1.Oxocrebanine inhibits proliferation of hepatoma HepG2 cells by inducing apoptosis and autophagy.
Zheng-Wen WANG ; Cai-Yan PAN ; Chang-Long WEI ; Hui LIAO ; Xiao-Po ZHANG ; Cai-Yun ZHANG ; Lei YU
China Journal of Chinese Materia Medica 2025;50(6):1618-1625
The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans
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Apoptosis/drug effects*
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Autophagy/drug effects*
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Cell Proliferation/drug effects*
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Hep G2 Cells
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Liver Neoplasms/genetics*
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Carcinoma, Hepatocellular/genetics*
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Caspase 3/genetics*
2.Constructing a Prediction Model for Anxiety and Depression among Elderly People in the Community Based on Machine Learning
Jieying LIU ; Wen ZHENG ; Feiteng FANG ; Cai ZHAO ; Jinping ZHENG
Chinese Journal of Geriatrics 2024;43(2):234-239
Objective:To develop a prediction model using machine learning to identify anxiety and depression in elderly individuals.Methods:This study collected data from 15079 elderly individuals in Shanxi Province, including their social demographic factors and disease status.Anxiety and depression were evaluated using GAD-7 and PHQ-9 scales to understand the characteristics of mental illness in the elderly.The evaluation indexes included accuracy, recall, precision, F1 score, Receiver Operating Characteristic Curve(ROC), and area under the curve(AUC), which were derived from the confusion matrix and several models.Results:The output of our study clearly demonstrates that the full feature prediction based on LightGBM is highly accurate, with an AUC of 0.805[95% CI: 0.794-0.811]. This outperforms the Random Forest model, which achieved an AUC of 0.730[95% CI: 0.702-0.741], and the XGboost model, which achieved an AUC of 0.802[95% CI: 0.780-0.807]. Therefore, LightGBM algorithm proves to be a strong prediction model.Our simplified model, based on eight selected features, also achieves a respectable AUC of approximately 0.75. Conclusions:The new prediction model for anxiety and depression specifically designed for the elderly can be effectively utilized in grassroots health surveys or for self-examinations to efficiently predict anxiety and depression levels among the elderly population in the community.
3.Therapeutic value of endoscopic ultrasound-guided pancreatic duct drainage (with video)
Shanshan SHEN ; Shuang NIE ; Wen LI ; Ruhua ZHENG ; Wei CAI ; Zhengyan QIN ; Bin ZHANG ; Ying LYU ; Xiaoping ZOU ; Lei WANG
Chinese Journal of Digestive Endoscopy 2024;41(11):889-894
Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.
4.Safety and efficacy of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis
Tian LIN ; Wanling WEN ; Juan DU ; Zheng WU ; Xiangkai KONG ; Wenbo DUAN ; Xiaoyun ZHANG ; Bin DU ; Yiling CAI ; Yongqiang CUI
Chinese Journal of Internal Medicine 2024;63(3):272-278
Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.
5.Basic and Clinical Research of Fecal Microbiota Transplantation in The Treatment of Central Nervous System Diseases
Hong-Ru LI ; Cai-Hong LEI ; Shu-Wen LIU ; Yuan YANG ; Hai-Xia CHEN ; Run ZHANG ; Yin-Jie CUI ; Zhong-Zheng LI
Progress in Biochemistry and Biophysics 2024;51(11):2921-2935
As a microbial therapy method, fecal microbiota transplantation (FMT) has attracted the attention of researchers in recent years. As one of the most direct and effective methods to improve gut microbiota, FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota. FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.
6.Development and validity test of alcohol-related cognitive scale among adolescents based on health belief model
Xiao-Tao YAN ; Wen-Jie GUO ; Cai-Fang SHEN ; Zi-Yi CUI ; Jia-Qian WU ; Ling FANG ; Yu-Chen ZHAO ; Chen-Yu QIAN ; Yan-Qiu YU ; Pin-Pin ZHENG
Fudan University Journal of Medical Sciences 2024;51(4):465-472
Objective To develop a health belief model(HBM)based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity.Methods The adolescents'alcohol-related cognitive scale was developed based on HBM model.By using purposive sampling,three general high schools in Qingpu District,Shanghai were selected.One-third of the classes from grades 10 and 11 in each school were randomly selected,and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability(internal consistency reliability and combination reliability)and validity(structural validity,convergent validity,discriminative validity and criterion validity).Results A total of 970 questionnaires were collected,of which 948 were valid,with an effective rate of 97.7%.The adolescents'alcohol-related cognitive scale contained 22 items.Five common factors were extracted from exploratory factor analysis,including perceived susceptibility,perceived severity,perceived benefits,perceived obstacles,and self-efficacy.The cumulative variance contribution rate reached 83.89%.The results of confirmatory factor analysis confirmed the overall fit of the model.The average variance extracted value(AVE)of each dimension was greater than 0.5,and the convergent validity of the model was ideal.The AVE square root of each dimension of the scale was greater than its correlation coefficient,indicating good discrimination validity.Cronbach's α coefficient of the total volume table was 0.892,indicating good overall reliability.Conclusion The adolescents'alcohol-related cognitive scale developed in this study has good reliability and validity,which can be used to measure adolescents'alcohol-related perceptions.
