Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe.

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines.

Pectoralis major muscle turnover flap reconstruction for treatment of deep sternal wound infection in infants and children.

OBJECTIVE: The aim of the study is to assess the therapeutic effect and applicability of pectoralis major muscle turnover flap (PMMTF) reconstruction for treatment of deep sternal wound infection (DSWI) after cardiac surgery in infants and children. METHODS: From March 2013 to October 2021, 23 patients with DSWI after cardiac surgery underwent PMMTF reconstruction. The data and outcomes of the patients were retrospectively analyzed. RESULTS: Twenty patients were treated with unilateral PMMTF reconstruction, and three patients were treated by bilateral PMMTF. All of the sternal wounds healed successfully. All patients survived and were discharged without evidence of infection. In a follow-up period, ranging from 15 to 83 months (mean 32.6 months), all patients demonstrated normal development with no limitations to limb movements. There were no signs of chronic sternal infection in all of them. CONCLUSION: PMMTF reconstruction is a simple, feasible, and effective treatment of DSWI after cardiac surgery in infants and children, with minimal developmental problems.

Complete chloroplast genome sequencing of ten wild Fragaria species in China provides evidence for phylogenetic evolution of Fragaria.

Complete chloroplast genomes of ten wild Fragaria species native to China were sequenced. Phylogenetic analysis clustered Fragaria species into two clades: The south clade (F. iinumae, F. chinensis, F. pentaphylla, F. nilgerrensis, F. daltoniana, F. corymbosa, F. moupinensis, F. tibetica, F. nipponica, F. gracilis, and F. nubicola and north clade (F. viridis, F. orientalis, F. moschata, F. mandshurica, F. vesca, F. chiloensis, F. virginiana, and F. × ananassa), while F. iinumae is the oldest extant species. Molecular clock analysis suggested present Fragaria species share a common ancestor 3.57 million years ago (Ma), F. moschata and octoploid species evolve 0.89 and 0.97 Ma, respectively, but F. moschata be not directly involved in current octoploid species formation. Drastic global temperature change since the Palaeocene-Eocene, approx. 55 Ma, especially during uplifting of the Qinghai-Tibet plateau and quaternary glaciation may have driven the formation of Fragaria, separation of two groups and polyploidization.

Genome-Wide Identification, Characterization, and Expression Analysis of Tubby-like Protein (TLP) Gene Family Members in Woodland Strawberry (Fragaria vesca).

Tubby-like proteins (TLPs) play important roles in plant growth and development and in responses to abiotic stress. However, TLPs in strawberry remain poorly studied. In this study, eight TLPs were identified in woodland strawberry (Fragaria vesca subspecies vesca 'Ruegen'). Protein structure analysis revealed that the structure of FvTLPs is highly conserved, but evolutionary and gene structure analyses revealed that the evolutionary pattern of FvTLP family members differs from that of their orthologous genes in Arabidopsis, poplar, and apple. Subcellular localization assays revealed that FvTLPs were localized to the nucleus and plasma membrane. FvTLPs showed no transcriptional activity. Yeast two-hybrid assays revealed that FvTLPs interact with specific FvSKP1s. The expression patterns of FvTLPs in different tissues and under various abiotic stresses (salt, drought, cold, and heat) and hormone treatments (ABA (abscisic acid) and MeJA (methyl jasmonate)) were determined. The expression patterns of FvTLPs indicated that they play a role in regulating growth and development and responses to abiotic stress in F. vesca. The GUS (beta-glucuronidase) activity of FvTLP1pro::GUS plants in GUS activity assays increased under salt and drought stress and abscisic acid treatment. The results of this study provide new insights into the molecular mechanisms underlying the functions of TLPs.

Genome-Wide Identification of Aquaporin Gene Family in Pitaya Reveals an HuNIP6;1 Involved in Flowering Process.

