Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Identification of ferroptosis-related subtypes, characteristics of TME infiltration and development of prognostic models in gastric cancer.

BACKGROUND: Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches. METHODS: FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR. RESULTS: In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC). CONCLUSION: Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug.

From Conversion to Resection for Unresectable Hepatocellular Carcinoma: A Review of the Latest Strategies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF­κB pathway.

Fine particulate matter (PM2.5) is a type of small particle that is <2.5 µm in diameter that may cause airway inflammation. Thus, the present study aimed to explore the effects of PM2.5 on endoplasmic reticulum (ER) stress and airway inflammation in human airway epithelial cells. For this purpose, HBE135­E6E7 airway epithelial cells were cultured and exposed to specific concentrations of PM2.5 for various periods of time, and cell viability was determined using a Cell Counting Kit­8 assay. The results of the present study demonstrated that exposure to PM2.5 increased the mRNA and protein expression levels of interleukin (IL)­6, tumor necrosis factor (TNF)­α and mucin 5AC (MUC5AC). Moreover, the expression levels of ER stress­related proteins, such as glucose­regulated protein 78, CCAAT­enhancer binding protein homologous protein, activating transcription factor 6, protein kinase R­like ER kinase (PERK), phosphorylated (p­)PERK, inositol­requiring enzyme 1α (IRE1α) and p­IRE1α, and nucleotide­binding oligomerization domain 1 (NOD1) expression levels were increased following exposure to PM2.5. Transfection with IRE1α small interfering RNA (siRNA) led to the increased production of IL­6, TNF­α and MUC5AC. Moreover, the expression of NOD1 and the translocation of NF­κB p65 were inhibited following transfection with IRE1α siRNA. In addition, the results of the present study demonstrated that transfection with NOD1 siRNA decreased the production of IL­6, TNF­α and MUC5AC, and decreased the translocation of NF­κB p65. The expression levels of IL­6, TNF­α and MUC5AC were increased in the HBE135­E6E7 cells following treatment with C12­iE­DAP, a NOD1 agonist. Moreover, treatment with C12­iE­DAP led to the activation of NF­κB p65. Collectively, the results of the present study suggest that PM2.5 promotes airway inflammation and mucin production by activating ER stress in HBE135­E6E7 airway epithelial cells, and that the IRE1α/NOD1/NF­κB pathway may be involved in this process.

Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

HDAC-an important target for improving tumor radiotherapy resistance.

Radiotherapy is an important means of tumor treatment, but radiotherapy resistance has been a difficult problem in the comprehensive treatment of clinical tumors. The mechanisms of radiotherapy resistance include the repair of sublethal damage and potentially lethal damage of tumor cells, cell repopulation, cell cycle redistribution, and reoxygenation. These processes are closely related to the regulation of epigenetic modifications. Histone deacetylases (HDACs), as important regulators of the epigenetic structure of cancer, are widely involved in the formation of tumor radiotherapy resistance by participating in DNA damage repair, cell cycle regulation, cell apoptosis, and other mechanisms. Although the important role of HDACs and their related inhibitors in tumor therapy has been reviewed, the relationship between HDACs and radiotherapy has not been systematically studied. This article systematically expounds for the first time the specific mechanism by which HDACs promote tumor radiotherapy resistance in vivo and in vitro and the clinical application prospects of HDAC inhibitors, aiming to provide a reference for HDAC-related drug development and guide the future research direction of HDAC inhibitors that improve tumor radiotherapy resistance.