7.Influence of Atmosphere on Solution Cathode Glow Discharge Spectroscopy of Silver,Lead and Thallium in Solutions
Zhao-Qing CAI ; Wen-Jing HUANG ; Zheng WANG
Chinese Journal of Analytical Chemistry 2024;52(10):1573-1580
The sensitivity issue encountered with solution cathode glow discharge optical emission spectrometry(SCGD-OES)in detecting heavy metals like Ag,Pb and Tl in solutions was alleviated.To enhance the analytical performance of SCGD-OES for heavy metal elements,a quartz chamber structure introducing discharge atmospheres was employed.Spectral characteristics and signal strengths of heavy metal elements under four different atmospheres(Air,pure argon,pure helium and hydrogen-helium mixture)were compared.The findings suggested that inert atmospheres could enhance the excitation capability of SCGD plasma,leading to boosted emission signals of the interested elements,while significantly reducing background radiation by isolating air.Compared to SCGD-OES sustained in air,enclosed SCGD-OES with pure helium as the discharge gas exhibited a signal intensity increase of 2.6-3.8 times for Ag,Pb and Tl,with detection limits improving from 2.5,112.1 and 14.8 μg/L to 0.7,28 and 1.9 μg/L,respectively.
8.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
9.Food intolerance characteristics and its relationship with Helicobacter py-lori infection in chronic gastritis patients of different age groups
Jia CHEN ; Jun CAI ; Wen-Yang ZHENG ; Yue-Ying CHEN
Chinese Journal of Infection Control 2024;23(7):874-880
Objective To explore food intolerance(FI)characteristics and its relationship with Helicobacter pylo-ri(Hp)infection in chronic gastritis(CG)patients of different age groups.Methods Patients admitted to a hospi-tal from August 2021 to August 2022 were selected as the study subjects.According to age,patients were divided into the young-middle-aged group and the elderly group.According to whether Hp infection occurred,they were di-vided into the infection group and non-infection group.Clinical data and 14 food allergen specific immunoglobulin G(IgG)levels of patients were collected.Testing results were analyzed by statistical software,risk factors were ana-lyzed by multivariate logistic regression,and predictive value of the model was evaluated.Results A total of 108 CG patients were admitted to the hospital,with 65 males and 43 females.There were 78 cases(18-64 years old)in the young-middle-aged group and 30(≥65 years old)in the elderly group,60 cases in the Hp infection group and 48 cases in the non-infection group.The total positive rate of FI tests of 14 kinds of food was 56.48%(61/108).Five food types with highest FI positive rates were shrimp(44.44%),egg(40.74%),crab(35.19%),soybean(31.48%),and cod(29.63%);five food types with highest FI positive rates in the young-middle-aged group were egg(46.15%),shrimp(38.46%),soybean(37.18%),cod(32.05%),and crab(29.49%);in elderly group,they were shrimp(60.00%),crab(50.00%),chicken(33.33%),rice(33.33%),and egg(26.67%).The FI positive rates for 6 food types(crab,egg,milk,shrimp,soybean,and wheat)in patients of different age groups were com-pared,and the differences were all statistically significant(all P<0.05).Compared with Hp non-infection group,the infection group had higher proportions of patients under 65 years old,male,smoking,and higher IgG antibody levels,differences were all statistically significant(all P<0.05).FI positive rates in the infection group and non-in-fection group were 65.00%and 45.83%,respectively.Difference between the two groups was statistically signifi-cant(x2=3.985,P=0.046).FI positive rates for 6 food types(cod,crab,egg,mushroom,milk,and shrimp)in the two groups of patients were compared,and differences were all statistically significant(all P<0.05).After ad-justing patient factors as age,gender,and smoking,seafood and non-seafood FI were risk factors for Hp infection(all P<0.05).The receiver operator characteristic(ROC)curve of the predictive model presented a high accuracy.Conclusion FI is generally present in CG patients,and FI is related to age.The FI test results can provide guidance for patient's diet and reduce the risk of food adverse reactions.Hp infection can easily induce FI,which can increase the risk of Hp infection.
10.The Factors Related to Treatment Failure in Children with Acute Lymphoblastic leukemia——Analysis of Multi-Center Data from Real World in Fujian Province
Chun-Xia CAI ; Yong-Zhi ZHENG ; Hong WEN ; Kai-Zhi WENG ; Shu-Quan ZHUANG ; Xing-Guo WU ; Shao-Hua LE ; Hao ZHENG
Journal of Experimental Hematology 2024;32(6):1656-1664
Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0%)treatment failure,including 140 cases (52.0%)relapse,and 129 cases (48.0%)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8%,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4%)were died from treatment-related complications,56 cases (20.8%)died from treatment abandonment,and 2 cases (0.7%)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

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