Research advances in the molecular classification of gastric cancer.

Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.

Spatiotemporal dynamics and functional characteristics of the composition of the main fungal taxa in the root microhabitat of Calanthe sieboldii (Orchidaceae).

BACKGROUND: Endophytic fungi play a critical ecological role in the growth and development of orchids, but little is known about the spatial and temporal dynamics of fungal diversity or the ecological functions of fungi during orchid growth and reproduction. Calanthe sieboldii Decne. is listed in the Chinese National Key Protected Wild Plants as a class I protected wild plant. To understand the community characteristics of root and soil fungi of the orchid during its reproductive seasons, we investigated the community composition, spatial and temporal dynamics, and functional characteristics of the orchid microhabitat fungi by using diversity and ecological functional analyses. RESULTS: We discovered that there were three, seven, and four dominant fungal families in the orchid's roots, rhizoplane soil, and rhizosphere soil, respectively. Tulasnellaceae, Aspergillaceae, and Tricholomataceae were the dominant fungi in this endangered orchid's microhabitats. The closer the fungal community was to the orchid, the more stable and the less likely the community composition to change significantly over time. The fungal communities of this orchid's roots and rhizoplane soil varied seasonally, while those of the rhizosphere soil varied interannually. Saprophytic fungi were the most abundant in the orchid's fungal community, and the closer the distance to the orchid, the more symbiotic fungi were present. CONCLUSIONS: The fungi in different parts of the root microhabitat of C. sieboldii showed different spatiotemporal dynamic patterns. The fungal community near the orchid roots was relatively stable and displayed seasonal variation, while the community further away from the roots showed greater variation. In addition, compared with the soil fungi, the dominant endophytic fungi were more stable, and these may be key fungi influencing orchid growth and development. Our study on the spatiotemporal dynamics and functions of fungi provides a basis for the comprehensive understanding and utilization of orchid endophytic fungi.

Successful outcome of neoadjuvant PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy for potentially unresectable esophagogastric junctional squamous cell carcinoma: a case report.

Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.

Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach.

Hepatoid adenocarcinoma of the stomach (HAS) is a particular subtype of Gastric cancer (GC) with distinct pathological characteristics and genetic profile, but most HAS patients were received identical regimens as common GC. To date, only a few studies has been conducted to investigate the molecular characteristics of HAS, which may prevent the rational application of new anticancer strategies. To further obtain the genetic features and potential predictive and prognostic biomarkers of HAS, our current study evaluated the clinical implications of spectrum molecular markers in 36 surgical resection specimens. None Epstein-Barr virus (EBV) positive and/or micro-satellite instable high (MSI-h) tumors occurred in our study implies that the molecular classification of HAS should be mainly categorized into genomic stable (GS) and chromosomal instability (CIN) phenotypes, and wild type P53 status predicts better prognosis. More importantly, although the prognosis and clinical characteristics were independent of programmed cell death-ligand 1 (PD-L1), the presence of tumor infiltrating lymphocytes (TILs) still suggested that a portion of the enrolled HAS patients are potentially appropriate candidates for immune checkpoint blockade therapy. Additionally, the immune prognostic index (IPI) and derived neutrophil to lymphocyte ratio (dNLR) demonstrated their potential as reliable and economic indicators for predicting prognosis of HAS. We hope this first systematic evaluation will help in deciphering the molecular characterization and potential individualized regimens for this particular subtype of GC.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1.

BACKGROUND: Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of C12orf48 in gastric cancer are largely unknown. METHODS: We used bioinformatics approaches and tissue microarray immunohistochemistry to analyze the expression profile of C12orf48 in gastric cancer tissues. Plasmid-mediated over-expression or knockdown were performed. CCK-8 assays and flow cytometry were employed to evaluate cellular proliferation and apoptosis respectively. Transwell assays were used to assess migrative and invasive abilities. The roles of C12orf48 were also evaluated in a xenograft tumor model. RESULTS: We found that C12orf48 was over-expressed in gastric cancer tissue, which associated with advanced stage and poor prognosis. In vitro and in vivo experiments showed depletion of C12orf48 attenuated cancer growth, while facilitated apoptosis. Further, the expression of Poly r(C)-Binding Protein (PCBP) 1 was found negatively regulated by C12orf48. Intended up-regulation of PCBP1 prevented C12orf48-mediated proliferation and rescued cells from apoptosis. Besides, C12orf48 promoted cellular migration and invasion, with E-cadherin down-regulated while vimentin and N-cadherin up-regulated, which was reversed by up-regulated PCBP1. CONCLUSIONS: Our findings indicate that depletion of C12orf48 inhibited gastric cancer growth and metastasis via up-regulating PCBP1. Targeting C12orf48-PCBP1 axis may be a potential therapeutic strategy.

