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 investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Ureteropelvic junction obstruction (UPJO) is a condition characterized by the blockage of urine flow from the kidney to the ureter.With advancements in endoscopic technology, robotic-assisted laparoscopic dismembered pyeloplasty has become the dominant approach.However, approximately 10% of patients who undergo pyeloplasty still experience treatment failure, often due to long-segment proximal ureteral strictures (length greater than 2 cm).This increases the difficulty and risk of subsequent surgeries.In the past, ileal ureter replacement or kidney autotransplantation procedures were used as alternatives to shorten or replace the ureter.However, these procedures are associated with metabolic and vascular complications and are not always preferred.A pelvic flap, which utilizes the enlarged wall of the renal pelvis, is a good solution for bridging longer segments of a diseased ureter.This article reviews the specific applications of pelvic flap pyeloplasty in the existing literature and summarizes the technical improvements and research progress of renal pelvic flap pyeloplasty in our center to provide a reference for clinical application.

OBJECTIVE To assess the profiles of elements in benzo[a]pyrene(BaP)induced carci-nogenesis,and explore the joint effects of copper with cisplatin or vinorelbine on cell proliferation.METHODS Forty-four elements were measured using an inductively coupled plasma mass spectrometer in 16HBE cells and BaP malignantly transformed 16HBE(T-16HBE-C1)cells.Partial least square was used to validate the robustness of cell classification of elements.Cell viability was measured by MTT assay for copper(0,237,340,487,1000 and 1432 μmol·L-1),cisplatin(0,4.4,6.1,8.6,12.0 and 16.8 μmol·L-1),and vinorelbine(0,3.8,9.8,25.0,40.0 and 64.0 μmol·L-1)to acquire their half maximal inhibitory concentra-tion(IC50).Mixtures of copper and chemotherapeutics were prepared according to the ratio of each IC50.Their joint effects on cell viability were assessed by MTT assay and isobolographic analysis.Inhibition effect of copper(0,50,100,200,400 and 800 μmol·L-1)with IC50 of cisplatin or vinorelbine on prolifera-tion of T-16HBE-C1 cells was also assessed.RESULTS A total of 29 elements were quantified in 16HBE and T-16HBE-C1 cells,among which concentrations of copper,zinc,silver,selenium and rubidium decreased(P<0.05,P<0.01),while those of molybdenum,arsenic,lithium,germanium,strontium,nickel,lanthanum,mercury,iron,and cesium increased(P<0.05,P<0.01)in T-16HBE-C1 cells.Element concen-tration could be used to distinguish T-16HBE-C1 cells from 16HBE cells.Copper concentration-dependently inhibited proliferation of both cells,with a statistically significant lower IC50 of(613±16)μmol·L-1 in 16HBE cells than(776±15)μmol·L-1 in T-16HBE-C1 cells(P<0.01).Mixtures of copper and cisplatin(1∶69.5)or vinorelbine(1∶33.4)could inhibit cell proliferation,and copper had additive effects with cisplatin or vinorelbine.When copper concentration was higher than 400 μmol·L-1,copper combined with IC50 of cisplatin or vinorelbine inhibited cell proliferation of T-16HBE-C1 cells compared with IC50 of cisplatin(11.2 μmol·L-1)or vinorelbine(23.2 μmol·L-1)alone.CONCLUSION Element profiles and correlations can change significantly after 16HBE cells are malignantly transformed by BaP.Copper could inhibit the proliferation of T-16HBE-C1 cells and have additive effects with cisplatin or vinorelbine in higher concentration.

Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P＜0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P＜0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.

Robotic surgery is known as the"third technological revolution"in the field of surgery,and is an important milestone in the development of modern surgery.However,our country's innovative surgical robot industry is still in its early stages,and it is only being utilized in certain surgical fields.To explore the effectiveness of the application of do-mestic surgical robot in oral and maxillofacial surgery,the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot.The operation was successful,facial nerve function was preserved,and postoperative wound healing was good.

AIM:This study aims to examine the ependymin-related protein 1(EPDR1)expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes(db/db)mice.The impact of EPDR1 on lipid accumulation in al-pha mouse liver 12(AML12)hepatocytes was also investigated.METHODS:Western blot was used to detect EPDR1 protein expression in the heart,liver,spleen,lung,kidney,gastrocnemius,brown adipose and brain tissues of C57BL/6 mice.Western blot and immunohistochemical(IHC)staining were also used to compare EPDR1 protein expression in the liver,gastrocnemius muscle,heart and kidney tissues of db/db and C57BL/6 mice.To develop an AML12 cell lipid deposi-tion model,palmitic acid(PA)+oleic acid(OA)was used,and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein(rEPDR1).ELISA was conducted to determine intracellu-lar triglyceride(TG)content,and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells.RESULTS:Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tis-sues of wild-type mice,with the liver exhibiting the highest protein expression level.However,EPDR1 expression was down-regulated in the liver,gastrocnemius muscle,heart and kidney tissues in diabetic db/db mice compared with wild-type mice.Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to re-duced lipid accumulation.Furthermore,the TG content significantly decreased compared with the model group(P<0.05).CONCLUSION:EPDR1 is expressed in various tissues of wild-type mice,but showed diminished expression in the liver tissues of diabetic mice.Nevertheless,enhancing the expression of EPDR1 can aid in reducing lipid accumula-tion in hepatocytes.These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue.

Objective To explore the effect of Kangxian Yixin decoction on PKA/CaMKⅡ Signal Pathway and Mitochondrial membrane potential of cardiomyocyte hypertrophy in dilated cardiomyopathy rats.Methods Drinking furazolidone to duplicate the DCM rats model for 10 weeks,then the rats were checked by ultrasound,the successfully established model rats were randomly divided into model group,low dose Kangxian Yixin decoction group,middle dose Kangxian Yixin decoction group,high dose Kangxian Yixin decoction group and captopril group.Normal group was separated.After 4 weeks of drug intervention,This experiment was over,ATP,Ca2+-Mg2+-ATP enzymatic activity,CaMKⅡ,PKA and UCP2 mRNA were tested.H9c2 cardiomyocyte hypertrophy model was set up by norepinephrine,after 24 h of drug intervention,mitochondrial membrane potential was tested.Results Compared with the normal group,cardiomyocyte mitochondria were damaged in each model group,ATP,Ca2+-Mg2+-ATP enzymatic activity and PKA mRNA were lower,UCP2 mRNA and CaMKⅡ mRNA were higer,mitochondrial membrane potential obviously decreased(P<0.05 or P<0.01).The mitochondria were protected in every drug group,the tested indexes get well in different degree,especially in hige dose Kangxian Yixin decoction group(P<0.05 or P<0.01).Conclusion Kangxian Yixin decoction can reduce myocardial cell mitochondrial damage in model rats with DCM,improve myocardial cell energy metabolism and cardiac systolic and diastolic functions,one of the mechanisms may be optimizing PKA/CaMKⅡ signal pathway and improving mitochondrial membrane potential.