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1.
Medicine (Baltimore) ; 103(19): e37981, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728508

RESUMO

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Humanos , Gastrite Atrófica/tratamento farmacológico , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Adulto , Resultado do Tratamento , Doença Crônica , Medicina Tradicional Chinesa/métodos , Idoso , Gastroscopia
2.
Medicine (Baltimore) ; 103(18): e38010, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701318

RESUMO

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.


Assuntos
Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Neoplasias , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9 , Humanos , Neoplasias/genética , Neoplasias/epidemiologia , Hidroximetilglutaril-CoA Redutases/genética , Feminino , Inibidores de PCSK9 , Hipolipemiantes/uso terapêutico , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
3.
ACS Omega ; 9(12): 14539-14550, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38559942

RESUMO

Liquefied petroleum gas (LPG) is widely used for its cleanliness and high efficiency in industry and city life. In order to improve the suppression effect on LPG explosion, a constant volume combustion bomb was used to investigate the synergistic influence of N2/ultrafine water mist on the explosion and combustion characteristics of 6% premixed LPG/air gas. The results showed that (1) the effect of a single ultrafine water mist on suppressing LPG explosion is unstable. When the concentration of ultrafine water mist is low, the flame acceleration in the initial stage of explosion is promoted, and when the ultrafine water mist with a mass fraction of 420 g/m3 is introduced, the maximum pressure rise rate increases. (2) The combination of N2/ultrafine water mist has a synergistic effect on LPG explosion. Compared to the individual suppression effects, the combination of N2/ultrafine water mist showed more effective suppression on the explosion pressure, flame propagation, and flame instability of LPG explosion. (3) Through the mechanism analysis, it is found that the combined action of N2/ ultrafine water mist can better reduce the mole fraction and ROP peak of active free radicals such as H, O, and OH by inhibiting the main reaction of generating H, O, and OH radicals during the explosion of LPG, resulting in the reduction of flame free radicals in the explosion system, thus effectively inhibiting the chain reaction of ignition and explosion of LPG. This research can provide guidance for a better understanding and implementation of gas-liquid two-phase suppression technology for LPG explosion.

4.
Hepatobiliary Surg Nutr ; 13(2): 258-272, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617474

RESUMO

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

5.
Medicine (Baltimore) ; 103(17): e37735, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669367

RESUMO

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.


Assuntos
Doenças do Sistema Digestório , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Doenças do Sistema Digestório/microbiologia , Doenças do Sistema Digestório/genética
6.
J Gastrointest Oncol ; 15(1): 468-477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482229

RESUMO

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

7.
J Gastrointest Oncol ; 15(1): 458-467, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482250

RESUMO

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

8.
Eur J Med Res ; 28(1): 601, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38111060

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a common cancer with a poor prognosis. Pyroptosis is an important process in the development and progression of LUAD. We analyzed the risk factors affecting the prognosis of patients and constructed a nomogram to predict the overall survival of patients based on different pyroptosis-related genes (PRGs) subtypes. METHODS: The genomic data of LUAD were downloaded from the TCGA and GEO databases, and all data were filtered and divided into TCGA and GEO cohorts. The process of data analysis and visualization was performed via R software. The data were classified based on different PRGs subtypes using the K-means clustering method. Then, the differentially expressed genes were identified between two different subtypes, and risk factors analysis, survival analysis, functional enrichment analysis, and immune cells infiltration landscape analysis were conducted. The COX regression analysis was used to construct the prediction model. RESULTS: Based on the PRGs of LUAD, the patients were divided into two subtypes. We found the survival probability of patients in subtype 1 is higher than that in subtype 2. The results of the logistics analysis showed that gene risk score was closely associated with the prognosis of LUAD patients. The results of GO analysis and KEGG analysis revealed important biological processes and signaling pathways involved in the differentially expressed proteins between the two subtypes. Then we constructed a prediction model of patients' prognosis based on 13 genes, including IL-1A, P2RX1, GSTM2, ESYT3, ZNF682, KCNF1, STK32A, HHIPL2, GDF10, NDC80, GSTA1, BCL2L10, and CCR2. This model was strongly related to the overall survival (OS) and also reflects the immune status in patients with LUAD. CONCLUSION: In our study, we examined LUAD heterogeneity with reference to pyroptosis and found different prognoses between the two subtypes. And a novel prediction model was constructed to predict the OS of LUAD patients based on different PRGs signatures. The model has shown excellent predictive efficiency through validation.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Piroptose/genética , Adenocarcinoma de Pulmão/genética , Fatores de Risco , Estratificação de Risco Genético , Neoplasias Pulmonares/genética , Prognóstico , Sinaptotagminas
9.
Front Med (Lausanne) ; 10: 1197536, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727768

