Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

With the increasing incidence of chronic diseases,the research is conducted to actively explore out of hospital management models for chronic disease patients globally.Among them,virtual ward is a management model based on multidisciplinary team collaboration to provide professional medical and nursing services for unplanned hospitalization high-risk population.This model not only facilitates the transition of patients from inpatient settings to home environments,improving disease prognosis and reducing hospitalization risk,but also alleviates the bed burden on large hospitals.This article provides a review of the concept,development,construction of the operational system,and patient management processes of virtual wards,and offers insights and suggestions to provide references for the optimization and development of out of hospital management models for chronic disease patients in China.

Objective:To evaluate the utility of pulse oximetry-derived parameters—specifically, the pulse oximetry plethysmographic waveform area under the curve (POP AUC) and the peripheral perfusion index (PPI)—in assessing disease severity and predicting prognosis in patients with sepsis. Methods:In this prospective descriptive study, 68 patients with sepsis were categorized based on illness severity into septic shock and non-shock groups, and by 28-day outcome into survival and non-survival groups. POP AUC, PPI, and lactate (Lac) levels were recorded at 0, 24, 48, 72, and 96 hours after admission. APACHEⅡ and SOFA scores were calculated within the first 24 hours. The prognostic value of these parameters was evaluated. Results:Significant differences were observed between the septic shock and non-shock groups in POP AUC, PPI, Lac (all P < 0.05 except at 96 h), APACHEⅡ, and SOFA scores (all P < 0.05). These differences were most pronounced at admission: POP AUC0 (2475.1 ± 899.0) vs. (4260.3 ± 1028.5), PPI 0 (0.78 ± 0.74) vs. (3.13 ± 2.18), Lac 0 (4.95 ± 4.32) vs. (2.07 ± 1.55), APACHE Ⅱ (16.78 ± 5.59) vs. 11.82 ± 4.89), and SOFA (8.89 ± 3.25) vs. (5.06 ± 2.60). Optimal prognostic cut-off values were 2741.43 for POP AUC, 0.97 for PPI, 2.05 for Lac, 12.5 for APACHEⅡ, and 5.5 for SOFA. ROC curve analysis showed that at 24 hours, POP AUC and PPI had significantly larger AUC values than Lac ( P < 0.05), while no significant differences were found among other parameters. Significant differences between non-survivors and survivors were also found in POP AUC, PPI (at 0, 24, and 48 h), APACHE II, and SOFA (all P < 0.05). No significant differences were observed in PPI (72 h and 96 h) or Lac between the two outcome groups. Conclusions:POP AUC and PPI, as derived from pulse oximetry, are non-inferior to Lac, SOFA, and APACHEⅡ scores in evaluating disease severity and predicting 28-day mortality in sepsis patients. These parameters show promise as practical and non-invasive tools for clinical assessment in sepsis.

With the increasing incidence of chronic diseases,the research is conducted to actively explore out of hospital management models for chronic disease patients globally.Among them,virtual ward is a management model based on multidisciplinary team collaboration to provide professional medical and nursing services for unplanned hospitalization high-risk population.This model not only facilitates the transition of patients from inpatient settings to home environments,improving disease prognosis and reducing hospitalization risk,but also alleviates the bed burden on large hospitals.This article provides a review of the concept,development,construction of the operational system,and patient management processes of virtual wards,and offers insights and suggestions to provide references for the optimization and development of out of hospital management models for chronic disease patients in China.

Since the National Health Commission launched the pilot work of " Internet+ nursing service" in 2019, medical institutions at all levels in China keep innovating their nursing service models to provide targeted high-quality care for discharged patients or special groups suffering from diseases and poor mobility. In April 2021, a tertiary hospital in Qingdao carried out the " Internet+ " whole course management practice with specialized nurses as the main service subjects, which center on discharged patients as the main service objects. By estabusing a management team and the construction of " Internet+ " information exchange platform, the hospital implemented the whole course of disease management process including patients′ pre-hospital management, in-hospital estimate, and post-hospital follow-up rehabilitation, to provide specialized nursing services such as PICC dressing change care, stoma care, and mother and infant care for patients at home. By February 2022, the " Internet+ " whole course management service had expanded to 50 kilometers away from hospital, with a total of 1 181 specialized nursing services. This management highlighted the characteristics of specialized nursing services in tertiary hospitals, accurately matched the needs of patients, reflected the concept of holistic care, and provided references for the rapid promotion of the development of " Internet+ nursing service" in China.

