[Epidemiological Characteristics of Lung Cancer Incidence 
in the Tumor Registration Area of Gansu Province from 2010 to 2019].

BACKGROUND: Lung cancer is the malignant tumor with the highest incidence rate and the heaviest disease burden in China. In recent years, lung cancer has shown a high incidence trend, seriously affecting the health of the population. In this paper, we analyze the characteristics of lung cancer incidence in 2019 and the trend of incidence rate from 2010-2019 in the tumor registration area of Gansu province, in order to provide a reference basis for the development of lung cancer prevention and control strategies in Gansu province. METHODS: By analyzing the cases of lung cancer incidence in the tumor registration area of Gansu province in 2019, we calculated the incidence rate, medium incidence rate, world incidence rate and other related indexes; we used Joinpoint to calculate the annual percentage change (APC) for trend analysis. RESULTS: In 2019, a total of 3757 new cases of lung cancer were reported in Gansu province, accounting for 14.96% of all new malignant tumors. The incidence rate, medium incidence rate and world incidence rate and world rate of lung cancer were 40.52/105, 25.78/105, 25.86/105; and the cumulative rate of 0-74 years old, and the truncation rate of 35-64 years old were 3.23%, 40.03/105, respectively. The incidence of lung cancer rises with age, and is high in the age group of 40 years and above, and the incidence peaks in the male and female populations in the group of 75 years and above, and the group of 80 years and above, respectively. The crude incidence rate of lung cancer in the tumor registration area of Gansu province from 2010-2019 showed an overall increasing trend, and the rate of increase was relatively fast, with an APC 5.39% (P<0.05); Separately, according to gender, urban and rural areas, the incidence of lung cancer in all populations showed an increasing trend, and the APC of male, female, urban and rural populations were 4.98%, 6.39%, 6.26%, and 4.64%, respectively (all P<0.05). According to the trend analysis of lung cancer incidence rate by age group, only lung cancer incidence in the age group of 65 years and above increased at an annual average rate of 4.15% (P<0.05). CONCLUSIONS: The incidence rate of lung cancer in the tumor registration area of Gansu province from 2010 to 2019 shows a rising trend year by year, and there are differences in the incidence of lung cancer in people of different genders, regions and age groups, so comprehensive prevention and control work should be carried out for the key populations of lung cancer incidence.

Effective Combination of Targeted Therapies with Sonodynamic Treatment for Use in Exploring Differences in Therapeutic Efficacy across Organelle Targets.

Acoustic kinetic therapy systems that target specific organelles can improve the precision of a sonosensitizer, which is a perfect combination of targeted therapy and sonodynamic therapy (SDT) and plays an important role in current acoustic kinetic therapy. In this study, we loaded PpIX, a sonosensitizer, on targeted-functional carbon dots (CDs) via an amide reaction and then generated the mitochondria-targeted system (Mit-CDs-PpIX) and nucleus-targeted system (Nuc-CDs-PpIX), respectively, to deliver the sonosensitizer. Both systems exhibited minimal cytotoxicity in the absence of ultrasound stimulation. The efficacy of the targeted SDT systems was investigated using methylthiazol tetrazolium (MTT) assays, live/dead staining, flow cytometry, etc. Compared with the free PpIX and mitochondria-targeted system, the nucleus-targeted system is more potent in killing effect under ultrasound stimulation and induces apoptosis with higher intensity. To achieve the equal killing effect, the effective concentration of Nuc-CDs-PpIX is just one third of that of Mit-CDs-PpIX.

Short-term outcomes in patients with lung cancer-associated acute ischemic stroke.

BACKGROUND: To investigate the independent risk factors of poor short-term outcomes in patients with lung cancer-associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short-term outcomes. METHODS: We retrospectively enrolled patients with lung cancer-associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0-2) and poor outcomes (score 3-6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS. RESULTS: A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short-term outcomes were significantly higher in D-dimer (OR = 1.001, 95% CI: 1.000-1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008-1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802-19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity. CONCLUSION: In this study, we have identified three independent risk factors associated with poor short-term outcomes in pLCAIS: higher NC, CRP, and D-dimer levels. These findings may be helpful for clinicians in identifying poor short-term outcomes patients.

Polydopamine coated Au-Pt nanorods: Enhanced photothermal properties and efficient reactive oxygen scavengers.

