Improvement of early-phase insulin secretion is an independent factor for achieving glycaemic control: A pooled analysis of SEED and DAWN study.

AIM: To investigate the effect of improving early phase insulin secretion function for glycaemic control in patients with type 2 diabetes mellitus treated with a new class of antidiabetic drug dorzagliatin. MATERIALS AND METHODS: Early insulin secretion function was studied in 726 participants of which 414 were treated with dorzagliatin in the SEED and DAWN study. The early insulinogenic index (IGI30min ) and disposition index (DI) were used to assess early-phase insulin secretion function in this study. Logistic regression analysis was performed to verify the importance of IGI30min and DI indices for achieving effective glycaemic control. RESULTS: The reduction in HbA1c has a significant correlation with the improvement of IGI30min for patients that received 24 weeks of dorzagliatin treatment (p < .001), and this correlation was not observed in the placebo group (p = .364). In the dorzagliatin treatment group, the responders showed significant improvements in homeostasis model assessment 2-ß, IGI30min and DI compared with the non-responders. Logistic regression analysis revealed that the odds ratio (OR) for achieving glycaemic control was 1.28 (95% CI 1.14-1.43) for baseline IGI30min , and 1.24 (95% CI 1.14-1.35) for the 24-week incremental IGI30min from baseline. The OR for baseline DI and 24-week changes in DI from baseline were 1.39 (95% CI 1.2-1.6) and 1.30 (95% CI 1.19-1.43) respectively. The timing of insulin secretion analysis showed the significant contribution of early-phase insulin secretion, rather than late-phase insulin secretion, to postprandial glucose control with the OR for the incremental IGI30min and IGI2h to postprandial glucose control were 1.3 (95% CI 1.19-1.42) and 1 (95% CI 1-1.01) respectively. CONCLUSIONS: Restoring the impaired early-phase insulin secretion function in patients with type 2 diabetes mellitus is a critical factor for improving the glycaemic control by dorzagliatin treatment.

Antiplatelet effect of ginkgo diterpene lactone meglumine injection in acute ischemic stroke: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

A meta-analysis of randomized controlled trials: efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section.

OBJECTIVE: Although ondansetron was considered to prevent post-anesthesia shivering during cesarean section, its efficiency remained controversial. Our review was conducted to estimate the efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section. METHODS: The literature were searched from their inception to October 2020 without restriction of language. All randomized controlled trials investigating the efficacy of ondansetron versus placebo in preventing shivering during cesarean section under neuraxial anesthesia were included. The meta-analysis was conducted using Stata software. RESULTS: Eleven randomized controlled studies with a total of 748 individuals were finally included in our meta-analysis. Our results manifested that intravenous ondansetron compared with intravenous placebo significantly reduced the incidence of post-anesthesia shivering (PAS) (RR 0.53, 95% CI 0.14-0.68). Subgroup analysis according to doses of ondansetron indicated that the efficacy of 4 mg doses of ondansetron (RR 0.37, 95% CI 0.21-0.64) is equivalent to that of 8 mg doses of ondansetron (RR 0.61, 95% CI 0.47-0.81) in preventing PAS. In addition, the intravenous ondansetron led to a lower incidence of hypotension than intravenous placebo (OR 0.47, 95% CI 0.32-0.70). We could not demonstrate differences in the incidence of bradycardia between intravenous ondansetron and intravenous placebo. CONCLUSION: Our results found that intravenous ondansetron was effective in preventing shivering during cesarean section under neuraxial anesthesia, and had an advantage in reducing the incidence of hypotension compared with intravenous placebo.

Intragenic heterochromatin-mediated alternative polyadenylation modulates miRNA and pollen development in rice.

Despite a much higher proportion of intragenic heterochromatin-containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic heterochromatin can be recognised by a protein complex, ASI1-AIPP1-EDM2 (AAE) complex, to regulate alternative polyadenylation. Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1-dependent regulation on rice development. We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of an miRNA precursor, to promote the processing of full-length OsXRNL and regulate miRNA abundance. We found that OsASI1-mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterised the rice AAE complex and its involvement in alternative polyadenylation and pollen development. Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.

