Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

BACKGROUND: Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi-omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi-omics technology-based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. METHODS: First, we provided a general review of epilepsy, BTRE, and multi-omics techniques. Next, we described the specific multi-omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. RESULTS: Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma-related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR-128 and miRNA-196b participate in BTRE development. miR-128 might be negatively associated with the possibility of tumor-related epilepsy development. The lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non-epileptic gliomas. In another proteomics study, a high expression of AQP-4 was detected in the brain of GBM patients with seizures. By using quantitative RT-PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki-67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma-related epileptogenesis. Another metabolomics study found that SV2A, P-gb, and CAD65/67 have the potential to function as biomarkers for BTRE. CONCLUSIONS: Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Unraveling the role of CD24 in Hepatocellular carcinoma: Involvement of inactivated Hippo signaling and SOX4-mediated regulation.

Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model and observed that CD24, induced by inactivation of the Hippo pathway, was highly expressed in HCC. Using a systematic molecular and genomic approach, we identified the Hippo-YAP1-SOX4 pathway as the mechanism through which YAP1 induces CD24 upregulation in HCC cells. CD24 knockdown significantly attenuated YAP1 activation-induced HCC. These findings shed light on the link between CD24 and HCC progression, particularly in the Hippo-inactivated subclass of HCC. Therefore, CD24 may serve as a potential target for specific treatment of this HCC subclass.

Multi-omics study identifies that PICK1 deficiency causes male infertility by inhibiting vesicle trafficking in Sertoli cells.

BACKGROUND: Infertility affects approximately 10-15% of reproductive-age men worldwide, and genetic causes play a role in one-third of cases. As a Bin-Amphiphysin-Rvs (BAR) domain protein, protein interacting with C-kinase 1 (PICK1) deficiency could lead to impairment of acrosome maturation. However, its effects on auxiliary germ cells such as Sertoli cells are unknown. PURPOSE: The present work was aimed to use multi-omics analysis to research the effects of PICK1 deficiency on Sertoli cells and to identify effective biomarkers to distinguish fertile males from infertile males caused by PICK1 deficiency. METHODS: Whole-exome sequencing (WES) was performed on 20 infertility patients with oligozoospermia to identify pathogenic PICK1 mutations. Multi-omics analysis of a PICK1 knockout (KO) mouse model was utilized to identify pathogenic mechanism. Animal and cell function experiments of Sertoli cell-specific PICK1 KO mouse were performed to verify the functional impairment of Sertoli cells. RESULTS: Two loss-of-function deletion mutations c.358delA and c.364delA in PICK1 resulting in transcription loss of BAR functional domain were identified in infertility patients with a specific decrease in serum inhibin B, indicating functional impairment of Sertoli cells. Multi-omics analysis of PICK1 KO mouse illustrated that targeted genes of differentially expressed microRNAs and mRNAs are significantly enriched in the negative regulatory role in the vesicle trafficking pathway, while metabolomics analysis showed that the metabolism of amino acids, lipids, cofactors, vitamins, and endocrine factors changed. The phenotype of PICK1 KO mouse showed a reduction in testis volume, a decreased number of mature spermatozoa and impaired secretory function of Sertoli cells. In vitro experiments confirmed that the expression of growth factors secreted by Sertoli cells in PICK1 conditional KO mouse such as Bone morphogenetic protein 4 (BMP4) and Fibroblast growth factor 2 (FGF2) were decreased. CONCLUSIONS: Our study attributed male infertility caused by PICK1 deficiency to impaired vesicle-related secretory function of Sertoli cells and identified a variety of significant candidate biomarkers for male infertility induced by PICK1 deficiency.

Case Reports: A role of postoperative radiation therapy in completely resected early stage intrathyroid thymic carcinoma: a case report and literature review of the diagnosis and treatment.

