Regulatory role of RGMb in lung injury promoted by the combination of carbon ion irradiation and anti-PD-1 antibody through Erk1/2 and p38 MAPK pathways.

The combination of carbon ion radiotherapy and anti-PD-1 antibody represents a new approach to treating thoracic tumors. However, the lung damage caused by this combination therapy may limit its use, and the potential mechanisms for this are worthy of investigation. The objective of this research was to examine the potential involvement of repulsive guidance molecule b (RGMb) in lung damage promoted by the utilization of carbon ion irradiation combined with an anti-PD-1 antibody. The C57BL/6 mice have been randomly separated into four distinct groups: control, anti-PD-1, whole thorax carbon ion irradiation, and irradiation in combination with anti-PD-1 treatment groups (combination group). Detection of pathological changes in lung tissue using HE staining. Detection of pulmonary fibrosis by Masson staining and the hydroxyproline assay. ELISA to detect TNF-α, TGF-ß, IL-6, and IL-1ß expression levels within lung homogenates. The expression of RGMb, p38 MAPK, and Erk1/2 pathways was detected using a fully automated digital Western blotting system WES (ProteinSimple, USA). Flow cytometry was employed to analyze tissue-resident memory T cells (TRM) within the lung. Subsequently, the siRNA gene was employed to induce the downregulation of RGMb in mice in order to validate the involvement of RGMb in radiation-immune lung injury. The present study observed a significant increase in both inflammatory and fibrotic indicators within the mice group's lung tissue that received the combination treatment. The combination group exhibited elevated levels of TGF-ß, TNF-α, IL-6, and IL-1ß in lung homogenates. Anti-PD-1 antibody and carbon ion irradiation, upregulated RGMb, phospho-p38 MAPK and phospho-Erk1/2. The results obtained from the flow cytometry analysis indicated that the combination group was significantly higher in the number of clonal expansion TRMs, which were predominantly characterized by the expression of CD8+CD103+CD69-TRMs. The downregulate of RGMb via siRNA in mice resulted in a decrease in phospho-p38 MAPK and phospho-Erk1/2. The combination group exhibited a reduction in TNF-α, TGF-ß, IL-6, and IL-1ß in their lung tissues, and the number of CD8+CD103+CD69-TRM was significantly reduced. The combination group exhibited a significant improvement in inflammatory and fibrotic indicators within the lung tissues. Anti-PD-1 antibody and carbon ion irradiation synergistically regulate RGMb, leading to strong clonal expansion of lung TRM through the p38 MAPK and Erk1/2 pathways. The present study offers valuable insights into the treatment of lung injury due to the combined administration of carbon ion radiotherapy and anti-PD-1 antibody therapy.

Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein.

Ulva prolifera, a type of green algae that can be consumed, was utilized in the production of an angiotensin-I converting enzyme (ACE) inhibitory peptide. The protein from the algae was isolated and subsequently hydrolyzed using a neutral protease. The resulting hydrolysate underwent several processes including Sephadex-G100 filtration chromatography, ultrafiltration, HPLC-Q-TOF-MS analysis, ADMET screening, UV spectrum detection test, molecular docking, and molecular dynamic simulation. Then, the ACE inhibitory peptide named KAF (IC50, 0.63 ± 0.26 µM) was identified. The effectiveness of this peptide in inhibiting ACE can be primarily attributed to two conventional hydrogen bonds. Additionally, it could activate endothelial nitric oxide synthase (eNOS) activity to promote the generation of nitric oxide (NO). Additionally, KAF primarily increased the intracellular calcium (Ca2+) level by acting on L-type Ca2+ channel (LTCC) and the ryanodine receptor (RyR) in the endoplasmic reticulum, and completed the activation of eNOS under the mediation of protein kinase B (Akt) signaling pathway. Our study has confirmed that KAF has the potential to be processed into pharmaceutical candidate functions on vasoconstriction.

Intrauterine Device Migrated into the Urachus: A Case Report.

