apoptosis level and cytotoxicity significantly increased(P＜0.05).Compared with the HG+mimics group,the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased,and the apop-tosis rate and cytotoxicity significantly decreased(P＜0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1.Conclusion High glucose promotes immune escape of PANC-1 cells by down-regulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.

Objective:To clarify the application effect of information-guided enteral nutrition-associated diarrhea (ENAD) management process in patients with chronic obstructive pulmonary disease (COPD) undergoing non-invasive assisted ventilation.Methods:A mixed cohort study of pre- and post-control was conducted. Thirty-nine patients with COPD who were admitted to the emergency intensive care unit (ICU) of Huzhou First People's Hospital from July 1, 2021 to July 31, 2022 were enrolled. Taking the completion of the software development of ENAD management software for critically ill patients on January 28, 2022 as the time node, 20 patients admitted from July 1, 2021 to January 28, 2022 were set as the control group, and 19 patients admitted from January 29 to July 31, 2022 were set as the observation group. The two groups of patients received the same enteral nutrition support treatment, and the control group implemented the conventional ENAD treatment process with enteral nutrition intolerance disposal process as the core. On the basis of the control group, the observation group implemented the information-guided ENAD treatment process, and the system software actively captured the information of ENAD patients and reminded the medical team to improve the patient's diarrhea-related examination and provide alternative treatment plans. The duration of antidiarrhea, feeding interruption rate, and energy and protein intake, blood biochemical indexes, incidence of abnormal blood electrolyte metabolism, daily continuous non-invasive assisted ventilation and endotracheal intubation after 7 days of targeted diarrhea intervention were compared between the two groups.Results:Except for the basal pulse rate, there were no significant differences in gender distribution, age, and vital signs, basic nutritional status, arterial blood gas analysis and blood biochemistry at admission between the two groups, indicating comparability between the two groups. When ENAD occurred, the patients in the observation group obtained earlier cessation of diarrhea than those in the control group [days: 3.00 (2.00, 3.25) vs. 4.00 (3.00, 5.00), P < 0.01], and the feeding interruption rate was significantly lower than that in the control group [10.53% (2/19) vs. 65.00% (13/20), P < 0.01]. After 7 days of diarrhea intervention, the energy intake of the observation group was significantly higher than that of the control group [kJ·kg -1·d -1: 66.28 (43.34, 70.36) vs. 47.88 (34.60, 52.32), P < 0.01], the levels of hemoglobin (Hb), albumin (Alb) and serum prealbumin (PAB) were significantly higher than those in the control group [Hb (g/L): 119.79±10.04 vs. 110.20±7.75, Alb (g/L): 36.00 (33.75, 37.25) vs. 31.00 (30.00, 33.00), PAB (mg/L): 155.79±25.78 vs. 140.95±14.97, all P < 0.05], the daily continuous non-invasive assisted ventilation duration was significantly shorter than that of the control group [hours: 14 (12, 16) vs. 16 (14, 18), P < 0.01], and the arterial partial pressure of carbon dioxide (PaCO 2) was significantly lower than that of the control group [mmHg (1 mmHg ≈ 0.133 kPa): 66.00 (62.00, 70.00) vs. 68.00 (67.50, 70.05), P < 0.05]. However, there were no significant differences in protein intake, incidence of abnormal electrolyte metabolism, and incidence of endotracheal intubation due to acute respiratory failure between the two groups. Conclusion:The information-guided ENAD treatment process can enable the COPD patients undergoing continuous non-invasive assisted ventilation who experience ENAD to receive earlier cessation of diarrhea, and improve the protein energy metabolism and respiratory function of the patients.