Background: Intrathyroid thymic carcinoma (ITTC) is a rare malignant tumor of the thyroid, probably arising from ectopic thymus or branchial pouch remnants. Most of the literature recommended radical resection as the fundamental treatment for ITTC, and postoperative radiation appears to be able to reduce the recurrence rate in patients with advanced ITTC. However, the issue of adjuvant radiotherapy in completely resected early-stage ITTC has been controversial. Case presentation: Here, we reported a new case of early-stage ITTC that treated with total thyroidectomy and the right central neck dissection. Postoperative external beam radiation therapy (50.0 Gy/25 fractions) was given to the thyroid bed and bilateral cervical lymph node area since the tumor involved part of the sternal thyroid muscle. At 4-year follow-up after completion of radiotherapy, she is without evidence of locally recurrent or distant disease. Conclusion: Since there are no current guidelines for early-stage ITTC, in combination with this case and previous literature, we may suggest routine adjuvant radiotherapy should be considered in patients with incompletely resected tumors and extraparenchymal extension of ITTC. Moreover, we summarized comprehensive and advanced diagnosis, treatment, prognosis of ITTC and comparison between ITTC, primary squamous cell carcinoma of thyroid gland, differentiated thyroid cancer, and anaplastic thyroid cancer.

Integrative landscape analysis of prognostic model biomarkers and immunogenomics of disulfidptosis-related genes in breast cancer based on LASSO and WGCNA analyses.

BACKGROUND: Disulfidptosis is a novel type of programmed cell death. However, the value of disulfidptosis-related genes (DRGs) in the prediction of breast cancer prognosis is unclear. METHODS: RNA-seq data of 1231 patients, together with information on patient clinical characteristics and prognosis, were downloaded from TCGA. DRGs were identified between cancerous and non-cancerous tissues. The LASSO algorithm was used to assign half of the samples to the training set. Risk scores were used for construction of a prognostic model for risk stratification and prognosis prediction, and the clinical applicability was examined using a line diagram. The relationships between risk scores, immune cell infiltration, molecular subtypes, and responses to immunotherapy and chemotherapy were examined. RESULTS: We identified and obtained four DRG-related prognostic lncRNAs (AC009097.2, AC133552.5, YTHDF3-AS1, and AC084824.5), which were used for establishing the risk model. Longer survival was associated with low risk. The DRG-associated lncRNAs were found to independently predict patient prognosis. The AUCs under the ROCs for one-, three-, and 5-year survival in the training cohort were 0.720, 0.687, and 0.692, respectively. The model showed that the high-risk patients had reduced overall survival as well as high tumor mutation burdens. Furthermore, high-risk patients showed increased sensitivity to therapeutic drugs, including docetaxel, paclitaxel, and oxaliplatin. CONCLUSION: The risk score model was effective for predicting both prognosis and sensitivity to therapeutic drugs, suggesting its possible usefulness for the management of patients with breast cancer.

Verifying AXL and putative proteins as SARS-CoV-2 receptors by DnaE intein-based rapid cell-cell fusion assay.

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.

Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice.

OBJECTIVE: The protein interacting with C kinase 1 (PICK1) plays a critical role in vesicle trafficking, and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome, which eventually disrupts acrosome formation and leads to male infertility. METHODS: An azoospermia sample was filtered, and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient. We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene, c.364delA (p.Lys122SerfsX8), and this protein structure truncating variant seriously affected the biological function. Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology (CRISPRc). RESULTS: The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities, as well as dysfunctional mitochondrial sheath formation. Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice. Moreover, the mitochondrial dysfunction was verified in the mice. These defects in the male PICK1 knockout mice may have eventually led to complete infertility. CONCLUSION: The c.364delA novel variant in the PICK1 gene associated with clinical infertility, and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.

Transfusion support for a patient with alloanti-D and the RHD*DV.1 allele.

BACKGROUND: Safe blood transfusion is significantly affected by the complex antigen polymorphism and a high proportion of autoantibodies of the Rh blood group system. THE PATIENT AND METHODS: A male Chinese patient with primary biliary cirrhosis, esophageal and gastric rupture, and bleeding was admitted to our hospital. Blood typing identified that he had serological O and D+ blood groups. Because autoantibody was not detected using routine immediate spin (IS) and indirect antiglobulin test (IAT), he was treated by transfusing D+ red blood cells (RBCs). However, this treatment was ineffective. Thus, manual polybrene test (MPT) and low ionic salt solution indirect antiglobulin test (LISS-IAT) were performed, followed by exon sequencing of the RHD gene. RESULTS: The patient was confirmed as a DV Type 1 individual by gene sequencing, and had 4+ RhD antigen agglutination. The anti-D in serum and elution could only be detected by MPT (2+ agglutination) and LISS-IAT methods (1+/3+ agglutination). It was presumed that attenuated alloantibody contributed to ineffective RBC transfusion, causing a transient increase in hemoglobin (HGB) before falling back to 50 g/L or even lower within four days. CONCLUSION: Genotyping helps to support the specificity of detecting autoantibodies and alloantibodies. Combining more serological methods with molecular technology in blood typing is beneficial to improve the safety and effectiveness of blood transfusion.