Genome-wide distribution and functions of the AAE complex in epigenetic regulation in Arabidopsis.

Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1-AIPP1-EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin-containing genes. However, the genome-wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome-wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin-containing genes, including not only intronic heterochromatin-containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin-overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin-containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.

EXPORTIN 1A prevents transgene silencing in Arabidopsis by modulating nucleo-cytoplasmic partitioning of HDA6.

In eukaryotic cells, transport of macromolecules across the nuclear envelope is an essential process that ensures rapid exchange of cellular components, including protein and RNA molecules. Chromatin regulators involved in epigenetic control are among the molecules exported across the nuclear envelope, but the significance of this nucleo-cytoplasmic trafficking is not well understood. Here, we use a forward screen to isolate XPO1A (a nuclear export receptor in Arabidopsis) as an anti-silencing factor that protects transgenes from transcriptional silencing. Loss-of-function of XPO1A leads to locus-specific DNA hypermethylation at transgene promoters and some endogenous loci. We found that XPO1A directly interacts with histone deacetylase HDA6 in vivo and that the xpo1a mutation causes increased nuclear retention of HDA6 protein and results in reduced histone acetylation and enhanced transgene silencing. Our results reveal a new mechanism of epigenetic regulation through the modulation of XPO1A-dependent nucleo-cytoplasm partitioning of a chromatin regulator.

Protective effects of pioglitazone on vascular endothelial cell dysfunction induced by high glucose via inhibition of IKKα/ß-NFκB signaling mediated by PPARγ in vitro.

PIO, a synthetic ligand for PPARγ, is used clinically to treat T2DM. However, little is known about its protective effects on endothelium and the underlying mechanisms. In this study, we sought to investigate the protective effects of PIO on endothelium and its probable mechanisms: 95% confluent wild type (WT) HUVECs and PPARγLow-HUVECs that we first injured with HG (33 mmol·L-1) were first pretreated with 10 µmol·L-1 of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5, 10, or 20 µmol·L-1) for 24 h. Finally, we measured the levels of NO, ET1, TNFα, and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKKα/ß mRNA, IKKα/ß, and NFκB-p65. Severe dysfunction and activation of IKKα/ß-NFκB signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKα/ß-NFκB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARγ. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKα/ß-NFκB signaling mediated by PPARγ.

Eliminating Plasmodium falciparum in Hainan, China: a study on the use of behavioural change communication intervention to promote malaria prevention in mountain worker populations.

BACKGROUND: In the island of Hainan, the great majority of malaria cases occur in mountain worker populations. Using the behavioral change communication (BCC) strategy, an interventional study was conducted to promote mountain worker malaria prevention at a test site. This study found the methods and measures that are suitable for malaria prevention among mountain worker populations. METHODS: During the Plasmodium falciparum elimination stage in Hainan, a representative sampling method was used to establish testing and control sites in areas of Hainan that were both affected by malaria and had a relatively high density of mountain workers. Two different methods were used: a BCC strategy and a conventional strategy as a control. Before and after the intervention, house visits, core group discussions, and structural surveys were utilized to collect qualitative and quantitative data regarding mountain worker populations (including knowledge, attitudes, and practices [KAPs]; infection status; and serological data), and these data from the testing and control areas were compared to evaluate the effectiveness of BCC strategies in the prevention of malaria. RESULTS: In the BCC malaria prevention strategy testing areas, the accuracy rates of malaria-related KAP were significantly improved among mountain worker populations. The accuracy rates in the 3 aspects of malaria-related KAP increased from 37.73%, 37.00%, and 43.04% to 89.01%, 91.53%, and 92.25%, respectively. The changes in all 3 aspects of KAP were statistically significant (p < 0.01). In the control sites, the changes in the indices were not as marked as in the testing areas, and the change was not statistically significant (p > 0.05). Furthermore, in the testing areas, both the percentage testing positive in the serum malaria indirect fluorescent antibody test (IFAT) and the number of people inflicted decreased more significantly than in the control sites (p < 0.01). CONCLUSION: The use of the BCC strategy significantly improved the ability of mountain workers in Hainan to avoid malarial infection. Educational and promotional materials and measures were developed and selected in the process, and hands-on experience was gained that will help achieve the goal of total malaria elimination in Hainan.

