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BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
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Genótipo , Papillomaviridae , Infecções por Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , China/epidemiologia , Adulto , Prevalência , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adolescente , Idoso , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , DNA Viral/genética , Colo do Útero/virologiaRESUMO
BACKGROUND: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. RESEARCH DESIGN AND METHODS: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. RESULT: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). CONCLUSION: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.
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OBJECTIVE: To explore the potential action mechanism of Huotu Jiji Pellets (HJP) in the treatment of erectile dysfunction (ED) based on network pharmacology and molecular docking. METHODS: We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine (TCMIP) and the therapeutic target genes of ED from the databases of Genecards. Then we obtained the common targets of HJP and ED using the Venny software, constructed a protein-protein interaction (PPI) network of HJP acting on ED, and screened out the core targets with the Cytoscape software. Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software. RESULTS: A total of 64 effective compounds, 822 drug-related targets, 1 783 disease-related targets and 320 common targets were obtained in this study. PPI network analysis showed that the core targets of HJP for ED included ESR1, HSP90AA1, SRC, and STAT3. GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus, positive regulation of kinase activity, and positive regulation of MAPK cascade. KEGG pathway enrichment analysis suggested that PI3K-Akt, apoptosis, MAPK, HIF-1, VEGF, autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED. Molecular docking prediction exhibited a good docking activity of the key active molecules of HJP with the core targets. CONCLUSION: This study showed that HJP acted on ED through multi-components, multi-targets and multi-pathways, which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.
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Medicamentos de Ervas Chinesas , Disfunção Erétil , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Masculino , Disfunção Erétil/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Transdução de SinaisRESUMO
Background: Is de novo metastatic breast cancer (dnMBC) the same disease in the elderly as in younger breast cancer remains unclear. This study aimed to determine the metastatic patterns and survival outcomes in dnMBC according to age groups. Methods: We included patients from the Surveillance Epidemiology and End Results program. Chi-square test, multivariate logistic regression analyses, and multivariate Cox regression models were used for statistical analyses. Results: A total of 17719 patients were included. There were 3.6% (n=638), 18.6% (n=3290), 38.0% (n=6725), and 39.9% (n=7066) of patients aged <35, 35-49, 50-64, and ≥65 years, respectively. Older patients had a significantly higher risk of lung metastasis and a significantly lower risk of liver metastasis. There were 19.1%, 25.6%, 30.9%, and 35.7% of patients with lung metastasis in those aged <35, 35-49, 50-64, and ≥65 years, respectively. Moreover, the proportion of liver metastasis was 37.6%, 29.5%, 26.3%, and 19.2%, respectively. Age was the independent prognostic factor associated with breast cancer-specific survival (BCSS) and overall survival (OS). Those aged 50-64 years had significantly inferior BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. Patients aged ≥65 years also had significantly lower BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. However, similar outcomes were found between those aged 35-49 and <35 years. Conclusion: Our study suggests that different age groups may affect the metastatic patterns among patients with dnMBC and the survival of younger patients is more favorable than those of older patients.
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Neoplasias da Mama , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Idoso , Fatores Etários , Adulto , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Prognóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/mortalidade , Programa de SEER , Taxa de Sobrevida , Metástase NeoplásicaRESUMO
Polarity establishment is one of the key factors affecting early embryonic development. Polarity establishment begins with myosin phosphorylation in the 8-cell embryo, and phosphorylation activates actin leading to its initiation of contractility. Subsequently, actin undergoes reorganization to form an apical domain rich in microvilli on the non-contacting surface of each blastomere, and form the actomyosin ring that marks the maturation of the apical domain in conjunction with polar protein complexes and others. From the process of polarity establishment, it can be seen that the formation of the apical domain is influenced by actin-related proteins and polar protein complexes. Some zygote genome activation (ZGA) and lineage-specific genes also regulate polarity establishment. Polarity establishment underlies the first cell lineage differentiation during early embryonic development. It regulates lineage segregation and morphogenesis by affecting asymmetric cell division, asymmetric localization of lineage differentiation factors, and activity of the Hippo signaling pathway. In this review, we systematically summarize the mechanisms of early embryonic polarity establishment and its impact on lineage differentiation in mammals, and discuss the shortcomings of the currently available studies in terms of regulatory mechanisms and species, thereby providing clues and systematic perspectives for elucidating early embryonic polarity establishment.
