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 explore the effect of gastrodin(GAS)on the polarization of M2 microglia under oxygen and glucose deprivation(OGD)and the effect of p38 MAPK inhibition on the polarization status of microglia.Methods BV2 microglia was divided into the control group(Ctrl),p38 MAPK inhibitor SB203580 group(Ⅰ),OGD group(OGD),OGD+I group,gastrodin treatment group(G+OGD),and G+OGD+Ⅰ group.The expressions of p38 MAPK,phosphorylated p38 MAPK(p-p38 MAPK),M2 microglia marker arginase-1(Arg-1)and chitinase like protein 1/2(YM1/2)were detected by immunofluorescent staining and Western blotting.Results Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia,enhanced the fluorescence expressions of Arg-1 and YM1/2.After pretreatment with SB203580,the fluorescence expressions of p-p38 MAPK further decreased,the fluorescence expressions of Arg-1 and YM1/2 further increased,both were significantly different from the G+OGD group(n=3,P＜0.05).The fluorescence expressions of p38 MAPK in each group was not statistically significant(n=3,P＞0.05).Western blotting results showed that the protein expressions of p-p38 MAPK,Arg-1 and YM1/2 in the OGD group enhanced,compared with that in the control group(n=3,P＜0.05).After the pretreatment with gastrodin,the protein expression of p-p38 MAPK was reduced significantly,the protein expressions of Arg-1 and YM1/2 was enhanced obviously,both were significantly different from the OGD group(n=3,P＜0.05).After pretreatment with SB203580,the protein expressions of p-p38 MAPK was further reduced,the protein expression of Arg-1 and YM1/2 were further enhanced,both were significantly different from the G+OGD group(n=3,P＜0.05).In addition,there was no significant change in p38 MAPK protein expression among groups(n=3,P＞0.05).Conclusion Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype,reducing inflammatory responses and exerting a protective effect.

Objective To develop a multicolor photoelectroencephalography evoked flash to identify photosensitive epilepsy patients during the selection of naval aircraft pilots.Methods The multicolor photoelectroencephalography evoked flash was composed of a main body,a control box and a bracket.There were four rows of LED lights in the main body,which emitted four colors of light including red,yellow,green and orange,respectively;there were three sockets for signal,light and power and one color changeover switch on the body of the control box,and a control circuit board was fixed at the bottom inside the control box;the bracket had a double-jointed arm folding structure.The flash developed was compared with the coventional photoelectroencephalography evoked flash to verify its effect for inducing photosensitive epilepsy.Results There were no significant differences between the two flashes in the numbers of identified cases with photosensitive epilepsy when the subjects were under awake and closed-eye conditions(P＞0.05).Condusion The flash developed can make up for the deficiency of the coventional photoelectroencephalography evoked flash when selecting naval aircraft pilots.[Chinese Medical Equipment Journal,2024,45(7):112-114]

Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures(OVCFs).Methods Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group(treatment group)and traditional Kirchner positioning group(control group).There were 30 patients in treatment group,including 4 males and 26 females,aged from 61 to 87 years old with an average of(73.61±7.17)years old;body mass index(BMI)ranged from 15.24 to 28.89 kg·m-2 with an average of(23.90±3.20)kg·m-2;bone mineral density T value ranged from-4.90 to-2.50 SD with an avergae of(-3.43±0.75)SD;fracture to operation time was 6.50(4.00,10.25)d;10 patients were grade Ⅰ,13 patients were grade Ⅱ,and 7 patients were grade Ⅲ according to Genant classification of fracture compression.There were 31 patients in control group,in-cluding 7 males and 24 females,aged from 61 to 89 years old with an average of(73.63±8.77)years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of(23.67±2.35)kg·m-2;bone mineral density T value ranged from-4.60 to-2.50 SD with an avergae of(-3.30±0.68)SD;fracture to operation time was 6.00(3.00,8.00)d;1l patients were grade Ⅰ,9 patients were grade Ⅱ,and 11 patients were grade Ⅲ according to Genant classification of fracture compression.The puncture times,X-ray fluoroscopy times and puncture time between two groups were observed and compared.Visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)and timed up and go test(TUGT)were observed and compared before operation,3 d and 1 month after operation.Results All patients were followed up for 1 to 3 months with an average of(2.10±0.80)months.Puncture times,X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00,6.00)times,(29.53±5.89)times and 14.83(12.42,21.20)min,respectively,while those in control group were 7.00(6.00,8.00)times,(34.58±5.33)times,22.19(17.33,27.01)min,treatment group was better than those of control group(P＜0.05).There were no significant differences in preoperative VAS,JOA and TUGT between two groups(P＞0.05).VAS,JOA and TUGT in both groups were sig-nificantly improved after opeation(P＜0.05).On the third day after operation,JOA score of treatment group was 23.00(20.75,25.00),which was higher than that of control group 20.00(19.00,23.00)(P＜0.05).TUGT of treatment group was 6.26(5.86,6.57)s,which was better than that of control group 6.90(6.80,7.14)s(P＜0.05).Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group.Conclusion The optimal scheme of self-made spinal locators for lo-cating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times,shorten puncture times and reduce number of X-ray fluoroscopy times,and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walk-ing ability of postoperative patients.

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L. litseifolius, this study screened out two CHS genes(LlCHS1 and LlCHS2) from the transcriptome data of this plant, and then bioinformatics analysis and functional characterization were performed for the two genes. The bioinformatics analysis showed that LlCHS1 and LlCHS2 were acidic hydrophilic stable proteins with no transmembrane domain, composed of 395 and 390 amino acid residues, respectively. Both of them contained the characteristic amino acid sequence "WGVLFGFGPGL" and highly conserved active sites(Cys-164, Phe-215, His-303, and Asn-336) of the CHS family. The phylogenetic tree showed that LlCHS1 shared the same clade with similar genes in Aquilaria sinensis, and LlCHS2 was closely related to similar genes in Malus domestica. Under exogenous addition of phloretic acid, co-expression of LlCHS1 or LlCHS2 with Aa4CL from Aromatoleum aromaticum in Escherichia coli catalyzed the production of phloretin from phloretic acid. This study laid a theoretical foundation for revealing the functions of CHS in plants and provided new enzymatic modules for producing phloretin by synthetic biology.
Acyltransferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Cloning, Molecular ; Amino Acid Sequence

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ² test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.
Male ; Female ; Humans ; Robotic Surgical Procedures/methods* ; Thyroid Neoplasms/surgery* ; Thyroidectomy/methods* ; Retrospective Studies ; Neck Dissection/methods* ; Axilla/pathology* ; Treatment Outcome