OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: To observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kidney yang-deficiency. METHODS: Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by randomized control method. The patients in the control group were treated with L-carnitine oral solution alone. And the patients in experimental group were treated with Huotujiji prescription. Semen volume, sperm concentration, PR, TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment. RESULTS: A total of 115 patients were included in the study, with 55 in the experimental group and 60 in the control group. In the experimental group, the sperm concentration before and after treatment were (160.71±53.7)×106/mL, (187.19±41.89)×106/mL, and PR were (20.37±9.42)%, (26.7±6.92)%, respectively. PR+NP were (32.06±8.49)% and (34.89±7.25)%. After the treatment, the sperm motility of both groups significantly improved compared to pre-treatment levels (P<0.05). And the experimental group's sperm concentration also showed a significant increase after the treatment (P<0.05). The pregnancy rate of spouses in the control group was 11.67%, which was 29.09% in the experimental group. The pregnancy rate of the spouses in the two groups showed a statistically significant difference (P<0.05). After 12weeks of treatment, the Traditional Chinese Medicine (TCM) symptom scores in the control group did not decrease significantly compared to those before treatment (P> 0.05). In contrast, the TCM symptom scores in the experimental group decreased significantly after treatment (P<0.05). Moreover, compared with the control group, the TCM symptom scores of the experimental group decreased significantly after treatment (P<0.05). CONCLUSION Huotujiji prescription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenospermia, improve the symptoms of patients, and increase the pregnancy rate of their spouses, which is worthy of clinical promotion.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Adult ; Yang Deficiency/drug therapy* ; Asthenozoospermia/drug therapy* ; Female ; Pregnancy ; Phytotherapy ; Sperm Motility ; Young Adult ; Spleen ; Treatment Outcome ; Sperm Count

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

Objective To investigate the anatomical and microscopic structures of interstitial fluid flow channels in the skin tissue of hand dorsum in human cadavers.Methods Totally 7 fresh cadavers within 12 hours post-mortem were included.MRI was used to observe the distribution of interstitial fluid flow from the first phalanx of the fingers to the wrist,precisely locating the flow channels.Based on imaging results,histological analyses were conducted to determine the histological characteristics of the flow channels.Furthermore,multi-immunofluorescence and microcomputed tomography(Micro-CT)techniques were employed to analyze the channels,and image post-processing was used to elucidate their anatomical structures at the microscopic level.Results After injecting a contrast agent into the first phalanx of ten finger specimens and applying repeated pressure,MRI image revealed centripetal long-range interstitial fluid flow along channels distinct from blood vessels and lymphatic vessels.Histological analysis and Micro-CT further confirmed that the flow primarily occurred within the fibrous connective tissue and adventitia of the skin.Conclusion The orderly fibrous connective tissue and adventitia in the skin form the interstitial fluid flow channels in the human hand dorsum skin,named as"stromal membrane channels"in the skin.

Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.

Objective To explore the application value of CT texture analysis for evaluating Ki-67 expression in patient with esophageal squamous cell carcinoma.Methods Sixty-one cases of pathologically confirmed esophageal squamous cell carcinoma patients were selected to obtain the Ki-67 protein expression status of the patients'pathological tissues,and the patients were divided into a high-expression group and a low-expression group.All patients underwent plain and enhanced chest CT within two weeks before surgery.Lesions delineation and texture feature extraction of esophageal cancer were obtained via Omni-Kinetics software.The texture parameters included Min Intensity,Max Intensity,Median Intensity,Mean Intensity,Deviation,Skewness,Kurtosis,Entropy,Energy,Correlation,Haralick,short run high grey level emphasis(SRHGLE),short run low grey level emphasis(SRLGLE),long run high grey level emphasis(LRHGLE),long run low grey level emphasis(LRLGLE),Grey Level Nonuniformity,Run Length Nonuniformity.The differences of texture features among different Ki-67 expression groups were compared,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of Ki-67 expression in patient with esophageal cancer.Results In plain CT images,the SRHGLE and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.010,0.002,respectively).In enhanced CT images,the Mean Intensity,Entropy and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.026,0.037,0.001,respectively),and SRHGLE and LRHGLE of the high expression group were significantly lower than those of the low expression group(P=0.016,0.010,respectively).The area under the curve(AUC)of texture features in plain CT were 0.676-0.740,and the AUC of combined diagnosis reached 0.770[95%confidence interval(CI):0.645,0.868],and sensitivity and specificity was 0.921,0.565,respectively.In enhanced CT,the AUC of texture features were 0.629-0.750,the AUC of combined diagnosis increased to 0.903(95%CI:0.799,0.964),and sensitivity and specificity was 0.816,0.826,respectively.Conclusion CT texture analysis can early and non-invasively predict Ki-67 expression in patient with esophageal squamous cell carcinoma,it can be used as an imaging marker to evaluate the proliferative activity of esophageal cancer cells,and may provide diagnosis and treatment information for clinical decision-making of esophageal squamous cell carcinoma.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(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 data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(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 regu-lation 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 doc-king 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.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.