As an emerging cancer treatment strategy, photothermal therapy (PTT) is precise, controllable, minimally invasive, low cost and less toxic side effects, thus photothermal transduction agents have been extensively investigated in recent years. Noble metal nanomaterials with unique localized surface plasmon resonance (LSPR) effects are particularly suitable as photothermal transduction agent, but the currently developed precious noble metal nano photothermal transduction agents face serious problems such as complex synthesis process, poor photothermal performance and high biotoxicity. Moreover, the large amount of reactive oxygen species (ROS) produced during PTT treatment could cause irreversible damage to the healthy tissues surrounding the tumor. In this work, we deposited platinum (Pt) on the tips of gold nanorods (AuNRs) to form dumbbell-shaped Au-Pt bimetallic nanorods (AuPtNRs), and functionalized AuPtNRs with biocompatible polydopamine (PDA) to obtain AuPt@PDA. With 808 nm laser irradiation, the prepared AuPt@PDA exhibited excellent photothermal stability, and its photothermal conversion efficiency (PCE) reached 81.78%, which was significantly higher than that of AuNRs (52.32%) and AuPtNRs (78.76%). With low cytotoxicity, AuPt@PDA decreased cell viability from 91.12% to 39.36% after PTT on cancer cells in vitro, while significantly reducing intracellular ROS levels generated by heat stress. Therefore, the excellent photothermal properties, high cancer cell killing and ROS scavenging activity of AuPt@PDA in PTT could be an ideal candidate for improving therapeutic efficacy while reducing the risk of toxic side effects due to heat stress-induced ROS formation.

Antibody-Drug Conjugates Derived from Cytotoxic seco-CBI-Dimer Payloads Are Highly Efficacious in Xenograft Models and Form Protein Adducts In Vivo.

This work discloses the first examples of antibody-drug conjugates (ADCs) that are constructed from linker-drugs bearing dimeric seco-CBI payloads (duocarmycin analogs). Several homogeneous, CD22-targeting THIOMAB antibody-drug conjugates (TDCs) containing the dimeric seco-CBI entities are shown to be highly efficacious in the WSU-DLCL2 and BJAB mouse xenograft models. Surprisingly, the seco-CBI-containing conjugates are also observed to undergo significant biotransformation in vivo in mice, rats, and monkeys and thereby form 1:1 adducts with the Alpha-1-Microglobulin (A1M) plasma protein from these species. Variation of both the payload mAb attachment site and length of the linker-drug is shown to alter the rates of adduct formation. Subsequent experiments demonstrated that adduct formation attenuates the in vitro antiproliferation activity of the affected seco-CBI-dimer TDCs, but does not significantly impact the in vivo efficacy of the conjugates. In vitro assays employing phosphatase-treated whole blood suggest that A1M adduct formation is likely to occur if the seco-CBI-dimer TDCs are administered to humans. Importantly, protein adduct formation leads to the underestimation of total antibody (Tab) concentrations using an ELISA assay but does not affect Tab values determined via an orthogonal LC-MS/MS method. Several recommendations regarding bioanalysis of future in vivo studies involving related seco-CBI-containing ADCs are provided based on these collective findings.

Synthesis, cytotoxicity for mimics of catalase: inhibitors of lactate dehydrogenase and hypoxia inducible factor.

Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. Two Mn(II) complexes with ligand containing di(pyridylmethyl) amine and pyrrol-ketone were used to attenuate the activity of LDH-A. The inhibition of the manganese(II) complexes on the proliferation of HepG-2 cells is related to their ability to disproportionate H2O2. Importantly, the synthesized mimic of catalase can decrease the expression of hypoxia inducible factor (HIF-1α) in HepG-2 cells. So we envision that the multifunctional mimics of catalase could attenuate the activity of LDH-A signaling the cancer cells to death through HIF-1α involved path.

The interaction between ionic liquids modified magnetic nanoparticles and bovine serum albumin and the cytotoxicity to HepG-2 cells.

The interaction between ionic liquids modified magnetic Fe3O4 (Fe2) and bovine serum albumin (BSA) is reported and is compared with NH2 functionalized magnetic nanoparticles Fe3O4 (Fe1) based on the UV-visible spectrum, steady-state fluorescence measurements, synchronous fluorescence and DSC methods. The results indicate a static quenching mechanism operating in both nanoparticles. The binding constant of the Fe2-BSA complex calculated from fluorescence data shows that BSA has a low binding affinity for Fe2 than Fe1. DSC data reveal that the thermal stability process of BSA in the Fe2-BSA complex is semi-reversible. This demonstrates that the ionic liquid modified magnetic nanoparticles (Fe2) enhance the thermostability of BSA in the range of 20-40°C, and protein attached Fe2 has higher thermal stability than free BSA. Moreover, the in vitro assay results show that Fe2 shows low cytotoxicity to HepG-2 cells.