1.Current Status and Prospects of Research on Traditional Chinese Medicine Prevention and Treatment for Gastric Precancerous Lesions
Haiyan BAI ; Tai ZHANG ; Ping WANG ; Lin LIU ; Weichao XU ; Yaxin TIAN ; Lanshuo HU ; Qian YANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(4):410-415
Traditional Chinese medicine (TCM), through its multi-target and systematic regulatory effects, has demonstrated unique advantages in the treatment of gastric precancerous lesions (GPL). At present, TCM theoretical research on GPL is mainly reflected in three aspects, the integration of macroscopic syndrome differentiation, the inflammation-carcinoma transformation mechanism, as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL, and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways, gene expression regulation, cellular epigenetics, histone modification, and intestinal microecology. It is proposed that future research on GPL should focus on four key directions, establishing multi-omics data, exploring targeted intervention strategies on key regulatory nodes, advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies, and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system, coupled with interdisciplinary research, will provide valuable references for the clinical treatment and scientific research of GPL.
2.Xianglian Huazhuo Prescription Regulates miR-34b-5p/PFKFB1 Signaling Pathway to Inhibit Glycolysis and Ameliorate Chronic Atrophic Gastritis
Yuxi GUO ; Pengli DU ; Ziqi JIN ; Yican LIN ; Yanru DU ; Haiyan BAI ; Xinran YANG ; Danyang ZHAO ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):29-38
ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription (XLHZ) ameliorates chronic atrophic gastritis (CAG) through regulating glycolysis via the microRNA-34b-5p (miR-34b-5p)/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1 (PFKFB1) signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments, a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), ranitidine, and irregular feeding. The mice were randomized into the following groups: normal, model, Morodan group (2 g·kg-1), and high-, medium-, and low-dose XLHZ groups(7.2,3.8,1.9 g·kg-1). In the cell experiments, GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows: GES-1, MNNG+GES-1, MNNG+GES-1+XLHZ(10%), MNNG+GES-1+miR-34b-5p mimics, MNNG+GES-1+miR-34b-5p inhibitor, MNNG+GES-1+PFKFB1 inhibitor, and MNNG+GES-1+PFKFB1 mimics+XLHZ(10%). The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 (CCK-8) was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) in each group of cells. The protein levels of HIF-1α, hexokinase 2 (HK2), PFKFB1, phosphofructokinase 1 (PFK1), and lactate dehydrogenase (LDHA) in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the content of adenosine triphosphate (ATP) in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group, the model group exhibited symptoms including mental fatigue, lethargy, sparse and dull fur, a tendency to curl up, sluggish responses, reduced food and water intake, and slow body weight gain. In addition, the model group showed decreased expression of miRNA-34b-5p (P<0.01), increased mRNA level of PFKFB1 (P<0.01), upregulated protein levels of HIF-1α, HK2, PFKFB1, PFK1, and LDHA (P<0.01), and increased glucose consumption, lactate content, and ATP content (P<0.01). Compared with the model group, the XLHZ group and Morodan group showed improved mental state, gradually improved fur, increased activity, food and water intake, and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands, reduced inflammatory cells, and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal, with no obvious irregular shape, complete and clear cristae, and uniform matrix. Furthermore, each treatment group showed increased expression of miRNA-34b-5p (P<0.05), reduced mRNA level of PFKFB1 (P<0.05), downregulated protein levels of HIF-1α, HK2, PFKFB1, PFK1, and LDHA (P<0.05), and decreased glucose consumption, lactic acid, and ATP (P<0.05). The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment (P<0.05). The cell transfection efficiency was satisfactory (P<0.05). miR-34b-5p exhibited an effect comparable to that of XLHZ, effectively inhibiting glycolysis, whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice (P<0.05). ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis, thereby ameliorating MNNG-induced gastric mucosal atrophy.