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Actinas , Actomiosina , Animais , Actomiosina/metabolismo , Citocinese , Diferenciação Celular , Linhagem da Célula , Polaridade Celular/fisiologia , Mamíferos/metabolismoRESUMO
Background: Fatty acid oxidation (FAO) is considered to play a vital part in tumor metabolic reprogramming. But the comprehensive description of FAO dysregulation in tumors has not been unknown. Methods: We obtained FAO genes, RNA-seq data and clinical information from the Msigdb, TCGA and GTEx databases. We assessed their prognosis value using univariate cox analysis, survival analysis and Kaplan-Meier curve. We determined the function of FAO genes using gene set variation analysis. The correlation analysis was calculated by corrplot R package. Immunotherapy response was assessed through TIDE scores. The protein expression levels of FAO genes were validated using immunohistochemistry (IHC). Results: The FAO scores were highest in COAD but lowest in PCPG. FAO scores were significantly associated with the prognosis of some cancers in OS, DSS, DFI and PFI. Besides, gene set variation analysis identified that FAO scores were related to immune-related pathways, and immune infiltration analysis showed FAO scores were positively related to cancer-associated fibroblasts and various immune-related genes. TIDE scores were significantly decreased in ACC, CHOL, ESCA, GBM, LAML, SARC, SKCM and THCA compared with normal samples, while it was significantly increased in BLCA, LUAD, LUSC, PCPG, PRAD and STAD. Besides, most FAO genes were downregulated in pan-cancer compared with normal samples. Moreover, we found copy number variation (CNV) of FAO genes played a positive role in their mRNA expression, while methylation was negative. We determined FAO genes were closely related to some drugs in pan-cancer. Conclusions: FAO score is a novel and promising factor for predicting outcomes.
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Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.
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Adenocarcinoma de Pulmão , Antineoplásicos , Neoplasias Pulmonares , Proteínas de Fusão Oncogênica , Compostos Organofosforados , Inibidores de Proteínas Quinases , Pirimidinas , Humanos , Compostos Organofosforados/uso terapêutico , Compostos Organofosforados/farmacologia , Pirimidinas/uso terapêutico , Pirimidinas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Animais , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Prognóstico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Lactamas/uso terapêutico , Carbazóis/uso terapêutico , Carbazóis/farmacologia , Sulfonas/uso terapêutico , Sulfonas/farmacologia , Crizotinibe/uso terapêutico , Crizotinibe/farmacologia , Linhagem Celular Tumoral , Piperidinas/uso terapêutico , Piperidinas/farmacologia , Feminino , Camundongos , Inflamação/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Pirazóis/uso terapêutico , Pirazóis/farmacologia , Masculino , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/metabolismo , Proliferação de Células/efeitos dos fármacos , Mutação , Aminopiridinas/uso terapêutico , Aminopiridinas/farmacologiaRESUMO
Purpose: The aim is to investigate the application value of dermoscopy combined with reflectance confocal microscopy (RCM) in assessing vitiligo disease activity and treatment response. Patients and Methods: We enrolled 279 patients with vitiligo and evaluated the disease activity by Vitiligo Disease Activity (VIDA) score, dermoscopy, RCM and dermoscopy combined with RCM respectively. The sensitivity and specificity of different assessment techniques were compared with VIDA score by the differences and consistency. The different characteristics of dermoscopy and RCM with different treatment responses were also analyzed. Results: The results showed that the sensitivity and specificity of dermoscopy combined RCM were higher than RCM or dermoscopy alone (P values less than 0.05). In the repigmentation process, leukotrichia, pigment network absent and perilesional hyperpigmentation under dermoscopy at the baseline suggested a poor treatment response, while the incompletely disappearing pigment rings under RCM and perifollicular hyperpigmentation under dermoscopy indicated a good treatment response. We also found the proportion of patients with telangiectasia, increased pigment at the lesions and around the hair follicles was significantly higher in the good treatment response group than that in the poor one by dermoscopy (χ2 = 4.423, 32.471, 4.348, P = 0.035 0.000, 0.037) and by RCM the proportion of patients with both increased pigment granules and dendritic melanocytes in the good treatment response group was higher than that in the poor one (χ2 = 38.215, 5.283, P = 0.000, 0.022, respectively). Conclusion: With the higher sensitivity and specificity than dermoscopy or RCM alone, a combination of dermoscopy and RCM may be a new more accurate measure to assess the vitiligo disease activity and the treatment response.
