Search

Backgrounds Hand grip strength (HGS) is one of diagnose criteria factors of sarcopenia and is associated with the survival of patients with cancer. However, few studies have addressed the association of HGS and 1 year mortality of patients with cancer cachexia. Methods This cohort study included 8466 patients with malignant solid tumour from 40 clinical centres throughout China. Cachexia was diagnosed using the 2011 International cancer cachexia consensus. The hazard ratio (HR) of all cancer cachexia mortality was calculated using Cox proportional hazard regression models. Kaplan–Meier curves were generated to evaluate the association between HGS and the 1 year mortality of patients with cancer cachexia. The interaction analysis was used to explore the combined effect of low HGS and other factors on the overall survival of patients with cancer cachexia. Results Among all participants, 1434 (16.9%) patients with cancer were diagnosed with cachexia according to the 2011 International cancer cachexia consensus with a mean (SD) age of 57.75 (12.97) years, among which there were 871 (60.7%) male patients. The HGS optimal cut‐off points of male and female patients were 19.87 and 14.3 kg, respectively. Patients with cancer cachexia had lower HGS than those patients without cachexia (P

Despite the known association between muscle mass/function and malnutrition-related mortality in upper gastrointestinal (UGI) cancer, no comprehensive study to determine the impact of muscle mass-dominant nutritional status on cancer prognosis has been conducted. The present study aimed to investigate the prognostic significance of integrated muscle mass and function in UGI cancer.Between July 2013 and March 2018, we enrolled 2546 cancer patients with risks of malnutrition (Nutrition Risk Screening 2002, ≥3 points) from a multicenter cohort study and split 527 patients with primary UGI cancer into an internal validation group. We prospectively performed instant nutritional assessment and recorded all general clinical characteristics of the participants, such as weight loss, body mass index, anthropometric measurements of muscle mass and function, dietary intake conditions, and disease burden and/or inflammation status based on the validated tools. Prognostic analyses were performed with post-assessment overall survival (OS).According to the entire set, UGI cancer was identified as the dominant risk factor for disease burden and inflammation criteria (hazard ratio (HR), 2.08, 95% confidence interval (Cl), 1.81-2.39, P 0.001). Integrated muscle mass/function analysis with validated cutoff values showed that hand grip strength/weight followed by triceps skinfold thickness and maximum calf circumference are the most potent predictors. Univariate and multivariate analyses revealed that reduced muscle mass/function (74.8%) and dietary intake (66.2%) independently affect OS of patients with UGI cancer. Significant associations were found between the reduced muscle mass/reduced dietary intake and the shortest OS (HR, 4.48; 95% Cl, 3.07-6.53; P 0.001). Appending subgroups of muscle mass/function and dietary intake to the pre-existing risk model increased the efficiency of the time-dependent receiver operating characteristic curve analysis for OS in UGI cancer, particularly within 2 years of instant nutritional assessment.Impaired muscle mass/function adversely affects the near-term prognosis in patients with UGI cancer. Along with a comprehensive evaluation of dietary intake conditions, the timely nutritional assessment might be useful for risk stratification of UGI cancers with potential for enteral and parenteral nutrition interventions.ChiCTR1800020329.

Xiao-Yue Liu,1– 4,&ast; Xi Zhang,1– 3,5,&ast; Guo-Tian Ruan,1– 3 Kang-Ping Zhang,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Meng-Meng Song,1– 3 Xiao-Wei Zhang,1– 3 Yi-Zhong Ge,1– 3 Ming Yang,1– 3 Hong-Xia Xu,6 Chun-Hua Song,7 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Oncology, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4School of Clinical Medicine, Hebei University, Baoding, 071000, People’s Republic of China; 5Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 6Department of Clinical Nutrition, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 7Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaEmail shihp@ccmu.edu.cnPurpose: Serum albumin can indicate the onset of cancer cachexia, provide information about a patient’s nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia.Patients and Methods: We conducted a nested case–control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for < 1 year and 266 patients who survived for ≥ 1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates.Results: Logistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia.Conclusion: Serum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia.Keywords: nutrition, survival, death, cachectic patients