3.Xianglian Huazhuo Prescription Regulates miR-34b-5p/PFKFB1 Signaling Pathway to Inhibit Glycolysis and Ameliorate Chronic Atrophic Gastritis
Yuxi GUO ; Pengli DU ; Ziqi JIN ; Yican LIN ; Yanru DU ; Haiyan BAI ; Xinran YANG ; Danyang ZHAO ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):29-38
ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription (XLHZ) ameliorates chronic atrophic gastritis (CAG) through regulating glycolysis via the microRNA-34b-5p (miR-34b-5p)/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1 (PFKFB1) signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments, a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), ranitidine, and irregular feeding. The mice were randomized into the following groups: normal, model, Morodan group (2 g·kg-1), and high-, medium-, and low-dose XLHZ groups(7.2,3.8,1.9 g·kg-1). In the cell experiments, GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows: GES-1, MNNG+GES-1, MNNG+GES-1+XLHZ(10%), MNNG+GES-1+miR-34b-5p mimics, MNNG+GES-1+miR-34b-5p inhibitor, MNNG+GES-1+PFKFB1 inhibitor, and MNNG+GES-1+PFKFB1 mimics+XLHZ(10%). The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 (CCK-8) was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) in each group of cells. The protein levels of HIF-1α, hexokinase 2 (HK2), PFKFB1, phosphofructokinase 1 (PFK1), and lactate dehydrogenase (LDHA) in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the content of adenosine triphosphate (ATP) in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group, the model group exhibited symptoms including mental fatigue, lethargy, sparse and dull fur, a tendency to curl up, sluggish responses, reduced food and water intake, and slow body weight gain. In addition, the model group showed decreased expression of miRNA-34b-5p (P<0.01), increased mRNA level of PFKFB1 (P<0.01), upregulated protein levels of HIF-1α, HK2, PFKFB1, PFK1, and LDHA (P<0.01), and increased glucose consumption, lactate content, and ATP content (P<0.01). Compared with the model group, the XLHZ group and Morodan group showed improved mental state, gradually improved fur, increased activity, food and water intake, and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands, reduced inflammatory cells, and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal, with no obvious irregular shape, complete and clear cristae, and uniform matrix. Furthermore, each treatment group showed increased expression of miRNA-34b-5p (P<0.05), reduced mRNA level of PFKFB1 (P<0.05), downregulated protein levels of HIF-1α, HK2, PFKFB1, PFK1, and LDHA (P<0.05), and decreased glucose consumption, lactic acid, and ATP (P<0.05). The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment (P<0.05). The cell transfection efficiency was satisfactory (P<0.05). miR-34b-5p exhibited an effect comparable to that of XLHZ, effectively inhibiting glycolysis, whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice (P<0.05). ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis, thereby ameliorating MNNG-induced gastric mucosal atrophy.
4.Effects of Electroacupuncture at Acute Phase on Cognitive Dysfunction at Later Stage of MCAO Rats
Jing LUO ; Wanqing LIN ; Zhaolian CAI ; Xiaoyong ZHONG ; Haiyan ZHENG ; Bin CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):69-74
Objective To explore the effects and potential mechanism of electroacupuncture at acute phase on cognitive dysfunction at later stage in rats with middle cerebral artery occlusion(MCAO).Methods Totally 39 SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 13 rats in each group.MCAO model was established by Zea Longa thread embolism method in model group and electroacupuncture group.The sham-operation group only separated blood vessels.Electroacupuncture group was treated with electroacupuncture at"Baihui"and"Shenting"acupoints at 5 min and 6 h after model establishment respectively,for 30 min.The body mass,modified neuropathy severity scale(mNSS),and percentage of stiff immobility time of rats were monitored weekly,Nissl staining was used to observe the morphology of hippocampal tissue on the 28 d,immunofluorescence staining was used to detect the expression of Ki67,dual cortin(DCX)and neuronal differentiation factor 1(NeuroD1)in dentate gyrus of the hippocampus,the expression of synaptic vesicle protein 2A(SV2A)protein in dentate gyrus of hippocampus was detected by Western blot.Results Compared with the sham-operation group,on the first day after operation,the body mass of the model group rats decreased,then gradually increased,and on the 28th day,the body mass was still lower than that of the sham-operation group(P<0.05);on the first day after operation,the mNSS score significantly increased,gradually decreased thereafter,and remained higher than the sham-operation group until the 28th day(P<0.01);the percentage of stiff immobility time significantly decreased on the first day after operation,gradually stabilized,and remained lower than the sham-operation group on the 28th day(P<0.05);the hippocampal tissue structure was significantly damaged,and the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus was significantly increased(P<0.05),the expression of SV2A protein in the dentate gyrus of hippocampal was significantly decreased(P<0.05).Compared with the model group,the body mass of rats in the electroacupuncture group showed an increasing trend(P<0.05),the mNSS score decreased(P<0.01),and the percentage of stiff immobility time increased(P<0.05);the ischemic injury area was significantly reduced,the structure was clearer,and the disordered and irregularly cells arrangement were reduced,the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus significantly increased(P<0.05),and the expression of SV2A protein in the dentate gyrus of hippocampal significantly increased(P<0.05).Conclusion Electroacupuncture at acute phase at"Baihui"and"Shenting"can promote the recovery of cognitive dysfunction in MCAO rats in the later stage,and its mechanism may be related to enhancing the proliferation and differentiation of neural precursor cells in the dentate gyrus of hippocampus,promoting neurogenesis.