Status and Influencing Factors of Body Image Disturbance in Patients With Hemifacial Spasm: A Quantitative and Qualitative Study.

OBJECTIVE: Patients diagnosed with hemifacial spasm (HFS) often experience significant facial changes that affect their body image and potentially have a negative impact on their physical and psychological well-being. This study therefore seeks to identify the current state of body image of Chinese patients with HFS, analyze the factors that influence it, and further explore their experiences based on their level of body image disturbance (BID) using a mixed methods approach. METHODS: A mixed-methods study was conducted between January 2021 and June 2023. Phase I encompassed the completion of questionnaires by 124 participants. Subsequently, in Phase II, in-depth interviews were conducted with 15 individuals selected from Phase I to gain deeper insights into their specific experiences with BID. RESULTS: Patients afflicted with HFS achieved Body Image Scale scores 9.00 (0.00, 12.00). Age, anxiety, depression, and fear of negative evaluation were identified as predictors of exacerbated BID (P < 0.05). Qualitative research predominantly centered on 2 primary themes: the experiences and outward manifestations of BID in HFS patients. These individuals expressed dissatisfaction with their appearance, apprehensions about being the focus of attention, and instances of social avoidance. CONCLUSIONS: Owing to varying degrees of anxiety, depression, and apprehension about external evaluation, individuals grappling with HFS are susceptible to experiencing BID. Consequently, when devising interventions, it is imperative to conduct a comprehensive assessment of the patient's condition and implement targeted measures aimed at ameliorating body image, ultimately enhancing the overall quality of life for the patient.

A fast and sensitive quantitative lateral flow immunoassay for Cry1Ab based on a novel signal amplification conjugate.

A novel lateral flow immunoassay (LFIA) signal amplification strategy for the detection of Cry1Ab based on amplification via a polylysine (PL) chain and biotin-streptavidin system (BSAS) is described. In this system, multiple fluorescence dyes (FL) were directly coated on the surface of PL and conjugated with antibody via the BSAS for construction of novel signal amplification (FLPL-BSAS-mAb1) conjugates, in which FL, PL and BSAS were employed to improve the sensitivity of LFIA. Compared with conventional LFIA, the sensitivity of FLPL-BSAS-mAb1-based LFIA was increased by approximately 100-fold. Quantified linearity was achieved in the value range of 0-1,000 pg/mL. The limit of detection (LOD) was reached 10 pg/mL after optimization of reaction conditions. To our knowledge, this represents one of the most sensitive LFIA for Cry1Ab yet reported. Furthermore, the detection time for this method was about 10 min. Therefore, it should be an attractive alternative compared to conventional immunoassays in routine control for Cry1Ab.

Microwave catalytic co-pyrolysis of chlorella vulgaris and oily sludge: Characteristics and bio-oil analysis.

Co-pyrolysis of Chlorella vulgaris (CV) and Oily sludge (OS) under different mixing ratios were investigated by microwave furnace. NiO, activated carbon (AC) and their 1:1 compound (N1A1) with different additions (5%, 10%, 15% and 20%) were selected as microwave additives to study the effects on optimum mixing ratio of co-pyrolysis. The results indicated that mixing ratio of CV/OS = 1:1 (C1O1) was optimum for co-pyrolysis. Besides, 10% AC was optimal on improving pyrolysis characteristics of the C1O1 group. The most significant synergistic interaction of NiO and AC occurred in the 10% N1A1 group. Moreover, hydrocarbons in bio-oil of the C1O1 group increased by 31.84% compared with theoretical values, while nitrogenous, oxygenated compounds decreased by 74.18% and 19.01%. Addition of 10% N1A1 in the C1O1 group increased aliphatic hydrocarbons by 22.44%, and decreased nitrogenous, oxygenated compounds by 41.79% and 36.58%. Overall, 10% N1A1 was conducive for the C1O1 group to obtain high-quality bio-oil.