A new furanone analog, (

Aim: To construct an edaravone-encapsulated liposomes (EDV-LIPs) formulation against acute ischemic stroke. Methods: EDV-LIPs were prepared by the film dispersion method. The biosafety was evaluated both in vitro and in vivo by flow cytometry and the histological staining method. Biodistribution and therapeutic effect of EDV-LIPs against acute ischemic stroke was investigated by fluorescent imaging, the behavior test, laser speckle imaging and triphenyltetrazolium chloride staining. Results: The nanoliposomes had a long circulation time and could accumulate in the brain lesion region in ischemic stroke rats. EDV-LIPs show good biosafety. EDV-LIPs could restore more cerebral blood flow, reduce infarct volume and decrease neuronal apoptosis. Conclusion: EDV-LIPs provide an effective alternative for drug-targeted delivery against acute ischemic stroke.

Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS).We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses.The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months).LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

A new diketopiperazine, cyclo-(d-8-acetoxyl-Pro-l-Leu) (1), together with eight known compounds (2-9) including three enterotoxins (2-4), four diketopiperazines (5-8) and maltol (9), were isolated from the mangrove derived-soil Streptomyces sp. SCSIO 41400. The planar structures of all compounds were determined from analysis of NMR spectra, MS, optical rotation and comparing with literature data. The absolute configuration of compound 1 was assigned by electronic circular dichroism (ECD). The isolated compounds (1-9) were tested for their acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Among them, the new diketopiperazine (1) displayed preferable PL enzyme inhibitory activity with IC50 value of 27.3 μg/mL, while compounds 2, 5 and 6 showed weak PL enzyme inhibitory activity. Further molecular docking simulation exhibited that compound 1 could be well bind with the catalytic pocket of the PL. Besides, compound 9 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, which was comparable to that of the positive control ampicillin with MIC value of 3.125 μg/mL.

Multifunctional nanoclusters based on Fe3O4 nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated Fe3O4 nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic Fe3O4@F127 nanoclusters via facile ultrasonic treatment. During this process, drug molecules can also be introduced into the nanoclusters and therefore the targeted drug delivery system was formed. Next, we verified the feasibility of the nanoclusters as drug delivery vehicles and magnetic contrast agents. The nanoclusters have an average size of 200 nm and remained stable in water for long periods. Folic acid-modified nanoclusters showed an enhanced intracellular uptake into HepG2 cells by using both cellular iron amount analysis and flow cytometry analysis. Besides, Fe3O4@F127@FA nanoclusters showed good compatibility in the tested concentration range and good sensitivity in T2-weighted MRI. The magnetic nanoclusters combined with drug delivery properties have greatly increased the significance in the diagnosis and therapy of diseases, which are suitable for systematical administration of hydrophobic drugs and simultaneously MRI diagnosis.

An ultra-sensitive T2-weighted MR imaging contrast agent was prepared based on Fe3O4 nanoparticles and Gd3+ ions (Fe3O4@Gd). Amino modified Fe3O4 nanoparticles were conjugated to diethylenetriamine pentaacetic acid, and finally coordinated with Gd3+ ions. The nanoparticles had a uniform morphology with a size of 100 nm and a Gd/Fe mass ratio of 1/110. The r2 (transverse relaxivity) of the Fe3O4 nanoparticles increased from 131.89 mM−1 s−1 to 202.06 mM−1 s−1 after coordination with Gd3+ ions. MR measurements showed that the aqueous dispersion of Fe3O4@Gd nanoparticles had an obvious concentration-dependent negative contrast enhancement. Hepatoma cells were selected to test the cytotoxicity and MR imaging effect. The application of Fe3O4@Gd nanoparticles as contrast agents was also exploited in vivo for T2-weighted MR imaging of rat livers. All the results showed the effectiveness of the nanoparticles in MR diagnosis.