Natural Hybrid Origin of the Controversial "Species" Clematis × pinnata (Ranunculaceae) Based on Multidisciplinary Evidence.

Interspecific hybridization is common and has often been viewed as a driving force of plant diversity. However, it raises taxonomic problems and thus impacts biodiversity estimation and biological conservation. Although previous molecular phylogenetic studies suggested that interspecific hybridization may be rather common in Clematis, and artificial hybridization has been widely applied to produce new Clematis cultivars for nearly two centuries, the issue of natural hybridization of Clematis has never been addressed in detail. In this study, we tested the hybrid origin of a mesophytic and cold-adapted vine species, Clematis pinnata, which is a rare and taxonomically controversial taxon endemic to northern China. Using field investigations, flow cytometry (FCM), phylogenomic analysis, morphological statistics, and niche modeling, we tested hybrid origin and species status of C. pinnata. The FCM results showed that all the tested species were homoploid (2n = 16). Phylonet and HyDe analyses based on transcriptome data showed the hybrid origins of C. × pinnata from either C. brevicaudata × C. heracleifolia or C. brevicaudata × C. tubulosa. The plastome phylogeny depicted that C. × pinnata in different sampling sites originated by different hybridization events. Morphological analysis showed intermediacy of C. × pinnata between its putative parental species in many qualitative and quantitative characters. Niche modeling results suggested that C. × pinnata had not been adapted to a novel ecological niche independent of its putative parents. These findings demonstrated that plants of C. × pinnata did not formed a self-evolved clade and should not be treated as a species. The present study also suggests that interspecific hybridization is a common mechanism in Clematis to generate diversity and variation, and it may play an important role in the evolution and diversification of this genus. Our study implies that morphological diversity caused by natural hybridization may overstate the real species diversity in Clematis.

Dickkopf-related protein 3 alters aerobic glycolysis in pancreatic cancer BxPC-3 cells, promoting CD4+ T-cell activation and function.

BACKGROUND: To investigate the value of Dickkopf-related protein 3 (DKK3) on aerobic glycolysis in pancreatic cancer cells, where DKK3-overexpression is used to determine its effects on CD4+ T cells. METHODS: The BxPC-3-DKK3 cell line was constructed, and peripheral blood mononuclear cell (PBMC) was prepared. After isolated the CD4+ T cells, the lactic acid, glucose uptake ability, cellular viability, proliferation, apoptosis, and markers were detected by PCR and western blot, and the concentrations of multiple cytokines were determined using the ELISA method. RESULTS: After co-culture with pancreatic cancer cells overexpressing DKK3, the glucose uptake markedly, proliferation enhanced and apoptosis inhibited in CD4+ T cells. The co-culture model also revealed that DKK3-overexpression promotes the activation and regulates the metabolism and function of CD4+ T cells. CONCLUSIONS: DKK3 alters the metabolic microenvironment of pancreatic cancer cells and further facilitates the function of CD4+ T cells which suggesting that DKK3 may have a therapeutic potential in pancreatic cancer.

An updated phylogenetic and biogeographic analysis based on genome skimming data reveals convergent evolution of shrubby habit in Clematis in the Pliocene and Pleistocene.

Convergent evolution, often viewed as the inevitable outcome of natural selection, has received special attention since the time of Darwin. Clematis is well known for its climbing habit, but it has some shrubby species, known as sect. Fruticella s.l. The shrubby Clematis species are distributed in the dry habitats of Central Asia and adjacent areas showing possible convergent evolution. In this study, we assembled the complete plastome and nuclear ribosomal DNA (nrDNA) sequences of 56 Clematis species, representing most sections and covering most of the shrubby species, to reconstruct their evolutionary histories. Using both maximum likelihood and Bayesian methods, the plastome and nrDNA datasets generated similar, but not identical, phylogenetic relationships, which are better resolved than in previous studies. Then, molecular dating, historical range reconstruction, and character optimization analyses were conducted based on this updated phylogenetic framework. All the morphological characters widely used for taxonomy were shown to have evolved multiple times. Molecular dating inferred that Clematis diverged from its sister in the mid Miocene, and all six major clades of Clematis originated during the late Miocene, with a species radiation during the Pliocene to Pleistocene. The results clearly showed that the shrubby habit evolved independently in four lineages of Clematis in Asia. We also revealed that the shrubby lineages have emerged since the very beginning of Pliocene. Asian monsoon variation in the Pliocene and glacial period fluctuation in the Pleistocene may be the driving forces for the origin and diversification of the shrubby Clematis in Central Asia and adjacent dry areas.