Objective:To provide information reference for resource allocation and decision-making in related fields, the cost-effectiveness of HIV input among men who have sex with men (MSM) in Ningbo. Different intervention coverages were compared.Methods:Taking MSM as the target population, data were collected and modeled by Optima HIV for the corresponding HIV health output and the budget under different intervention coverages.Results:According to the estimated size of the MSM population, which was 19 584 in Ningbo in 2020, if the coverage of 2020 baseline intervention is maintained in the next ten years, the number of HIV cases, new HIV infections, and HIV-related deaths among this population will show an upward trend. It is estimated that from 2021 to 2030, 7.9% of new infections and 1.7% of deaths can be avoided and the relevant funding investment comed to 2.4 time the baseline if the intervention coverage rate expanded to 3.0 times the 2020 baseline. After the coverage rate of intervention expanded to 3 times the baseline, it continued to grow, the health effect did not increase.Conclusions:At present, expanding the baseline coverage of HIV-related intervention projects among MSM in Ningbo and increasing capital investment will still reverse HIV-related death and reduce new infections. Moreover, there is a saturation point of the intervention effect. Researchers and policymakers must explore more effective interventions/combinations to obtain more significant health outcomes.

Objective:To investigate the association of muscle mass loss with atherosclerosis in elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 322 patients with T2DM aged≥60 years old were divided into muscle mass loss group( n=152) and non-muscle mass loss group( n=170) according to their appendicular skeletal muscle mass index(ASMI). All participants underwent physical examination, dual-energy X-ray absorptiometry check, carotid and lower extremity ultrasound, as well as laboratory tests. Results:Among 322 patients, 49(15.22%) patients were suffered from sarcopenia and 152(47.2%) patients with reduced muscle mass. The carotid and lower extremity atherosclerosis grades in the muscle mass loss group were significantly higher than those in the non-muscle mass loss group( P<0.05), with lower body mass index(BMI), T-score, ASMI, uric acid, and homeostasis model assessment of insulin resistance index( P<0.05). Multivariate logistic regression analysis showed that carotid atherosclerosis and lower extremity atherosclerosis were risk factors for muscle mass loss while BMI and 25-(OH)D 3 were protective factors for muscle mass loss. There existed a consistency in carotid atherosclerosis grade and lower extremity atherosclerosis grade of elderly patients with T2DM( P<0.01). Conclusion:Atherosclerosis has a predictive value for early sarcopenia in elderly patients with T2DM.

Objective:To investigate the effect of individualized positive end-expiratory pressure (PEEP) on postoperative lung complications in patients undergoing cardiac valve replacement.Methods:Sixty-four patients of both sexes, aged 40-70 yr, with body mass index of 18-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, undergoing elective cardiac valve replacement (single or double) from July to October 2020, were enrolled in this study.The patients were divided into 2 groups ( n=32 each) using a random number table method: control group (group C) and individualized PEEP group (group P). After recruitment maneuver, group C was set with a fixed PEEP of 4 cmH 2O, group P was titrated using a PEEP-step method, and PEEP was set at 4 cmH 2O after admission to intensive care unit (ICU). Before induction of anesthesia (T 0), before recruitment maneuver (T 1), at 20 min after PEEP ventilation (T 2), at 2 h after surgery (T 3), and at 24 h after surgery (T 4), arterial blood samples were taken for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations.The hemodynamic indicators (heart rate, mean arterial pressure and central venous pressure) at T 1-T 4 were recorded.Pulmonary complications were diagnosed according to clinical manifestations, imaging and blood gas analysis during the postoperative hospitalization.The postoperative length of hospital stay, extubation time and duration of ICU stay were recorded. Results:PEEP in group P [(6.1±1.4)cmH 2O] was significantly higher than that in group C ( P<0.05). Compared with group C, the concentrations of serum IL-6 and TNF-α at T 3 were significantly decreased, central venous pressure at T 2 was increased, and the incidence of postoperative pulmonary complications was decreased ( P<0.05), and no significant change was found in the length of hospital stay, extubation time and duration of ICU stay in group P ( P>0.05). Conclusion:Early application of individualized PEEP after termination of cardiopulmonary bypass can decrease the risk of postoperative pulmonary complications in patients undergoing cardiac valve replacement.