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIPgt;1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

Background Systemic inflammatory responses caused by tumor cells play an important role in the occurrence and development of tumors. Most of these responses are accompanied by a decrease in muscle mass. The aim of this study was to identify biomarkers that most accurately predict prognoses in patients with non-metastatic cancer and to evaluate their clinical significance when combined with muscle markers. Methods This study retrospectively evaluated 2,797 cancer patients diagnosed with cancer at TNM stages I, II, and III. Lymphocyte-C-reactive protein ratio (LCR) in conjunction with calf circumference (CC) were used (or chosed) after evaluating the predictive value of 13 inflammatory marker combinations and five anthropometric indicators for patient outcomes using the C-index. The Kaplan-Meier method and Cox’s proportional hazards regression modeling were used to analyze the individual and combined effects of these two potential biomarkers on overall survival. Results This study enrolled 1,604 men (57.3%) and 1,193 women (42.7%) with a mean age of 58.75 years. Among the 13 inflammatory nutritional indicators, the LCR was the most accurate predictor of prognoses in patients with non-metastatic cancer. The optimal threshold for the LCR was 2,500. After multifactorial adjustment, we found that low LCR had an adverse effect on overall survival (hazard ratio [HR]: 2.50; 95% confidence interval [CI]: 2.17, 2.88; P

Long non-coding RNA play an importantr role in the differentiation of chondrocytes. This study aims to explore the role of long non-coding RNA in the transcriptional regulation of Notch4. In previous studies, it has been found that Notch signal can be used as the downstream of TGF-β signal to affect the proliferation and differentiation of deer antler chondrocytes, but the specific mechanism remains unclear. Here we found that lncRNA27785.1 was involved in the regulation of TGF-β/ Smad3 signal and Notch4 gene. The overexpression lncRNA27785.1 can negatively regulate the expression of Notch4 to inhibit cell proliferation and differentiation, while interference with lncRNA27785.1 can promote the expression of Notch4 gene to promote the proliferation and differentiation of chondrocytes. Subsequently, through luciferase experiment and CHIP experiment, we found that lncRNA27785.1 is regulated by Smad3 transcription, and Smad3 inhibited the expression of lncRNA27785.1. In addition, activated TGF-β signaling can reduce the inhibitory effect of lncRNA27785.1 on Notch4 signaling. In summary, we found that lncRNA27785.1 and TGF-β/Smad3 play an important role in Notch4 signaling. Our findings provided evidence to explain how TGF-β signaling regulate the Notch signaling pathway to influence chondrocyte proliferation and differentiation by a specific lncRNA27785.1.

A new furanone analog, (E)-2-(8,9-dihydroxy-6,8-dimethyldec-4-en-2-yl)-met-hylfuran-3(2H)-one (1), together with six known compounds, including two diterpenoids (2 and 3), one butyrolactone (4) and three isocoumarins (5–7), were isolated from a deep-sea fungus, Purpureocillium sp. SCSIO 06693. Among them, compound 1 existed as two tautomeric forms (1a and 1b) differing in configuration of the furan ring. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Isolated compounds were evaluated for their cytotoxic, antiviral, antibacterial, antioxidant, acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Biological evaluation results revealed that compound 4 showed modest antioxidant activity against DPPH with IC50 value of 72.03 μM. In addition, compounds 1–4 exhibited PL enzyme inhibitory activities.

The body's immune-nutrition status affects prognosis in patients with lung cancer. The Controlling Nutritional Status (CONUT) score is an immune-nutrition-related index associated with prognosis in other tumors. We aimed to assess the value of CONUT scores in predicting prognosis in patients with lung cancer.In this retrospective, multicenter study, 1339 patients with lung cancer were divided into low and high CONUT score groups. The relationship between CONUT scores and overall survival (OS) was assessed by survival curves and Cox proportional hazards regression modeling. A nomogram, including CONUT scores and other clinical variables, was established.There were 659 (49.2%; mean age, 59.91 years) low and 680 (50.8%; mean age, 62.23 years) high CONUT score patients. OS was significantly worse in patients with high than in those with low CONUT scores (P0.001), even after stratification by pathological types (non-small-cell lung cancer and small-cell lung cancer) and Tumor, Node, Metastasis (TNM) stages. A high CONUT score independently predicted risk in patients with lung cancer (adjusted hazard ratio, 1.48; 95% CI, 1.26-1.73; P0.001). The CONUT-based nomogram could predict prognosis well (C-index, 0.701), with better resolution and accuracy than TNM staging for predicting OS at 1, 2, and 3 years (area under the receiver operating characteristic curve, 0.735 vs 0.678, 0.742 vs 0.696, and 0.768 vs 0.743, respectively).The CONUT score can predict prognosis in patients with lung cancer. A CONUT-based nomogram can improve the accuracy of survival prediction in such patients.

