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Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17â 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10â mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.
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Terapia por Acupuntura , Estreñimiento , Fibras de la Dieta , Trasplante de Microbiota Fecal , Probióticos , Estreñimiento/terapia , Estreñimiento/microbiología , Humanos , Trasplante de Microbiota Fecal/efectos adversos , Fibras de la Dieta/uso terapéutico , Probióticos/uso terapéutico , Probióticos/efectos adversos , Enfermedad Crónica , Terapia por Acupuntura/métodos , Resultado del Tratamiento , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida , Laxativos/uso terapéuticoRESUMEN
Background: Esophageal cancer (EC) is an aggressive malignant tumor with poor prognosis and high incidence. It is the sixth leading cause of cancer-related death in the world, and the 5-year overall survival (OS) rate is only 12-20%. The rapid development of next-generation sequencing (NGS) has provided powerful help for the treatment and management of EC patients. Methods: Tumor tissue and blood samples of 43 Chinese patients with nonsurgical esophageal squamous cell carcinoma (ESCC) were sequenced using a 425 gene-panel. Genomic profiling was explored and and the Cox proportional hazards model was used to analyze the correlations between gene or signaling pathway alterations and prognosis. Results: In this study, the most common mutated genes were TP53 (90.5%), CCND1 (45.2%), FGF19 (38.1%), NOTCH1 (26.2%), PI3KCA (21.4%) and CDKN2A (19%). Among these mutations, PI3KCA and NOTCH1 showed mutual exclusion to some extent. In the univariate model, mutations in NOTCH1, CBLB and TSC2 genes and tumor mutation burden (TMB) ≥7 were independent biomarkers of OS. NOTCH1 (P=0.007, HR =2.87), CBLB (P=0.011, HR =4.68) and TSC2 (P=0.024, HR =3.7) were significantly associated with poorer OS, and patients with TMB ≥7 had longer OS (P=0.151, HR =0.31). In addition, patients who carried alteration in NOTCH signaling pathway had reduced OS (P=0.014, HR =2.54). Conclusions: NOTCH1, CBLB and TSC2 alterations were found to be potential indicators of poor prognosis in patients with ESCC. TMB was also positively correlated with the OS of ESCC patients, providing valuable insights for their treatment strategies.
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BACKGROUND: Infertility affects many couples globally, causing physical, emotional, and financial burdens. While observational studies suggest a link between psychiatric disorders and female infertility, causal relationships remain uncertain. Mendelian randomization analysis, using genome-wide association studies data, minimizes confounding factors and reverse causation, providing valuable insights into causal associations. METHODS: We conducted Mendelian randomization analysis to explore the potential causal relationship between female infertility and psychiatric disorders. Genome-wide association studies summary data for female infertility (112,105 individuals of European ancestry, comprising 11,442 cases and 100,663 controls), depression (807,553 individuals of European ancestry, comprising 246,363 cases and 561,190 controls), anxiety (21,763 individuals of European ancestry, comprising 7,016 cases and 14,745 controls), bipolar disorder (51,710 individuals of European ancestry, comprising 20,352 cases and 31,358 controls), and eating disorders (72,517 individuals of European ancestry, comprising 16,992 cases and 55,525 controls) were utilized. Instrumental variables were selected based on significant single nucleotide polymorphisms associated with each phenotype. We assessed instrumental variable strength, examined confounding factors, and employed inverse variance weighting, weighted median, and MR-Egger approaches for analysis. RESULTS: Our analysis included 85 single nucleotide polymorphisms for female infertility and 62 single nucleotide polymorphisms for psychiatric disorders. Results suggest a potential causal relationship between depression and female infertility, with both inverse variance weighting and weighted median methods showing increased infertility risk in depressed patients. Evidence is weak regarding bipolar disorder not increasing female infertility risk. We found no evidence supporting causal links between anxiety, eating disorders, and female infertility. Similarly, no causal relationship was found between female infertility and psychiatric disorders in the opposite direction. Sensitivity analyses and tests for heterogeneity and polymorphism supported result robustness. CONCLUSIONS: This analysis provides evidence for a potential causal relationship between depression and female infertility. Addressing depression in infertile women may improve fertility outcomes. Further research is needed to explore underlying mechanisms and potential interventions for improving fertility outcomes in women with psychiatric disorders.