RESUMO

Background: Airway management failure is associated with increased perioperative morbidity and mortality. Airway-related complications can be significantly reduced if difficult laryngoscopy is predicted with high accuracy. Currently, there are no large-sample studies on difficult airway assessments in Chinese populations. An airway assessment model based on the Chinese population is urgently needed to guide airway rescue strategy. Methods: This prospective nested case-control study took place in a tertiary hospital in Shanghai, China. Information on 10,549 patients was collected, and 8,375 patients were enrolled, including 7,676 patients who underwent successful laryngoscopy and 699 patients who underwent difficult laryngoscopy. The baseline characteristics, medical history, and bedside examinations were included as predictor variables. Laryngoscopy was defined as 'successful laryngoscopy' based on a Cormack-Lehane Grades of 1-2 and as 'difficult laryngoscopy' based on a Cormack-Lehane Grades of 3-4. A model was developed by incorporating risk factors and was presented in the form of a nomogram by univariate logistic regression, least absolute shrinkage and selection operator, and stepwise logistic regression. The main outcome measures were area under the curve (AUC), sensitivity, and specificity of the predictive model. Result: The AUC value of the prediction model was 0.807 (95% confidence interval [CI]: 0.787-0.828), with a sensitivity of 0.730 (95% CI, 0.690-0.769) and a specificity of 0.730 (95% CI, 0.718-0.742) in the training set. The AUC value of the prediction model was 0.829 (95% CI, 0.800-0.857), with a sensitivity of 0.784 (95% CI, 0.73-0.838) and a specificity of 0.722 (95% CI, 0.704-0.740) in the validation set. Conclusion: Our model had accurate predictive performance, good clinical utility, and good robustness for difficult laryngoscopy in the Chinese population.

10.
Front Med (Lausanne) ; 10: 1203023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636580

RESUMO

Background: Unanticipated difficult mask ventilation (DMV) is a potentially life-threatening event in anesthesia. Nevertheless, predicting DMV currently remains a challenge. This study aimed to verify whether three dimensional (3D) facial scans could predict DMV in patients scheduled for general anesthesia. Methods: The 3D facial scans were taken on 669 adult patients scheduled for elective surgery under general anesthesia. Clinical variables currently used as predictors of DMV were also collected. The DMV was defined as the inability to provide adequate and stable ventilation. Spatially dense landmarks were digitized on 3D scans to describe sufficient details for facial features and then processed by 3D geometric morphometrics. Ten different machine learning (ML) algorithms, varying from simple to more advanced, were introduced. The performance of ML models for DMV prediction was compared with that of the DIFFMASK score. The area under the receiver operating characteristic curves (AUC) with its 95% confidence interval (95% CI) as well as the specificity and sensitivity were used to evaluate the predictive value of the model. Results: The incidence of DMV was 35/669 (5.23%). The logistic regression (LR) model performed best among the 10 ML models. The AUC of the LR model was 0.825 (95% CI, 0.765-0.885). The sensitivity and specificity of the model were 0.829 (95% CI, 0.629-0.914) and 0.733 (95% CI, 0.532-0.819), respectively. The LR model demonstrated better predictive performance than the DIFFMASK score, which obtained an AUC of 0.785 (95% CI, 0.710-0.860) and a sensitivity of 0.686 (95% CI, 0.578-0.847). Notably, we identified a significant morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. Conclusion: Our study indicated a distinct morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. 3D geometric morphometrics with ML could be a rapid, efficient, and non-invasive tool for DMV prediction to improve anesthesia safety.

11.
Support Care Cancer ; 31(9): 508, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37548752

RESUMO

OBJECTIVE: The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. METHODS: Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). RESULTS: In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = - 1.66, 95% CI = - 2.05, - 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. CONCLUSION: Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality.


Assuntos
Moxibustão , Neoplasias , Humanos , China , Fadiga/etiologia , Fadiga/terapia , Estudos Multicêntricos como Assunto , Neoplasias/complicações , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Quant Imaging Med Surg ; 13(7): 4663-4675, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37456309