An efficient, mild, and green method was developed for the synthesis of indeno[1,2-b]quinoxaline derivatives via o-phenylenediamine (OPD) and 2-indanone derivatives utilizing β-cyclodextrin (β-CD) as the supramolecular catalyst. The reaction can be carried out in water and in a solid state at room temperature. β-CD can also catalyze the reaction of indan-1,2-dione with OPD with a high degree of efficiency. Compared to the reported methods, this procedure is milder, simpler, and less toxic, making it an eco-friendly alternative. In addition, the β-CD can be recovered and reused without the loss of activity.

Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia.This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil-lymphocyte ratio (NLR) = neutrophil (× 10The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [p = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385-0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39-5.97), p = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality (p 0.001, 95% CI 1.99,7.38).ECW/TBW was better than other indicators in predicting survival of cancer patients with sarcopenia. High ECW/TBW combined with high NLR would further increase the risk of mortality.The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) (Chinese Clinical Trial Registry: ChiCTR1800020329, URL of registration: http://www.chictr.org.cn/showprojen.aspx?proj=31813 ).

Objective: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet–lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC).Methods: A total of 1131 patients with GC (811 men and 320 women, average age: 59.45 years) were evaluated. Receiver operating characteristic curves were used to determine the best cut-off values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. Results: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.06; 95% CI: 0.95-1.18; adjusted P = 0.271). In patients with SII >1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI: 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score, the worse the OS (PConclusion: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A Higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

One new citrinin monomer derivative (

Guo-Tian Ruan,1– 3,&ast; Ming Yang,1– 3,&ast; Xiao-Wei Zhang,1– 3,&ast; Meng-Meng Song,1– 3 Chun-Lei Hu,1– 3 Yi-Zhong Ge,1– 3 Hai-Lun Xie,1– 3 Tong Liu,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Xi Zhang,1– 3 Kang-Ping Zhang,1– 3 Xiang-Rui Li,1– 3 Qin-Qin Li,1– 3 Yong-Bing Chen,1– 3 Kai-Ying Yu,1– 3 Ming-Hua Cong,4 Kun-Hua Wang,5 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, People’s Republic of China; 5Department of Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery and Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, People’s Republic of ChinaTel +86-10- 6392 6985Fax +86-10 -6392 6325Email shihp@ccmu.edu.cnBackground: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality.Patients and Methods: This multicenter cohort study included 746 EPCC (age > 65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria.Results: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (< 25.03) had a worse overall survival (OS) than patients with high ALI (≥ 25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590– 2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups.Conclusion: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.Keywords: ALI, systemic inflammation, cancer cachexia, elderly, overall survival

Cancer cachexia is a systemic paraneoplastic phenomenon involving multiple organs, including the liver. Total bilirubin (TBIL) is an easily obtained blood biomarker that reflects liver homeostasis. The aim of this study was to evaluate the prognostic value of serum TBIL in patients with cancer cachexia.This study included 2282 patients from a multicenter research database who were diagnosed with cancer cachexia between June 2012 and December 2019. The hazard ratio (HR) for all-cause mortality was analyzed using Cox proportional hazards regression models. The association of serum TBIL with all-cause mortality was modeled with restricted cubic splines. The optimal cutoff value for TBIL was calculated with maximally selected rank statistics.Of the participants, there were 1327 (58.2%) men and 955 (41.8%) women. The mean patient age was 60.4 ± 1.5 y. The 12-mo all-cause mortality rate for patients with cancer cachexia was 29.5% (95% confidence interval [CI], 27.6%-31.3%), resulting in a rate of 209.58 events per 1000 patient-years. An inverted L-shaped association between TBIL and all-cause mortality was observed. The cutoff point for TBIL for the prediction of the time to mortality was21.7 µmol/L. A high TBIL level but not the direct bilirubin or indirect bilirubin level was identified as an independent prognostic factor (HR, 1.60; 95% CI, 1.32-1.93). For patients with digestive system tumors, a high serum TBIL level (≥21.7 µmol/L) was significantly associated with mortality.High TBIL levels are associated with increased all-cause mortality in patients and might be a promising prognostic indicator in patients with cancer cachexia.

