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 ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

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.

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.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

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".

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]

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Purpose To investigate the predictive value of placental microflow combined with serum cystatin C(Cys C)for late-onset preeclampsia(LOP).Materials and Methods This was a prospective study including 188 singleton pregnant women who underwent prenatal ultrasound examination and delivered in the First Affiliated Hospital,School of Medicine,Shihezi University from October 2021 to October 2022.The placental microvascular indexes,including vascularization index,flow index and vascularization-flow index(VFI),were detected by three-dimensional power Doppler ultrasound in the second trimester,and the serum Cys C level was detected.The pregnancy outcome of the pregnant women was divided into LOP group and normal group(NLOP group),and the predictive value of placental microflow combined with serum Cys C for LOP was analyzed.Results Placental vascularization index and VFI of the LOP group were lower than those of the NLOP group(29.77±11.97 vs.44.44±9.86,9.23±3.51 vs.15.05±4.38).However,serum Cys C in the LOP group was higher than that in the NLOP group[(1.13±0.17)mg/L vs.(0.84±0.18)mg/L],and the differences were statistically significant(t=-3.616,-4.790,4.682,all P<0.05).The area under the curve of placental VFI combined with serum Cys C for predicting LOP was 0.899,which had the highest predictive value.Conclusion Placental VFI combined with serum Cys C detection can help to improve the prediction efficiency of LOP,and it is better than each single item.

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]

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.