Background: The intrauterine device is the most commonly used female contraceptive device, but the related complications of intrauterine devices are also common. Sometimes, intrauterine devices can cause uterine perforation, migrating into the abdominal cavity or other organs. At the same time, the intrauterine device may break into several small segments, migrate to distant organs, and even cause misdiagnosis. Objective: This study assessed the role of laparoscopy in treating intrauterine device migration. Design: This was a retrospective study involving in a review of a single case. Setting: This study was conducted at Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University. Participants: This study focued on a single case acout a 64-year-old female patient presented with repeated painless gross hematuria. She had a history of placing an intrauterine device and "removed the intrauterine device" in a local hospital for 20 years. Interventions: Laparoscopic ureterectomy was chosen based on the specific findings from the computerized tomography scan and cystoscopy. Abdominal computerized tomography showed high-density foreign body under the abdominal wall, size 2.29×0.51 cm, showed signs of edema in the surrounding tissue, and it was connected to the bladder wall. High-density lesions in the urachus and urachus calculi were considered. Cystoscopy showed the bubble position on the top of the bladder was depressed, a dark foreign body seemed to be seen inside, and the local mucosa was congested. The urachus foreign body, the urachus stone, was considered. Results: Computerized tomography examination showed a high-density space-occupying lesion at the position of the bladder and urachus tube. Cystoscopy showed local congestion at the top of the bladder, like urachus and dark foreign bodies, and no obvious abnormality in other parts of the bladder. Laparoscopy showed the urachus position was congested and edema, with local adhesion of the greater omentum and foreign bodies. The foreign bodies and surrounding tissues were removed by laparoscopic ureterectomy. Pathology showed tubular tissue, metal and plastic foreign bodies, fibrous tissue proliferation, and chronic inflammatory cell infiltration around the foreign bodies. Conclusion: The intrauterine device is a common contraceptive tool, and intrauterine device rupture and migration are normal. Migration to rare locations can lead to misdiagnosis. It can be removed by endoscopy, and combined with imaging and pathological examination, a correct diagnosis can finally be obtained. The patients should be advised to undergo regular check-ups after the procedure. These cases may provide diagnostic reference for similar symptoms of intrauterine device migration.

Lactobacillus plantarum strains attenuated DSS-induced colitis in mice by modulating the gut microbiota and immune response.

Gut microbiota has become a new therapeutic target in the treatment of inflammatory Bowel Disease (IBD). Probiotics are known for their beneficial effects and have shown good efficacy in the clinical treatment of IBD and animal models of colitis. However, how these probiotics contribute to the amelioration of IBD is largely unknown. In the current study, the DSS-induced mouse colitis model was treated with oral administration of Lactobacillus plantarum strains to investigate their effects on colitis. The results indicated that the L. plantarum strains improved dysbiosis and enhanced the abundance of beneficial bacteria related to short-chain fatty acids (SCFAs) production. Moreover, L. plantarum strains decreased the level of pro-inflammatory cytokines, i.e., IL-17A, IL-17F, IL-6, IL-22, and TNF-α and increased the level of anti-inflammatory cytokines, i.e., TGF-ß, IL-10. Our result suggests that L. plantarum strains possess probiotic effects and can ameliorate DSS colitis in mice by modulating the resident gut microbiota and immune response.

Agmatine and glycolipid metabolism. / 胍丁胺与糖脂代谢.

The prevalence of abnormal glucose and lipid metabolism and its relevant diseases has increased year by year, and it has become a problem that threatens human health. Therefore, finding a more effective way to prevent and treat diseases related to abnormal glucose and lipid metabolism has become an urgent public problem. Agmatine is a polyamine substance which widely presents in mammals.It is a metabolite produced by decarboxylation of L-arginine under the action of arginine decarboxylase, hence also known as decarboxylated arginine. Its biological effects have been confirmed. Previous studies have shown that agmatine possesses anti-diabetic effects in diabetic animals. Agmatine not only increases the insulin secretion form ß-pancreatic cells to inhibit the hyperglycemia, but also attenuates insulin resistance in rats. Agmatine also plays a positive role in lipid metabolism disorders and related diseases by modulating lipid metabolism and fatty acid oxidation.

Fertility preservation in BRCA mutation carriers-efficacy and safety issues: a review.