A new indole diketopiperazine alkaloid, named penilline D (

In this paper, by designing a new type of mechanism, the time-varying cylinder load ofthe reciprocating compressor is simulated. The time-varying cylinder pressure load includes fourprocesses of expansion, suction, compression and exhaust, where the pressure of the expansionprocess is gradually reduced until it is equal to the suction pressure, and the pressures of the suctionand exhaust processes are almost constant. The pressure of the compression process is graduallyincreased until it is equal to the exhaust pressure value. Through the motion simulation of themechanism, four processes of time-varying cylinder pressure load can be realized. This newmechanism will provide new ideas for the time-varying load involved in the simulation of thereciprocating compressor fault test bench.

In this paper, the cold launch test platform is taken as the research object, theoptimization model of this test platform is established by using topology optimization method. First,the topology optimization goal of the structure is determined, and then the constraints are carriedout. Finally, optimized and non-optimized areas are identified, and the result is processed. Afteroptimization, the quality of the test platform was reduced by 2.9 tons under the conditions of use.

Nanostructure-based materials for multimodal imaging have attracted great attentions. Here we report a new formulation integrated gadolinium (Gd) and magnetite (Fe3O4) nanoparticles as magnetic resonance (MR) imaging contrast agent at both T1 mode and T2 mode. Polyetherimide coated iron oxide (Fe3O4@PEI) nanoparticles were first synthesized and then conjugated to diethylenetriamine pentaacetic acid (DTPA), which further chelated with Gd3+ ions (Fe3O4@PEI@DTPA-Gd). Both phantom and MR studies showed Fe3O4@PEI@DTPA-Gd nanocomposites could be applied in two modes (r1 = 4.7 mM−1 s−1, r2 = 131.82 mM−1 s−1). MTT and fluorescent staining results also suggested that the nanocomposites had good biocompatibility. Besides, Fe3O4@PEI@DTPA-Gd nanocomposites exhibited high entrap efficiency when the mass ratio of nanocomposites to DNA was up to 30:1. The in vitro gene transfection ability was also evidenced. Therefore, Fe3O4@PEI@DTPA-Gd nanocomposites can be employed as a potential candidate for MRI guided clinical diagnosis and gene delivery guided therapy.

OBJECTIVES To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

Objective Malnutrition is common and related to negative prognosis in patients with gastric cancer (GC). The Global Leadership Initiative on Malnutrition (GLIM), a novel consensus for the diagnosis of malnutrition, was proposed recently. However, the roles of GLIM in diagnosing malnutrition and predicting overall survival (OS) in patients with GC have been unclear. Method We conducted a multicenter, observational cohort study including 877 hospitalized patients with GC 2013 through 2018. Different anthropometric measurements were compared to assess reduced muscle mass. Kaplan-Meier curves and multivariate Cox regression were used to analyze the relationship between GLIM-defined malnutrition and the OS of patients with GC. Independent prognostic variables were incorporated to develop a nomogram for individualized survival prediction. The calibration curve was used to determine the predictive accuracy and discriminatory capacity of the nomogram. In addition, 219 patients with GC were enrolled for external validation. Results A total of 464 (53%) patients with GC were diagnosed with malnutrition. Patients diagnosed with severe malnutrition based on either midarm circumference or body weight–standardized hand grip strength had a shorter median survival time (16.7 mo; interquartile range, 8.4–32.7 mo) and a higher hazard ratio (HR, 1.49; 95% CI, 1.15–1.92; P = 0.002). Severe malnutrition was an independent risk factor for OS (HR, 1.32; 95% CI, 1.02–1.71; P = 0.038). The GLIM nomogram showed good performance in predicting 3-y survival in patients with GC. Conclusions Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in patients with GC.

Background Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients.Patients and Methods 8,749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and Decision Curve Analysis. Kaplan-Meier survival curves were used to compare the survival rate.Results Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score Ps < 0.001).Conclusion Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, validated and shown a better predictive validity for the overall survival of cancer patients.