Relationship Between Postoperative Complications and the Prognosis of Gastric Carcinoma Patients Who Underwent Surgical Resection: A Systematic Review and Meta-Analysis.

BACKGROUND: Whether the presence of postoperative complications was associated with poor prognosis of gastric carcinoma (GC) patients remain controversial. This meta-analysis was designed and reported to compare the survival difference between patients with complications and non-complications. METHODS: Cochrane Library, PubMed and Embase databases were comprehensively searched for published literatures to review current evidence on this topic. The survival data were extracted, and a random-effect or fixed-effect model was used to analyze the correlation between postoperative complications and oncologic outcome of GC patients. RESULTS: Of all studies identified, 32 were eligible for this pooled analysis, with a total of 32,067 GC patients. The incidence of postoperative complications was approximately 12.5% to 51.0%. Among them, infectious complications varied from 3.0% to 28.6%, anastomotic leakage varied from 1.1% to 8.7% and postoperative pneumonia varied from 1.6% to 12.8%. The presence of postoperative complications resulted in a significant poorer overall survival (OS) of gastric carcinoma patients (hazard ratio [HR]:1.49, 95% confidence interval [CI]: 1.33-1.67, P < 0.001). Additionally, the pooled results showed a significant correlation between infectious complications and decreased OS (HR: 1.61, 95%CI: 1.38-1.88, P < 0.001). Concerning specific postoperative complications, we found that both anastomotic leakage (HR: 2.36, 95%CI: 1.62-3.42, P < 0.001) and postoperative pneumonia (HR: 1.74, 95%CI: 1.22-2.49, P = 0.002) impaired the OS of gastric carcinoma patients. CONCLUSION: Postoperative complications were significantly correlated to recurrence and poor survival in gastric carcinoma patients. To gain a better surgical outcome and long-term oncological outcome, postoperative complications should be minimized as much as possible.

De-Ubiquitinating Enzymes USP21 Regulate MAPK1 Expression by Binding to Transcription Factor GATA3 to Regulate Tumor Growth and Cell Stemness of Gastric Cancer.

USP21 is a kind of deubiquitinating enzymes involved in the malignant progression of various cancers, while its role in gastric cancer (GC) and the specific molecular mechanism are still unclear. This study probed into the function of USP21 in vitro and in vivo, and discussed the regulatory mechanism of USP21 in GC in vitro. We reported that USP21 promoted GC cell proliferation, migration, invasion, and stemness in vitro, and regulated GC tumor growth and cell stemness in mice in vivo. USP21 stabilized the expression of GATA3 by binding to GATA3. Besides, GATA3 also regulated the expression of MAPK1 at the transcriptional level. A series of in vitro experiments testified that USP21 regulated the expression of MAPK1 by binding to transcription factor GATA3, thereby regulating the tumor growth and cell stemness of GC. Overall, this study identified a new USP21/GATA3/MAPK1 axis, which plays a pivotal role in promoting the malignant progression of GC and might provide a potential target for treatment.

Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway.

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway. Methods: Sprague-Dawley rats (male, 250-280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions. Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05). Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.

The complete chloroplast genome of a distinctive meadow-rue, Thalictrum foeniculaceum (Ranunculaceae).

Thalictrum foeniculaceum is a morphologically distinctive species in the genus with very reduced filiform compound leaves and big pinkish flowers occurring in dry slopes of northern China. Herein, we report the first complete chloroplast genome sequence of T. foeniculaceum. The chloroplast genome sequence was 155,923 bp in length, with large and small single-copy regions (LSC with 85,323 bp and SSC with 17,628 bp in length) separated by two inverted repeat regions (IRs with 26,486 bp). The total GC content was 38.3%. The complete plastome sequence contained 111 genes, including 77 protein-coding, 30 tRNA, and four rRNA genes. The phylogenetic analysis of Thalictrum based on the complete chloroplast genomes available online was also presented in this study.

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT2 and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA3 and GEO4 databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM5 B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

Diagnostic and Categorization Criteria for Palpitations Below the Heart in Traditional Chinese Medicine: A Delphi Consensus Study.