BRCA mutation carriers face various situations that influence their fertility potential. There is still a lack of guideline or expert consensus on Fertility Preservation (FP) in BRCA mutation carriers and the necessity and safety of FP in BRCA mutation carriers is still in dispute. This review aims to focus on the population of BRCA mutation carriers by analyzing the existing FP strategies, comprehensively comparing the pros and cons of each strategy and its applicability.FP is a suggestion for BRCA mutation carriers with birth planning. Different FP strategies have different characteristics. Considering the particularity of BRCA mutation carriers, multiple factors need to be carefully considered. This review focuses on the applicability of each FP method for carriers under various circumstances. Available FP strategies including oocyte cryopreservation, ovarian tissue cryopreservation, preimplantation genetic diagnosis, and egg/embryo donation are analyzed by comparing existing methods comprehensively. In the attempt to provide an up-to-date decision-making guidance. Conditions taking into consideration were the carrier's age, the risk of breast and ovarian metastasis, plans for oncotherapy, FP outcome, time available for FP intervention and accessibility.Overall, FP is necessary and safe for BRCA mutation carriers. Among all available FP methods, oocyte cryopreservation is the most reliable procedure; ovarian tissue cryopreservation is the only way for preserving both fertility and endocrine function, recommended for pre-pubertal carriers and when time is limited for oocyte stimulation. A clear framework provides frontline clinical practitioners a new thought and eventually benefit thousands of BRCA mutation carriers.

Differential protein expression in patients with urosepsis.

PURPOSE: Urosepsis in adults comprises approximately 25% of all sepsis cases, and is due to complicated urinary tract infections in most cases. However, its mechanism is not fully clarified. Urosepsis is a very complicated disease with no effective strategy for early diagnosis and treatment. This study aimed to identify possible target-related proteins involved in urosepsis using proteomics and establish possible networks using bioinformatics. METHODS: Fifty patients admitted to the Urology Unit of Lanzhou General PLA (Lanzhou, China), from October 2012 to October 2015, were enrolled in this study. The patients were further divided into shock and matched-pair non-shock groups. 2-DE technique, mass spectrometry and database search were used to detect differentially expressed proteins in serum from the two groups. RESULTS: Six proteins were found at higher levels in the shock group compared with non-shock individuals, including serum amyloid A-1 protein (SAA1), apolipoprotein L1 (APOL1), ceruloplasmin (CP), haptoglobin (HP), antithrombin-III (SERPINC1) and prothrombin (F2), while three proteins showed lower levels, including serotransferrin (TF), transthyretin (TTR) and alpha-2-macroglobulin (A2M). CONCLUSION: Nine proteins were differentially expressed between uroseptic patients (non-shock groups) and severe uroseptic patients (shock groups), compared with non-shock groups, serum SAA1, APOL1,CP, HP, SERPINC1and F2 at higher levels, while TF, TTR and A2M at lower levels in shock groups.these proteins were mainly involved in platelet activation, signaling and aggregation, acute phase protein pathway, lipid homeostasis, and iron ion transport, deserve further research as potential candidates for early diagnosis and treatment. (The conclusion seems too simple and vague, please re-write it. You may focus at what proteins have been expressed and introduce more detail about its significance.).

Identification and Validation of Immune Implication of R-Spondin 1 and an R-Spondin 1-Related Prognostic Signature in Esophagus Cancer.

R-spondin 1 (RSPO1), which encodes a secretory-activating protein, is a promising therapeutic target for various tumors. The aim of this study was to establish a robust RSPO1-related signature specific to esophageal cancer (ESCA). Our comprehensive study involved meticulous analysis of RSPO1 expression in ESCA tissues and validation across ESCA cell lines and clinical samples using The Cancer Genome Atlas (TCGA) and GTEx databases. Using TCGA-ESCA dataset, we employed single-sample gene set enrichment analysis (ssGSEA) to elucidate the complex interaction between RSPO1 expression and the abundance of 22 specific immune cell types infiltrating ESCA. The biological significance of RSPO1 was further elucidated using KEGG, GO, and GSEA, demonstrating its relevance to pivotal tumor and immune pathways. This study culminated in the construction of prognostic nomograms enriched by calibration curves, facilitating the projection of individual survival probabilities at intervals of one, three, and five years. A substantial decrease in RSPO1 expression was observed within ESCA tissues and cell lines compared to their normal esophageal counterparts, and a significant decrease in the proportion of activated dendritic cells was evident within ESCA, accompanied by an augmented presence of macrophages and naive B cells relative to normal tissue. GSEA and KEGG analyses showed that RSPO1 was associated with tumor and immune pathways. Additionally, an independent prognostic risk score based on the RSPO1-related gene signature was developed and validated for patients with ESCA. Finally, RT-qPCR and western blotting were performed to confirm RSPO1 expression in normal and ESCA cell lines and tissue samples. In summary, our investigation underscores the pivotal role of RSPO1 in orchestrating tumor immunity and proposes RSPO1 as a prospective target for immunotherapeutic interventions in ESCA. Furthermore, the intricate profile of the two RSPO1-related genes has emerged as a promising predictive biomarker with notable potential for application in ESCA.