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Infertilidad Femenina , Femenino , Humanos , Infertilidad Femenina/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Endometriosis (EM) greatly affects women's reproductive health, identifying new drug targets for EM is urgently needed. This study utilizes comprehensive genome-wide Mendelian randomization (MR) and colocalization analyses, using genomic data, to identify potential therapeutic approaches for EM. METHODS: Genome-wide cis-expression quantitative trait loci (cis-eQTL) data were obtained from GTEx V8, which included 838 participants across 49 tissues or cells, and the eQTLGen consortium, which included 31,684 participants. Genome-wide association analysis (GWAS) data for EM were sourced from the FinnGen study, which consisted of 8,288 cases and 68,969 controls, as well as the UK Biobank study, which included 1,496 cases and 359,698 controls. This study utilized MR analysis to assess the correlation between genes and the risk of EM. Subsequently, colocalization analysis was conducted to investigate potential shared causal variants between the identified genes and EM. RESULTS: After conducting MR and colocalization analyses, we identified a total of 13 genes that showed significant evidence of colocalization. These genes are considered promising therapeutic candidates for treating EM. Among them, inner membrane mitochondrial protein (IMMT), src kinase associated phosphoprotein 1 (SKAP1), lysine methyltransferase 5A (KMT5A), KLF transcription factor 12 (KLF12), GRB10 interacting GYF protein 1 (GIGYF1), Wnt family member 7A (WNT7A), Sad1 and UNC84 domain containing 1 (SUN1), and poly (ADP-ribose) polymerase family member 3 (PARP3) were found to have positive associations with the risk of EM. On the other hand, progestin and adipoQ receptor family member 8 (PAQR8), adaptor related protein complex 3 subunit mu 1 (AP3M1), surfeit 6 (SURF6), TUB bipartite transcription factor (TUB), and DNA polymerase delta interacting protein 2 (POLDIP2) were found to have inverse relationships with the risk of EM. CONCLUSIONS: Through genome-wide MR studies, a comprehensive set of genes associated with EM has been identified. Among them, IMMT, PAQR8, SKAP1, KMT5A, AP3M1, SURF6, KLF12, GIGYF1, TUB, WNT7A, SUN1, POLDIP2, and PARP3 show potential as therapeutic targets for EM treatment. Nonetheless, it is crucial to conduct further rigorous investigations to validate these prospects.
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Endometriosis , Femenino , Humanos , Endometriosis/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Sitios de Carácter Cuantitativo , Genómica , Polimorfismo de Nucleótido Simple , Proteínas Nucleares , Proteínas Portadoras , Factores de Transcripción de Tipo KruppelRESUMEN
Laser desorption ionization mass spectrometry (LDI-MS) aroused intensive concerns for the merits of label-free and high-throughput analysis. Here, we designed a silver nanoparticles (AgNP)-modified indium vanadate nanosheets with doping samarium (AgNP@InVO4:Sm) nanosheets. The developed AgNP@InVO4:Sm nanosheets (AIVON) were synthesized based on the microemulsion-mediated solvothermal method and ultraviolet-assisted in situ formation of AgNP, then for the first time applied as a matrix in LDI-MS analysis. With the advantages including enhanced MS signal, little matrix-related background, high reproducibility, and good salt tolerance, AIVON exhibited much better prospect than non-modified indium vanadate nanosheets with doping samarium (IVON) and traditional organic matrix, thus allowing sensitive MS detection for a wide range of low-molecular-weight (LMW) molecules. Moreover, by coupling with headspace sampling thin-film microextraction (TFME), a kind of representative pollutant chlorophenols were identified and quantified via AIVON-assisted LDI-MS in environmental and biological samples. Volatile LMW pollutants could be preconcentrated after TFME, hence a sensitive and rapid assay with negligible sample matrix effect was realized by using AIVON-assisted LDI-MS. It is anticipated that this novel nano-matrix AIVON and the proposed TFME coupling detection strategy were of competitive merits for LDI-MS analysis in the fields of environment, biomedicine, and agriculture.
