BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

OBJECTIVE: Although dietary preferences influence chronic diseases, few studies have linked dietary preferences to mortality risk, particularly in large cohorts. To investigate the relationship between dietary preferences and mortality risk (all-cause, cancer, and cardiovascular disease [CVD]) in a large adult cohort. METHODS: A cohort of 1,160,312 adults (mean age 62.48 ± 9.55) from the Shenzhen Healthcare Big Data Cohort (SHBDC) was analyzed. Hazard ratios ( HRs) for mortality were estimated using the Cox proportional hazards model. RESULTS: The study identified 12,308 all-cause deaths, of which 3,865 (31.4%) were cancer-related and 3,576 (29.1%) were attributed to CVD. Compared with a mixed diet of meat and vegetables, a mainly meat-based diet (hazard ratio [ HR] = 1.13; 95% confidence interval [ CI]: 1.02, 1.27) associated with a higher risk of all-cause mortality, while mainly vegetarian ( HR = 0.87; 95% CI: 0.78, 0.97) was linked to a reduced risk. Furthermore, there was a stronger correlation between mortality risk and dietary preference in the > 65 age range. CONCLUSION A meat-based diet was associated with an increased risk of all-cause mortality, whereas a mainly vegetarian diet was linked to a reduced risk.
Humans ; China/epidemiology* ; Middle Aged ; Male ; Female ; Prospective Studies ; Aged ; Cardiovascular Diseases/mortality* ; Diet/statistics & numerical data* ; Neoplasms/mortality* ; Adult ; Cause of Death ; Food Preferences ; Proportional Hazards Models ; Mortality ; Cohort Studies

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective To construct the demand model of four types of medical resources including beds in hospi-tal,beds in intensive care unit(ICU),ventilators and medical human resources during the major infectious disease epidemic events,simulate and analyze the treatment of infectious diseases when different medical resources are in short supply.Methods Based on the susceptible-exposed-infectious-recovered(SEIR)model,considering the infec-tivity of infected persons,the susceptibility of the population and the immunity of convalescents,the characteristics of asymptomatic COVID-19 patients and different clinical types,the"COVID-19 infection-hospitalization model"was constructed.By collecting and setting the parameters of disease transmission,clinical course and medical re-source shortage scenarios,an analysis model of allocation and supply of urban medical resources during infectious di-sease epidemic events was initially formed based on Anylogic platform,the supply and demand of medical resources during infectious disease events in different scenarios were analyzed.Results In the non-intervention scenario,the peak time of bed demand was on the 107th day,and the peak value was 160.92 beds per thousand people;the peak time of ventilator demand was on the 122nd day,and the peak value was 5.61 units per thousand people;the peak time of ICU bed demand was on the 117th day,and the peak value was 12.78 beds per thousand people;the peak time of the demand for medical human resources was on the 109th day,and the peak value was 151.12 persons per thousand persons.The simulation results suggested that there were some differences in the impact of different medi-cal resources on the outcome of medical treatment.Conclusion This study constructs an analytical tool for the allo-cation and supply of urban medical resources under the epidemic events of infectious diseases,and the results of mul-tiple simulation experiments suggest that bed resources and medical human resources play more important roles in the outcome of medical treatment.

Based on the principle of'treating disease and seeking the root cause',Professor FU Wen-Bin proposed'treating radiation encephalopathy(REP)from yang',pointing out that the main pathogenesis of REP is yang qi deficiency,brain spirit dystrophy,phlegm and blood stasis blocking orifices.Using'supplementing yang and unblocking yang simultaneously','treating spirit from heart and gallbladder',combined with the method of regulating spirit and unblocking orifices at acupoints of governor vessol and conception vessel,and using the integrated acupuncture mode of'firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation'to play the role of supporting yang and treating spirit can effectively relieve symptoms and delay the development of the disease.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*