Unveiling the Renoprotective Mechanisms of Schisandrin B in Ischemia-Reperfusion Injury Through Transcriptomic and Pharmacological Analysis.

Objective: This study investigates the targets, pathways, and mechanisms of Schisandrin B (Sch B) in alleviating renal ischemia-reperfusion injury (RIRI) using RNA sequencing and network pharmacology. Methods: The effects of Sch B on RIRI were assessed using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining, along with measurements of blood creatinine and urea nitrogen (BUN). Differential gene expression in mouse models treated with RIRI and Sch B+RIRI was analyzed through RNA-Seq. Key processes, targets, and pathways were examined using network pharmacology techniques. The antioxidant capacity of Sch B was evaluated using assays for reactive oxygen species (ROS), mitochondrial superoxide, and JC-1 membrane potential. Molecular docking was employed to verify the interactions between key targets and Sch B, and the expression of these targets and pathway was confirmed using qRT-PCR, Western blot, and immunofluorescence. Results: Sch B pre-treatment significantly reduced renal pathological damage, inflammatory response, and apoptosis in a mouse RIRI model. Pathological damage scores dropped from 4.33 ± 0.33 in the I/R group to 2.17 ± 0.17 and 1.5 ± 0.22 in Sch B-treated groups (p < 0.01). Creatinine and BUN levels were also reduced (from 144.6 ± 21.05 µmol/L and 53.51 ± 2.34 mg/dL to 50.44 ± 5.61 µmol/L and 17.18 ± 0.96 mg/dL, p < 0.05). Transcriptomic analysis identified four key targets (AKT1, ALB, ACE, CCL5) and the PI3K/AKT pathway. Experimental validation confirmed Sch B modulated these targets, reducing apoptosis and oxidative stress, and enhancing renal recovery. Conclusion: Sch B reduces oxidative stress, inflammation, and apoptosis by modulating key targets such as AKT1, ALB, ACE, and CCL5, while activating the PI3K/AKT pathway, leading to improved renal recovery in RIRI.

Carbon ion irradiation combined with PD-1 inhibitor trigger abscopal effect in Lewis lung cancer via a threshold dose.

Background and goal: Carbon ion beam is radio-biologically more efficient than photons and is beneficial for treating radio-resistant tumors. Several animal experiments with tumor-bearing suggest that carbon ion beam irradiation in combination with immunotherapy yields better results, especially in controlling distant metastases. This implies that carbon ion induces a different anti-tumor immune response than photon beam. More complex molecular mechanisms need to be uncovered. This in vivo and in vitro experiment was carried out in order to examine the radio-immune effects and the mechanism of action of carbon ion beam versus X-ray in combination with PD-1 inhibitors. Methods and Materials: Lewis lung adenocarcinoma cells and C57BL/6 mice were used to create a tumor-bearing mouse model, with the non-irradiated tumor growing on the right hind leg and the irradiated tumor on the left rear. 10Gy carbon ion beam or X-ray radiation, either alone or in combination with PD-1 inhibitor, were used to treat the left back tumor. The expression of molecules linked to immunogenicity and the infiltration of CD8+ T lymphocytes into tumor tissues were both identified using immunohistochemistry. IFN-ß in mouse serum was measured using an ELISA, while CD8+ T cells in mouse peripheral blood were measured using flow cytometry. Lewis cells were exposed to different dose of X-ray and carbon ion. TREX1, PD-L1, and IFN-ß alterations in mRNA and protein levels were identified using Western blot or RT-PCR, respectively. TREX1 knockdown was created by siRNA transfection and exposed to various radiations. Using the CCK8 test, EdU assay, and flow cytometry, changes in cell viability, proliferation, and apoptosis rate were discovered. Results: Bilateral tumors were significantly inhibited by the use of carbon ion or X-ray in combination with PD-1, particularly to non-irradiated tumor(p<0.05). The percentage of infiltrating CD8+ T cells and the level of IFN-ß expression were both raised by 10Gy carbon ion irradiation in the irradiated side tumor, although PD-L1 and TREX1 expression levels were also elevated. Lewis cell in vitro experiment further demonstrated that both X-ray and carbon ion irradiation can up-regulate the expression levels of PD-L1 and TREX1 with dose-dependent in tumors, particularly the trend of up-regulation TREX1 is more apparent at a higher dose in carbon ion, i.e. 8 or 10Gy, while the level of IFN-ß is decreased. IFN-ß levels were considerably raised under hypofractionated doses of carbon ion radiation by gene silencing TREX1. Conclusions: By enhancing tumor immunogenicity and increasing CD8+T infiltration in TME through a threshold dosage, X-ray or carbon ion radiation and PD-1 inhibitors improve anti-tumor activity and cause abscopal effect in Lewis lung adenocarcinoma-bearing mice. TREX1 is a possible therapeutic target and prognostic marker.

