1.Rubioncolin C targets cathepsin D to induce autophagosome accumulation and suppress gastric cancer.
Liang ZHANG ; Jun-Jie CHEN ; Man-Xiang GU ; Yi-Fan ZHONG ; Yuan SI ; Ying LIU
China Journal of Chinese Materia Medica 2025;50(5):1267-1275
This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans
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Stomach Neoplasms/enzymology*
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Cathepsin D/chemistry*
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Cell Line, Tumor
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Molecular Docking Simulation
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Cell Proliferation/drug effects*
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Autophagosomes/metabolism*
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Autophagy/drug effects*
2.Clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern
Jia-man YANG ; Tong LIU ; De-hui FAN ; Mei-yi SU ; Ying LIN ; Man-guang LIANG ; Zhi-wen OU ; Shun-cong ZHANG
Chinese Traditional Patent Medicine 2025;47(11):3630-3634
AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P<0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P<0.05),and shortened PT,APTT(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.
3.Pilot study and suggestions on brain death determination training for physicians in secondary comprehensive hospitals in China
Linlin FAN ; Pengxiang LI ; Man XIA ; Lin FU ; Hao LIU ; Xiaowei XU ; Yingying SU
Chinese Journal of Organ Transplantation 2025;46(10):717-722
Objective:To evaluate the feasibility of training physicians from secondary comprehensive hospitals in the clinical assessment of brain death and to provide recommendations for nationwide implementation.Methods:This prospective cohort study enrolled physicians who completed standardized training in clinical brain death determination at five pilot hospitals between June and December 2023. Participants were from internal medicine, neurology, critical care, emergency, or anesthesiology departments of secondary comprehensive hospitals and had ≥5 years of clinical experience. Organ donation coordinators and surgeons involved in organ donation or transplantation were excluded. The training program comprised four modules: didactic lectures, bedside demonstrations, simulation-based practice, and written theoretical assessment with review. The theoretical assessment was considered qualified if the score was 60 or above. Participants were categorized into ≥80 and <80 groups based on assessment scores. Between-group comparisons were conducted using rank-sum or chi-square tests.Results:A total of 191 physicians from 74 secondary comprehensive hospitals were enrolled. Most held a bachelor's degree [89.5%(171/191)] and had intermediate [47.1%(90/191)] or associate senior [36.1%(69/191)] professional titles; [59.7%(114/191)] were from non-neurology specialties. The overall pass rate was 99.5% (190/191), with a mean score of 82.4±7.1. Compared with those scoring<80 (56 participants), physicians scoring ≥80 (135 participants) differed significantly by professional title, province, and department ( P=0.014, 0.019 and 0.039). The proportion scoring<80 was higher among junior/intermediate versus senior titles [38.0%(41/108) vs 18.1%(15/83), P=0.003), and among non-neurology/critical care departments (emergency, internal medicine, anesthesiology) versus neurology/critical care [39.7%(31/78) vs 22.1%(25/113), P=0.009]. Only 2.09%(4/191) achieved a perfect score. Across all test items, the overall error rate was 14.99%(700/4 670). The five knowledge points with the highest error rates were mistriggering of mechanical ventilation [96.97%(32/33)], corneal reflex [42.25%(30/71)], spinal reflexes [24.25%(65/268)], documentation of the determination [21.21%(7/33)], and the apnea test procedure [20.73%(57/275)]. Conclusions:The pilot hospitals can effectively deliver clinical training for brain death determination, supporting nationwide promotion. However, physicians' theoretical grounding in neurology at secondary comprehensive hospitals appears relatively weak. Training curricula should be optimized to further improve training quality.
