The chemical constituents of sesquiterpenes from 95% ethanol extract of Aquilariae Lignum Resinatum were isolated and purified by various column chromatography techniques, including silica gel, Sephadex LH-20, octadecylsilyl(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their planar structures and absolute configurations were elucidated by ultraviolet(UV) spectrometry, infrared(IR) spectroscopy, mass spectrometry(MS), nuclear magnetic resonance(NMR), electronic circular dichroism(ECD), and other techniques. Eight sesquiterpenoids were isolated and identified as(+)-(7R,10R)-selina-4,11-dien-12-dimethoxy-15-al(1),(+)-(7R,10R)-selina-4,11-diene-12,15-dial(2), agalleudesmanol B(3), aquisinenoid C(4), 12,15-dioxo-α-selinen(5), agarospiranic aldehyde B(6), neopetasane(7), and eremophila-7(11),9-dien-8-one(8). Compound 1 was a new compound, and it was the first time to find a dimethoxy substitution on the side chain of eudesmane-type sesquiterpene skeleton.
Sesquiterpenes/isolation & purification* ; Thymelaeaceae/chemistry* ; Molecular Structure ; Drugs, Chinese Herbal/isolation & purification* ; Magnetic Resonance Spectroscopy

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

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 role of nucleolin (NCL) in acute myeloid leukemia (AML) Kasumi-1 cells and its underlying mechanism. METHODS: The Kasumi-1 cells were infected with lentivirus carrying shRNA to downregulate NCL expression. Cell proliferation was detected by CCK-8 assay, and cell apoptosis and cell cycle were determined by flow cytometry. Transcriptome next-generation sequencing (NGS) was performed to predict associated signaling pathways, the expression levels of related genes were measured by RT-PCR. RESULTS: Down-regulation of NCL expression significantly inhibited the proliferation of Kasumi-1 cells (P <0.01) and markedly increased the apoptosis rate (P <0.001). Cell cycle analysis showed significant changes in the distribution of cells in the G₁ and S phases after NCL knockdown (P <0.05), while no significant difference was observed in the G₂ phase (P >0.05). Transcriptome sequencing analysis demonstrated that differentially expressed genes in Kasumi-1 cells with low expression of NCL were primarily enriched in key signaling pathways, including ribosome, spliceosome, RNA transport, cell cycle, and amino acid biosynthesis. qPCR validation showed that the expression of BAX, CASP3, CYCS, PMAIP1, TP53 , and CDKN1A was significantly upregulated after NCL downregulation (P <0.05), with CDKN1A exhibiting the most pronounced difference. CONCLUSION NCL plays a critical role in regulating the proliferation, apoptosis, and cell cycle progression of Kasumi-1 cells. The mechanism likely involves suppressing cell cycle progression through activation of the TP53-CDKN1A pathway and promoting apoptosis by upregulating apoptosis-related genes.
Humans ; Leukemia, Myeloid, Acute/pathology* ; Down-Regulation ; Cell Proliferation ; Apoptosis ; RNA-Binding Proteins/genetics* ; Nucleolin ; Cell Line, Tumor ; Phosphoproteins/metabolism* ; Cell Cycle ; Signal Transduction ; RNA, Small Interfering

BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P＜0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P＞0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P＜0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P＜0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.

Objective:To investigate the risk factors and their diagnostic efficacy of perioperative lower limb deep vein thrombosis (DVT) in polytrauma patients with predominant severe limb trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 155 polytrauma patients with predominant severe trauma who were admitted to Wuxi Ninth People′s Hospital from January 2021 to December 2024, including 64 males and 91 females, aged 13-95 years [(52.1±16.9)years]. Abbreviated injury scale (AIS) was 5-15 points [(7.4±2.1)points] and injury severity score (ISS) was 17-59 points [(21.3±6.5)points]. Based on the occurrence of DVT in the perioperative period, the patients were divided into preoperative DVT group with 17 patients (11.0%) and non-preoperative DVT group with 138 patients (89.0%) as well as postoperative DVT group with 24 patients (15.5%) and non-postoperative DVT group with 131 patients (84.5%). Basic clinical data were collected, including gender, age, body mass index (BMI), underlying diseases (hypertension, diabetes mellitus), hemoglobin level (Hb), platelet count (PLT), D-dimer, ISS, trauma site [cranial and brain trauma, thoracic and abdominal trauma, upper limb trauma, lower limb trauma (femoral fracture, patellar fracture, tibial or fibular fracture, foot fracture, vascular injury), and pelvic fracture], preoperative waiting time for surgery, surgical site (pelvis and lower limb, other areas), surgical protocols (pelvic and lower limb internal fixation, external fixation of lower limb, lower limb amputation), operation duration less or more than 2 hours, amount of intraoperative blood loss, intraoperative blood transfusion requirement, venous thromboembolism (VTE) prophylaxis (pharmacological and mechanical modalities) and length of hospital stay. Univariate analysis and multivariate binary Logistic regression analysis were conducted to investigate the correlation between the aforementioned indicators and incidence of perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma and determine the independent risk factors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) of the relevant risk factors were analyzed to evaluate and compare the diagnostic efficacy of the risk factors for perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma.Results:Univariate analysis results showed that age, history of hypertension, D-dimer, thoracic and abdominal trauma, pelvic fracture, preoperative waiting time for surgery, and length of hospital stay were significantly correlated with preoperative of DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), pelvic fracture ( OR=5.03, 95% CI 1.09, 23.20, P<0.05), preoperative waiting time for surgery ( OR=1.10, 95% CI 1.00, 1.22, P<0.05) and length of hospital stay ( OR=0.89,95% CI 0.81,0.98, P<0.05) were highly correlated with preoperative DVT of the lower limbs in the patients ( P<0.05). Univariate analysis results showed that age, D-dimer, ISS, foot fracture, and length of hospital stay were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.01, 1.08, P<0.01), D-dimer ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), ISS ( OR=1.09, 95% CI 1.01, 1.17, P<0.05), and foot fracture ( OR=3.51 , 95% CI 1.25 , 9.87 , P<0.05) were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of the ROC curve analysis indicated that preoperative waiting time for surgery (AUC=0.83, 95% CI 0.75, 0.91) had the highest diagnostic efficacy for preoperative DVT of the lower limbs in the patients, with the diagnostic efficacies of pelvic fracture (AUC=0.75, 95% CI 0.65, 0.85) and age (AUC=0.70, 95% CI 0.59, 0.82) decreasing successively. For postoperative DVT of the lower limbs in the patients, D-dimer (AUC=0.71, 95% CI 0.61, 0.81) exhibited the highest diagnostic efficacy, followed by age (AUC=0.70, 95% CI 0.59, 0.81), ISS (AUC=0.64, 95% CI 0.51, 0.76) and foot fracture (AUC=0.62, 95% CI 0.49, 0.74), with diagnostic efficacy decreased successively. Conclusions:For polytrauma patients with predominant severe limb trauma, age, pelvic fracture and preoperative waiting time for surgery are independent risk factors for preoperative DVT, while age, D-dimer, ISS and foot fracture are independent risk factors for postoperative DVT. Additionally, preoperative waiting time for surgery has the best diagnostic efficacy for preoperative DVT, followed by pelvic fracture and age. D-dimer has the best diagnostic efficacy for postoperative DVT, followed by age, ISS and foot fracture.

Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.