Objective:To investigate the long-term efficacy of self-designed posterior atlas polyaxial screw-plate in the treatment of unstable atlas fracture.Methods:A retrospective case series study was conducted to analyze the clinical data of 20 patients with unstable atlas fracture who were admitted to Affiliated Honghui Hospital of Xi′an Jiaotong University from January 2011 to April 2013, including 14 males and 6 females, aged 23-60 years [(42.7±8.6)years]. All the patients were treated with internal fixation using self-designed posterior atlas polyaxial screw-plate. The operation time and intraoperative bleeding volume were recorded. The fracture reduction was evaluated by CT scan at 3 days after surgery. The bone healing was observed by X-ray (anterior-posterior and lateral views of the cervical spine) and CT scan at 9 months after surgery. The delayed spinal cord injuries were evaluated by Frankel grade at 1 and 2 years after surgery and at the last follow-up. The Visual Analogue Scale (VAS) before surgery, at 3 months, 1 year, 2 years after surgery and at the last follow-up were compared. The axial rotation, flexion and extension range of the cervical spine at 3 months, 1 year, 2 years after surgery and at the last follow-up were compared. Intraoperative and postoperative complications were observed.Results:All the patients were followed up for 121-148 months [(135.0±6.8)months]. The operation duration was 68-122 minutes [(86.0±14.1)minutes], with the intraoperative blood loss of 90-400 ml [(120.0±67.9)ml]. The CT scan of the cervical spine at 3 days after surgery showed all satisfactory fracture reduction. Satisfactory bone reunion was observed at 9 months after surgery. All patients were scaled as Frankel grade E at 1 year, 2 years and at the last follow-up after surgery, with no delayed spinal cord injuries observed. The VAS scores of the cervical spine at 3 months, 1 year, 2 years after surgery and at the last follow-up were 2.0(1.3, 3.0)points, 1.0(1.0, 1.8)points, 1.0(0.3, 1.0)points and 1.0(0.3, 1.0)points, which were significantly lower than that before surgery [7.0(6.0, 7.8)points] ( P<0.05), with significantly lower scores at 1-, 2-year after surgeny and at the last follow-up than at 3 months after surgery ( P<0.05). There were no significant differences among the other time points ( P>0.05). The axial rotation ranges of the cervical spine were (103.0±8.3)°, (128.3± 11.4)° and (129.8±13.6)° at 1 year, 2 years after surgery and at the last follow-up respectively, which were significantly higher than that at 3 months after surgery [(85.3±7.0)°] ( P<0.05); It was further improved at 2 years after surgery and at the last follow-up compared with that at 1 year after surgery ( P<0.05), with no significant difference at the last follow-up compared with that at 2 years after surgery ( P>0.05). The flexion and extension range of the cervical spine at 1 year, 2 years after surgery and at the last follow-up were (65.5±4.8)°, (78.3±6.5)° and (79.3±6.9)° respectively, which were significantly higher than that at 3 months after surgery [(54.3±4.4)°] ( P<0.05); It was further improved at 2 years after surgery and at the last follow-up compared with that at 1 year after surgery ( P<0.05), with no significant difference between the last follow-up and 2 years after surgery ( P>0.05). No intraoperative injuries such as arteriovenous injury were observed. No incision infection or dehiscence occurred after surgery, with no complications caused by long-term bed rest such as lung or urinary tract infection, pressure sore formation or deep vein thrombosis occurred. No loosening or breakage of the screw and atlas plate was observed at the long-term follow-up. One patient had mild cervical pain, snap during rotation, and limited range of motion at the last follow-up. Conclusion:Self-designed posterior atlas polyaxial screw-plate has merits including small surgical wounds, satisfactory reduction, solid fixation, obvious pain relief, effective preservation of the previous cervical motion, few complications, and satisfactory long-term efficacy in the treatment of unstable atlas fracture.