Aquaporins (AQPs) are essential membrane proteins involved in seed maturation and germination, stomata movement, photosynthesis, and regulation of plant flowering processes. Pitaya flowers are open at night and wither at daybreak, which shows an obvious circadian rhythm. In this study, a comprehensive genome-wide analysis of AQPs in Hylocereus undantus was conducted to screen key genes associated with flowering processes. A total of 33 HuAQP genes were identified from the H. undantus genome. The 33 HuAQPs were grouped into four subfamilies: 10 PIPs, 13 TIPs, 8 NIPs, and 2 SIPs, which were distributed on 9 out of 11 pitaya chromosomes (Chr) (except for Chr7 and Chr10). Results from expression profiles showed that HuNIP6;1 may be involved in pitaya's floral opening. HuNIP6;1 was localized exclusively in the cell membrane. Overexpression of HuNIP6;1 in Arabidopsis thaliana significantly promoted early flowering through regulating negative flowering regulators of MJM30, COL9, and PRR5, suggesting that HuNIP6;1 plays key roles in regulating flowering time. The present study provides the first genome-wide analysis of the AQP gene family in pitaya and valuable information for utilization of HuAQPs.

SAV1, regulated by microRNA-21, suppresses tumor growth in colorectal cancer.

This study investigated the role and action of the Salvador 1 protein (SAV1, also called WW45) in colorectal cancer (CRC). For this, CRC SW480 and HCT116 cells were infected with lentiviruses of SAV1 overexpression vector (lenti-SAV1) and SAV1 short hairpin RNA (sh-SAV1) to overexpress and silence SAV1 respectively, or transfected with microRNA-21 (miR-21) mimic to overexpress miR-21. Relative mRNA levels of SAV1 and relative miR-21 levels in CRC tissues or cells were detected. The effects of SAV1 and miR-21 on cell proliferation and apoptosis were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and annexin V - fluorescein isothiocyanate (FITC) - propidium iodide (PI) flow cytometry, respectively. Our results revealed that SAV1 was downregulated in CRC tissues compared with the adjacent noncancerous tissues. Furthermore, SAV1 overexpression inhibited proliferation and promoted apoptosis in SW480 and HCT116 cells, whereas knockdown of SAV1 exerted the opposite effect. Additionally, the tumorigenesis of SW480 cells in xenografted mice was significantly inhibited by SAV1 overexpression but promoted by SAV1 knockdown. MiR-21 levels significantly and negatively correlated with SAV1 expression in CRC tissues. More importantly, miR-21 overexpression significantly abolished the SAV1-mediated inhibition of proliferation and stimulation of apoptosis of SW480. In conclusion, SAV1 suppresses tumor growth in CRC and is regulated by miR-21.

BES1-regulated BEE1 controls photoperiodic flowering downstream of blue light signaling pathway in Arabidopsis.

BRI1-EMS-SUPPRESSOR 1 (BES1) functions as a key regulator in the brassinosteroid (BR) pathway that promotes plant growth. However, whether BES1 is involved in photoperiodic flowering is unknown. Here we report that BES1 acts as a positive regulator of photoperiodic flowering, but it cannot directly bind FLOWERING LOCUS T (FT) promoter. BR ENHANCED EXPRESSION 1 (BEE1) is the direct target of BES1 and acts downstream of BES1. BEE1 is also a positive regulator of photoperiodic flowering. BEE1 binds directly to the FT chromatin to activate the transcription of FT and promote flowering initiation. More importantly, BEE1 promotes flowering in a blue light photoreceptor CRYPTOCHROME 2 (CRY2)  partially dependent manner, as it physically interacts with CRY2 under the blue light. Furthermore, BEE1 is regulated by both BRs and blue light. The transcription of BEE1 is induced by BRs, and the BEE1 protein is stabilized under the blue light. Our findings indicate that BEE1 is the integrator of BES1 and CRY2 mediating flowering, and BES1-BEE1-FT is a new signaling pathway in regulating photoperiodic flowering.

Functional characterization of GI and CO homologs from Eriobotrya deflexa Nakai forma koshunensis.

