Abstract Frailty is a clinical state characterized by increased vulnerability due to the decline of multiple organ functions. It is clinically manifested as slow movement, reduced activity, low energy level and involuntary weight loss. Frailty heightens the risk of disability, long-term hospitalization and mortality in the elderly when they face stressful events. Early assessment of frailty and personalized interventions can prevent and delay its progression, thereby reducing the occurrence of adverse events. This article reviews the literature on frailty published both domestically and internationally from January 2015 to January 2024. It provides an overview of the tools for assessing frailty in the elderly, such as the Clinical Frailty Scale, Frailty Index, Fried Frailty Phenotype, FRAIL Scale, and biological markers, and the management of frailty, including exercise, nutritional interventions, oral health management, and medication management, so as to provide the evidence for early assessment and intervention of frailty.

OBJECTIVES: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). METHODS: Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. RESULTS: HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. CONCLUSIONS NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism* ; Animals ; Hepatocytes/metabolism* ; Lipid Metabolism ; Mice ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; AMP-Activated Protein Kinases/metabolism* ; Carnitine O-Palmitoyltransferase/metabolism* ; Diet, High-Fat ; Male ; Mice, Inbred C57BL ; Signal Transduction

Objective To investigate the optimal scanning parameters for cone beam computed tomography(CBCT)of the nasal bone,to achieve low-dose scanning of the nasal bone CBCT.Methods Utilizing Prangmerka CBCT 3D single-tooth sequence,nasal bone scans were performed on two human-equivalent phantoms using two dose protocols,five body types,and five resolutions,resul-ting in 50 scanning sequences.The dose area product(DAP)and volume CT dose index(CTDIvol)were recorded.Objective image quality assessment was conducted by calculating the contrast-to-noise ratio(CNR),signal-to-noise ratio(SNR),noise,and figure of merit(FOM)in region of interest(ROI)set on sagittal images.Subjective scoring was performed using a five-point Likert scale.Differences in radiation dose and image quality among various scanning parameters were compared and analyzed.Results(1)Signifi-cant differences in DAP were observed among different dose modes,body types,and resolutions(P＜0.05),with the lowest DAP values recorded for the XS body type.(2)Statistically significant differences in CNR,SNR,noise,and FOM were found among differ-ent dose modes and resolutions(P＜0.05).The XS body type exhibited the highest SNR and FOM values and the lowest noise.The 200 μm resolution demonstrated the higher CNR value and the highest SNR value,with moderate noise and FOM value.(3)Signifi-cant differences in image quality,contrast,sharpness,and noise were observed among different dose modes,body types,and resolu-tions(P＜0.05).Higher subjective scores were assigned to the 200 μm and 150 μm resolutions,indicating clear anatomical details.Conclusion The scanning parameters of 200 μm resolution combined with an ultra-low-dose protocol for the XS body type achieve a balance between low radiation dose and high image quality,making them suitable for low-dose nasal bone CBCT examinations.

Environmental pollution is closely linked to the occurrence and development of cancer. Chemical carcinogens are the most important environmental factors causing cancer in humans. Among them, persistent organic pollutants (POPs) are characterized by their widespread distribution, persistence, and bioaccumulation. Research on the carcinogenic effects of POPs has received considerable attention in recent years. This article reviewed the internal exposure, association with cancer risk, and potential carcinogenic mechanisms of five typical classes of POPs in the environment, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants (BFRs), and short-chain chlorinated paraffins (SCCPs). These five types of POPs have distinct carcinogenic mechanisms, including interfering with cell proliferation cycle, altering epigenetic inheritance, promoting oxidative stress, altering energy metabolism, and affecting immune function. The development of cancer is the result of interaction between intrinsic genetic factors and external environmental factors. In addition to focusing on how environmental POPs affect the genetic material of organisms, it is also important to consider their effects on the tumor microenvironment, including tumor immunity and angiogenesis. Understanding these effects is crucial for guiding future efforts in pollution control and precision medicine in cancer treatment.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective:To investigate the effect of hemoglobin (Hb) volatility on cardiovascular prognosis in peritoneal dialysis (PD) patients.Methods:Retrospective cohort study was designed. Patients undergoing stable PD for more than 3 months and followed up regularly for at least 1 year were enrolled from May 1, 2013 to October 31, 2014 in the General Hospital of Ningxia Medical University. According to the Hb variation based on the mean changes in Hb standard deviation at 1 month, 3 months, 6 months, 12 months over baseline Hb, all patients were divided into low volatility group (≤10 g/L), moderate volatility group (>10-20 g/L) and high volatility group (>20 g/L), and baseline information were compared among these groups. Kaplan-Meier survival analysis and Cox regression equation were used to analyze the relationship between Hb variation and cardiovascular mortality and all-cause mortality. Besides, the patients were divided into qualified group (Hb≥110 g/L) and substandard group (Hb<110 g/L) by the Hb level at the study endpoint (cardiovascular death and all-cause death) according to KDIGO guidelines and relevant literature. Cox regression analysis was used to analyze the relationship between Hb variation and cardiovascular death in qualified group or substandard group. Multivariate linear regression analysis was used to analyze the related factors of Hb fluctuation in PD patients.Results:A total of 267 patients were enrolled. There were 160 males (59.93%) in this study. The age was (52.66±13.72) years old, and the median dialysis age was 37(21, 61) months. The patients' baseline Hb (before dialysis) was (80.16±14.89) g/L and at the end of the study Hb was (105.34±22.08) g/L. Body mass index and baseline Hb levels in the high volatility group were lower than those in low volatility group and moderate volatility group (all P<0.05). Both moderate and high volatility groups had lower estimated glomerular filtration rate than that in low volatility group, and high volatility group had higher urea nitrogen level than that in low volatility group (all P<0.05). The amount of erythropoietin usage in the high volatility group was higher than that in moderate volatility group ( P<0.05). The Kaplan-Meier survival analysis results showed that there was no significant difference in survival rate for all-cause death (Log-rank χ2=0.735, P=0.693) and cardiovascular death (Log-rank χ2=2.961, P=0.228) in different Hb volatility groups. Cox regression analysis showed that after adjusting for age, sex, serum creatinine, and blood albumin, higher Hb volatility was associated with a lower risk of cardiovascular death ( HR=0.972, 95% CI 0.947-0.999, P=0.040). After adjusting for related confounding factors, higher Hb volatility was still a protective factor for cardiovascular death in the substandard group ( HR=0.946, 95% CI 0.903-0.992, P=0.022), but there was no significant correlation between Hb fluctuation and all-cause death. Multivariate linear regression analysis results showed that the fluctuation level of Hb was positively correlated with Kt/V ( B=4.682, 95% CI 2.480-6.884, P<0.001) and erythropoietin dosages ( B=0.001, 95% CI 0-0.001, P=0.003), and negatively correlated with baseline Hb ( B=-0.554, 95% CI -0.651--0.457, P<0.001). Conclusions:High Hb variability is a protective factor for cardiovascular death in PD patients with lower Hb level (substandard Hb). Adopting a reasonable program to correct anemia timely to reach the standard level has a greater impact on reducing risk of cardiovascular death in PD patients than Hb variation in anemia treatment.