Purification identification and function analysis of ACE inhibitory peptide from Ulva prolifera protein.

In the present study, Ulva prolifera, an edible alga, was used to prepare angiotensin-I converting enzyme (ACE) inhibitory peptide. The algae protein was isolated and later hydrolyzed by five commercial enzymes (alcalase, papain, pepsin, trypsin, neutral protease), either individually or in combination. Hydrolysate, with the highest in vitro ACE inhibitory activity, was processed using the Sephadex-G100, ultrafiltration, HPLC-Q-TOF-MS, ADMET screening and molecular docking, respectively. The ACE inhibitory peptide DIGGL with a IC50 value of 10.32 ± 0.96 µM was then identified. The peptide against ACE by a non-competitive mode and mainly attributable to the three Conventional Hydrogen Bonds. It could activate Endothelial nitric oxide synthase activity in NO generation and reduce Endothelin-1 secretion induced by Angiotensin II in Human umbilical vein endothelial cells. Meanwhile, DIGGL could promote mice splenocytes proliferation, which was also effective when co-incubated with Con A or LPS, respectively. Besides, the anti-ACE peptide could remain active during the digestion of gastrointestinal proteases (pepsin-trypsin) in vitro.

Multi-phase-combined CECT radiomics models for Fuhrman grade prediction of clear cell renal cell carcinoma.

Objective: This study aimed to evaluate the effectiveness of multi-phase-combined contrast-enhanced CT (CECT) radiomics methods for noninvasive Fuhrman grade prediction of clear cell renal cell carcinoma (ccRCC). Methods: A total of 187 patients with four-phase CECT images were retrospectively enrolled and then were categorized into training cohort (n=126) and testing cohort (n=61). All patients were confirmed as ccRCC by histopathological reports. A total of 110 3D classical radiomics features were extracted from each phase of CECT for individual ccRCC lesion, and contrast-enhanced variation features were also calculated as derived radiomics features. These features were concatenated together, and redundant features were removed by Pearson correlation analysis. The discriminative features were selected by minimum redundancy maximum relevance method (mRMR) and then input into a C-support vector classifier to build multi-phase-combined CECT radiomics models. The prediction performance was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC). Results: The multi-phase-combined CECT radiomics model showed the best prediction performance (AUC=0.777) than the single-phase CECT radiomics model (AUC=0.711) in the testing cohort (p value=0.039). Conclusion: The multi-phase-combined CECT radiomics model is a potential effective way to noninvasively predict Fuhrman grade of ccRCC. The concatenation of first-order features and texture features extracted from corticomedullary phase and nephrographic phase are discriminative feature representations.

Ultrasound Radiomics-Guided Iliac Fascia Block on Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Hip Surgery.

Objective: Elderly patients with hip surgery are prone to postoperative cognitive dysfunction (POCD), leading to health management difficulties. This study is aimed at investigating the effect of ultrasound radiomics-guided iliac fascia block on POCD. Methods: A total of 67 cases of patients who had undergone hip joint surgery were divided into a training set (n = 47) and a validation set (radiomics-guided group, n = 20). The patients were intervened with ultrasound radiomics-guided iliac fascia block, and the maximum relevance minimum redundancy sifts out the image omics features obtained from 2D ultrasound images of patients. Another 20 patients undergone general anesthesia served as control. The incidence of POCD, the total amount of fentanyl, the visual analogue score (VAS) at different time points, and the levels of CRP and NSE in plasma were compared between the two groups. Results: The AUC on the training and validation sets were higher than 0.940. The incidence of POCD in the radiomics-guided and general anesthesia group was 5% and 30%, respectively (P = 0.037). Compared with the general anesthesia group, the dosage of fentanyl in the radiomics-guided was lower, the VAS score at 6 h, 1 d, and 2 d after operation was smaller, and the levels of CRP and NSE were lower (all P < 0.05). Conclusions: For elderly patients with hip surgery, the ultrasound radiomics-guided iliac fascia block can reduce the incidence of POCD and improve the effect of nerve block.