4.CiteSpace-based bibliometric analysis of China's research literature in the field of luminal instrumentation
Xiao-shuang ZHANG ; Fan LIU ; Man-li LIU
Chinese Medical Equipment Journal 2025;46(3):69-74
The literature related to luminal instruments published in CNKI,Wanfang and VIP databases from the establish-ment of the databases to September 27th,2024,was analyzed statistically and visually by applying CiteSpace in terms of the number of publications,authors,institutions and keywords.It's pointed out that the number of publications on luminal instru-ments in China was on a rising trend in general,and that the operating room,cleaning,disinfection,sterilization and manage-ment were the current hot spots in the research.A new thought was provided on the management and scientific research of luminal instruments in China.[Chinese Medical Equipment Journal,2025,46(3):69-74]
5.Evaluations of physical training by pilots or cadets
Siming DU ; Hang XING ; Fenghua ZHAO ; Jia WANG ; Man ZHAO ; Fan YANG ; Xiangyang ZHANG
Chinese Journal of Aerospace Medicine 2025;36(2):126-131
Objective:To find out about the sentiment about the current physical training among Air Force pilots (cadets), propose methods for optimizing their programs of physical training, and to enhance the effectiveness of training in order to improve flight adaptability.Methods:A total of 1 135 pilots (cadets) were randomly selected as the subjects and divided into 3 groups according to types of aircraft and types of personnel: group A (pilots of fighters, bombers and advanced trainers), group B (pilots of fighter bombers, transporters, helicopters, special aircraft and junior trainers), and group C (flying cadets). A questionnaire survey was conducted to collect data on current physical training among pilots and flying cadets.Results:A total of 1 135 questionnaires were distributed, with 1 086 valid responses collected, yielding an effective response rate of 95.68%. Of the 1 086 participating pilots (cadets), 209 were in Group A, 499 in Group B, and 378 in Group C.There was statistically significant difference in the frequency and duration of weekly physical training between the 3 groups ( χ2=82.23, 61.56, both P<0.001). The proportion of participants engaging in >3 h weekly physical training sessions was significantly higher in group C (71.7%) than in group A (38.8%) and group B (44.9%). Significant differences were observed in weekly training durations between group C and group A (all P<0.05), as well as between group C and group B in the training durations of <3 h and 5-7 h (all P<0.05). The percentage of subjects who trained for 5-7 h per week was the highest in group C (41.5%). In groups A and B, pilots mostly trained for 3-<5 h per week (51.7% and 39.9%, respectively). The survey on the willingness to adjust training programs revealed statistically significant differences between the 3 groups in their willingness to engage in muscle strength training, coordination training, specific ability training, and adjustment of intensities of core training ( H=46.23, 16.12, 22.03, 60.68, all P<0.001). No significant difference was observed in their willingness to have aerobic training programs adjusted ( P>0.05). Group C was significantly different from groups A and B in their preference for adjustment in training programs related to muscle strength, coordination, specific abilities, and in core training programs (all P<0.01). Group C was mostly in favor of "increasing" muscle strength, coordination, and core training while opting for "no change" in aerobic training and specific ability training. Groups A and B preferred "no change". Regarding their willingness to have training intensities revised, statistically significant differences were observed between the 3 groups ( H=15.58, 19.08, 8.17, 58.01, P<0.001, <0.001, =0.017, <0.001), but no significant difference was found in their preference for adjustment of aerobic training intensities ( P>0.05). Group C showed much more preference for intensity adjustment related to muscle strength, coordination, specific abilities, and core training programs than groups A and B (all P<0.05 or 0.01). All the 3 groups predominantly favored "no change" in training intensities. Conclusions:Pilots of different aircraft types generally meet the requirements of the current physical training programs. However, the frequency of physical training for pilots (cadets) requires more rigorous supervision. Flying cadets can adaptively engage in targeted training programs. Pilots of fighters, fighter bombers and advanced trainers should care about the intensity of aerobic training while giving more weight to load resistance physical training. Pilots of other types of aircraft should devote more effort to core training programs.