OBJECTIVES: To explore and establish the diagnosis, syndrome classification and syndrome differentiation criteria of palpitations below the heart in traditional Chinese medicine (TCM) in order to lay a foundation for the clinical diagnosis, treatment and research of palpitations below the heart. METHODS: In the early stage of this study, we searched the literature related to palpitations below the heart in TCM in domestic and foreign databases, analyzed the results and developed an expert consultation questionnaire. Using the Delphi method, a survey was conducted by 19 expert TCM practitioners. The survey results were statistically analyzed, aggregated and categorized to create the next round of questionnaires, and the process was repeated was repeated for a total of 4 rounds of expert opinions and until a consensus was achieved. Finally, the questionnaire items were classified into the main diagnosis (primary disease) and secondary diagnosis (secondary disease) for each syndrome. RESULTS: This study was completed ahead of schedule after 2 rounds of expert questionnaire surveys. A total of 19 exceptional TCM experts from all over China reached a consensus on 1 diagnostic standard and 4 syndrome types. The main diagnoses of palpitations below the heart included "conscious sub cardiac epigastric beating," "throbbing at the lower part of the heart" and "palpitation rhythm consistent with the pulse and obvious pulsation in the heart area," while the secondary diagnosis was "palpitation obvious after nervous tension, fatigue, drinking water or changing body position." Based on the balance of TCM Yin (negative, dark, feminine) and Yang (positive, bright, masculine) energy, TCM syndrome differentiation (Bian Zheng - the comprehensive analysis of clinical information obtained from the 4 main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, that is used to guide the choice of treatment by acupuncture and/or TCM) of palpitations below the heart are differentiated as heart yang deficiency syndrome, middle yang deficiency syndrome, kidney yang deficiency syndrome and phlegm drink syndrome, and the main and secondary syndromes of each are established. In the consultation process, the expert opinions were highly correlated, questionnaire reliability was strong and the results were credible. CONCLUSIONS: The criteria proposed in this study do not claim to be the best or the most accurate, but they do provide some guidelines for practitioners, a basis for clinical differentiation and treatment with TCM and a basis for further randomized controlled trials in the future. Further research is needed in order to reach a consensus regarding TCM treatment of palpitations below the heart.

A novel prognostic signature of immune-related genes for patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with an estimated 1.8 million new cases worldwide and associated with high mortality rates of 881 000 CRC-related deaths in 2018. Screening programs and new therapies have only marginally improved the survival of CRC patients. Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets. The aim of this study was to identify an immune-related prognostic signature for CRC. To this end, we combined gene expression and clinical data from the CRC data sets of The Cancer Genome Atlas (TCGA) into an integrated immune landscape profile. We identified a total of 476 IRGs that were differentially expressed in CRC vs normal tissues, of which 18 were survival related according to univariate Cox analysis. Stepwise multivariate Cox proportional hazards analysis established an immune-related prognostic signature consisting of SLC10A2, FGF2, CCL28, NDRG1, ESM1, UCN, UTS2 and TRDC. The predictive ability of this signature for 3- and 5-year overall survival was determined using receiver operating characteristics (ROC), and the respective areas under the curve (AUC) were 79.2% and 76.6%. The signature showed moderate predictive accuracy in the validation and GSE38832 data sets as well. Furthermore, the 8-IRG signature correlated significantly with tumour stage, invasion, lymph node metastasis and distant metastasis by univariate Cox analysis, and was established an independent prognostic factor by multivariate Cox regression analysis for CRC. Gene set enrichment analysis (GSEA) revealed a relationship between the IRG prognostic signature and various biological pathways. Focal adhesions and ECM-receptor interactions were positively correlated with the risk scores, while cytosolic DNA sensing and metabolism-related pathways were negatively correlated. Finally, the bioinformatics results were validated by real-time RT-qPCR. In conclusion, we identified and validated a novel, immune-related prognostic signature for patients with CRC, and this signature reflects the dysregulated tumour immune microenvironment and has a potential for better CRC patient management.

Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017.

OBJECTIVES: To investigate sex difference in global gastric cancer incidence by year, age and socioeconomical status. DESIGN: An international comparative study. SETTING: We obtained the global and national sex-specific incidence of gastric caner by year and age from the Global Burden of Disease Study 2017. The human development index (HDI) in 2017 as an indicator of national socioeconomical status was extracted from the Human Development Report. MAIN OUTCOME MEASURES: Sex-specific incidence of gastric cancer was compared by year and age at the global level. Linear regression analyses were performed to explore socioeconomic-associated sex difference in gastric cancer incidence. RESULTS: Despite declining incidence of global gastric cancer in both sexes between 1990 and 2017, relative sex difference showed an increasing trend, with male to female ratios of age-standardised incidence rates (ASRs) rising from 1.86 to 2.20. Sex difference was almost negligible under 45 years of age and relative difference maximised in the age range of 65-69 years with male to female ratios of ASRs being 2.74. Both absolute sex difference (standardised ß=0.256, p<0.001) and relative difference (standardised ß=0.387, p<0.001) in ASRs were positively associated with HDI. CONCLUSIONS: This study revealed that decreasing incidence of global gastric cancer was accompanied by widening sex difference in the past few decades. Men always had higher incidence than women. Greater sex difference was found in older age and in more developed countries. These findings highlight the importance of making sex-sensitive health policy to cope with the global gastric cancer burden.