RESUMO

Background: Unsuccessful airway management is associated with increased perioperative morbidity and mortality. Difficult laryngoscopy is a leading cause of unanticipated difficult airways and presents a challenge for anesthesiologists. Airway ultrasound assessment can be used as a priority diagnostic strategy for difficult laryngoscopy because of its diagnostic performance in difficult airways. This study was designed to develop a comprehensive model based on multivariate statistical analysis (including bedside examination tests and ultrasonography) for difficult laryngoscopy. Methods: This study was conducted from December 27, 2021, to September 16, 2022. All patients underwent an airway ultrasonographic measurement with a standard operating procedure. The baseline characteristics and bedside examination tests were also recorded. Laryngoscopy with a Cormack-Lehane (CL) grade of 1-2 was defined as "easy laryngoscopy", whereas "difficult laryngoscopy" was based on a CL grade of 3-4. The prediction model was built by using baseline characteristics, bedside examination tests, and ultrasonographic measurements as independent variables and easy/difficult laryngoscopy as the dependent variable. Results: A total of 516 patients were eligible, and 456 patients were finally enrolled in the study. A 4-variable analysis, including inter-incisor gap (IIG), thyromental distance (TMD), the distance from the skin to the tongue root, and airway-related diseases, was performed to construct the optimum prediction model. The area under curve (AUC) value of the prediction model was 0.933 [95% confidence interval (CI): 0.770 to 0.935] in the training set and 0.956 (95% CI: 0.915 to 0.997) in the validation set. Conclusions: The comprehensive model and nomogram, especially the integration of tongue root thickness, can predict the risk of difficult laryngoscopy more accurately and reliably than any other screening method alone, allowing for reasonable individualized regimen decision-making.

13.
Psychogeriatrics ; 23(5): 864-875, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37464888

RESUMO

BACKGROUND: Post-stroke depression (PSD) as one of the most common neuropsychiatric disorders after a stroke and is caused by many factors. However, the relationships among different factors and their potential contributions to PSD remain unclear. METHODS: Two hundred and seventy-six patients were recruited into this study. The general information questionnaire, the Patient Health Questionnaire-9, the Perceived Social Support Scale, the Family Assessment Device, the General Well-Being Scale, the Barthel Index, and the modified Rankin Scale were used to assess the condition of patients. Subsequently, we identify the main causes associated with the PSD and then performed a path analysis to clarify the direct, indirect and total effects among the variables. RESULTS: We found that age, stroke with coronary heart disease, neurological function, family function, social support, and general well-being had a significant impact on PSD (P < 0.05). Of these, neurological function had the largest total effect on PSD (ß = 0.451), social support contributed the most as a direct effect (ß = -0.306), and family function showed the largest indirect effect (ß = -0.264). CONCLUSION: Individual, disease, and social-psychological factors all contributed to the development of PSD. We should pay more attention to comprehensive assessment, especially for those with poor neurological function, and lacking family or social support. In addition, it would be preferable to provide them with necessary support and care strategies to reduce the incidence of PSD.


Assuntos
Depressão , Acidente Vascular Cerebral , Humanos , Depressão/diagnóstico , Depressão/etiologia , Depressão/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários
14.
Front Oncol ; 13: 1165040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324019

RESUMO

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.

15.
Front Genet ; 14: 1152414, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37144125

RESUMO

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis. Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM. Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower. Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment.

16.
Transl Pediatr ; 12(12): 2222-2231, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38197113

RESUMO

Background: Selecting the optimal tracheal tube size is critically important for pediatric patients. Age-based formulas are often used, but still have limitations. The aim of this prospective study was to investigate whether middle finger measurements correlate with cuffed tracheal tube size and to further develop a prediction model based on these measurements. Methods: Patients under 12 years of age scheduled for elective surgery involving tracheal intubation were enrolled in the study. The length was determined from the tip of the distal metacarpal to the palm's root on the palm side, while the circumference was measured at the base of the palm using a soft tape measure. The appropriate cuffed tracheal tube size was determined based on specific criteria. If the tube encountered resistance during insertion or required an airway pressure >25 cmH2O to detect an audible leak, it was replaced with a tube 0.5 mm smaller. Conversely, if an audible leak occurred at an airway pressure <10 cmH2O, or peak pressure >25 cmH2O, or the cuff pressure >25 cmH2O to achieve a seal, the tube was exchanged for one with a 0.5 mm larger. Linear regression analysis was used to examine the association between middle finger circumference and length with the cuffed tracheal tube size. Subsequently, regression equations were constructed based on the results of the linear regression analysis and their predictive performance was compared to the conventional age-based formulas, including the Khine formula and Motoyama formula. The predictive performance was evaluated by mean absolute error (MAE), root mean square error (RMSE), and prediction accuracy. Results: A total of 261 patients were analyzed in our study. The mean age of the patients was 46.19±35.83 months. The linear relationship was observed between the cuffed tracheal tube size and the middle finger circumference and middle finger length with R2 values of 0.77 and 0.73, respectively. In comparison to conventional age-based formulas, both middle finger circumference and middle finger length demonstrated superior predictive performance, characterized by lower MAE and RMSE, as well as higher prediction accuracy. Notably, the regression equation based on the middle finger circumference obtained the higher predictive accuracy of 0.590, with an MAE of 0.259 and an RMSE of 0.333 as opposed to the predictive accuracy of 0.391, MAE of 0.349, and RMSE of 0.473 derived from conventional age-based formulas. Based on the regression coefficients of linear regression, simplified formulas were proposed, with the middle finger circumference-based formula emerging as the most accurate and simple option. Conclusions: The appropriate cuffed tracheal tube size could be predicted by the middle finger circumference. Our proposed formula 'cuffed tracheal tube internal diameter (mm) = middle finger circumference (cm) - 0.2' has the potential to improve the selection of the cuffed tracheal tube size in pediatric patients.