Characteristics of gastric cancer gut microbiome according to tumor stage and age segmentation.

With the development of 16S rRNA technology, gut microbiome evaluation has been performed in many diseases, including gastrointestinal tumors. Among these cancers, gastric cancer (GC) exhibits high morbidity and mortality and has been extensively studied in its pathogenesis and diagnosis techniques. The current researches have proved that the gut microbiome may have the potential to distinguish GC patients from healthy patients. However, the change of the gut microbiome according to tumor node metastasis classification (TNM) has not been clarified. Besides, the characteristics of gut microbiome in GC patients and their ages of onset are also ambiguous. To address the above shortcomings, we investigated 226 fecal samples and divided them according to their tumor stage and onset age. The findings revealed that surgery and tumor stage can change the characteristic of GC patients' gut microbiota. In specific, the effect of surgery on early gastric cancer (EGC) was greater than that on advanced gastric cancer (AGC), and the comparison of postoperative microflora with healthy people indicated that EGC has more differential bacteria than AGC. Besides, we found that Collinsella, Blautia, Anaerostipes, Dorea, and Lachnospiraceae_ND3007_group expressed differently between EGC and AGC. More importantly, it is the first time revealed that the composition of gut microbiota in GC is different between different onset ages. KEY POINTS: •Gut microbiota of gastric cancer (GC) patients are either highly associated with TNM stage and surgery or not. It shows surgery has more significant changes in early gastric cancer (EGC) than advanced gastric cancer (AGC). •There existed specific gut microbiota between EGC and AGC which may have potential to distinguish the early or advanced GC. •Onset age of GC may influence the gut microbiota: the composition of gut microbiota of early-onset gastric cancer (EOGC) and late-onset gastric cancer (LOGC) is significantly different.

Characteristics of gut microbiota in patients with gastric cancer by surgery, chemotherapy and lymph node metastasis.

BACKGROUND: Gastric cancer (GC) is a malignant gastrointestinal tumor that can result in high mortality. Surgery and chemotherapy are often used for the effective treatment of GC. In addition, lymph node metastasis is a significant factor affecting the therapy of GC. Current researches have revealed that gut microbiota has the potential as biomarkers to distinguish healthy people and GC patients. However, the relationship between surgery, chemotherapy, and lymph node metastasis is still unclear. METHODS: In this study, 16S rRNA sequencing was used to investigate 157 GC fecal samples to identify the role of surgery, chemotherapy, and lymph node metastasis. Immunohistochemical analysis was used to value the expression of Ki67, HER2 in GC patient tissues. RESULTS: There exist some gut microbiotas which can distinguish surgery from non-surgery GC patients, including Enterococcus, Megasphaera, Corynebacterium, Roseburia, and Lachnospira. Differences between lymph node metastasis and chemotherapy in GC patients are not significant. Moreover, we found the abundance of Blautia, Ruminococcus, Oscillospira were related to the expression of Ki67 and the abundance of Prevotella, Lachnospira, Eubacterium, Desulfovibiro were correlated with the expression of HER2. CONCLUSIONS: The choice of treatment has a certain impact on the intestinal flora of patients with gastric cancer. Our research shows that surgery has a great effect on the intestinal flora of patients with gastric cancer. However, there were no significant differences in the characteristics of intestinal flora in patients with gastric cancer whether they received chemotherapy or whether they had lymph node metastasis. In addition, the association of gut microbiota with Ki67 and HER2 indicators is expected to provide the possibility of gut microbiota as a tumor prognostic marker.

Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

Purpose: To identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer. Methods: Ferroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan-Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase-PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored. Results: Internal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA. Conclusions: The FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.

Electronic transfusion consent and blood delivering pattern improve the management of blood bank in China.