5.Therapeutic value of visual endoscopic retrograde appendicitis therapy in children with acute suppurative appendicitis
Anding ZHANG ; Na FAN ; Mingzhong WANG ; Lingchao ZENG ; Chunhui WANG ; Yan LIN ; Jiaren ZHOU ; Yaping SONG ; Nini ZHANG ; Haiyan WANG ; Hongwei GUO ; Ying ZHOU ; Baoxi WANG ; Xun JIANG
Chinese Journal of Pediatrics 2025;63(7):754-758
Objective:To investigate the therapeutic value of visual endoscopic retrograde appendicitis therapy (vERAT) in pediatric patients with acute suppurative appendicitis (ASA).Methods:This was a retrospective cohort study. A total of 55 ASA patients who underwent vERAT at the Pediatric Department of the Tangdu Hospital of Air Force Medical University between November 2023 and January 2025 were selected and divided into groups based on the presence or absence of fecaliths: fecalith group and non-fecalith group. The baseline characteristics, initial treatment success rates, treatment costs, hospital stay duration, procedure time, and recurrence rates between two groups were compared. Mann-Whitney U test and χ2 test were used to evaluate group differences. Results:A total of 55 ASA patients were enrolled, including 38 males and 17 females, with the age of 11.2 (9.2, 13.1) years. Based on the presence of fecaliths, patients were divided into two groups: fecalith group (32 cases) and non-fecalith group (23 cases). No statistically significant differences were observed between the two groups in terms of age, gender, duration of abdominal pain, white blood cell count, neutrophil percentage, diameter of appendix, thickness of appendix clinical symptoms or signs (all P>0.05). The initial treatment success rates were 91% (29/32) in fecalith group and 96% (22/23) in non-fecalith group, with no statistically significant difference ( P=0.632). However, significant differences were noted in stent placement ( χ2=5.85, P=0.026) and procedure time ( Z=4.75, P<0.001). The follow-up duration time was 6.0 (2.0, 12.0) and 7.0 (2.0, 8.5) months for the fecalith and non-fecalith groups, respectively, with no significant difference ( Z=0.05, P=0.962). The recurrence rates were 14% (4/29) in fecalith group and 5% (1/22) in non-fecalith group, with no statistically significant difference ( P=0.375). Conclusions:vERAT can safely and effectively treat pediatric ASA, regardless of the presence or absence of fecaliths. It can provide a new treatment option for ASA.