KEY MESSAGE: The first report of the cloning and characterization of the flowering time-regulating genes GI and CO homologs from loquat. Flowering time is critical for successful reproduction in plants. In fruit trees, it can also influence the fruit yield and quality. In the previous work, we cloned the important florigen one EdFT and two EdFDs from wild loquat (Eriobotrya deflexa Nakai forma koshunensis); however, the upstream transcription factors are still unknown. The photoperiod pathway genes GIGANTEA (GI) and CONSTANS (CO) have been reported to mainly regulate FT expression in model plants. In this work, we first cloned photoperiod pathway orthologs EdGI and EdCO from E. deflexa Nakai f. koshunensis. Phylogenetic analysis showed they are highly conserved to those from Arabidopsis. They are mainly expressed in the leaves. The EdGI and EdCO were localized in the nucleus. Their expression showed in photoperiodic regulation, while the EdCO transcripts reached the peak at different periods from that of CO in Arabidopsis. Moreover, EdCO significantly activated the EdFT promoter activity. In the transgenic Arabidopsis, downstream-flowering genes like FT and AP1 were obviously upregulated, and consequently resulted in early-flowering phenotype compared to the wild type. These data revealed that the EdGI and EdCO may play a similar role as GI and CO in Arabidopsis, and regulate flower initiation in loquat.

The Role of EjSPL3, EjSPL4, EjSPL5, and EjSPL9 in Regulating Flowering in Loquat (Eriobotrya japonica Lindl.).

The age pathway is important for regulating flower bud initiation in flowering plants. The major regulators in this pathway are miR156 and SPL transcription factors. To date, SPL genes have been identified in many species of plants. Loquat, as a woody fruit tree of Rosaceae, is unique in flowering time as it blooms in winter. However, the study of its SPL homologous genes on the regulation mechanism of flowering time is still limited. In this study, four SPL homologs-EjSPL3, EjSPL4, EjSPL5, and EjSPL9-are cloned from loquat, and phylogenetic analysis showed that they share a high sequence similarity with the homologues from other plants, including a highly conserved SQUAMOSA promoter binding protein (SBP)-box domain. EjSPL3, EjSPL4, EjSPL5 are localized in the cytoplasm and nucleus, and EjSPL9 is localized only in the nucleus. EjSPL4, EjSPL5, and EjSPL9 can significantly activate the promoters of EjSOC1-1, EjLFY-1, and EjAP1-1; overexpression of EjSPL3, EjSPL4, EjSPL5, and EjSPL9 in wild-type Arabidopsis thaliana can promote flowering obviously, and downstream flowering genes expression were upregulated. Our work indicated that the EjSPL3, EjSPL4, EjSPL5, and EjSPL9 transcription factors are speculated to likely participate in flower bud differentiation and other developmental processes in loquat. These findings are helpful to analyze the flowering regulation mechanism of loquat and provide reference for the study of the flowering mechanism of other woody fruit trees.

The clinical characteristics and treatment of intestinal hamartomas.

The study aims to investigate the intestinal (small and large intestine) clinical features and treatment of hamartoma. Nowadays, with the rapid development of new technologies, digestive system endoscopy has been proven to be an effective device for treatment, rather than just a diagnostic tool. Such development plays a revolutionary role in diagnosis and treatment for digestive diseases. And endoscopic treatment was used in this study (LED light source, wavelength 580 ∼ 595 nm, power 200 W). A retrospective analysis of 20 cases of intestinal hamartomas performed from January 2012 to January 2016 to summarize its clinical characteristics and follow-up study on the therapeutic effect of the patients. There were 8 cases for endoscopic operation, and 12 cases for surgical operation. Comparison of tumor size between endoscopic and surgical estimated by using Wilcoxon rank sum test for tumor length (Z = -3.134, p = 0.001), and for tumor diameter (Z = -2.920, p = 0.002). The results of this study showed that intestinal hamartomas and gender have no significant relationship. The incidence of the disease is concentrated under 60 years, the incidence of the small intestine is significantly higher than that of the large intestine, and the rate of misdiagnosis is high. Endoscopic and surgical treatment are the main treatment, the prognosis is good, and after the radical resection, the recurrence was less.

Sternal reconstruction of deep sternal wound infections following median sternotomy by single-stage muscle flaps transposition.