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BACKGROUND: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population. METHODS: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed. RESULTS: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis. CONCLUSIONS: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.
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Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Feminino , Transmissão Vertical de Doenças Infecciosas , Nomogramas , Selenoproteínas/genéticaRESUMO
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Osteoblastos , Osteopontina/metabolismoRESUMO
PURPOSE: Most Hepatocellular carcinoma (HCC) patients are in advanced or metastatic stage at the time of diagnosis. Prognosis for advanced HCC patients is dismal. This study was based on our previous microarray results, and aimed to explore the promising diagnostic and prognostic markers for advanced HCC by focusing on the important function of KLF2. METHODS: The Cancer Genome Atlas (TCGA), Cancer Genome Consortium database (ICGC), and the Gene Expression Comprehensive Database (GEO) provided the raw data of this study research. The cBioPortal platform, CeDR Atlas platform, and the Human Protein Atlas (HPA) website were applied to analyze the mutational landscape and single-cell sequencing data of KLF2. Basing on the results of single-cell sequencing analyses, we further explored the molecular mechanism of KLF2 regulation in the fibrosis and immune infiltration of HCC. RESULTS: Decreased KLF2 expression was discovered to be mainly regulated by hypermethylation, and indicated a poor prognosis of HCC. Single-cell level expression analyses revealed KLF2 was highly expressed in immune cells and fibroblasts. The function enrichment analysis of KLF2 targets indicated the crucial association between KLF2 and tumor matrix. 33-genes related with cancer associated fibroblasts (CAFs) were collected to identify the significant association of KLF2 with fibrosis. And SPP1 was validated as a promising prognostic and diagnostic marker for advanced HCC patients. CXCR6 CD8+ T cells were noted as a predominant proportion in the immune microenvironment, and T cell receptor CD3D was discovered to be a potential therapeutic biomarker for HCC immunotherapy. CONCLUSION: This study identified that KLF2 is an important factor promoting HCC progression by affecting the fibrosis and immune infiltration, highlighting its great potential as a novel prognostic biomarker for advanced HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Linfócitos T CD8-Positivos , Prognóstico , Neoplasias Hepáticas/genética , Fibrose , Microambiente Tumoral/genética , Fatores de Transcrição Kruppel-Like/genéticaRESUMO
BACKGROUND: Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.
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Helicobacter pylori , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Furazolidona/efeitos adversos , Estudos Retrospectivos , Tetraciclina/efeitos adversos , Antibacterianos/efeitos adversosRESUMO
Voltage-gated sodium channel 1.7 (Nav1.7) remains one of the most promising drug targets for pain relief. In the current study, we conducted a high-throughput screening of natural products in our in-house compound library to discover novel Nav1.7 inhibitors, then characterized their pharmacological properties. We identified 25 naphthylisoquinoline alkaloids (NIQs) from Ancistrocladus tectorius to be a novel type of Nav1.7 channel inhibitors. Their stereostructures including the linkage modes of the naphthalene group at the isoquinoline core were revealed by a comprehensive analysis of HRESIMS, 1D, and 2D NMR spectra as well as ECD spectra and single-crystal X-ray diffraction analysis with Cu Kα radiation. All the NIQs showed inhibitory activities against the Nav1.7 channel stably expressed in HEK293 cells, and the naphthalene ring in the C-7 position displayed a more important role in the inhibitory activity than that in the C-5 site. Among the NIQs tested, compound 2 was the most potent with an IC50 of 0.73 ± 0.03 µM. We demonstrated that compound 2 (3 µM) caused dramatical shift of steady-state slow inactivation toward the hyperpolarizing direction (V1/2 values were changed from -39.54 ± 2.77 mV to -65.53 ± 4.39 mV, which might contribute to the inhibition of compound 2 against the Nav1.7 channel. In acutely isolated dorsal root ganglion (DRG) neurons, compound 2 (10 µM) dramatically suppressed native sodium currents and action potential firing. In the formalin-induced mouse inflammatory pain model, local intraplantar administration of compound 2 (2, 20, 200 nmol) dose-dependently attenuated the nociceptive behaviors. In summary, NIQs represent a new type of Nav1.7 channel inhibitors and may act as structural templates for the following analgesic drug development.