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Contaminantes Ambientales , Nanopartículas del Metal , Vanadatos , Indio , Reproducibilidad de los Resultados , Samario , Plata , Espectrometría de Masas , Rayos Láser , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Background: Preterm birth is the leading cause of neonatal death, and there are no effective clinical means for the prevention and treatment of spontaneous preterm birth, mainly because the mechanism for labor initiation has not been fully elucidated. Objective: The effect of enucleation with Zhuyun I Recipe Capsule enema (ZRC) on the maternal-fetal interface microenvironment in SD rats with kidney deficiency and blood stasis. Methods: In this study, poor endometrial tolerance was induced by hydroxyurea and epinephrine in SD rats with kidney deficiency and blood stasis type of endometrium, and gavage with norethindrone (estradiol) or Bamboo Rhythm No.1 formula. HOXA10 mRNA levels were measured by qPCR. In addition, the expression of IL-6, VEGF, TGF-ß, and IGFBP-1 in the uterus was detected by IHC and ELISA. Results: Hydroxyurea- and epinephrine-induced PER was associated with low levels of HOXA10 in the endometrium and reduced levels of IL-6, TGF-ß, VEGF, and IGFBP-1 in the endometrium. These were abolished by ZRC and Progynova treatment compared to PER rats, resulting in a dramatic increase in the levels of HOXA10 mRNA, IL-6, TGF-ß, VEGF, and IGFBP-1 proteins. Conclusions: ZRC improves metaplasticization of endometrial stromal cells and promotes angiogenesis in rats with kidney deficiency and blood stasis. The moderate dose of kidney tonic to promote blood circulation method is superior in promoting angiogenesis, facilitating the establishment and maintenance of pregnancy, limiting trophoblast invasion of metaplasia, reducing miscarriage, and improving pregnancy rate.
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Objective To investigate the risk factors and countermeasures for endoscopic retrograde cholangiopancreatography (ERCP) related duodenal papilla hemorrhage. Methods Retrospective analysis was performed on the clinical data of 890 patients who underwent ERCP. According to whether the patients with ERCP related duodenal papilla hemorrhage, they were divided into the hemorrhage group and the non hemorrhage group. And the risk factors of duodenal papilla hemorrhage and their countermeasures were investigated. Results 51 patients had ERCP related duodenal papilla hemorrhage, and the overall incidence rate was 5.7%. Compared with the non hemorrhage group, the patients proportion of common bile duct stones was lower, but the cholangiocarcinoma and pancreatic head cancer were higher in the hemorrhage group (P < 0.05). The incidence of hypertension and duodenal diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Subgroup analysis showed that patients with stone diameter >2 cm, stone incarceration and the duodenal papilla into diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Conclusion Common bile duct stone diameter >2 cm, stone incarceration, malignant biliary and pancreatic cancer, hypertension and duodenal papilla into diverticulum were objective risk factors of ERCP related duodenal papilla hemorrhage, focus on prevention of bleeding. Endoscopic hemostasis was safe and effective.
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Objective To investigate the risk factors and countermeasures for endoscopic retrograde cholangiopancreatography (ERCP) related duodenal papilla hemorrhage. Methods Retrospective analysis was performed on the clinical data of 890 patients who underwent ERCP. According to whether the patients with ERCP related duodenal papilla hemorrhage, they were divided into the hemorrhage group and the non hemorrhage group. And the risk factors of duodenal papilla hemorrhage and their countermeasures were investigated. Results 51 patients had ERCP related duodenal papilla hemorrhage, and the overall incidence rate was 5.7%. Compared with the non hemorrhage group, the patients proportion of common bile duct stones was lower, but the cholangiocarcinoma and pancreatic head cancer were higher in the hemorrhage group (P < 0.05). The incidence of hypertension and duodenal diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Subgroup analysis showed that patients with stone diameter >2 cm, stone incarceration and the duodenal papilla into diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Conclusion Common bile duct stone diameter >2 cm, stone incarceration, malignant biliary and pancreatic cancer, hypertension and duodenal papilla into diverticulum were objective risk factors of ERCP related duodenal papilla hemorrhage, focus on prevention of bleeding. Endoscopic hemostasis was safe and effective.