Coptisine inhibits Helicobacter pylori and reduces the expression of CagA to alleviate host inflammation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) is a major pathogen colonized in the human stomach and is implicated in gastritis, peptic ulcer, and gastric carcinoma. Antibiotics are useful for eradicating H. pylori but failed for drug resistance, making it urgent to develop effective and safe drugs. Rhizoma Coptidis was reported as one of the most effective Chinese medicines to treat H. pylori-related gastrointestinal diseases, while the precise antimicrobial mechanism remains unclear. Thus, it is of great significance to study the antimicrobial ingredients and corresponding mechanisms of Rhizoma Coptidis. AIM OF THE STUDY: To search for the most effective alkaloid against H. pylori in Rhizoma Coptidis and illustrate the probable mechanisms. MATERIALS AND METHODS: Five main alkaloids in Rhizoma Coptidis were isolated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested to determine the most effective one. Bacterial growth experiments, Annexin V-FITC/PI staining, TUNEL staining, and transmission electron microscopy (TEM) were performed to further study the anti-H. pylori activity of coptisine (Cop). The in vivo effect of Cop on H. pylori eradication rate and H. pylori-induced inflammation was investigated in mice. Transcriptomics was used to understand the underlying mechanism of eradicating H. pylori and reducing host inflammation. Western blot, RT-PCR, and ELISA experiments were utilized and confirmed that cagA was one of the targets of Cop. RESULTS: According to the MIC and MBC, Cop was the most effective alkaloid against H. pylori, especially with no drug resistance developed. In vitro experiments showed that Cop inhibited H. pylori by inducing DNA fragmentation, phosphatidylserine exposure, and membrane damage. Cop (150 mg/kg/day) effectively eradicated H. pylori in mice and reduced the levels of IL-2 and IL-6 to relieve gastric inflammation. Transcriptomic analysis revealed that virulence factor cagA was one of the hub genes associated with the inflammation-improving effect of Cop. That is, Cop could decrease the expression of CagA and subsequently reduce the translocation of CagA to gastric epithelial cells, thereby improving the morphology of hummingbird-like phenotype induced by CagA and alleviating inflammation. CONCLUSIONS: Cop is the most effective alkaloid in Rhizoma Coptidis and might act through multiple mechanisms for H. pylori eradication along with reducing the expression of CagA to alleviate inflammation.

Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 ( CFAP43 ) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43 , including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43 -deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43 , and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.

Berberine promotes IGF2BP3 ubiquitination by TRIM21 to induce G1/S phase arrest in colorectal cancer cells.

The increasing incidence of colorectal cancer (CRC) has become a major global public health burden. The natural drug Berberine (BBR) has shown potential in preventing CRC, and IGF2 mRNA binding protein 3 (IGF2BP3) may be a target of BBR. This study aims to investigate the mechanisms of BBR acting on IGF2BP3 to improve CRC. The results showed that IGF2BP3 played an important role in the development of CRC. BBR down-regulated IGF2BP3 expression and inhibited CRC growth in mice. Cell thermodynamic stability analysis (CETSA) and drug affinity responsive target stability (DARTS) analysis showed BBR may bind to IGF2BP3. BBR may induce structural changes in IGF2BP3 and decrease its protein stability in cytoplasm. The results from Co-Immunoprecipitation (Co-IP) suggested that BBR promoted the ubiquitination of IGF2BP3 by tripartite motif-containing protein 21 (TRIM21). Through RNA binding protein Immunoprecipitation (RIP) assay, it was found BBR inhibited the stabilization of CDK4/CCND1 mRNA by IGF2BP3 and promoted G1/S phase arrest in CRC cells. Overexpression of IGF2BP3 in vitro and in vivo attenuated the inhibition of CRC growth by BBR. This work demonstrated the potential of BBR targeting to IGF2BP3 in improving CRC and provided a new strategy for clinical treatment on CRC as well as novel anticancer drug design based on IGF2BP3 and TRIM21.

Immunotherapy combination with regorafenib for refractory hepatocellular carcinoma: A real-world study.

PURPOSE: To compare the efficacy and safety of immunotherapy plus regorafenib versus regorafenib only in patients with pretreated hepatocellular carcinoma (HCC). METHODS: Immunotherapy plus regorafenib or regorafenib alone was analyzed in patients with advanced HCC with documented tumor progression on front-line therapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs) were assessed. RESULTS: Of the 125 patients enrolled in this study, 50 patients received combination (pCOM) treatment as front-line treatment, and 60 patients received monotherapy (pMONO) as front-line treatment. In the pCOM cohort, median OS was significantly longer with for patients regorafenib plus immunotherapy than regorafenib alone treatment (15.0 vs. 2.0 months; P = 0.035). The DCR numerically increased in the regorafenib plus immunotherapy treatment in both cohorts (40.6 % vs. 22.2 %, 72.7 % vs. 54.7 %, respectively). There were no differences in PFS with regorafenib according to whether or not regorafenib was combined with immunotherapy in the pCOM and pMONO cohorts (PFS, P = 0.17, P = 0.91, respectively). Regarding the number of TRAEs occurred, regorafenib plus immunotherapy group was comparable to regorafenib group in the pCOM cohort (65.6 % vs. 72.2 %). In the pMONO cohort, TRAEs occurred in fewer patients receiving regorafenib than regorafenib plus immunotherapy (69.8 % vs. 95.5 %). CONCLUSIONS: Immunotherapy plus regorafenib may significantly improve clinical outcomes and have a manageable safety profile compared with regorafenib monotherapy in advanced HCC after front-line therapy failure. The efficacy of combination therapy needs to be validated in prospective studies with large samples.