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Alcaloides , Canal de Sódio Disparado por Voltagem NAV1.7 , Camundongos , Animais , Humanos , Células HEK293 , Dor/tratamento farmacológico , Neurônios , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Gânglios Espinais , Bloqueadores dos Canais de Sódio/farmacologia , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
BACKGROUND: COVID-19 is a global pandemic. Currently, the predominant strain is SARS-CoV-2 Omicron subvariant BA.2 in many countries. Understanding its infection characteristics can facilitate clinical management. OBJECTIVES: This study aimed to characterize the clinical, laboratory, and high-resolution computed tomography (HRCT) findings in patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2. METHODS: We performed a retrospective study on patients infected with SARS-CoV-2 Omicron subvariant BA.2 between April 4th and April 17th, 2022. The clinical characteristics, laboratory features, and HRCT images were reviewed. RESULTS: A total of 805 patients were included (411 males and 394 females, median age 33 years old). The infection was mild, moderate, severe, and asymptomatic in 490 (60.9%), 37 (4.6%), 0 (0.0%), and 278 (34.5%) patients, respectively. Notably, 186 (23.1%), 96 (11.9%), 265 (32.9%), 11 (3.4%), 7 (0.9%), and 398 (49.4%) patients had fever, cough, throat discomfort, stuffy or runny nose, fatigue, and no complaint, respectively. Furthermore, 162 (20.1%), 332 (41.2%), and 289 (35.9%) patients had decreased white blood cell counts, reduced lymphocytes, and elevated C-reactive protein levels, respectively. HRCT revealed pneumonia in 53 (6.6%) patients. The majority of the lung involvements were ground-glass opacity (50, 94.3%) mostly in the subpleural area. The grade of lung injury was mainly mild (90.6%). Short-term follow-ups showed that most patients with pneumonia recovered. CONCLUSION: Most patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2 were adults, with fever and upper respiratory symptoms as the main clinical presentations. Lower respiratory infection was mild, with ground-glass opacity in the subpleural area as the main finding.
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Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.
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Carcinoma Hepatocelular , Glioma , Neoplasias Hepáticas , Selênio , Humanos , FosfatosRESUMO
Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.
RESUMO
OBJECTIVE: To observe the clinical effect of Simiaotongzhuo Decoction (SMTZD) on the symptoms of type III prostatitis with damp-heat stagnation syndrome. METHODS: Using the randomized control method, we divided 140 cases of type III prostatitis with damp-heat stagnation syndrome into two groups and treated them orally with SMTZD at 200 ml per time bid (n = 65) and Tamsulosin Hydrochloride Sustained Release Capsules (THSRC) at 0.2 mg per time qd (n = 75), both for 6 weeks. Before and after medication, we recorded the counts of white blood cells (WBC) and lecithin bodies in the prostatic fluid, NIH-CPSI scores and traditional Chinese medicine syndrome (TCMS) scores, and compared them between the two groups of patients. RESULTS: Compared with the baseline, the WBC count and NIH-CPSI scores were decreased and the number of lecithin bodies increased in both the SMTZD (NIH-CPSI score: ï¼»18±6.47ï¼½ vs ï¼»9±5.02ï¼½) and THSRC groups after medication, with statistically significant difference only in the former group (P<0.05), the TCMS scores were significantly reduced in both the SMTZD (ï¼»21.97±5.12ï¼½ vs ï¼»6.4±4.88ï¼½, P<0.05) and the THSRC group (ï¼»20.73±4.97ï¼½ vs ï¼»11.33±5.93ï¼½, P<0.05), even more significantly in the former. No statistically significant difference was observed in the incidence of adverse reactions between the SMTZD and THSRC groups (9.2% vs 9.3%, P>0.05), and all the adverse reactions were mild. CONCLUSION: Simiaotongzhuo Decoction is safe and effective for the treatment of type III prostatitis with damp-heat stagnation syndrome, which can reduce the WBC count in the prostatic fluid, increase the number of lecithin bodies and improve the NIH-CPSI and TCMS scores of the patient.