6.Clinical features of infection-related eosinophilic lung diseases caused by common respiratory pathogens in children
Changchang LI ; Haiyan LI ; Lili ZHU ; Shunhang WEN ; Ming XU ; Miaoshang SU ; Lin DONG
Chinese Journal of Pediatrics 2025;63(7):778-783
Objective:To analyze the clinical features of children with infection-related eosinophilic lung diseases (ELD) caused by common respiratory pathogens.Methods:A retrospective cohort study was conducted. The clinical features, auxiliary examinations, treatments, and prognoses of 134 children with infection-related ELD caused by common respiratory pathogens at Yuying Children′s Hospital from January 2014 to June 2024 were collected. Participants were divided into the mild and severe groups based on whether the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) exceeded 0.25. Chi-square test or Fisher exact test was used to analyze the differences between the two groups, and Logistic regression was performed to examine the correlation between BALF eosinophilia and the clinical outcomes.Results:Among the 134 children, 73 were males and 61 were females, with an age of 6.9 (4.6, 8.8) years on admission. A total of 154 pathogen detections were recorded, including 116 cases (75.3%) of Mycoplasma pneumoniae, 8 cases (5.2%) of influenza A virus, 6 cases (3.9%) of Streptococcus pneumoniae, and 6 cases (3.9%) of Chlamydia pneumoniae, among others. The percentage of eosinophils in the BALF of all children was 0.10 (0.07, 0.15). There were 117 cases in the mild group and 17 cases in the severe group. Compared with the mild group, significantly greater proportion of children in the severe group presented dyspnea (10/17 vs. 17.1% (20/117)), wheezing (7/17 vs. 8.5% (10/117)), respiratory failure (8/17 vs. 7.7% (9/117)), single lobe ≥2/3 consolidation (7/17 vs. 12.8% (15/117)), atelectasis (7/17 vs. 12.0% (14/117)), pleural effusion (7/17 vs. 16.2% (19/117)), plastic bronchiolitis (4/17 vs. 4.3% (5/117)), and systemic corticosteroid prescription (14/17 vs. 51.3% (60/117)) (all P<0.05). Univariate Logistic regression analysis revealed that severe eosinophilia in BALF was significantly associated with an elevated risk of respiratory failure ( OR=10.67, 95% CI 3.31-34.38, P<0.001), single lobe ≥2/3 consolidation ( OR=4.76, 95% CI 1.57-14.41, P=0.006), atelectasis ( OR=5.15, 95% CI 1.69-15.72, P=0.004), pleural effusion ( OR=3.61, 95% CI 1.22-10.67, P=0.020), and plastic bronchitis ( OR=6.89, 95% CI 1.64-28.94, P=0.008). Among the 126 children who were followed up, 106 cases (84.1%) were cured, 20 cases (15.9%) improved, and no relapses or deaths occurred. Conclusions:Mycoplasma pneumoniae and influenza A virus are common pathogens in children with infection-related ELD and the percentage of eosinophils in BALF is mildly increased, and the severe cases exhibit more severe clinical features and more significant pulmonary abnormalities, such as lobar consolidation and lung atelectasis. The prognosis is generally favorable.
7.Exploration on the anti-inflammatory effect of Duhuo Jisheng Decoction on rheumatoid arthritis rats based on the balance of M1/M2 macrophages
Chaoyu HAN ; Chunsheng LIN ; Haiyan ZHAO ; Hongting ZHANG
International Journal of Traditional Chinese Medicine 2025;47(6):790-797
Objective:To investigate the anti-inflammatory effects of Duhuo Jisheng Decoction on type Ⅱ collagen emulsion induced arthritis (CIA) model rats from the perspective of M1/M2 macrophage balance mediated development of rheumatoid arthritis.Methods:SD rats were divided into a normal group of 8 and a model group of 32. The CIA model was established using collagen antibody induction method for modeling. The successfully modeled rats were randomly divided into model group, methotrexate group, and Duhuo Jisheng Decoction medium- and high-dosage groups using a random number table method, with 8 rats in each group. Duhuo Jisheng Decoction medium- and high-dosage groups were orally administered with Duhuo Jisheng Decoction at dosages of 13.5 and 27.0 g/kg, once a day; methotrexate group received oral administration of 2.0 mg/kg methotrexate twice a week; normal group and model group were given equal volumes of physiological saline by gavage once a day for 28 consecutive days. The general condition of each group of rats was observed, the degree of swelling in the right knee joint was measured, and the arthritis index was scored; HE was used to observe pathological changes in synovial tissue; immunofluorescence was used to detect the expressions of markers CD86 and CD206 in synovial macrophages; Real time PCR was used to detect the mRNA levels of IL-6, TNF-α, IL-10, and TGF-β in synovial tissue.Results:Duhuo Jisheng Decoction could significantly improve the mental state of the rats and reduced the swelling of the knee joints and the arthritis index ( P<0.01). Compared with the model group, the cartilage structure in the knees of rats in the Duhuo Jisheng Decoction group was more intact and clearer. The expression level of the M1 macrophage marker CD86 significantly decreased, and the expression level of the M2 macrophage marker CD206 significantly increased; the mRNA expressions of IL-6 and TNF-α in the knee joint synovial tissue were significantly reduced ( P<0.05), while IL-10 and TGF-β levels significantly increased ( P<0.05). Conclusion:Duhuo Jisheng Decoction may promote macrophage polarization towards M2 type, thereby achieving M1/M2 macrophage balance, alleviating inflammatory response in rheumatoid arthritis rats, and exerting therapeutic effects on rheumatoid arthritis.