Novel Self-Assembled Micelles With Increased Tumor Penetration and Anti-Tumor Efficiency Against Breast Cancer.

PURPOSE: Recently, docetaxel (DTX) micelles based on retinoic acid derivative surfactants showed lower systemic toxicity and bioequivalence to polysorbate-solubilized docetaxel (Taxotere®) in a phase II clinical study. However, the poor stability of these surfactants in vitro and in vivo led to extremely harsh storage conditions with methanol, and the formed micelles were quickly disintegrated with rapid drug burst release in vivo. To further enhance the stability and accumulation in tumors of DTX micelles, a novel surfactant based on acitretin (ACMeNa) was synthesized and used to prepare DTX micelles to improve anti-tumor efficiency. METHODS: Novel micelle-forming excipients were synthesized, and the micelles were prepared using the thin film hydration technique. The targeting effect in vitro, distribution in the tumor, and its mechanism were observed. Pharmacokinetics and anti-tumor effect were further investigated in rats and tumor-bearing female mice, respectively. RESULTS: The DTX-micelles prepared with ACMeNa (ACM-DTX) exhibited a small size (21.9 ± 0.3 nm), 39% load efficiency, and excellent stability in vitro and in vivo. Long circulation time, sustained and steady accumulation, and strong penetration in the tumor were observed in vivo, contributing to a better anti-tumor effect and lower adverse effects. CONCLUSIONS: The micelles formed by ACMeNa showed a better balance between anti-tumor and adverse effects. It is a promising system for delivering hydrophobic molecules for cancer therapy.

Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development.

Acetyl-CoA synthetase 2 (ACSS2), an important member of the acetyl-CoA synthetase (ACSS) family, can catalyze the conversion of acetate to acetyl coenzyme A (acetyl-CoA). Currently, acetyl-CoA is considered an important intermediate metabolite in the metabolism of energy substrates. In addition, nutrients converge through acetyl-CoA into a common metabolic pathway, the tricarboxylic acid cycle and oxidative phosphorylation. Not only does ACSS2 play a crucial role in material energy metabolism, it is also involved in the regulation of various acetylation processes, such as regulation of histone and transcription factor acetylation. ACSS2-mediated regulation of acetylation is related to substance metabolism and tumorigenesis. In mammalian cells, ACSS2 utilizes intracellular acetate to synthesize acetyl-CoA, a step in the process of DNA and histone acetylation. In addition, studies in tumors have shown that cancer cells adapt to the growth conditions in the tumor microenvironment (TME) by activating or increasing the expression level of ACSS2 under metabolic stress. Therefore, this review mainly outlines the role of ACSS2 in substance metabolism and tumors and provides insights useful for investigating ACSS2 as a therapeutic target.

Long-term effects of total vs. partial pancreatectomy among patients with pancreatic cancer: a population-based study.

Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations. Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis. Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05). Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.

Norcantharidin Nanostructured Lipid Carrier (NCTD-NLC) Suppresses the Viability of Human Hepatocellular Carcinoma HepG2 Cells and Accelerates the Apoptosis.

Malignant tumors have become the main cause of harm to human life and health. Development for new antitumor drugs and the exploration to drug carriers are becoming the concerned focus. In this study, we exploited our experiments to explore the effect of NCTD-NLC on liver cancer cells: the HepG2 cells cultured in vitro were given with NCTD-NLC administration; then, the estimation on cellular proliferation and apoptosis was accomplished through MTT and flow cytometry. Six hours after the administration, we performed the High Performance Liquid Chromatography (HPLC) detection to estimate the NCTD content in the heart, liver, spleen, lung, kidney and plasma of rats. Then, our outcomes showed that NCTD-NLC had a notable inhibitory effect on HepG2 cells, leading to a gradually decreased cellular viability. Cell viability was negatively correlated with NCTD-NLC concentration. Along with the concentration increasing, significantly increasing cellular apoptosis and gradually decreasing cellular viability were observed. The apoptosis rate was positively correlated with the concentration of NCTD-NLC. On the basis of the data we obtained, we found that the group with NCTD-NLC tail vein injection had an obvious advantage in drug delivery when compared with other groups. Through the tumorigenesis test to nude mice, we found that the tumor inhibition rate of the NCTD-NLC tail vein injection group had a 27.48% elevation in contrast to the NCTD gavage group, and it was also the group with the best tumor inhibition efficiency. In conclusion, the NCTD-NLC prepared in this study had a mighty inhibitory effect towards HepG2 cellular viability and an accelerating work on apoptosis. Tail vein injection of NCTD-NLC has the best drug delivery effect.