Effects of Ginsenoside Rg1 on the Biological Activity of Human Periodontal Ligament Cells.

, Objective. To investigate the effect of ginsenoside Rg1 on the biological activity of primary cultured human periodontal ligament cells (PDLC). Methods. The effects of ginsenoside Rg1 on the proliferation activity, protein synthesis, and alkaline phosphatase (ALP) activity of primary cultured human periodontal ligament cells were investigated by thiazole blue (MTT) colorimetric method, Coomassie brilliant blue method, and enzyme kinetics method. The effect of ginsenoside Rg1 on cell cycle was detected by flow cytometry, and the cells were labeled with calcium ion-sensitive fluorescent probe Fluo3/AM, and the effect of ginsenoside Rg1 on intracellular free calcium concentration was detected by laser scanning confocal microscope. Results. Compared with the control group, the experimental groups of ginsenoside Rg1 at various concentrations could significantly promote cell proliferation, and the effect time was the longest in the concentration range of 0.01-0.05 µmol/L;, Rg1 0.01umol/L and 0.05umol/L. The protein content in the 72-hour cell culture medium of the µmol/L group was significantly higher than that of the control group; the ALP activity in the 72-hour cell culture medium of the Rg1 0.01 µmol/L, 0.05 µmol/L, and 0.1 µmol/L groups was significantly higher than that of the control group; FCM assay showed that after 0.1 µmol/L Rg1 for 48 hours, compared with the control group, the proportion of cells in the early stage of DNA synthesis (G1%) of PDLC was significantly reduced, while the proportion of cells in the DNA synthesis stage (S%) and the value of cell proliferation index PrI (S + G2M)% were significantly increased; Rg1 increased intracellular calcium in PDLC cells at first and then decreased and finally maintained at a slightly higher resting calcium level than before drug addition. Conclusion. Ginsenoside Rg1 can increase the proliferation activity, protein synthesis, and alkaline phosphatase activity of periodontal ligament cells within a certain concentration range; Rg1 reduces the cells in G1 phase and increases cells in S phase of periodontal ligament fibroblasts. Change the concentration of free calcium ions in cells and promote more cells to enter a proliferative state.

Antibiotics Resistance Prevalence of Helicobacter pylori Strains in Northwest China.

Purpose: This study aims to estimate the resistance rate of Helicobacter pylori (HP) to commonly used antibiotics and analyze the potential influencing factors in northwest regions of China. Patients and Methods: HP-positive patients visiting the outpatient department of multiple hospitals were enrolled in the study. Then, gastric mucosal biopsy specimens were collected for HP isolation, culture, and investigation of the resistance rate of HP to amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin by Epsilometer test (E-test) antibiotic susceptibility testing. In addition, multi-drug resistance, the influence of HP eradication history, age, and region of residence on drug resistance rate were analyzed. Results: In total, 198 HP clinical strains were successfully isolated and cultured. The resistance rates of amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin were 16.16%, 85.86%, 7.58%, 46.46%, and 55.05%, respectively. The multi-drug resistance rates demonstrated that dual and triple resistances were 30.30% and 22.73%, respectively. The quadruple resistance rate reached 9.60%. Our results revealed that the prior eradication history of HP significantly increased levofloxacin and clarithromycin resistance. Metronidazole and levofloxacin resistances significantly differed among different age groups, which presented an upward trend with increasing age. Drug resistance rates varied with geographic regions, especially amoxicillin and clarithromycin resistance, which were highest in Hexi Corridor and Longnan regions. Conclusion: The current situation of HP resistance to common antibiotics is severe. Tetracycline is the most sensitive antibiotic, followed by amoxicillin, the first choice for HP eradication. However, the eradication failure of HP may lead to an increase in the resistance rate. Therefore, it is necessary to strengthen the standardized diagnosis and treatment of HP to improve the primary eradication rate.