Microwave-assisted co-pyrolysis of chlorella vulgaris and polypropylene: Characteristic and product distribution analyses.

The co-pyrolysis characteristics and product yield of Chlorella vulgaris (CV) and polypropylene (PP) under different mixing ratios (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10) were studied by microwave oven. Then the effects of different graphite (GP) additions (10%, 20%, 30% and 40%) on the optimum mixing ratio of CV and PP were investigated. The composition of bio-oil was analyzed by GC-MS. The results indicated that the C8P2 (CV/PP = 8:2) group had the best pyrolysis characteristics. The maximum weight loss rate (Rm) and average weight loss rate (Rv) of the C8P2 with 30% GP addition achieved the peak value. In the absence of GP, compared with C10P0 group, the contents of nitrogen compounds in bio-oil of the C8P2 group decreased by 21.58%. After adding GP to the C8P2 group, the nitrogen compounds in bio-oil of 30% GP group was 1.93% lower than that in 0% GP group.

Study on co-pyrolysis and products of Chlorella vulgaris and rice straw catalyzed by activated carbon/HZSM-5 additives.

The weight loss characteristics, product distribution and bio-oil composition of co-pyrolysis of rice straw (RS) and Chlorella vulgaris (CV) were investigated by microwave oven. Then, the catalytic effect of activated carbon (AC) and HZSM-5 on these characteristics were studied. Results showed that AC strongly improved co-pyrolysis weight loss characteristics and obtained maximum average weight loss rate (Ra) at 30% addition with 0.01639 wt.%/s. While HZSM-5 promoted the characteristics as addition was lower than 10%. In the case of compound additives, 20% A7H3 obtained the maximum Ra (0.01413 wt.%/s). Furthermore, both single AC and HZSM-5 showed negative effect on bio-oil production, while 20% A7H3 (AC/HZSM-5 = 7:3) achieved the maximum production (24%). For bio-oil composition, 30% A10H0 showed strong selectivity for phenol and N-heterocycle and 10% A0H10 showed strong aromatization capacity, and the addition of 20% A7H3 increased the hydrocarbons content from 20.79% to 31.63% compared with the blank group.

Microwave catalytic co-pyrolysis of Chlorella vulgaris and high density polyethylene over activated carbon supported monometallic: Characteristics and bio-oil analysis.

Activated carbon (AC) has attracted much attention owing to its low cost and abundant sources. In this paper, three monometallic supported catalysts were prepared using AC as support (Ce/AC, Fe/AC, Ni/AC), and the effects of three catalysts on the microwave co-pyrolysis of Chlorella vulgaris (C. vulgaris) with high density polyethylene (HDPE) were studied. The results showed that the co-pyrolysis characteristics of C. vulgaris/HDPE = 1:1 (C1HP1) were significantly improved by three catalysts at high additions (>20 %). Among them, the C1HP1 group with 50 % Fe/AC addition had the shortest co-pyrolysis reaction time (2901 s). Besides, Ce/AC and Fe/AC have a promoting effect on bio-oil yields, while Ni/AC has an inhibiting effect. The maximum bio-oil yield (25.6 %) was obtained under 40 % addition of Fe/AC. Moreover, Ce/AC obtained the highest hydrocarbons content (66.68 %), while Fe/AC obtained the highest aromatic hydrocarbons content (36.64 %). Additionally, Ce/AC had the highest deoxygenation efficiency (47.33 %) and denitrification efficiency (42.28 %).

microRNA-497 prevents pancreatic cancer stem cell gemcitabine resistance, migration, and invasion by directly targeting nuclear factor kappa B 1.