Age-specific spectrum of etiological pathogens for viral diarrhea among children in twelve consecutive winter-spring seasons (2009-2021) in China.

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

Post-Translational Modifications of BRD4: Therapeutic Targets for Tumor.

Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extraterminal (BET) family, is considered to be a major driver of cancer cell growth and a new target for cancer therapy. Over 30 targeted inhibitors currently in preclinical and clinical trials have significant inhibitory effects on various tumors, including acute myelogenous leukemia (AML), diffuse large B cell lymphoma, prostate cancer, breast cancer and so on. However, resistance frequently occurs, revealing the limitations of BET inhibitor (BETi) therapy and the complexity of the BRD4 expression mechanism and action pathway. Current studies believe that when the internal and external environmental conditions of cells change, tumor cells can directly modify proteins by posttranslational modifications (PTMs) without changing the original DNA sequence to change their functions, and epigenetic modifications can also be activated to form new heritable phenotypes in response to various environmental stresses. In fact, research is constantly being supplemented with regards to that the regulatory role of BRD4 in tumors is closely related to PTMs. At present, the PTMs of BRD4 mainly include ubiquitination and phosphorylation; the former mainly regulates the stability of the BRD4 protein and mediates BETi resistance, while the latter is related to the biological functions of BRD4, such as transcriptional regulation, cofactor recruitment, chromatin binding and so on. At the same time, other PTMs, such as hydroxylation, acetylation and methylation, also play various roles in BRD4 regulation. The diversity, complexity and reversibility of posttranslational modifications affect the structure, stability and biological function of the BRD4 protein and participate in the occurrence and development of tumors by regulating the expression of tumor-related genes and even become the core and undeniable mechanism. Therefore, targeting BRD4-related modification sites or enzymes may be an effective strategy for cancer prevention and treatment. This review summarizes the role of different BRD4 modification types, elucidates the pathogenesis in the corresponding cancers, provides a theoretical reference for identifying new targets and effective combination therapy strategies, and discusses the opportunities, barriers, and limitations of PTM-based therapies for future cancer treatment.

Gastric Cancer Screening Methods: A Comparative Study of the Chinese New Gastric Cancer Screening Score and Kyoto Classification of Gastritis.

Objective: To evaluate the Chinese new gastric cancer screening score (i.e., Li's score) and Kyoto Classification of Gastritis for screening gastric cancer. Methods: A total of 702 patients were scored using the two scoring methods. Gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were compared between the two scoring methods. The area under the ROC curve, sensitivity, and specificity of the two scoring methods were evaluated. Results: Both of the two scoring methods found that gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were all significantly higher in the medium-risk and high-risk group patients than those in the low-risk group patients. According to the Kyoto Classification of Gastritis, patients in the high-risk group had more gastric atrophy, intestinal metaplasia, and gastric cancer than those in the medium-risk group patients. Gastric atrophy, intestinal metaplasia, and gastric cancer in the low-risk and medium-risk group patients evaluated by the Li score were all significantly higher than those in patients with corresponding risk level evaluated by Kyoto Classification of Gastritis, respectively. The area under the ROC curve of the Li score was 0.702, and the sensitivity and specificity were 57.6% and 85.3%, respectively. The area under the ROC curve of the Kyoto Classification of Gastritis was 0.826, and the sensitivity and specificity were 75.4% and 83.6%, respectively. Conclusion: Both Li's score and Kyoto Classification of Gastritis showed good screening value for gastric cancer, but Kyoto Classification of Gastritis was more sensitive than the Li score.

Molecular Epidemiology of Human Adenovirus, Astrovirus, and Sapovirus Among Outpatient Children With Acute Diarrhea in Chongqing, China, 2017-2019.