OBJECTIVE: To assess clinical effectiveness of using bilateral pectoralis major or plus rectus abdominis muscle flaps in treating deep sternal wound infection (DSWI) following median sternotomy. METHODS: Between January 2009 and December 2013, 19 patients with DSWI after median sternotomy for cardiac surgery were admitted to our hospital, including 14 males (73.7%) and 5 females (26.3%), aged 55±13 (18-78) years. According to the Pairolero classification of infected median sternotomies, 3 (15.8%) patients were type II, and the other 16 (84.2%) were type III. Surgical procedure consisted of adequate debridement of infected sternum, costal cartilage, granulation, steel wires, suture residues and other foreign substances. Sternal reconstruction used the bilateral pectoralis major or plus rectus abdominis muscle flaps to obliterate dead space. The drainage tubes were placed and connected to a negative pressure generator for adequate drainage. RESULTS: There were no intraoperative deaths. In 15 patients (78.9%), bilateral pectoral muscle flaps were mobilized sufficiently to cover and stabilize the defect created by wound debridement. 4 patients (21.0%) needed bilateral pectoral muscle flaps plus rectus abdominis muscle flaps because their pectoralis major muscle flaps could not reach the lowest portion of the wound. 2 patients (10.5%) presented with subcutaneous infection, and 3 patients (15.8%) had hematoma. They recovered following local debridement and medication. 17 patients (89.5%) were examined at follow-up 12 months later, all healed and having stable sternum. No patients showed infection recurrence during the follow-up period over 12 months. CONCLUSION: DSWI following median sternotomy may be effectively managed with adequate debridement of infected tissues and reconstruction with bilateral pectoralis major muscle or plus rectus abdominis muscle flap transposition.

[Clinical outcome of deep sternal wound infection after cardiac surgery].

OBJECTIVE: To retrospectively evaluate the results of deep sternal wound infection (DSWI) after cardiac surgery. METHODS: Between January 2010 and September 2013, 139 patients suffering from DSWI after median sternotomy. The incidence of DSWI was 0.47% (139/29 574). There were 111 (79.9%) male and 28 (20.1%) female patients. The mean age was (61 ± 11) years, the mean body weight was (74 ± 14) kg. The incidence of postoperative DSWI was 0.88% (91/10 341) after isolated coronary artery bypass grafting (CABG), 0.70% (15/2 143) after valve surgery or other cardiac surgery plus CABG, 0.21% (24/11 429) after valve surgery, 0.15% (3/2 002) after thoracic aortic surgery, and 0.19% (6/3 158) after congenital heart disease. The sternotomy was re-opened and extensive debridement of the wound was performed in all patients. When the wound was clean and there was a bed of fresh granulation tissue, the sternum was rewired. The surgical procedure performed included debridement, drainage, sternal wire reclosure and pectoralis major muscular transpositions depended on the clinical condition of the patient. RESULTS: The in-hospital mortality was 9.3%. Failure of secondary sternal refixation appeared in 15 (10.8%) patients, the reoperation procedure of these 15 patients was pectoralis major muscular transpositions. Other complications included sepsis in 13 patients, perivalvular leakage in 3 patients, and cardiac rupture during the surgical procedure in 3 patients. The mean hospitalization was (39 ± 30) days. CONCLUSION: Deep sternal wound infection is a life-threatening complication after cardiac surgery associated with high morbidity and mortality.

Proteomic profiling and biomarker discovery for predicting the response to PD-1 inhibitor immunotherapy in gastric cancer patients.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation. Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model. Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959). Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

Identification of the exosomal PD-L1 inhibitor to promote the PD-1 targeting therapy of gastric cancer.

Programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) targeting therapy is widely applied in clinics for gastric cancer treatment. Nevertheless, the clinical response is not well acceptable due to the exosomal PD-L1. Hence, abrogation of the exosomal PD-L1 may be a strategy to sensitize the gastric cancer cell to PD-1 targeting therapy. With the aid of CD63 targeting antibody and PD-L1 targeting aptamer, HTRF based assay was established to quantify the exosomal PD-L1, and applied to our in-house compound library, resulting in the identification of moclobemide. Further optimization of moclobemide lead to EP16, which can inhibit the generation of exosomal PD-L1 with IC50 = 0.108 µM. By applying EP16 to gastric cancer cell line coupled with T-cell activity related experiment, it was validated to activate T-cell and can promote the response of PD-1 targeting therapy for gastric cancer treatment in vitro and in vivo. Collectively, our findings give a promising tool to promote the sensitivity of anti-PD-1 for gastric cancer treatment, and EP16 can serve as a leading compound for exosomal PD-L1 abrogation.

