Vision is closely tied to quality of life. Traditional drug delivery routes for clinical therapy of key ocular diseases, such as glaucoma, are topical and systemic administrations, which are less invasive but often face some physiological barriers such as tear film turnover, corneal penetration, and blood-ocular barrier. These barriers may limit penetration and distribution of ophthalmic drugs, resulting in limitation of information about pharmacokinetic characteristics of drugs in human eye. To address this, some ocular based compartment models, including classical ocular compartmental model and physiologically based pharmacokinetic(PBPK)model, have been established to illustrate dispositions of drugs in eyes. For classical ocular compartmental model, cornea or vitreous humor serves as central compartment and other ocular tissues are identified as peripheral compartments. The PBPK model, incorporating dynamic factors such as changes in ocular blood flow, effects of transporters, blood-ocular barrier, may characterize complex ocular physiology structure and dispositions of drugs in eyes. These models can contribute to development of new ophthalmic drugs and therapy strategies for ocular diseases. Here, the characteristics of drugs in eye following administrations via various routes, general ocular compartmental model and PBPK model as well as their applications in the development of new ophthalmic drugs and drug regimen for ocular diseases are reviened.

BACKGROUND: Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. METHODS: Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. RESULTS: An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. CONCLUSIONS The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.
Male ; Humans ; Female ; United States ; Middle Aged ; Incidence ; Lung Neoplasms/epidemiology* ; Linear Models ; China/epidemiology*

Objective:To investigate the influencing factors for the recurrence of TNM(T3~4N0M0)stage Ⅱ colorectal cancer in patients aged 75 years and over after radical resection.Methods:Clinicopathologic data of 161 colorectal cancer patients aged 75 years and over undergone radical resection in our hospital from January 2012 to August 2017 were retrospectively analyzed.They were followed up for 49 months(range: 2-84 months). Survival analysis was conducted by the Kaplan-Meier method and the survival rate was examined using the Log-rank method.Multivariate analysis was conducted by the proportional hazards regression model.Results:Univariate analysis showed that age≥80 years, preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, preoperative CA199 elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12, vascular invasion, nerve invasion, deficient mismatch repair(dMMR), risk stratification and adjuvant chemotherapy were related factors for the prognosis in patients with TNM stage Ⅱ colorectal cancer aged 75 years and over after radical resection.Multivariate analysis showed that preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12 and vascular invasion were independent risk factors for poor prognosis, and adjuvant chemotherapy was an independent factor for favorable prognosis.The 5-year-disease-free survival(DFS)rate was 41.6% in all patients.The Kaplan-Meier curves indicated that disease-free survival(DFS)between the low-risk, middle-risk and high-risk groups had a statistically significant difference( χ2=14.632, P=0.001). Kaplan-Meier survival analysis showed that high-risk patients receiving Oxaliplatin combined with Capecitabine adjuvant chemotherapy had better DFS than those receiving Capecitabine or non-adjuvant chemotherapy( χ2=11.157, P=0.004). Conclusions:DFS is improved in strictly selected patients with stage Ⅱ colorectal cancer aged 75 years and over and at high risk who receive Oxaliplatin combined with Capecitabine adjuvant chemotherapy.

Objective:To investigate the effect of a tankyrase inhibitor NVP-TNKS656 on the growth of hepatocellular carcinoma(HCC)cell lines and the involved molecular mechanisms.Methods:Five HCC cell lines were treated with 0, 2.5, 5.0, 10.0 μmol/L of NVP-TNKS656.The cell lines of HLE and HLF were selected and divided into four groups: 0.0 μmol/L(control or DMSO), 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups.Cells were cultured for 48 h for subsequent experiments.Crystal violet staining was used to count the number of the newly formed cell clones.Western blotting was used to detect the protein expression levels of Yes-associated protein(YAP), angiomotin-like 1(AMOTL1)and AMOTL2.The real-time qRT-PCR was used to detect the mRNA expression of YAP and its downstream connective tissue growth factor(CTGF)and cysteine-rich 61(Cyr61). Dual luciferase reporter gene was used to detect the luciferase activity of transcriptional enhancer activator domain(TEAD)family.Results:NVP-TNKS656 inhibited the growth of 5 HCC cell lines in a dose-dependent manner in HLE, HLF, Huh7, MHCC97-H, and MHCC97-L cell lines.There were significant differences in the newly formed cell clone numbers between control(0 μM of NVP-TNKS656)and each of 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups in a dose-dependent manner( F=90.46, 68.58, 191.8, 114.6 and 201.4, all P<0.05). In HLE and HLF cell lines, NVP-TNKS656 significantly reduced the protein level of YAP in a dose-dependent manner and decreased the YAP target gene CTGF(HLE cells: 1.02±0.02, 0.90±0.03, 0.57±0.02, 0.38±0.03, HLF cells: 0.98±0.03, 0.86±0.02, 0.66±0.02, 0.43±0.01)and Cyr61(HLE cells: 1.00±0.01, 0.86±0.02, 0.74±0.03, 0.44±0.03 and HLF cells: 0.99± 0.02, 0.87±0.01, 0.72±0.02, 0.54±0.01)( P<0.05), and inhibited the activity of YAP/TEAD luciferase.At the same time, NVP-TNKS656 up-regulated two major negative regulators of YAP, namely AMOTL1 and AMOTL2 proteins, and promoted the apoptosis of HLE and HLF cells in a dose-dependent manner. Conclusion:NVP-TNKS656 can inhibit the proliferation of HCC by stabilizing AMOTL1/ AMOTL2 and down-regulating the YAP target gene.This study indicates that NVP-TNKS656 can be used as a potential drug for treating HCC.