A new diketopiperazine, cyclo-(

BackgroundColorectal cancer (CRC) is a common malignancy with high incidence of malnutrition. Increasing evidence showed that nutritional status could be a prognostic indicator of cancer survival. However, there were few prognostic models involving nutrition-related indicators in CRC. This study aimed to develop a nutrition-related prognostic model for CRC survival.MethodsThis multicenter retrospectively primary cohort data included 1,373 CRC patients, and the external validation cohort enrolled other 108 CRC patients. LASSO and multivariate regression analyses were used to select prognostic indicators and develop the nomogram. We performed C-index, calibration curves, and DCA to assess the discrimination, calibration, and applicability. Finally, the indicators of the nomogram model were used as adjustment factors. Multivariate Cox survival analyses were performed to investigate the benefit of the Patient-Generated Subjective Global Assessment (PG-SGA) and Global Leadership Initiative on Malnutrition (GLIM) malnutrition criteria to CRC prognosis.ResultsFive prognostic indicators (TNM stage, radical resection, reduced food intake, activities and function decline, and low albumin) were chosen to develop the nomogram. C-index of the nomogram was 0.74 (95% CI 0.72-0.77) and 0.72 (95% CI 0.62-0.81) in the primary cohort and validation cohort, which were higher than other models. Calibration plots and DCA showed that the nomogram model has a good consistency and clinical benefit in predicting CRC survival. Multivariate Cox survival analysis suggested moderate (PPP>0.05). Finally, stratified analysis suggested that malnourished CRC patients with low albumin synergistically increased the death risk of CRC OS both in PG-SGA and GLIM. (P for interaction = 0.007 and 0.004, respectively)ConclusionThis study established a prospective model to predict the OS in CRC patients using nutrition-related indicators. Moreover, we also found that PG-SGA had a better prognostic and predictive efficiency in CRC than GLIM. These findings grant further verification.

An ultra-sensitive

The facile fabrication of multifunctional nanocomposites (Fe3O4/HBC@F127) consisting of superparamagnetic Fe3O4 nanoparticles and fluorescent organic hexa-peri-hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid–polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a T2 relaxivity (r2) of 214.61 mM−1 s−1, which may be used as T2-weighted MR imaging agents. In vitro imaging studies indicated that the nanocomposites had good MR and fluorescence imaging effects with low cytotoxicity. Besides, the developed nanocomposites could also be applied as drug delivery vehicles. Doxorubicin (DOX) loaded Fe3O4/HBC@F127 nanocomposites significantly inhibited the growth of human hepatoma cells (HepG2). These findings suggested that the facile synthesized multifunctional nanocomposites may be used as a platform for dual mode imaging (both MR and fluorescence) and drug delivery.

Multifunctional nanoclusters based on Fe

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

Adsorption is used extensively to deal with increasingly serious water pollution. In this paper, beta-cyclodextrin-graphene oxide aerogel microspheres (CD-GAM) with 3D porous structure was prepared by electrospraying combining with freeze-casting and sequently mild self-assembly. Owing to the integration of graphene oxide (GO) and beta-cyclodextrin (β-CD), the CD-GAMs exhibit excellent broad-spectrum adsorption capabilities for dyes and organic micropollutants, including anionic dyes of methylene blue (439 mg/g) and Rhodamine B (388 mg/g), cationic dyes of acid red 87 (234 mg/g) and methyl orange (167 mg/g), organic micropollutants aromatic model compound of carcinogen 2,4-dichlorophenol (17 mg/g), pharmaceuticals of propranolol hydrochloride (49 mg/g), contraceptive ethynyl estradiol (19 mg/g) and plastic components bisphenol A (38 mg/g). The adsorption capacity of CD-GAM for most pollutants reach equilibrium within 10 min. In addition, the CD-GAM maintained stable regenerative adsorption capacity more than 80 % in five cycles. The broad-spectrum adsorbent CD-GAM is an ideal choice for removing complex and diverse pollutants from wastewater.