BACKGROUND: The aim of this study was to improve the blood transfusion treatment consent accuracy, simplify the verification process, prolong the temperature control time before the blood transfusion, and save the blood transportation labor cost. METHODS: We designed the blood transfusion consent electronic signing process, which can generate personalized the text content and can automatically check the filling accuracy. The signal can be transmitted to the blood transfusion management system (TMS) to relieving the blood distribution. For blood delivering pattern, we established the blood transport center, recruited full-time nurses and used temperature-controlled blood transfer boxes to deliver blood in batches on a regular basis. RESULTS: A quarterly data analysis of blood transfusion quality showed a 100% blood transfusion consent accuracy after an electronic signing process was implemented. The average confirmation time savings between the electronic content and paper content was 26 min for the Department of Emergency (estimated difference 95% CI = 26 (20 to 36), p < 0.05). The blood delivering pattern reduced the time for each unit by leaving the average temperature control by 7.24 min (estimated difference 95% CI = 7.24 (6.92 to 7.56), p < 0.05). Furthermore, $3.67 was saved for the blood transportation labor cost for each unit as well. CONCLUSION: Blood transfusion consent electronic signing process not only ensures the accuracy, but also saves the verification time. Moreover, the blood delivering pattern prolongs the blood temperature control time and saves blood transportation labor costs. Thus, these two improvements could enhance transfusion management.

A multiple-dimension model for microbiota of patients with colorectal cancer from normal participants and other intestinal disorders.

Gut microbiota is a primary driver of inflammation in the colon and is linked to early colorectal cancer (CRC) development. Thus, a novel and noninvasive microbiome-based model could promote screening in patients at average risk for CRC. Nevertheless, the relevance and effectiveness of microbial biomarkers for noninvasive CRC screening remains unclear, and researchers lack the data to distinguish CRC-related gut microbiome biomarkers from those of other common gastrointestinal (GI) diseases. Microbiome-based classification distinguishes patients with CRC from normal participants and excludes other CRC-relevant diseases (e.g., GI bleed, adenoma, bowel diseases, and postoperative). The area under the receiver operator characteristic curve (AUC) was 92.2%. Known associations with oral pathogenic features, benefits-generated features, and functional features of CRC were confirmed using the model. Our optimised prediction model was established using large-scale experimental population-based data and other sequence-based faecal microbial community data. This model can be used to identify the high-risk groups and has the potential to become a novel screening method for CRC biomarkers because of its low false-positive rate (FPR) and good stability. KEY POINTS: • A total of 5744 CRC and non-CRC large-scale faecal samples were sequenced, and a model was constructed for CRC discrimination on the basis of the relative abundance of taxonomic and functional features. • This model could identify high-risk groups and become a novel screening method for CRC biomarkers because of its low FPR and good stability. • The association relationship of oral pathogenic features, benefits-generated features, and functional features in CRC was confirmed by the study.

Non-RBM Mutations Impaired SARS-CoV-2 Spike Protein Regulated to the ACE2 Receptor Based on Molecular Dynamic Simulation.

The emergence of novel coronavirus mutants is a main factor behind the deterioration of the epidemic situation. Further studies into the pathogenicity of these mutants are thus urgently needed. Binding of the spinous protein receptor binding domain (RBD) of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor was shown to initiate coronavirus entry into host cells and lead to their infection. The receptor-binding motif (RBM, 438-506) is a region that directly interacts with ACE2 receptor in the RBD and plays a crucial role in determining affinity. To unravel how mutations in the non-RBM regions impact the interaction between RBD and ACE2, we selected three non-RBM mutant systems (N354D, D364Y, and V367F) from the documented clinical cases, and the Q498A mutant system located in the RBM region served as the control. Molecular dynamics simulation was conducted on the mutant systems and the wild-type (WT) system, and verified experiments also performed. Non-RBM mutations have been shown not only to change conformation of the RBM region but also to significantly influence its hydrogen bonding and hydrophobic interactions. In particular, the D364Y and V367F systems showed a higher affinity for ACE2 owing to their electrostatic interactions and polar solvation energy changes. In addition, although the binding free energy at this point increased after the mutation of N354D, the conformation of the random coil (Pro384-Asp389) was looser than that of other systems, and the combined effect weakened the binding free energy between RBD and ACE2. Interestingly, we also found a random coil (Ala475-Gly485). This random coil is very sensitive to mutations, and both types of mutations increase the binding free energy of residues in this region. We found that the binding loop (Tyr495-Tyr505) in the RBD domain strongly binds to Lys353, an important residue of the ACE2 domain previously identified. The binding free energy of the non-RBM mutant group at the binding loop had positive and negative changes, and these changes were more obvious than that of the Q498A system. The results of this study elucidate the effect of non-RBM mutation on ACE2-RBD binding, and provide new insights for SARS-CoV-2 mutation research.