Body size and risk of Hodgkin's lymphoma by age and gender: a population-based case-control study in Connecticut and Massachusetts.

PURPOSE: Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS: A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS: These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.

Subtype of dietary fat in relation to risk of Hodgkin lymphoma: a population-based case-control study in Connecticut and Massachusetts.

Few epidemiological studies have examined the relationship between dietary fat, which may affect immune function and risk of Hodgkin lymphoma (HL). The aim of this study was to test the hypothesis that high dietary intake of fat and specific subtypes of fat is associated with the risk of HL among 486 HL cases and 630 population-based controls recruited between 1997 and 2000 in Connecticut and Massachusetts. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) stratified by age and gender. Among younger adults, HL risk was significantly and positively associated with higher intake of saturated fat [ORs for increasing quartiles = 1.3, 1.8, and 2.1; p trend = 0.04] and negatively associated with higher intake of monounsaturated fat [ORs for increasing quartiles = 0.5, 0.5, and 0.4; p trend = 0.03), after adjustment for potential confounders including lifestyle and other dietary factors. The associations with saturated fat (ORs for increasing quartile = 2.4, 3.2, and 4.4; p trend < 0.01] and monounsaturated fat (ORs for increasing quartile = 0.3, 0.6, and 0.3; p trend = 0.04) were most apparent in younger women, whereas there was no significant association between intake of total fat or any type of fat and risk of HL in older females or younger or older males. These findings show that the associations between dietary fat and risk of HL may vary by gender and age and require confirmation in other populations.

Analysis of two L-Galactono-1,4-lactone-responsive genes with complementary expression during the development of Arabidopsis thaliana.

Unraveling the role of genes annotated as protein of unknown function is of importance in progression of plant science. l-Galactono-1,4-lactone (l-GalL) is the terminal precursor for ascorbic acid (AsA) biosynthesis in Arabidopsis thaliana, and a previous study showed two DUF (domains of unknown function) 642 family genes (At1g80240 and At5g25460, designated as DGR1 and DGR2, respectively) to be sensitive to it. In this work, leaves from wild-type Arabidopsis were fed with d-glucose, l-galactose, l-GalL and AsA, and the expression level of the At1g80240 and At5g25460 genes showed a specific response to l-GalL, but not to the other supplements despite the increases of the tissue AsA contents. Analysis of promoter-ß-glucuronidase (GUS) transgenic plants showed the two genes to be complementarily expressed at the root apex and in the rest of the root excluding the apex, respectively, in both young and old seedlings, and to be expressed at the leaf primordia. The GUS activity under the control of the At5g25460 promoter was high in the cotyledon and leaf veins of young seedlings. These findings were consistent with the results of quantitative real-time PCR. Interestingly, the T-DNA insertion mutant of At5g25460 (SALK_125079) displayed shorter roots and smaller rosettes than Col-0; however, no phenotypic difference was observed between the T-DNA insertion mutant of At1g80240 and the wild type. This is the first report on the expression and functional analysis of these two DUF642 family genes, with the results revealing the contribution of DGR genes to the development of Arabidopsis.

Translocation and the alternative D-galacturonate pathway contribute to increasing the ascorbate level in ripening tomato fruits together with the D-mannose/L-galactose pathway.