17.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 172-176, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38279448

RESUMO

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Apoptose , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
18.
Transl Pediatr ; 11(8): 1389-1397, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36072535

RESUMO

Background: Awake fiberoptic intubation is conventionally performed in anticipated difficult airways. However, obstruction by secretions and sputum makes it challenging for novices. A prototype of a novel multimodal endotracheal intubation assistant device (MEIAD) was developed for an indication of airway according to end-tidal carbon dioxide (ETCO2) and image. At the tip, 4 sampling tubes collected ETCO2 concentration. The airway direction is located according to an advanced algorithm based on 4 directions' concentrations. It assists awake intubation, especially with unclear view field. The objective was to analyze the learning curve of MEIAD for novices on a manikin by cumulative sum method (CUSUM) and evaluate the utility. Methods: A total of 16 novice residents with less than 2-year clinical experience were enrolled. After instruction, each individual exercised 40 insertions with MEIAD on a difficult airway simulation. Insertion success (defined as a visualization of the carina within 120 seconds), insertion time (the time from when the guiding scope entered the nasal cavity to the carina was visible), and self-confidence score (subjective score with a numerical rating scale from 0 to 10) were recorded. The acceptable and unacceptable failure rates of CUSUM were set as 15% and 30%, respectively. The exercises were divided into 2 phases (phase 1: 1-20, phase 2: 21-40) for further evaluation. All continuous data were expressed by median (IQR, interquartile ranges) and analyzed using Mann-Whitney test. All categorical variables were expressed as percentages and compared by the χ2 test. Results: Among the 16 residents, 15 were able to cross the lower decision boundary in an average of 21.27±9.51 attempts using the novel device. The insertion time [24.0 (17.0-42.0) vs. 17.5 (14.0-28.0) seconds, P<0.001] and success rate (88.4% vs. 97.5%, P<0.001) were improved with increased experience. The confidence score was significantly improved from 2.5 (1.3-4.0) to 7.0 (7.0-8.0). Conclusions: MEIAD showed a satisfactory learning curve and efficacy on the manikin for novices. However, as a small exploratory manikin trial, the results cannot be replicated in clinical practice. MEIAD is expected to be further improved and potential to be an alternative device for difficult airways.

19.
Front Bioeng Biotechnol ; 10: 994628, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147539

RESUMO

Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.

20.
Environ Toxicol ; 37(12): 2957-2964, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36039874

RESUMO

The purpose of this study is to explore the anti-colorectal cancer of Xiaotansanjiefang, a famous traditional Chinese medicine, and its potential anti-cancer mechanism. In this study, the HCT116 cell spheres were prepared as in vitro study model. We found the Xiaotansanjiefang medication was able to inhibit the proliferation of HCT116 cell spheres in a dose-dependent manner, especially in 3 and 6 mg/ml Xiaotansanjiefang medication treated groups. We also found the high concentration of Xiaotansanjiefang medication could suppress the migration and promote the apoptosis of HCT116 cell spheres. Moreover, we found the expression of Jagged 1, Notch 3, Snail, and Hes 1 were decreased in HCT116 cell spheres treated with Xiaotansanjiefang medication. Furthermore, the proliferation and apoptosis behaviors of HCT116 cell spheres treated with Xiaotansanjiefang medication were reversed with the addition of Jagged 1 Fc chimera protein. The expression of Jagged 1, Notch 3, Snail, and Hes 1 were also increased again in HCT116 cells treated with Xiaotansanjiefang medication plus with Jagged 1 Fc chimera protein. The presented study may provide a promising strategy to treat and prevent colorectal cancer.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias , Proteína Jagged-1/metabolismo , Proteínas Serrate-Jagged/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células , Proteínas de Membrana/metabolismo , Transdução de Sinais
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