8.Clinicopathological characteristics of HER2 low expression gastric adenocarcinoma
Yilin MU ; Dongliang LIN ; Shuchao ZHAO ; Hailei SHI ; Hui HE ; Haiyan ZHANG ; Xiaoming XING
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):334-339
Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10%)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.
9.Prenatal Screening and Genetic Analysis of Fetal Aberrant Right Subclavian Ar-tery
Mengjie ZHU ; Haiyan TANG ; Yanyan LI ; Yongyan CHU ; Lilu NONG ; Libing LUO ; Ting ZENG ; Xiaoying DAI ; Shengmou LIN
Journal of Practical Obstetrics and Gynecology 2025;41(6):508-513
Objective:To investigate the clinical significance of prenatal screening and genetic analysis in the diagnosis of fetal aberrant right subclavian artery(ARSA).Methods:The ultrasonographic features of ARSA fetu-ses detected by prenatal ultrasound at the University of Hong Kong-Shenzhen Hospital from October 2017 to March 2022 were retrospectively analyzed.The fetuses were divided into isolated ARSA group and complicated ARSA group.Their genetic analysis results and pregnancy outcome were analyzed.Results:Among 30,260 preg-nant women,185 fetuses were diagnosed with ARSA by prenatal ultrasound screening,with an incidence of 0.6%;5 fetuses(2.6%)were diagnosed by ultrasound in the first trimester,and the remaining were diagnosed by fetal grade Ⅲ structural ultrasound examination at 20~24 weeks' gestation.Among them,158 fetuses(85.4%)had isolated ARSA,and 27(14.6%)had complicated ARSA.Among fetuses with ARSA and other structural abnormal-ities,cardiovascular system accounted for the highest proportion(44.4%),followed by nervous system(22.2%)and urinary system(22.2%).Through genetic analysis,8.3%(4/48)fetuses with isolated ARSA and 40.0%(4/10)fetuses with complicated ARSA were found to have chromosomal numerical or structural abnormalities,with statis-tically significant difference between the two groups(P=0.024).Genetic analysis was completed in 48 isolated ARSA,and the positive rate of pathogenic copy number variants(CNV)was 4.2%(2/48),which was not signifi-cantly different from the pathogenic CNV incidence rate of 0.4%(1/239)in elderly pregnant cases during the same period(P=0.074).The Down syndrome positive likelihood ratio(LR+)for isolated ARSA was 2.5 and the Down syndrome LR+for complicated ARSA was 49.6.Conclusions:Complicated ARSA is often associated with cardiovascular abnormalities and is more likely to develop Down syndrome than isolated ARSA.Although the inci-dence of pCNV in isolated ARSA is slightly higher than the natural incidence,the correlation between pCNV and i-solated ARSA has not been clearly determined by the current sample size.
10.L-Mimosine Modulates the ROS/JNK/c-Jun Signaling Axis to Trigger Mitochondrial Apoptosis in Melanoma Cells
Ying ZHAO ; Pan JIANG ; Dan LEI ; Haiyan LIN ; Zhaohai PAN ; Defang LI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(5):678-688
OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.

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