Searching for the methylation sites involved in human papillomavirus type 16 and 18­positive women with cervical cancer.

It has been reported that >90% of women with cervical cancer are human papillomavirus (HPV)-positive, with HPV16 and 18 being the most 'highest-risk' HPV genotypes. However, in numerous women, HPV infection will not progress to cervical cancer. Accordingly, more appropriate screening markers need to be explored. In the present study, genome-wide DNA methylomic differences between cervical cancer tissues with HPV-16 or HPV-18 infection and normal cervical tissues were detected by using an Illumina Human Methylation 850 K BeadChip. The Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted in order to define the nearest neighbouring genes of differentiated methylation sites. Moreover, differentiated methylation sites were verified using pyrosequencing. KEGG analyses suggested that the focal adhesion pathway and pathways in cancer were highly enriched. Bioinformatics and statistical analysis indicated that the nine CpG loci had the most significant differences amongst the genes involved in these pathways. Among these, six CpG sites in the CHRM2, LAMA4, COL11A1, FGF10, IGF1 and TEK genes were highly associated with HPV-16-positive cervical cancer, as validated using pyrophosphate sequencing. Additionally, 10 significantly different CpG sites of the HPV-18-positive group were selected and verified in The Cancer Genome Atlas, indicating their possible diagnostic roles in cervical cancer development and determination. In addition, eight hypermethylated CpG island sites that were associated with HPV-16-positive cervical cancer tissues and 10 hypermethylated CpG island sites that were associated with HPV-18-positive cervical cancer tissues were identified, highlighting their potential roles in screening and evaluating targeted therapy efficacy and prognosis. The main focus of the present study was to identify the genetic variability in HPV-16- and HPV-18-positive samples and to elucidate possible methylation biomarkers in HPV-positive women with a risk of developing cervical cancer.

The Global research of protein post-translational modifications in the cancer field: A bibliometric and visualized study.

Objectives: Protein post-translational modifications (PTMs) are closely associated with tumorigenesis, targeting PTMs of key proteins might be the focus of antitumor drug discovery. This study aimed to analyze the research progress on protein PTMs in tumorigenesis by performing qualitative and quantitative evaluations. Methods: The Web of Science Core Collection was selected as the database, and Science Citation Index Expanded was selected as the citation index. Visualization tools such as VOSviewer, CiteSpace, HistCite, and Online Analysis Platform of Bibliometrics were used to deeply explore the information of the retrieved research papers and analyze them in terms of research trends and main aspects of research. Results: The search yielded 3777 relevant articles. The results showed that the total number of PTMs related papers in cancer field has been increasing annually, with the largest number of papers published in the United States of America. The co-word cluster analysis showed that the research on PTMs and tumorigenesis was primarily focused on the following four areas, mechanism, histone, P53, key Technologies. Tumor metabolism, autophagy, and protein-protein interaction, histone ubiquitination have become new research topics. Conclusion: This study provides an important reference for the research direction and selection of topics of interest in the PTMs of cancer field.

Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells.

Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein-protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.

Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells.

PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.

Methylation of the promoter A of estrogen receptor alpha gene in hBMSC and osteoblasts and its correlation with homocysteine.

Recent studies have shown that adult osteoporosis could be induced by ageing and estrogen deficiency and homocysteine (Hcy) is an independent risk factor of fracture in osteoporosis patients. In this study, we found hypermethylation of the promoter A region in the estrogen receptor alpha (ERα) gene, and methylation in 70.59% of 68 post-menopausal women, whose methylation degree was significantly higher than the pre-menopausal women (P < 0.05). Their methylation frequency was detected only 26.67% in 30 subjects. An obvious correlation between the degree of methylation in ERα gene and the level of Hcy (r = 0.809, P < 0.05) was explored. The cultured human bone marrow strom cells (hBMSC) and osteoblasts treated by Hcy resulted in de novo methylation of the promoter A region in the ERα gene and suppressed proliferation and differentiation with time and dose dependence. Meanwhile, ERα gene mRNA in osteoblast-like cells treated by Hcy was much lower than the control group (P < 0.05). Thus, both in vivo and in vitro data showed that Hcy could promote hypermethylation of the promoter A region and reduce ERα mRNA transcription, which may be an important mechanism for the pathogenesis of postmenopausal osteoporosis.