Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*

Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.

Objective:To investigate the correlation between serum lipoprotein (a) [LP(a)] and the severity of white matter hyperintensities (WMHs) in the middle-aged and elderly people in the community.Methods:Consecutive middle-aged and elderly residents residing in the community underwent physical examinations in the Affiliated Jiangning Hospital of Nanjing Medical University from June 2016 to August 2021 were retrospectively collected. Fasting venous blood was collected on the next day of admission to detect the level of Lp(a). During hospitalization, cranial MRI examination was performed and the severity of WMHs was graded using the Fazekas visual scoring method. Ordinal multivariate logistic regression analysis was used to determine independent related factors for the severity of WMHs.Results:A total of 1 752 patients were included in the analysis. There were 969 males (55.31%) and 783 females (44.69%). Their age was 66.18±10.32 years old. There were 1 167 patients (66.61%) in the mild WMHs group, 407 (23.23%) in the moderate WMHs group, and 178 (10.16%) in the severe WMHs group. Ordinal multivariable logistic regression analysis showed that after adjusting for confounding factors, a higher serum Lp(a) level was independently related to the severity of WMHs (with the first quartile as a reference, the third quartile: odds ratio 1.441, 95% confidence interval 1.050-1.976, P=0.023; the fourth quartile: odds ratio 1.717, 95% confidence interval 1.252-2.354, P=0.001). Conclusion:Serum Lp(a) is independently correlated with the severity of WMHs.

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.

Objective:To explore the effects of aloe vera extra (AVE) on lipopolysaccharide (LPS)-induced inflammatory response of human periodontal ligament cells(hPDLCs).Methods:hPDLCs were induced with LPS at 1 μg/ml for the simulation of periodontitis model(model group) and then treated by AVE at 0.05,0.1,0.2 mg/ml respectively(AVE group).Cell viability was examined by MTT assay.The level of interleukin-6(IL-6) from cell culture medium was measured by ELISA.The expression of Toll like receptor 4(TLR4) protein was detected by immunocytochemistry staining and the transfer of nuclear factor-kappa B p65 (NF-κB-p65) was observed by immunofluorescence staining.Results:There was no significant difference of the cell viabilities among the groups.IL-6 in culture medium,the expression of TLR4 protein and the transfer of NF-κB-p65 into the nucleus were increased in model group.AVE at 0.05-0.2 mg/ml inhibited the secretion of IL-6 in the cell culture supernatant down-regulated the TLR4 expression,attenuated the transfer of NF-κB-p65 into the nucleus in a concentration-dependent manner.Conclusion:Aloe vera extract can inhibit the inflammation response of hPDLCs induced by LPS through TLR4/ NF-κB-p65 signaling pathway.

Objective To explore the anti-inflammatory and antipruritic effects of Chushizhiyang ointment in a mouse model. Methods A total of 40 male 8-week-old BALB/c mice were included in this study, and randomly and equally divided into 4 groups. A mouse model of atopic dermatitis (AD)was established in three groups of mice by repeated application of 2,4-dinitroflurobenzene (DNFB)to shaved abdominal skin for sensitization and to shaved dorsal skin for stimulation. After establishment of the AD model, the three groups were topically treated with sodium chloride physiological solution (model group), hydrocortisone cream (hydrocortisone group)and Chushizhiyang ointment (Chushizhiyang group)respectively for 14 consecutive days. The remaining group receiving no sensitization or treatment served as the normal control group. All the mice were sacrificed 12 hours after the final treatment, and the dorsal skin of mice was resected followed by the determination of skin thickness and weight as well as hematoxylin-eosin(HE)staining and toluidine blue staining for the counting of leukocytes and mast cells respectively. Moreover, enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of interferon-gamma(IFN-γ), tumor necrosis factor alpha(TNF-α), interleukin 4(IL-4)and IL-5 in dorsal skin lesions. In addition, a local skin itching model was induced by histamine phosphate in Hartley guinea pigs, which was used to explore the effect of Chushizhiyang ointment on itch thresholds. Results Compared with the model group, both the Chushizhiyang group and hydrocortisone group showed reduced thickness and weight of dorsal skin in mice (all P < 0.01), numbers of infiltrating lymphocytes and mast cells (all P < 0.01)and levels of IFN-γ, TNF-α, IL-4 and IL-5 in skin lesions (P < 0.05 or 0.01)on day 15 after the start of treatment. The thickness and weight of dorsal skin in mice were significantly decreased in the hydrocortisone group (P <0.01), but experienced no significant changes in the Chushizhiyang group compared with the normal control group. Additionally, Chushizhiyang ointment could significantly increase itch thresholds in guinea pigs induced by histamine phosphate(P < 0.01). Conclusions Chushizhiyang ointment can significantly inhibit DNFB-induced AD in mice, likely by restoring the balance between Th1 and Th2 type cytokines. Moreover, Chushizhiyang ointment could markedly relieve itching induced by histamine phosphate in guinea pigs.

Objective To investigate the potential vascular stimulation of potassium chloride and sodium chloride injection.Methods Sixteen rabbits were divided equally into two groups:group one and group two,with six rabbits in each group.According to the highest dose and maximum infusion speed for routine potassium supplementation in clinic,potassium chloride and sodium chloride injection or 0.9％ sodium chloride injection was administrated,respectively,at the same infusion speed and the same infusion volume via the marginal ear veins of rabbits.The vascular stimulation and the pathological changes of marginal ear vein and its surrounding tissue of rabbits were observed by the blinding method.Results Vascular stimulation,including hyperaemia,tumidness,necrosis and pathological changes,such as inflammatory cell infiltration and cellular necrosis,were not found in two groups.Conclusions Potassium chloride and sodium chloride injection has no stimulation to the wall of blood vessels.

To study the influence of hypercholesterolemia with caveolin-1 on the plasmalemma of vascular endothelium, we used the methods of immunohistochemistry to detect the dynamic changes of caveolin-1 in cultured ECV-304 cells which were stimulated high cholesterol serum and the arterial endothelium of hypercholesterolemia rats. It is resulted that high cholesteorol level can upregulate the expression of caveolin-1 both in vitro and in vivo. In the initial stage of hypercholesterolemia model, the expression of caveolin-1 increased as the time of high cholesterol level added, but in the later period it was decreased slightly.
Animals ; Aorta ; pathology ; Caveolin 1 ; Caveolins ; biosynthesis ; genetics ; Cells, Cultured ; Cholesterol ; blood ; Endothelium, Vascular ; cytology ; metabolism ; Female ; Humans ; Hypercholesterolemia ; metabolism ; Male ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Umbilical Veins ; cytology

Excessive release of glutamic acid plays an important role in the occurring and development of many nervous system diseases.Ionotropic glutamate receptors antagonists are shown to have therapeutic effect in animal models,but their clinical application is limited by their effects of blocking the normal excitatory neurotransmission.However,metabotropic glutamate receptors can suppress the release of glutamic via presynaptic mechanisms,which makes them the new targeting points of certain nervous system disease.This paper reviews the recent research progress of mGluRs in nervous diseases both at home and abroad.

Parkinson’s disease (PD) is a degenerative disease of the basal ganglia which caused tremor at rest, muscle rigidity and hypokinesia. The exact cause of PD is not clear so far, but what can be certain is that it has something to do with many factors. Administration of drugs is the major therapy for patients all over the world at present. This article introduces the characteristics of most of the drugs used in PD, as well as the trend of PD’s drug therapy.