AIM: To study the effect of intense pulsed light(IPL)combined with meibomian gland massage on postoperative dry eye in cataract patients with meibomian gland dysfunction(MGD).METHODS: A retrospective analysis was conducted on the general data of 100 patients(100 eyes)with cataract and postoperative dry eye syndrome accompanied by MGD treated in our hospital from June 2022 to June 2023. They were divided into a control group(n=50)and an observation group(n=50)according to different treatment methods, and received meibomian gland massage and meibomian gland massage combined with IPL treatment, respectively. The tear film break-up time(BUT), Schirmer I test(S I t), meibomian gland secretion score, ocular surface disease index(OSDI), ocular staining score(OSS), and treatment efficacy of the two groups of patients were compared before treatment and at 1 wk and 1 and 3 mo after treatment.RESULTS: The BUT and SIt in both groups after treatment were higher than those before treatment, while the secretion of meibomian gland, OSS score, and OSDI score were lower than those before treatment(all P<0.05); the observation group had higher levels of BUT and SIT at 1 wk, 1 and 3 mo compared to the control group(all P<0.05), and lower levels of meibomian gland secretion, OSS score, and OSDI score compared to the control group(all P<0.05); the effective rate of treatment in the observation group was 86.0%, which was higher than that in the control group(68.0%; P<0.05).CONCLUSION: IPL combined with meibomian gland massage for treating postoperative dry eye in cataract patients with MGD can promote the extension of BUT, increase tear secretion, and reduce OSS and OSDI scores.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Objective:To explore the application effect of the teaching method combining process-oriented-guided inquiry learning (POGIL) theory and micro-class in orthopedic clinical internship.Methods:The 118 interns who completed internship from January 2022 to December 2022 were randomly divided into a control group (58) and an experimental group (60). The control group received traditional teaching, while the experimental group received a teaching method combining POGIL theory and micro-class. After the internship, the two groups were compared for assessment scores (basic theoretical knowledge and professional theoretical knowledge), learning status (classroom performance and self-learning ability), clinical practice ability (Leicester Assessment Scale), and teaching satisfaction. The t-test and chi-square test were performed using SPSS 21.0. Results:After the internship, the assessment scores, classroom performance, self-directed learning ability scores, clinical skills, case writing scores, and teaching satisfaction of the experimental group were all higher than those of the control group ( t/ χ2=5.01, 3.72, 2.20, 6.57, 3.56, 4.52, P<0.05). Conclusions:The teaching method combining POGIL theory and micro-class can enhance the master of theoretical knowledge by orthopedic interns, optimize classroom performance, cultivate self-learning ability, and improve clinical practice ability and teaching satisfaction.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To explore the actor-partner interdependence between depressive symptoms and social participation, comorbidity in older couples in China, so as to provide new directions for depression intervention in older adults.Methods:A total of 4 346 older adults (2 173 older couples) were included using data from the 2020 China Health and Retirement Longitudinal Study (CHARLS). Spearman correlation was used to analyze the correlation between social participation, comorbidities, and depressive symptoms among older couples in China. AMOS software was used to establish an actor-partner interdependence model of depressive symptoms and social participation, comorbidities in older couples in China, and to analyze the actor-partner effects of social participation and comorbidities on depressive symptoms in older adults and their spouses.Results:The detection rate of depressive symptoms among 4 346 older adults was 38.66% (1 680/4 346), and the depressive symptom score of wives was higher than that of husbands ( Z=15.445, P<0.01). The analysis of the actor-partner interdependence model showed that the social participation and comorbidity of wives and husbands had a actor effect on their own depressive symptoms ( β=-0.097, P<0.01; β=0.275, P<0.01; β=-0.070, P<0.01; β=0.282, P<0.01), and the social participation of wives and husbands had a partner effect on their spouse's depressive symptoms ( β=-0.054, P<0.01; β=-0.054, P<0.01), and the comorbidity of husband had a partner effect on his wife's depressive symptoms ( β=0.057, P<0.01) . Conclusions:The dualistic interaction effects of actor-partner exist in the depressive symptoms, social participation, and comorbidities of older couples in China. Medical and nursing staff should pay attention to the dual effects of "patient-family caregiver" when intervening in depression and chronic diseases, and focus on the depressive symptoms of older women.