Glucocorticoids (GCs) play an important role in the treatment of several hematological malignancies, such as immune thrombocytopenia (ITP). The glucocorticoid receptor (GR) mediates the effects of GCs. Five isoforms of GR mRNA were described: GRα, GRβ, GRγ, GRP, and GRA. GR levels are regulated by alternative splicing of GR mRNA. Several studies demonstrated that a lower GR expression was associated with poor GC response.This study investigated the expression of GR isoforms and the relationship between GC resistance in ITP.This study determined GRα/β/γ/P mRNA and GRα/β protein expression levels using SYBR Green Real-time PCR and Western blot, respectively, in 49 newly diagnosed ITP patients and 31 controls.The expression of GR isoform mRNA in ITP and controls showed the following trend: GRα GRP GRγ GRβ. The expression of GRα, β mRNA and the total frequency of the four GR isoforms in ITP was significantly higher than in controls (P 0.05). The expression of GRα mRNA and protein in the GC-resistant group was significantly lower than that in the GC-sensitive group and controls (P 0.05). GRβ could not be detected at the protein level in our experimental conditions.GRα and GRP were the main GR isoforms responsible for the effects of GC, and GRα and GRP exhibited synergistic effects. The down-regulation of GRα levels may play an important role in GC resistance in ITP. The effects of GCs in ITP were not associated with changes in GRβ and GRγ.

The facile fabrication of multifunctional nanocomposites (Fe

The research of hydrogels has been increasingly focused on designing an effective energy dissipation structure in recent years. Here, we report a kind of novel supramolecular cross-linker, which was formed by self-assembling amphiphilic block copolymers with guest groups at the end and vinyl-functionalized cyclodextrin (CD) through host–guest interaction. These cross-linkers could dissipate energy effectively since they combined multiple sacrificial mechanisms across multiscales through physical interactions. The resulted hydrogel shows distinguishing mechanical properties (fracture toughness of 2.68 ± 0.69 MJ/m3, tension strength of up to 475 kPa, uniaxial stretch over 2100%), remarkable fatigue resistance, and thermal- and light-responsive behaviors.

Nickel nanowires (Ni NWs) have great potential to be used as a living cell manipulation tool and developed into an anticancer agent. However, their candidacy as biomedical appliances need detailed human cell studies, such as study of the interaction between Ni NWs and tumor cells. The present study investigated the cytotoxicity of Ni NWs in HeLa cells. A dose-dependent inhibition of cell growth was observed by using the MTT assay. We demonstrated that Ni NWs induced oxidative stress by generation of reactive oxygen species (ROS). Apoptosis induction was evidenced by flow cytometry, annexin V binding assay and DAPI staining. DNA flow cytometric analysis indicated that Ni NWs significantly increased the percentages of cells in S phase compared with control cells. This process was accompanied by the loss of mitochondrial membrane potential. These results revealed that Ni NWs induced apoptosis in HeLa cells via ROS generation and cell cycle arrest.

Fluorescent DNA probes based on the fluorescence resonance energy transfer (FRET) were presented in this paper when AuNPs were as the energy acceptors and CdTe quantum dots and CdTe/SiO2 core/shell nanoparticles were as the energy acceptors, respectively. The DNA probes were prepared when energy donors and acceptors were conjugated with two single-stranded complementary oligonucleotides and hybridized with each other and the fluorescent intensity of probes could be decreased. The quenching efficiency of DNA probe was about 67 % when CdTe QDs were as the energy donors, while that of DNA probe was about 75 % when CdTe/SiO2 fluorescent core/shell nanoparticles were as the energy acceptors, which indicated that CdTe/SiO2 core/shell nanoparticles were suitable donors compared with CdTe QDs in DNA probe field.

This study reports inorganic nanoparticles modified molecular beacons as fluorescent DNA biosensors. MBs were modified by using CdTe quantum dots as energy donors and 4-(4'-(dimethylamino) phenylazo) benzoic acid, black hole quencher 1 and Au nanoparticles as energy acceptors, respectively. CdTe quantum dots were linked to molecular beacons when 1-ethyl-3-(3-dimethylaminopropyl) carbodi-imide hydrochloride was added. The fluorescence intensity of the modified molecular beacons decreased tremendously compared to the fluorescence intensity of CdTe quantum dots, which indicated that the fluorescence resonance energy transfer occurred between the donors and acceptors. The results indicated that this type of molecular beacons has high specificity and can be used to distinguish complementary DNA and its mutants.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe3O4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe3O4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe3O4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe3O4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe3O4, Lf@GO@Fe3O4@DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe3O4 nanocomposites for therapeutic application in the treatment of gliomas.