Lycopene, as a high value-added terpene compound, has been widely concerned by researchers at home and abroad. Firstly, the ability of lycopene synthesis of Saccharomyces cerevisiae model strains S288c and YPH499 was analyzed and compared. The results showed that YPH499 was more suitable for lycopene synthesis as yeast chassis. Subsequently, the effects of constitutive promoters GPDpr, TEF1pr and inducible promoters GAL1pr, GAL10pr on Lycopene synthesis were compared. The results showed that when GPDpr and TEF1pr were used as promoters of crtE, crtB and crtI in lycopene synthesis pathway, the production of lycopene was 15.31 mg/L after 60 h fermentation in shaking flask. When GAL1pr and GAL10pr were used as promoters, the production was 123.89 mg/L, which was 8.09 times higher. In addition, the methylvaleric acid (MVA) pathway was further modified to overexpress the key enzyme gene of N-terminal truncation, tHMG1 (3-hydroxy-3-methylglutaryl coenzyme A reductase). The lycopene production was 265.68 mg/L, and the yield per cell was 72.79 mg/g. The Saccharomyces cerevisiae strain designed and constructed in this study can express lycopene in high yield per cell, thus could be used in the industrial production of lycopene after further construction and optimization.
Biosynthetic Pathways ; genetics ; Fermentation ; Industrial Microbiology ; Lycopene ; metabolism ; Saccharomyces cerevisiae ; genetics ; metabolism ; Species Specificity

Objective:To explore the related factors of muscle mass loss in patients with type 2 diabetes mellitus, and to provide evidence for prevention of sarcopenia in type 2 diabetic patients.Methods:A cross-sectional survey was used to select type 2 diabetic patients admitted to the Department of Endocrinology, Affiliated Hospital of Qingdao University from January 2019 to August 2019. All subjects underwent dual-energy X-ray absorptiometry check. According to the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), the subjects were divided into a muscle reduction group and a non-muscle reduction group. Data including age, gender, body mass index, course of disease, blood index, urinary albumin-creatinin ration (UACR), and appendicular skeletal muscle index (ASMI) were collected. The relevant clinical data of viscera fat/subcutaneous fat (VAT/SAT), percentage of abdominal fat/percentage of hip fat (A/G), grip strength, and pace were analyzed for the related factors of muscle mass loss in type 2 diabetic patients.Results:A total of 369 patients with type 2 diabetes were enrolled, including 42 patients with sarcopenia (an incidence rate of 11.38%), and 155 patients with reduced muscle mass (an incidence of 42.01%). Age, systolic blood pressure, high density lipoprotein-cholesterol, UACR, VAT/SAT, and A/G in the muscle reduction group were higher than those in the non-muscle reduction group ( P<0.05). The parameter of body mass index, homeostasis model assessment for insulin resistance, estimated glomerular filtration rate (eGFR), ASMI, and grip strength were lower in the muscle reduction group than in the non-muscle reduction group ( P<0.05). Multivariate logistic regression analysis showed age, UACR, A/G, and VAT/SAT were risk factors for muscle loss, body mass index, eGFR, and grip strength were protective factors for muscle mass reduction. Conclusion:It is of great practical significance for type 2 diabetic patients, especially those with advanced age, central obesity, low body mass index, low grip strength, low glomerular filtration rate, and high UACR to perform an early screening and to begin an early intervention.