ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

OBJECTIVE: Improvement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship. METHODS: Annual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants. RESULTS: Although LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap. CONCLUSION In megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans.
Cities ; Health Status ; Humans ; Infant, Newborn ; Life Expectancy ; Quality of Life ; Social Determinants of Health

ObjectiveThe purpose of this study was to explore the difference in expression of gene between the osteosarcoma metastasis and primary specimens through NGS detection， in order to find the molecular mechanism of inducing osteosarcoma occurrence and metastasis. MethodsNext generation sequencing （NGS） was used to detect the tumor tissue samples of paired primary and metastatic lesions in 12 patients with metastasis， including 9 pairs of Panel detection （678 genes） and 3 pairs of whole exon detection （WES）. Copy number variation was detected by Excavator. DNA mutations were detected by Lumpy fusion， and RNA mutations were detected with Defuse + Star fusion. The distribution of mutations was shown by Circos. Metascape was used to analyze the enrichment of Go and KEGG signal pathways of differential genes. Pyclone+Citup/LICHEE was used for clonal evolution analysis. ResultsThe most frequent gene mutation mode of osteosarcoma was gene amplification， high-frequency mutation genes were FLCN（37.5%），GID4（37.5%），TP53（33.3%），ATRX（25%），CALR（25%），CCND3（25%），CCNE1（25%），NOCR1（25%），TFEB（25%），VEGFA（25%）， and the mutation frequency of cell cycle pathway was the highest. KT1， PLCG2 and EGFR were closely related to the metastasis of osteosarcoma. The frequency of tumor mutation burden （TMB） in metastatic lesions was significantly higher than primary lesions （P = 0.013）. Three patients detected by WES showed linear clonal evolution， suggesting that the mutations of osteosarcoma metastasis genes may be accumulated sequentially. We identified new candidate genes that may play an important role in the progression of osteosarcoma， including PLCG2， MYO15A and PEX6. ConclusionsThe most frequent gene mutation pattern of osteosarcoma occurrence and metastasis is gene amplification， and the frequency of tumor mutation burden （TMB） in metastatic lesions is significantly higher than that in primary lesions. There is an interrelated linear gene clonal evolution in patients with metastasis. This study suggests that PLCG2， MYO15A and PEX6 may play an important role in the progression of osteosarcoma.

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Background: Secondary preventive therapies play a key role in the prevention of adverse outcomes after coronary artery bypass grafting (CABG). However, medication adherence after CABG is often poor, and conventional interventions for improving adherence have limited success. With increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve adherence. Carefully designed trials are needed to provide reliable evidence for the use of these applications in patients after CABG. Methods: The Measurement and Improvement Studies of Surgical Coronary Revascularization: Medication Adherence (MISSION-2) study is a multicenter randomized controlled trial, aiming to randomize 1000 CABG patients to the intervention or control groups in a 1:1 ratio. We developed the multifaceted, patient-centered, smartphone-based Heart Health Application to encourage medication adherence in the intervention group through a health self-management program initiated during hospital admission for CABG. The application integrated daily scheduled reminders to take the discharge medications, cardiac educational materials, a dynamic dashboard to review cardiovascular risk factors and secondary prevention targets, and weekly questionnaires with interactive feedback. The primary outcome was secondary preventive medication adherence measured by the Chinese version of the 8-item Morisky Medication Adherence Scale at 6 months after randomization. Secondary outcomes included all-cause death, cardiovascular rehospitalization, and a composite of death, myocardial infarction, stroke, and repeat revascularization. Discussion: Findings will not only provide evidence regarding the feasibility and effectiveness of the described intervention for improving adherence to CABG secondary preventive therapies but also explore a model for outpatient health self-management that could be translated to various chronic diseases and widely disseminated across resource-limited settings. Trial Registration https://clinicaltrials.gov (NCT02432469).
Coronary Artery Bypass ; methods ; Humans ; Medication Adherence ; Myocardial Infarction ; prevention & control ; Secondary Prevention ; methods ; Smartphone ; Stroke ; prevention & control