The D-mannose/L-galactose pathway for the biosynthesis of vitamin C (L-ascorbic acid; AsA) has greatly improved the understanding of this indispensable compound in plants, where it plays multifunctional roles. However, it is yet to be proven whether the same pathway holds for all the different organs of plants, especially the fruit-bearing plants, at different stages of development. Micro-Tom was used here to elucidate the mechanisms of AsA accumulation and regulation in tomato fruits. The mRNA expression of the genes in the D-mannose/L-galactose pathway were inversely correlated with increasing AsA content of Micro-Tom fruits during ripening. Feeding L-[6-(14)C]AsA to Micro-Tom plants revealed that the bulk of the label from AsA accumulated in the source leaf was transported to the immature green fruits, and the rate of translocation decreased as ripening progressed. L-Galactose feeding, but neither D-galacturonate nor L-gulono-1,4-lactone, enhanced the content of AsA in immature green fruit. On the other hand, L-galactose and D-galacturonate, but not L-gulono-1,4-lactone, resulted in an increase in the AsA content of red ripened fruits. Crude extract prepared from insoluble fractions of green and red fruits showed D-galacturonate reductase- and aldonolactonase-specific activities, the antepenultimate and penultimate enzymes, respectively, in the D-galacturonate pathway, in both fruits. Taken together, the present findings demonstrated that tomato fruits could switch between different sources for AsA supply depending on their ripening stages. The translocation from source leaves and biosynthesis via the D-mannose/L-galactose pathway are dominant sources in immature fruits, while the alternative D-galacturonate pathway contributes to AsA accumulation in ripened Micro-Tom fruits.

From Anti-HER-2 to Anti-HER-2-CAR-T Cells: An Evolutionary Immunotherapy Approach for Gastric Cancer.

Current Therapeutic modalities provide no survival advantage to gastric cancer (GC) patients. Targeting the human epidermal growth factor receptor-2 (HER-2) is a viable therapeutic strategy against advanced HER-2 positive GC. Antibody-drug conjugates, small-molecule tyrosine kinase inhibitors (TKIs), and bispecific antibodies are emerging as novel drug forms that may abrogate the resistance to HER-2-specific drugs and monoclonal antibodies. Chimeric antigen receptor-modified T cells (CAR-T) targeting HER-2 have shown considerable therapeutic potential in GC and other solid tumors. However, due to the high heterogeneity along with the complex tumor microenvironment (TME) of GC that often leads to immune escape, the immunological treatment of GC still faces many challenges. Here, we reviewed and discussed the current progress in the research of anti-HER-2-CAR-T cell immunotherapy against GC.

Clinical role of miR-421 as a novel biomarker in diagnosis of gastric cancer patients: A meta-analysis.

BACKGROUND: Gastric cancer (GC) has been identified as one of the most common malignancies. It was found that microRNAs can be used as potential biomarkers for GC diagnosis. The aim of this study was to estimate the diagnostic value of 4 potential microRNAs in GC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were used to search published studies. The quality of the studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity and specificity, diagnostic odds ratio (DOR) and area under the curve (AUC) were calculated. The heterogeneity was evaluated using Cochrane Q statistics and the inconsistency index. RESULTS: A total of 22 studies reporting the diagnostic value of miR-21 (n = 9), miR-106 (n = 10), miR-421 (n = 5) and miR-223 (n = 3) were included. Quality Assessment of Diagnostic Accuracy Studies scores showed the high quality of the selected 22 articles. The random effects model was adopted by evaluating the heterogeneity between articles. The DOR, AUC, and Q value of miRNA-21 were 12.37 (95% confidence interval [CI]: 5.36-28.54), 0.86 and 0.79, respectively. The DOR, AUC and Q value of miRNA-106 were 12.98 [95% CI: 7.14-23.61], 0.85 and 0.78, respectively. The DOR, AUC and Q value of miRNA-421 were 27.86 [95% CI: 6.04-128.48], 0.92 and 0.86, respectively. The DOR, AUC and Q value of miRNA-223 were 18.50 [95% CI: 7.80-43.86], 0.87 and 0.80, respectively. These results indicate that miRNA-421 has the highest diagnostic accuracy, followed by miR-223, miRNA-21, and miRNA-106 among the 4 microRNAs in GC. CONCLUSIONS: miR-21, miR-106, miR-421, and miR-223 have good diagnostic efficacy, especially miR-421, could be used as auxiliary diagnostic indicator for GC.