Objective: To investigate the epidemiology of human adenovirus (HAdV), human astrovirus (HAstV), and sapovirus (SaV), children with acute diarrhea in Chongqing, China from 2017 to 2019 were enrolled. Improved surveillance could provide better guidance for diarrhea prevention. Methods: Between 2017 and 2019, fecal specimens were collected from children <14 years of age presenting with acute diarrhea for treatment at the outpatient department of the Children's Hospital, Chongqing Medical University. Human HAdV in the fecal specimens was detected by PCR, while RT-PCR was adopted for the detection of HAstV and SaV. Results: A total of 1,352 fecal specimens were screened in this study. The detection rate of HAdV was 4.44% (60/1352), HAstV was 2.81% (38/1352), and SaV was 1.04% (14/1352). The prevalence of enteric viruses in males was not significantly different to females (p > 0.05). We found 96.67% (58/60) of the HAdV-positive cases, 92.11% (35/38) of the HAstV-positive cases, and 100% (14/14) of the SaV-positive cases among the children under 4 years old. HAdV cases were identified throughout the year, while the infection of HAstV peaked from March to May every year. By contrast, SaV was detected in May, July, and from September to December. In total, 41 strains of HAdV-F were identified, including F41 (39/60) and F40 (2/60). Furthermore, A31, B3, B7, C1, C2, C5, and C6 were also detected in the study. In addition, we detected two genotypes of HAstV, HAstV-1 (34/38) and HAstV-5 (4/38), and two genotypes of SaV, GI0.1 (13/14), GI0.2 (1/14). Conclusion: The enteric viruses HAdV, HAstV, and SaV contribute to the overall burden of diarrhea in Chongqing, especially in children <4 years of age. Two genotypes were identified for HAstV (HAstV-1 and HAstV-5) and SaV (GI.1 and GI.2) with an additional nine genotypes detected in HAdV cases. While the F41 HAdV strain was predominant, HAdV-A31 was also detected in 10% of cases. The study results along with continuous surveillance of enteric viruses will aid in the design and implementation of future enteric vaccines and diarrhea mitigation strategies.

Research progress on SLC7A11 in the regulation of cystine/cysteine metabolism in tumors.

Solute carrier family 7 member 11 (SLC7A11) is a major transporter regulating cysteine metabolism and is widely expressed in a variety of tumor cells. SLC7A11 plays an important role in the occurrence, development, invasion and metastasis of tumors by regulating the transport of cysteine in the tumor microenvironment. SLC7A11 is expected to become a new therapeutic target and prognostic indicator for the individualized treatment of patients. According to relevant research reports, SLC7A11 can predict the stages and metastasis of liver, breast and lung cancer. Therefore, an in-depth exploration of the role of SLC7A11 in tumors may be important for the screening, early diagnosis, treatment and prognosis of patients with tumors. The current review summarizes the research progress on SLC7A11 in liver cancer, lung cancer and other tumors on the basis of previous primary studies. In addition, the present review systematically elaborates on the three main aspects of SLC7A11 pathways in some tumors, the cancer-promoting mechanisms, and the therapeutic relationship between SLC7A11 and tumors. Finally, the present review aims to provide a reference for assessing whether SLC7A11 can be used as a prognostic indicator and treatment target for tumor patients, and the future research direction with regard to SLC7A11 in tumors.

Cell therapy in patients with heart failure: a comprehensive review and emerging concepts.

This review summarizes the results of clinical trials of cell therapy in patients with heart failure (HF). In contrast to acute myocardial infarction (where results have been consistently negative for more than a decade), in the setting of HF the results of Phase I-II trials are encouraging, both in ischaemic and non-ischaemic cardiomyopathy. Several well-designed Phase II studies have met their primary endpoint and demonstrated an efficacy signal, which is remarkable considering that only one dose of cells was used. That an efficacy signal was seen 6-12 months after a single treatment provides a rationale for larger, rigorous trials. Importantly, no safety concerns have emerged. Amongst the various cell types tested, mesenchymal stromal cells derived from bone marrow (BM), umbilical cord, or adipose tissue show the greatest promise. In contrast, embryonic stem cells are not likely to become a clinical therapy. Unfractionated BM cells and cardiosphere-derived cells have been abandoned. The cell products used for HF will most likely be allogeneic. New approaches, such as repeated cell treatment and intravenous delivery, may revolutionize the field. As is the case for most new therapies, the development of cell therapies for HF has been slow, plagued by multifarious problems, and punctuated by many setbacks; at present, the utility of cell therapy in HF remains to be determined. What the field needs is rigorous, well-designed Phase III trials. The most important things to move forward are to keep an open mind, avoid preconceived notions, and let ourselves be guided by the evidence.