ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

ObjectiveTo clarify the associations between plasma fibrinogen （Fbg） and volumetric bone mineral density （vBMD） as well as osteoporosis measured by quantitative computed tomography （QCT）， and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis. MethodsPatients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis. The study analyzed the correlation between plasma Fbg and osteoporosis in patients. The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）. ResultsTotally 441 subjects were included in the analysis， with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4% （28/441）. As the level of plasma fibrinogen increased， the incidence of osteoporosis significantly increased （P<0.000 1）while the average bone mineral density of L1 and L2 were significantly decreased （P<0.05）. Compared with the first quartile of plasma Fbg（1.99g/L -2.37g/L）， the risk of osteoporosis in the fourth quartile of plasma Fbg （3.67g/L-4.46g/L） increased by 8.85 times after adjusting for related confounding factors. ConclusionThis study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension. Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis， aiding in early diagnosis and therapeutic monitoring. This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

The food effect(FE)on drug absorption is an important part of clinical pharmacological studies of new drugs.The caloric ratios for each component of a high-fat meal are specified in the"Technical Guidelines for Food Bioavailability and Postprandial Bioequivalence Studies"approved by the US Food and Drug Administration(FDA)and the"Technical Guidelines for Food Effect Studies in New Drug Development"approved by the National Medical Products Administration.However,the recipes for high-fat meals vary among clinical research centers,showing their advantages and disadvantages.Thus,we present a modified version of high-fat meal recipes with easy-to-quantify calories,which is a combination of Western and Chinese flavors,easy to prepare,and meets Chinese tastes.The center satisfaction surveys showed that our modified version of the high-fat meal recipe greatly improved subject satisfaction and compliance,thus better safeguarding the quality of the trial.

Objective To explore the correlation between endoscopic ultrasound features and immunohistochemical results of gastric stromal tumors at different risk levels,and provide reference for clinical diagnosis and treatment.Methods Retrospective collection of relevant indicators of gastric stromal tumor patients who received concurrent surgical treatment at Lanzhou University Second Hospital from January 2018 to July 2023,and analysis of differences in risk levels.Results The average age of onset of gastric stromal tumors was(56.02±10.94)years old,and the initial symptom of black stool was significant for different grades of gastric SMTs.Patients with different risk levels also received significant differences in treatment methods(P＜0.05).There was no difference in the classification of risk levels among the four groups of extremely low risk,low risk,medium risk,and high risk in terms of location,origin level,boundary,echo,presence or absence of cystic changes,calcification,or blood flow signals(P＜0.05);Tumor size,growth pattern,shape,internal echo uniformity,and appearance are significant factors for postoperative risk grading of gastric stromal tumors(P＜0.05).Multivariate logistic regression showed that tumor size is an independent influencing factor(P＜0.05).The immunohistochemical results showed that the positivity of DOG-1,CD34,SMA,and Desmin had no effect on the postoperative risk grading of gastric SMTs(P＜0.05);The positive expression of Vimentin,Ki-67 index,and mitosis were significantly correlated with risk(P＜0.05).Conclusion The different invasion grades of gastric stromal tumors are related to the size,shape,and echo of the lesion.Endoscopic ultrasound can effectively diagnose gastric stromal tumors,and combining with immunohistochemical related indicators can better evaluate the overall condition of patients with gastric stromal tumors,providing reference for clinical diagnosis and treatment.