OBJECTIVES: Cancer stem cells (CSCs) comprise a small population of cells in cancerous tumors and play a critical role in tumor resistance to chemotherapy. miRNAs have been reported to enhance the sensitivity of pancreatic cancer to chemotherapy. However, the underlying molecular mechanism requires better understanding. METHODS: Cell viability and proliferation were examined with CCK8 assays. Quantitative real-time polymerase chain reaction was executed to assess mRNA expression. StarBase database was used to select the target genes of miRNA, which were further affirmed by dual luciferase assay. Transwell assay was used to analyze cell invasion and migration. RESULTS: We proved that miR-497 could be obviously downregulated in pancreatic cancer tissues and CSCs from Aspc-1 and Bxpc-3 cells. In addition, inhibition of miR-497 evidently accelerated pancreatic CSC gemcitabine resistance, migration and invasion. Moreover, we revealed that nuclear factor kappa B 1 (NFκB1) was prominently upregulated in pancreatic cancer tissues and pancreatic CSCs, and NFκB1 was also identified as a direct target of miR-497. Furthermore, we demonstrated that overexpression of NFκB1 could also notably promote the viability, migration, and invasion of gemcitabine-treated pancreatic CSCs, but this effect could be partially abolished by miR-497 overexpression. CONCLUSIONS: Those findings suggest that miR-497 overexpression could suppress gemcitabine resistance and the metastasis of pancreatic CSCs and non-CSCs by directly targeting NFκB1.

Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.

Study on microwave pyrolysis and production characteristics of Chlorella vulgaris using different compound additives.

Pyrolysis characteristics and bio-oil of Chlorella vulgaris were investigated under SiC and ZnO (SZ) mixture (compound additive) with various mixing ratios (S/Z = 10:0, 7:3, 5:5, 3:7, 0:10) and addition amounts (5%, 10%, 15%) by thermogravimetric analysis and GC-MS. At three experimental groups of 10% compound additive, as ZnO in compound additive increased, maximum weight loss rate (Rp) increased, the time (tp) corresponding to Rp and the weight stabilization time (tf) first decreased and then increased, while average rate of weight loss (Ra) and total weight loss (M) first increased and then decreased; maximum temperature rising rate (Hx) and average rate of temperature rising (Hg) increased, while the time (tx) corresponding to Hx decreased. Compound additives reduced the bio-oil yield, increased the gas yield, and reduced the acid compounds in bio-oil. Besides, it might promote the production of alicyclic hydrocarbons and oxygen/nitrogen-containing long-chain compounds.

The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier.

Background: Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM). Methods: The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion in vivo while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed. Results: LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found. Conclusions: Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.

A comprehensive pan-cancer analysis of CD274 gene amplification, tumor mutation burden, microsatellite instability, and PD-L1 expression in Chinese cancer patients.

BACKGROUND: Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need. METHODS: This study retrospectively analyzed clinical information and genetic profiling results of 16,013 samples from Chinese patients with various cancer types in order to investigate the prevalence of CD274 (also known as PD-L1) amplification in various cancer types and its association with existing PD-1/PD-L1 biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression. RESULTS: Amplification of CD274 was identified in 174 samples with an overall prevalence of 1.09% among all cancer types in the cohort. The prevalence of CD274 amplification in different cancer types and histological subtypes of lung cancer was varied, with cervical cancer having the highest prevalence. Distinct distributions of TMB, MSI, and PD-L1 expression between CD274-amplified and wild-type samples were observed in several cancer types as well as among different histological subtypes of lung cancer. CONCLUSIONS: Although CD274 amplification was only observed in a small proportion of patients, it demonstrated an association with TMB, MSI, and PD-L1 expression in several common cancer types. The molecular features of CD274 in different cancer types are heterogeneous. The role of CD274 amplification as a novel biomarker of PD-1/PD-L1 inhibitors remains to be characterized in future prospective clinical studies.