Research progress on gut microbiota in patients with gastric cancer, esophageal cancer, and small intestine cancer.

The pathogenesis of gut microbiota in humans can be indicated due to the wide application of techniques, such as 16S rRNA sequencing. Presently, several studies have found a significant difference in fecal flora between normal individuals and patients with gastric cancer. Although clinical research on the feedback mechanism of gastric flora and gut microbiota is lacking, clarifying the relationship between gut microbiota and the characteristics of cancer is significant for the early diagnosis of gastric cancer. This study was conducted to review the results of several studies in the past 5 years and analyze the intestinal bacteria in patients with gastric cancer and compare them with those in patients with esophageal and small intestine cancers. It was found that the gut microbiota in patients with gastric cancer was similar to that in patients with esophageal cancer. However, making an analysis and comparing the gut microbiota in patients with small intestine and gastric cancers was impossible due to the low incidence of small intestinal cancer. Our review summarized the research progress on using the gut microbiota for early screening for gastric cancer, and the results of this study will provide a further direction in this field. KEY POINTS: • We reviewed several relative mechanisms of the gut microbiota related to gastric cancer. • The gut microbiota in gastric, esophageal, and small intestine cancers are significantly different in types and quantity, and we have provided some tips for further research. • A prospective review of sequencing methods and study results on the gut microbiota in gastric, esophageal, and small intestine cancers was described.

"Without the need for a second visit" initiative improves patient satisfaction with updated services of outpatient clinics in China.

BACKGROUND: To implement the "without the need for a second visit" (WNASV) initiative in our hospital by optimizing the outpatient clinic services via an upgraded information system, in order to increase the quality of outpatient medical services and improve patients' satisfaction. METHODS: An Internet-based care delivery approach was developed and applied to improve the delivery of health care services, simplify the treatment process, and reduce patient waiting time. The patient waiting time and consultation time in the outpatient clinics of our hospital during the peak service intervals and the proportions of various payment methods for outpatient services during the period from May 2017 to September 2019 were retrospectively analyzed. Also, the patients' satisfaction with the outpatient process was surveyed. RESULTS: The waiting time for consultation was shortened from 32.25 min to 28.42 min; the consultation time was shortened from 6.52 min to 3.15 min; and the waiting time for payment decreased from 7.40 min to 4.31 min. The proportion of payment via a counter was reduced from 86.80 to 21.79%, the proportion of self-service payment increased from 9.99 to 16.05%, and the proportion of payment during a consultation increased from 3.21 to 61.91%. The scores of the patients' satisfaction with the outpatient services increased from an average of 89.10 points in 2017 to an average of 90.26 points in 2019. CONCLUSION: The continuous improvement of the service process markedly increases the efficiency of the outpatient services, and effectively improves patient's satisfaction with the outpatient process, this initiative thus deserves further application.

Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer.

Protein interacting with C-kinase 1 (PICK1) is a 415-aa multidomain scaffold protein encoded by the PICK1 gene. Accumulating evidence suggests that PICK1 is involved in the progression of cancer. However, the role of PICK1 in gastric cancer (GC) remains largely unknown. Using integrated analysis of publicly available GC transcriptome data from the Gene Expression Omnibus (GEO) database and immunohistochemistry analysis of samples obtained from clinical GC patients, we found that PICK1 expression was significantly down-regulated in gastric tumor tissues in comparison with adjacent normal tissues. Our analyses also revealed that decreased expression of PICK1 conferred a disadvantage on overall survival time in GC patients. Additionally, PICK1 expression showed a strong association with the epithelial-mesenchymal transition (EMT) pathway, and PICK1 might represent a functional bridge for EMT. Moreover, PICK1 expression was significantly decreased in the EMT subtype of GC and was negatively correlated with the expression of fibronectin 1 (FN1) and myosin light chain 9 (MYL9) mRNAs. Thus, our study provides evidence that PICK1 is a promising biomarker for the molecular etiology of GC.