Objective:To develop and validate a model to predict the risk of malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. Methods:From April 2022 to August 2023, 430 patients with nasopharyngeal carcinoma who were admitted to the department of radiotherapy of the first affiliated hospital of Guangxi medical university in Nanning were conveniently selected as the study subjects, and they were divided into the modelling group (300 cases) and the internal validation group (130 cases) in the internal validation group in the ratio of 7:3, and 61 patients with nasopharyngeal carcinoma admitted to the affiliated cancer hospital of Guangxi medical university in Nanning City were selected as the external validation group. Logistic regression was used to establish the risk prediction model and draw nomograms,Hosmer-Lemeshow, calibration curve and ROC were used to verify the goodness of fit and predictive power of the model, and clinical decision curve was used to assess the clinical utility. Results:Logistic regression analysis showed that skeletal muscle mass index, self-rated anxiety scale score, Pittsburgh sleep quality questionnaire score, Chinese diet pagoda score, regular exercise, and digestive symptom groups were the influencing factors for malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. In the modelling group, the area under the ROC curve was 0.853 (95％CI:0.81 ～ 0.89), the maximum Youden was 0.600, and the corresponding specificity was 0.764 and the sensitivity was 0.836. The Hosmer-Lemeshow test=4.040 and P=0.853 indicated that the model had good predictive ability. Calibration curve of the calibration showed that the predictive effect of the model matched actual probability well, with an average absolute error was 0.024. When the threshold probability of the clinical decision curve is 0.05 ～ 0.85, the clinical response rate is higher. The area under the operating curve of the subjects in the internal validation group was 0.891, the sensitivity was 77.36％, the specificity was 89.61％, and the practical application accuracy was 84.62％. The area under the operating curve of the subjects in the external validation group was 0.886, the sensitivity was 76.00％, the specificity was 83.33％, and the overall accuracy was 80.33％. Conclusion:The risk prediction model constructed in this study has a good effect, which can effectively predict the incidence of malnutrition in patients receiving concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma, and provide a reference for clinical staff to formulate and implement nutritional interventions.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective:To explore the characteristics and patterns of gene mutations in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) patients and their relationship with TKI-resistant CML.Methods:A retrospective case series study was performed. Clinical data and next-generation sequencing results from TKI-resistant CML patients in Nanfang Hospital of Southern Medical University and Yuebei People's Hospital of Shantou University Medical College from August 2018 to November 2022 were retrospectively analyzed, and the gene mutations of the patients in general and at different disease stages were analyzed.Results:Sixty patients were enrolled, with the age [ M ( Q1, Q3)] of 41.5 years old (32 years old, 53 years old); 38 cases (63.33%) were male and 22 cases (36.67%) were female; 43 cases were in the chronic stage, and 17 cases were in the progression stage (3 cases were in the accelerated stage and 14 cases were in the blast stage). non-ABL1 mutations were detected in 30 patients (50.00%) including 45 times of 15 non-ABL1 genes. The number of non-ABL1 mutation gene was 1 (0, 2) in 60 patients. Of the 60 patients, 21 (35.00%) had ASXL1 mutations, 5 (8.33%) had DNMT3A mutations, 5 (8.33%) had RUNX1 mutations, and 3 (5.00%) had SETBP1 mutations; the proportions of patients with 1 and ≥2 non-ABL1 mutations were 33.33% (20/60) and 16.67% (10/60), respectively. The total detection rates of non-ABL1 mutations were 52.94% (9/17) and 48.84% (21/43), and the detection rates of ≥2 non-ABL1 mutations were 23.53% (4/17) and 13.95% (6/43) in patients with progression and patients with chronic disease, and the differences were not statistically significant ( χ2 = 0.08, P = 0.774; χ2 = 0.80, P = 0.370). Seventeen of 60 patients (28.33%) had mutations in the ABL1 kinase region, of which 14 (82.35%) had non-ABL1 mutations; of these 17 cases, 6 patients with progressive disease all had non-ABL1 mutations, in 11 patients with chronic disease, 8 patients had non-ABL1 mutations, and the difference was not statistically significant ( P = 0.452). Conclusions:Patients with TKI-resistant CML have high frequencies of non-ABL1 mutations, and there is a trend for higher mutation rates in patients with progressive disease than in patients with chronic disease, and these may be related to the abnormal activation of ABL1 kinase by BCR-ABL1 fusion gene in patients with drug-resistant CML, which leads to the genome-level and epigenome-level mutations, and driving disease progression from chronic phase to accelerated or blast phase.