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*

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

Ureteropelvic junction obstruction, as a common urological disorder, not only affects the renal function of patients, but also seriously reduces their quality of life. Pyeloplasty, as the first-line therapy for ureteral stricture at present, is a key approach to eliminating hydronephrosis and improving renal function. The quality of life of postoperative patients, as an important criterion for measuring the therapeutic effect, has also attracted increasing attention. Therefore, this article reviews the evaluation tools, research status and influencing factors of the postoperative quality of life of ureteropelvic junction obstruction patients, aiming to provide a reference for the formulation of relevant nursing intervention measures in clinical practice.

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.

Extracting extracts of secondary metabolites from the karst cave fungus Metarhizium anisopliae NHC-M3-2 from the Yilingyan Scenic Area in Guangxi. Ten compounds were isolated and purified from fungal secondary metabolites using thin-layer chromatography and high-performance liquid chromatography. 7-Hydroxy-3-hydroxypropyl-5,6-dimethylisochrome-1-one (1) and 7-hydroxy-3,5,6-trimethyl-isochromen-1-one (2) were new isocoumarin compounds, N-acetyl phenylalanine (3), chaetosumin J (4), 2-one-13-hydroxy-3,5,8,7(11)-eudesmatetraen-12,8-olide (5), 1H-indole-3-carboxaldehyde (6), irpexolaceus B (7), irlactin L (8), cytochalasin K (9), and helvolic acid (10), a total of 8 known compounds. The structure of the compound was determined using methods such as NMR and mass spectrometry. The tumor cytotoxicity of the compound was evaluated using the CCK-8 method. The results showed that the IC₅₀ of compound 2 on HepG2 cells was 29.83 µmol·L^-1, and compound 9 on HCT116 cells was 27.44 µmol·L^-1.

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Objective Data mining method was used to analyze the Chinese herbal prescriptions for oral use in treating venomous snake bites collected from the major domestic literature databases and the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions),so as to explore their potential prescription and medication rules,and to provide references for the treatment of venomous snake bites in the primary hospitals.Methods The Chinese herbal prescriptions for oral use in treating venomous snake bites were retrieved from the CNKI,VIP and Wanfang databases,and the ancient formulas for treating venomous snake bites were screened in the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions).Excel software was used to extract the relevant information of the formulas,and R language was used to analyze the medication frequency,properties,flavors and meridian tropism of the herbs as well as their association rules and clustering analysis.Results A total of 187 prescriptions for oral use in treating venomous snake bite were obtained,involving 284 Chinese herbal medicines.The top 15 Chinese herbal medicines in decreasing sequence of medication frequency were Lobeliae Chinensis Herba,Rhei Radix et Rhizoma,Angelicae Dahuricae Radix,Glycyrrhizae Radix et Rhizoma,Paridis Rhizoma,Rehmanniae Radix,Coptidis Rhizoma,Scutellariae Radix,Lonicerae Japonicae Flos,Paeoniae Radix Rubra,Moutan Cortex,Hedyotis Diffusae Herba,Imperatae Rhizoma,Plantaginis Herba,and Scutellariae Barbatae Herba.The flavor of herbs in the prescription for the treatment of venomous snakebite was usually bitter,pungent and sweet,and their property was relatively cold.Most of the herbs had the meridian tropism of the liver meridian and lung meridian.The core prescription mainly composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,and Paridis Rhizoma was obtained after association rule analysis and cluster analysis.Conclusion The herbs for the treatment of venomous snake bites often have the actions of clearing heat and removing toxins,and the prescription is usually composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,Paridis Rhizoma together with the compatibility of medicines for clearing heat and cooling blood,extinguishing wind and arresting convulsion,clearing heat and promoting urination.

Objective:To compare the impact of orthodontic treatment on pulp volume in adolescents and adults.Methods:Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results:Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P ( t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC ( t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P ( t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm 3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm 3, respectively ( t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment ( t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively ( t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 ( t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P ( r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P ( r=0.11, P>0.05). Conclusions:The effect of orthodontic treatment on pulp volume in adolescents and adults were different.