Gut microbiome analysis as a predictive marker for the gastric cancer patients.

Gut microbiota have been implicated in the development of cancer. Colorectal and gastric cancers, the major gastrointestinal tract cancers, are closely connected with the gut microbiome. Nevertheless, the characteristics of gut microbiota composition that correlate with gastric cancer are unclear. In this study, we investigated gut microbiota alterations during the progression of gastric cancer to identify the most relevant taxa associated with gastric cancer and evaluated the potential of the microbiome as an indicator for the diagnosis of gastric cancer. Compared with the healthy group, gut microbiota composition and diversity shifted in patients with gastric cancer. Different bacteria were used to design a random forest model, which provided an area under the curve value of 0.91. Verification samples achieved a true positive rate of 0.83 in gastric cancer. Principal component analysis showed that gastritis shares some microbiome characteristics of gastric cancer. Chemotherapy reduced the elevated bacteria levels in gastric cancer by more than half. More importantly, we found that the genera Lactobacillus and Megasphaera were associated with gastric cancer.Key Points• Gut microbiota has high sensitivity and specificity in distinguishing patients with gastric cancer from healthy individuals, indicating that gut microbiota is a potential noninvasive tool for the diagnosis of gastric cancer.• Gastritis shares some microbiota features with gastric cancer, and chemotherapy reduces the microbial abundance and diversity in gastric cancer patients.• Two bacterial taxa, namely, Lactobacillus and Megasphaera, are predictive markers for gastric cancer.

Platelet-Tumor Cell Hybrid Membrane-Camouflaged Nanoparticles for Enhancing Therapy Efficacy in Glioma.

PURPOSE: Cell membrane-camouflaged nanoparticles (NPs) are drawing increasing attention because their surfaces acquire some characteristics of the cell membranes, making them a unique class of biomimetic materials for diverse applications. Modification of cell membrane or combination of different types of membranes can enhance their functionality. METHODS: We prepared platelet and tumor cell membrane camouflaged ß-mangostin-loaded NPs, which were synthesized with platelet-C6 hybrid biomimetic coating, poly(lactic-co-glycolic acid), and ß-mangostin (ß-PCNPs). Then, we evaluated their targeting ability and anticancer activity against glioma in vitro and in vivo. RESULTS: Biomimetic coating enhanced active drug targeting and immune escape properties of nanocarrier in C6 and THP-1 cells, respectively, which improved their cytotoxicity. ß-PCNPs were characterized to study the inherent properties of both source cells. Compared with bare ß-NPs, ß-PCNPs exhibited high tumor-targeting capability and induced apoptosis of C6 cells in vitro. Similarly, intravenous administration of drug through ß-PCNPs resulted in enhanced tumor-targeting and exhibited excellent rate of inhibition of glioma tumor growth in mice. Moreover, the blood circulation time of drug in mice in the ß-PCNP group was markedly prolonged and these mice exhibited better outcome than those in the ß-NP group. CONCLUSION: These results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.

C21 Fraction Refined from Marsdenia tenacissima-Induced Apoptosis is Enhanced by Suppression of Autophagy in Human Gastric Cell Lines.

C21 steroidal glycosides have been extensively reported for treating several types of cancer and are widely found in Marsdenia tenacissima. In this study, a C21 fraction was synthesized from M. tenacissima, and its anti-cancer potency was assessed against in vitro gastric cell lines BGC-823, SGC-7901, and AGS. Significant growth inhibition and cell cycle arrest were observed in C21 fraction-treated gastric cancer cells. The results of apoptotic staining techniques in C21 fraction-treated gastric cells were confirmed with excess reactive oxygen species generation. Moreover, SOD and H2O2 levels were increased by C21 fraction, especially when combined with chloroquine (CQ). The apoptotic inducing potential of C21 fraction was also evidenced by upregulation of proapoptotic proteins cleaved-PARP and BAX and downregulation of antiapoptotic proteins Bcl-2 and p-AKT by western blot, especially in the presence of the autophagy inhibitor CQ. The results showed that the apoptosis of gastric cancer cells caused by C21 fraction was enhanced by inhibiting autophagy. The current findings reveal a new mechanism for the antitumor activity of C21 fraction on gastric cancer.