6.A Sequential Survey of Vitamin D Levels in Elderly Pregnant Women Through-out Pregnancy and Evaluation of the Effectiveness of Supplemental Programs
Lin FAN ; Man ZHANG ; Xinghui LIU
Journal of Practical Obstetrics and Gynecology 2025;41(2):164-168
Objective:To investigate the serum vitamin D levels of elderly pregnant women in Chengdu and e-valuate the effectiveness of the existing conventional supplementation programs.Methods:Pregnant women who met the inclusion and exclusion criteria were selected from the samples of elderly pregnant women collected from the Second Hospital of West China,Sichuan University from September 2017 to June 2020 as the research sub-jects.Relevant survey questionnaires were filled out.Calcium tablets were supplemented with multivitamins.Their serum vitamin D levels were detected by liquid chromatography tandem mass spectrometry in early pregnancy(<14 weeks of gestation),mid pregnancy(14-28 weeks of gestation),and late pregnancy(>28 weeks of gestation)for sequential investigation and effect evaluation.Results:The average serum vitamin D level of 359 elderly preg-nant women in the early stage of pregnancy was 23.47±10.12 ug/L,with only 22.01%of the pregnant women having sufficient vitamin D.The vitamin D levels of vitamin D-deficient elderly pregnant women increased as the gestational weeks increased after the routine supplementation of vitamin D.Vitamin D levels increased significantly in early pregnancy,reaching 33.47±10.12 ug/L and remain normal thereafter(F=187.255,P<0.01).Conclu-sion:Elderly pregnant women included in this study generally have vitamin D deficiency or insufficiency,and it is necessary to screen for vitamin D.Those with severe vitamin D deficiency should be supplemented with vitamin D preparations in the early stage of pregnancy.
7.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.
8.Analysis of Clinical Features and Multi-Slice Spiral CT Image Features of Acute Appendicitis in Soldiers Who Have Been Living in Plateau for A Long Time
Li-na YUE ; Juan-qin NIU ; Gang CHEN ; Man-ping CHENG ; Ning-xia MU ; Jia FAN ; Kang LIU ; Yu-lan NIU ; Ya-ping HE ; Zhong-hua LI
Progress in Modern Biomedicine 2025;25(11):1869-1878
Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14%),lower ileum 10 cases(17.86%),posterior cecum 16 cases(28.57%),lower cecum 9 cases(16.07%),lateral cecum 2 cases(3.58%),posterior ileum 6 cases(10.71%),high(subhepatic)9 cases(16.07%),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter>6 mm in 49 cases(87.50%),appendicular wall thickening>2 mm in 42 cases(75.00%),ppendiceal dilation lumen and effusion in 29 cases(51.79%),appendix indistinctness in 3 cases(5.36%),lppendix fecalith:27 cases(48.21%),gas in the appendix in 16 cases(28.57%).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14%),appendiceal cellulitis with peripheral abscess in 9 cases(16.07%),peritonitis and ascites in 13 cases(23.21%),ileocecal intestinal wall thickening in 22 cases(39.29%),mesenteric lymph node enlargement in 16 cases(28.57%),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93%).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.
9.Diagnostic value of novel inflammatory markers related to routine blood tests in elderly patients with chronic cardiovascular disease complicated with frailty
Xing-Man FAN ; Yan-Yan LI ; Qiong-Yi HE ; Wei-Na LUO ; Xiao-Hua LAN ; Kai-Jie ZHANG ; Meng WANG ; Xiang-Ren KONG ; Hai-Tao ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(3):301-308
Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.
10.Based on data mining to explore the characteristics of acupoint selection and the law of acupoint compatibility in the treatment of Guillain-Barré syndrome
Jingyi NING ; Shuochen FAN ; Diwei TANG ; Weifeng LI ; Man QIN ; Zili LIU
China Modern Doctor 2025;63(30):11-15
Objective To explore the characteristics of acupoint selection and the law of acupoint compatibility in the treatment of Guillain-Barré syndrome(GBS)based on data mining.Methods Literature on acupuncture treatment of GBS was searched and screened from China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,SioMed,PubMed,Embase,Web of Science,and Cochrane Library from the establishment of the database to December 1,2024 and to build database.The author information and acupuncture prescriptions were modified and imported according to the data entry requirements of the Traditional Chinese medicine inheritance computing platform V3.5,the relevant data were analyzed and integrated through the"Acupoint Analysis"module of the platform.Results A total of 140 related papers,145 valid prescriptions,involving 237 acupoints.The acupoints with higher frequency were Zusanli,Hegu,Quchi,Yanglingquan and etc.The analysis yielded 42 core acupoints,22 sets of strong association rules for core acupoints,and 5 new core acupuncture prescriptions.Conclusion Acupuncture treatment for GBS follows the principle of"treating impotence by taking Yangming alone",takes"benefiting Qi and draining heat,supporting the correctness and opening up the collaterals"as the main method,and attaches importance to"regulating the spirit and connecting the internal organs".

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