INTRODUCTION For patients with refractory secondary hyperparathyroidism (SHPT), parathyroidectomy (PTX) has received increasing attention. However, evidence-based medicine shows that there is still controversy regarding surgical methods, efficacy, and safety. We retrospectively analyzed the process of diagnosis and treatment in one patient with severe SHPT and long-term chronic renal failure (CRF), so as to further improve the therapeutic effect. CASE PRESENTATION A 61-year-old female with SHPT and CRF manifested as no urine for 18 years, underwent PTX 4 times since September 2010, with satisfactory final recovery. The first operation involved resection of 3 parathyroid glands in the normal position; the second operation involved removal of an ectopic parathyroid gland, combined with parathyroid gland autotransplantation; the third operation was performed to resect suspected recurrent parathyroid gland; the fourth operation involved partial excision of the autotransplanted parathyroid glands. CONCLUSION Accurate preoperative localized diagnosis and optimal surgical approach play key roles in the prevention and treatment of SHPT; postoperative recurrence of SHPT caused by ectopic or autotransplanted parathyroid gland should receive more attention.

The toxicity of nanostructured materials and nanoparticles are very important considerations for many nanotechnology applications. Iron nanowires (NWs), as useful magnetic nanomaterials, may be good candidates for several biomedical applications. Here Fe NWs with an average diameter of about 50 nm were prepared by electrodeposition within the nanopores of anodic aluminum oxide (AAO) templates, and characterized by using scanning electron microcopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The cytotoxicity of the Fe NWs was studied at cell level. Specifically, the influence of concentration and size on the cytotoxicity of Fe NWs to HeLa cells was evaluated by MTT assay combined with direct morphology observations by TEM and phase contrast microscopy. The results clearly showed that the presence of Fe NWs had no significant effect on the cell proliferation and cell viability, even the HeLa cells exposed to Fe NWs at the high concentration of 10,000 per cell for 72 h still showed high cell viability of about 80%. From phase contrast microscopy, confocal laser scanning microscopy (CLSM) and TEM observations, it was found that Fe NWs were indeed internalized by HeLa cells. The cellular uptake process and results of Fe NWs demonstrated that as-prepared Fe NWs had not only a good biocompatibility but also a very low cytotoxicity.

Micelle-to-vesicle morphological transition has been achieved by light-induced rapid hydrophilic arm detachment from a star polymer. This provides a remote and clean method to control morphology transition of polymeric assemblies.

AIM To present clinical characteristics, diagnosis and treatment strategies in elderly patients with biliary diseases. METHODS A total of 289 elderly patients with biliary diseases were enrolled in this study. The clinical data relating to these patients were collected in our hospital from June 2013 to May 2016. Patient age, disease type, coexisting diseases, laboratory examinations, surgical methods, postoperative complications and therapeutic outcomes were analyzed. RESULTS The average age of the 289 patients with biliary diseases was 73.9 ± 8.5 years (range, 60-102 years). One hundred and thirty-one patients (45.3%) had one of 10 different biliary diseases, such as gallbladder stones, common bile duct stones, and cholangiocarcinoma. The remaining patients (54.7%) had two types of biliary diseases. One hundred and seventy-nine patients underwent 9 different surgical treatments, including pancreaticoduodenectomy, radical resection of hilar cholangiocarcinoma and laparoscopic cholecystectomy. Ten postoperative complications occurred with an incidence of 39.3% (68/173), and hypopotassemia showed the highest incidence (33.8%, 23/68). One hundred and sixteen patients underwent non-surgical treatments, including anti-infection, symptomatic and supportive treatments. The cure rate was 97.1% (168/173) in the surgical group and 87.1% (101/116) in the non-surgical group. The difference between these two groups was statistically significant (χ2 = 17.227, P < 0.05). CONCLUSION Active treatment of coexisting diseases, management of indications and surgical opportunities, appropriate selection of surgical procedures, improvements in perioperative therapy, and timely management of postoperative complications are key factors in enhancing therapeutic efficacy in elderly patients with biliary diseases.