Objective: To establish a scoring system for predicting the risk of side branch occlusion(SBO) in coronary bifurcation intervention based on visual estimation of quantitative coronary angiography (QCA). Methods: RESOLVE scoring system was developed from QCA. A total of 1545 patients with 1601 bifurcation lesions by RESOLVE study were enrolled. Based on RESOLVE scoring system, visual estimation was conducted to compare the consistency. According to SBO occurrence after main branch stent implantation, our research was divided into 2 groups: SBO group, which was defined by coronary angiography confirmed TIMI grade decreasing, n=114 patients with 118 lesions and Non-SBO group, n=1431 patients with 1483 lesions. Using RESOLVE scoring method as reference,V-RESOLVE scoring system was established, the discrimination, goodness-of-fit and V-RESOLVE score for the incidence of SBO were assessed;the diagnostic value for predicting the risk of SBO in coronary bifurcation intervention was compared between 2 scoring systems. Results: The consistency between visual and QCA was from fair to moderate (weighted Kappa=0.22-0.44). Compared with Non-SBO group, SBO group had the higher degrees of pre-operative bifurcation stenosis and side branch stenosis before main branch stent implantation; larger bifurcation angle and vessel diameters in main/side branches, all P<0.01. The area of V-RESOLVE under ROC curve was 0.76(95%CI 0.71-0.81) which was similar to the area of RESOLVE under ROC curve:0.77 (95% CI 0.72-0.81), P=0.74, Hosmer-Lemeshow P=0.17. The patients were categorized into 2 conditions by V-RESOLVE: high risk (V-RESOLVE score≥12)and non-high risk (V-RESOLVE score<12), the incidence of SBO was higher in high risk patients (16.7% vs 4.3%), P<0.01. The incidences of SBO were similar in non-high risk patients by V-RESOLVE and RESOLVE (4.3% vs 3.4%), P=0.22 and in high risk patients (16.7% vs 18.0%), P=0.60. Conclusion: V-RESOLVE scoring system may predict the risk of SBO in patients with coronary bifurcation intervention.

Objective To establish a 3D finite element model of an anti-shearing force Ni-Ti memory shape alloy patella claw for fixing patellar fracture, and analyze its mechanical performance. Methods The internal fixation model of transverse patellar fracture by patella claw was established by Pro/E 5.0, and then imported it into ABAQUS 10.1 for finite element analysis on its mechanical properties. The mechanical performance and deformation of the patella claw under two different patella femoral joint forces FQ at the knee flexion angle of 30°, 60°, 90° were analyzed, respectively. Results Under the same boundary condition, with the respective FQ as 367.5 N and 3 675 N, the maximum displacements of deformation were different at different flexion angles. As compared to fixation by tension band, using patella claw was preferable, with stronger resistance to tension and more stable anti-shearing force. Conclusions Deformation and displacement of the patella claw are in accordance with the biomechanical results needed in clinic, and its stability can satisfy clinical requirements for functional exercise as early as possible.

OBJECTIVETo study the feasibility of hand-assisted laparoscopic radical resection of rectal carcinoma and compare the short-term outcomes of HALS versus traditional laparoscopy approach.

METHODSClinical data of 42 cases of rectal carcinoma between January 2010 and March 2011 were enrolled in this study. Nineteen cases underwent HALS total mesorectal excision and 23 cases underwent traditional laparoscopy approach.

RESULTSAll the operations were successfully accomplished without conversions to open surgery. The mean operation time of the HALS group was shorter than that of the traditional laparoscopic group (152 min vs. 168 min, P=0.009). Incision length was significantly longer in the HALS group (5.6 cm vs. 4.5 cm, P=0.000). The median overall costs were lower in HALS group (26 000 RMB vs. 29 000 RMB, P=0.008). The number of lymph nodes in resected specimen, intra-operative blood loss, length of hospital stay, time to passage of flatus were comparable between the two groups.

CONCLUSIONSHand-assisted laparoscopic surgery has the advantages of laparoscopic surgery including minimal invasiveness, safety, and quicker postoperative recovery.

Colectomy ; Hand-Assisted Laparoscopy ; Humans ; Laparoscopy ; Rectal Neoplasms ; surgery ; Treatment Outcome

OBJECTIVESTo evaluate the characteristic morphology of heel spur, and to investigate the relationship of heel spur and plantar heel pain.

METHODSFrom June 2005 to April 2009, 210 cases (254 feet) with heel spur (according to Denis Pain Scale) were divided into cases group 1 (P2, n = 46), 2 (P3, n = 44), 3 (P4, n = 42), 4 (P5, n = 36) and controls group (P1, n = 42). Three-dimensional reconstruction of heel spur was performed in all groups using volume rendering based on multi-slice CT data by Super Image orthopedics edition 1.0. The characteristic morphology of heel spur was observed and the data were measured and analyzed, involving the width of basilar part, the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur.

RESULTSParts of cases groups displayed coarse arcuate edge and undersurface with one or more little heel spurs adhere to heel spur, of which the numbers were greater than controls group, especially in cases group 4. No significant difference of the width of basilar part of heel spur was found among 5 groups (F = 2.32, P > 0.05). However, obvious difference was found in the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur (F = 8.23, 6.82, 5.87, P < 0.05). Compared with the controls group, the angle between heel spur and planta pedis of cases groups had higher degrees, but the difference of the other data presented irregular.

CONCLUSIONSThe characteristic morphology of heel spur varies in patients associated with plantar heel pain. No correlation is found between the severity and the morphological data, including the width of basilar part, the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur.

Aged ; Calcaneus ; diagnostic imaging ; pathology ; Case-Control Studies ; Female ; Heel Spur ; complications ; diagnostic imaging ; pathology ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Tomography, X-Ray Computed