Objective To investigate the clinical characteristics,prognosis,and influencing factors of digestive system tumors in elderly patients complicated with acute pulmonary thromboembolism(PTE).Methods In this retrospective cohort study,we analyzed data from 86 elderly patients with digestive system tumors from the Oncology Department of Beijing Hospital from January 2007 to January 2017.Forty-one elderly patients who had digestive system tumors with PTE were assigned into an observation group and forty five without PTE into a control group.We analyzed the clinical characteristics of the two groups.Kaplan-Meier survival analysis was used to assess the median survival time;and Cox regression analysis was used to evaluate the influencing factors for prognosis.Results Eighty-six elderly patients with a mean age of(75.8 ± 13.7)years ranging from 60 to 92 years were enrolled.There was a statistically significant difference in the D-dimer level between the groups at baseline (P ＜ 0.05).In the observation group,the primary symptom was dyspnea(78.0％,n=67).Of all primary tumors complicated with PTE,colorectal cancers had the highest prevalence,accounting for 56.1％ (n =23),followed by gastric cancers,representing 31.7％ (n=13).Twenty-three patients in the observation group were complicated with deep venous thrombosis(56.1％,n-23),which mostly located in the lower limbs (56.5 ％,n =23).Meanwhile,90.2 ％ of PTE(n =37) occurred during chemotherapy or follow-up.Sixty-seven patients (77.9 ％) died during the follow-up,and the difference in mortality between the two groups was statistically significant(P ＜ 0.05).Kaplan Meier survival analysis showed a significant difference in median survival time between the two groups (3.7 vs.8.5 months,P ＜ 0.05).Cox regression analysis indicated that age,PTE,and metastasis were risk factors for median survival time(all P ＜0.05) Conclusions Elderly patients with digestive system tumors complicated with acute pulmonary thromboembolism show no typical characteristics and poor prognosis.Therefore,preventive measures and care should be taken to improve the prognosis,especially for patients at high risk of PTE.

Objective To observe the efficacy and safety of albumin bound paclitaxel in the treatment of retreatment advanced non-small-cell lung cancer (NSCLC).Methods Retreatment NSCLC patients failed from first line regimen or beyond were treated with albumin bound paclitaxel weekly by intravenous dose of 130 mg/m2 on day 1 and day 8,with a 21-day cycle.Efficacy was evaluated every two cycles and side effects were observed during each cycle.Results None of 69 patients achieved complete remission (CR),15 patients (21.7 ％) achieved partial remission (PR),and 23 patients (33.4 ％) achieved stable disease (SD).Objective response rate (ORR) was 21.7 ％,disease control rate (DCR) was 55.1％,and progress free survival (PFS) time was 3.8 months.Efficacy was not correlated with gender,age,histology and lines of previous treatment (all P ＞ 0.05).Main adverse reactions included neutropenia,alopccia and neurotoxicity,which were all tolerable.Conclusion Weekly albumin bound paclitaxel is effective and well tolerated in the treatment of retreatment advanced NSCLC,which can be considered as the second line or beyond regimen.

OBJECTIVETo develop a method for detecting the topical concentration of hydrocortisone (HC) in the subcutaneous adipose of rats using microdialysis sampling technique and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).

METHODSTopical samples were collected by applying the probe into the subcutaneous adipose of rats, with alcohol (5%)-ringers solution as the perfusion solution. A LC-MS/MS method was established for detecting the HC concentration in the dialysates.

RESULTSThe protonated precursor to produce ion transitions monitored for HC was m/z 363.2→121.1. The calibration curve was linear over the range of 0.5-1000 ng/ml, with the intra- and inter-day precision and accuracy within ∓15%, and no significant matrix effect was noted. The in vivo recovery of the probe was about 59%.

CONCLUSIONA selective and sensitive method has been successfully established for the on-line HC detection in the subcutaneous adipose of rats.

Administration, Cutaneous ; Animals ; Chromatography, Liquid ; methods ; Hydrocortisone ; administration & dosage ; pharmacokinetics ; Male ; Microdialysis ; methods ; Rats ; Rats, Wistar ; Subcutaneous Fat ; chemistry ; metabolism ; Tandem Mass Spectrometry ; methods