Evaluation of the efficacy of triamcinolone acetonide in the treatment of keloids by high-frequency ultrasound.

BACKGROUND: Intralesional injection of triamcinolone acetonide is an effective method for treating keloids. It still lacks effective and objective evaluation methods. This study aimed to observe the efficacy of intralesional triamcinolone acetonide injections for the treatment of keloids and to explore the role of high-frequency ultrasound in the monitoring and evaluation of keloids therapy. METHODS: Fifty-one patients with keloids were treated with triamcinolone acetonide, once a week for 4 weeks. Lesions were detected, recorded, and evaluated using digital photography and high-frequency ultrasound before and after treatment. RESULTS: High-frequency ultrasound showed the depth of drug injection. After the last treatment, an average decrease in dermal tissue layer thickness of 39.0% is compared with before treatment. In addition, there are significant differences in the effectiveness of clinical assessments and ultrasound assessments of keloids with or without subjective symptoms. CONCLUSION: The observed results confirmed that intralesional injections of triamcinolone acetonide can effectively treat keloids. High-frequency ultrasound can be used as a therapeutic monitoring and therapeutic evaluation tool for intralesional injections of triamcinolone acetonide.

The melanogenic effects and underlying mechanism of paeoniflorin in human melanocytes and vitiligo mice.

Vitiligo is a common depigmentary disease characterized as diagnosis simplicity and cure difficulty in view of the ambiguity of etiology, thus novel and effective treatments are urgently needed. Paeoniflorin, the major active compound extracted from the root of Paeonia lactiflora Pall, a traditional Chinese medicine, has been validated pharmacological properties such as antioxidant stress, a theory participating in the occurrence of vitiligo, but the effect on melanogenesis is still unclear. In this study, melanosythesis effect of paeoniflorin and the potential mechanism were evaluated. We found that treatment with paeoniflorin at the concentration of 10 µg/ml significantly increased melanin content and intracellular tyrosinase activity of human melanocytes, in accordance with the elevation of protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1). In addition, we also investigated that paeoniflorin promoted phosphorylation of cAMP-response element binding (CREB) and extracellular signal-regulated kinase (ERK) without affecting p38 and c-Jun N-terminal kinase (JNK). These results demonstrated that paeoniflorin had a synergistic effect on normal human melanocytes via ERK/CREB pathway with up-regulation of MITF and TRP-1, enhancing melanin synthesis. Meanwhile, the milder pathological changes in vitiligo mice treat with paeoniflorin also confirmed its potential in treating vitiligo. To sum up, we suggest that paeoniflorin may be a potential medicine of vitiligo treatment in clinical.

Structural variation of the complete chloroplast genome and plastid phylogenomics of the genus Asteropyrum (Ranunculaceae).

Two complete chloroplast genome sequences of Asteropyrum, as well as those of 25 other species from Ranunculaceae, were assembled using both Illumina and Sanger sequencing methods to address the structural variation of the cp genome and the controversial systematic position of the genus. Synteny and plastome structure were compared across the family. The cp genomes of the only two subspecies of Asteropyrum were found to be differentiated with marked sequence variation and different inverted repeat-single copy (IR-SC) borders. The plastomes of both subspecies contains 112 genes. However, the IR region of subspecies peltatum carries 27 genes, whereas that of subspecies cavaleriei has only 25 genes. Gene inversions, transpositions, and IR expansion-contraction were very commonly detected in Ranunculaceae. The plastome of Asteropyrum has the longest IR regions in the family, but has no gene inversions or transpositions. Non-coding regions of the cp genome were not ideal markers for inferring the generic relationships of the family, but they may be applied to interpret species relationship within the genus. Plastid phylogenomic analysis using complete cp genome with Bayesian method and partitioned modeling obtained a fully resolved phylogenetic framework for Ranunculaceae. Asteropyrum was detected to be sister to Caltha, and diverged early from subfamily Ranunculoideae.