OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Pancreatic cancer is a malignant tumor with a very poor prognosis,characterized by early me-tastasis and high invasiveness,and is unresponsive to traditional treatments like chemotherapy and radio-therapy.In recent years,the study of metabolic products has become a new hotspot in pancreatic cancer research,showing that the metabolic reprogramming of tumor cells is a key factor for their growth and pro-liferation,and that regulatory factors of metabolic pathways may serve as new therapeutic targets.Meta-bolic reprogramming primarily manifests as alterations in three major nutrient metabolic pathway and oxi-dative phosphorylation processes.Additionally,the tumor microenvironment of pancreatic cancer exhibits unique metabolic features.Mechanistic studies are actively underway,and future research may focus on integrating omics,artificial intelligence,and other novel research techniques to further explore how meta-bolic changes drive the development of pancreatic cancer and to improve treatment strategies,including the development of targeted drugs and metabolomics-based diagnostic tools.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

Pancreatic cancer is a malignant tumor with a very poor prognosis,characterized by early me-tastasis and high invasiveness,and is unresponsive to traditional treatments like chemotherapy and radio-therapy.In recent years,the study of metabolic products has become a new hotspot in pancreatic cancer research,showing that the metabolic reprogramming of tumor cells is a key factor for their growth and pro-liferation,and that regulatory factors of metabolic pathways may serve as new therapeutic targets.Meta-bolic reprogramming primarily manifests as alterations in three major nutrient metabolic pathway and oxi-dative phosphorylation processes.Additionally,the tumor microenvironment of pancreatic cancer exhibits unique metabolic features.Mechanistic studies are actively underway,and future research may focus on integrating omics,artificial intelligence,and other novel research techniques to further explore how meta-bolic changes drive the development of pancreatic cancer and to improve treatment strategies,including the development of targeted drugs and metabolomics-based diagnostic tools.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

Objective:To compare the precision and stability of handheld full-course visual navigation and robot-assisted total hip arthroplasty (THA), as well as to evaluate perioperative laboratory indicators and clinical efficacy.Methods:A retrospective analysis was performed on 68 patients with unilateral hip joint disorders who underwent primary THA at the General Hospital of the People's Liberation Army of China from January to June 2024. Patients were divided into two groups based on the assistance method: the Visual Treatment Solution (VTS) group, which included 34 patients (13 males, 21 females; mean age 56.92±8.31 years; body mass index[BMI] 24.20±3.55 kg/m 2), and the MAKO group, also with 34 patients (18 males, 16 females; mean age 57.97±6.54 years; BMI 25.20±3.91 kg/m 2). Among the VTS group, 1 there were 18 cases on the left side and 16 cases on the right side, including 14 cases of femoral head necrosis, 8 cases of congenital hip dysplasia, and 12 cases of hip osteoarthritis. In the MAKO group, there were 19 cases on the left side and 15 cases on the right side, including 13 cases of femoral head necrosis, 10 cases of congenital hip dysplasia, and 11 cases of hip osteoarthritis. Preoperative planning, intraoperative verification deviations, postoperative acetabular prosthesis anteversion and abduction angles, and limb length discrepancies were analyzed. Acetabular angle distribution scatter plots were generated for intraoperative verification and postoperative imaging. The operation time, hospital stay, and laboratory values, including hemoglobin (Hb) loss, fibrinogen degradation products (FDP), D-dimer, high-sensitivity C-reactive protein (hCRP), as well as postoperative pain (measured by the visual analogue scale, VAS), hip Harris score (HHS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were recorded. Results:No statistically significant differences were observed between postoperative imaging measurements of anteversion and abduction angles and intraoperative verification values ( P>0.05). Postoperative imaging indicated that 91% (31/34) of the VTS group and 100% (34/34) of the MAKO group were within the Lewinnek safety zone. The scatter distribution of angles in the MAKO group was more concentrated than that in the VTS group. Furthermore, the angle deviation between intraoperative verification and preoperative planning was significantly greater in the VTS group for both anteversion (2.00° [-1.00°, 4.00°] vs. 0.00° [-1.00°, 1.00°]) and abduction angles (-1.00° [-5.00°, 0.00°] vs. 0.00° [-1.00°, 1.00°]; P<0.05). The bilateral limb length discrepancies were 1.35(0.67, 2.45) mm in the VTS group and 1.65(0.50, 2.52) mm in the MAKO group, with no significant difference noted ( P>0.05). Both methods achieved effective hip biomechanical reconstruction. Additionally, no significant differences in operation time, Hb loss, FDP, D-dimer, hCRP, or postoperative hospital stay were found ( P>0.05). Follow-up at one and three months postoperatively showed no significant differences in VAS (2.94±0.92 vs. 2.97±0.83), HHS (69.88±4.20 vs. 70.06±3.88), or WOMAC scores (22.44±3.15 vs. 22.76±3.39) between the two groups ( P>0.05). Conclusion:The stability of preoperative planning and design in robot-assisted total hip arthroplasty is superior to that of handheld navigation methods. Nevertheless, both approaches demonstrate comparable postoperative prosthesis stability, laboratory indicators, and clinical outcomes.

Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.

ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.