OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Based on the pathogenesis of erectile dysfunction (ED) from the meridian-zangfu relationship and the "brain-heart-kidney-essence chamber" axis, it proposes that dysfunction of the "brain-heart-kidney-essence chamber" axis is closely related to the occurrence of ED. Among these, brain-heart disharmony is the key pathogenic factor, kidney deficiency and essence depletion constitute an important basis, and essence chamber stasis is a critical mechanism. The treatment approach emphasizes harmonizing the brain and heart, regulating the mind, tonifying the kidney and replenishing qi, unblocking qi and blood to harmonize the essence chamber. The primary acupoints include Baihui (GV20)-Neiguan (PC6)-Shenmen (HT7), Taixi (KI3)-Guanyuan (CV4)-Sanyinjiao (SP6), and Zhongji (CV3)-Dahe (KI12)-Gongsun (SP4), with additional acupoints selected based on syndrome differentiation. This approach aims to restore the clarity of the brain and heart, replenish kidney qi, and unblock the essence chamber, thereby facilitating the restoration of normal functions of the brain, heart, kidney, and essence chamber, and alleviating ED symptoms and improving overall clinical efficacy.
Humans ; Male ; Meridians ; Erectile Dysfunction/physiopathology* ; Kidney/physiopathology* ; Brain/physiopathology* ; Acupuncture Therapy ; Acupuncture Points ; Heart/physiopathology*

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

Objective:To evaluate the effects of arginine on the mechanic properties of Clinpro? pit and fissure sealant.Methods:Experimental pit and fissure sealants were formulated with arginine at 3％,5％,and 10％(Arg3,Arg5 and Arg10)respectively added into ClinproTM,the surface microhardness(SMH),degree of conversion(DC)and microleakage of the samples were investigated.The morphology of different pit and fissure sealants after curing were observed by scanning electron microscope(SEM).The concentration of arginine released at different time points were analyzed by Liquid Chromatography Mass Spectrometry(LC-MS/MS).Results:The SMH and DC was not statistically different among the groups,the microleakage level in Arg 10 group was higher than that in other groups(P＜0.05),and there was no significant difference among other groups.There were some aggregation of arginine particles in modified agents under SEM.The Arg5 showed a significantly higher release rate of arginine at any time point than Arg3 in 24 hours(P＜0.05).Conclusion:Incorporation of 5％arginine does not affect the physical and mechanical properties of ClinproTM pit and fissure sealant and exhibites good arginine release ability.

Objective:To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.Methods:Undergraduates from four classes at Guanghua School of Stomatology, Sun Yat-Sen University were taken as research subjects. Students from two classes ( n=198) were taught using the semi-flipped classroom combined with the knowledge point auction learning method, while students from the other two classes ( n=172) were taught with the regular classroom teaching method as controls. Classroom quizzes were used to compare the two classes' mastery of important and difficult points, and a questionnaire was used to investigate students' feedback on the class outcomes. SPSS 22.0 was used for the independent samples t-test. Results:The mean test score of the experimental class was higher than that of the control class (88.51±11.02 vs. 80.40±8.53). The results of the questionnaire showed that students' interest in the course, comprehension and absorption of knowledge points, degree of satisfaction with the class, and mastery of the contents in sections in the experimental class were significantly higher than those in the control class (7.28±1.51 vs. 9.10±0.73, 6.92±1.44 vs. 8.69±1.62, 6.09±1.87 vs. 7.61±1.46, 6.40±1.04 vs. 7.70±0.86 ).Conclusions:The semi-flipped classroom combined with the knowledge point auction learning method is innovative and achieves good teaching outcomes. It holds promise for wider use in the theoretical teaching of various clinical subjects. To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.

Mineralocorticoid receptor(MR) overactivation plays an important role in the development and progression of diabetic kidney disease(DKD) by mediating pro-inflammatory and pro-fibrotic processes, making it a key therapeutic target for DKD. Finerenone, a third-generation, highly selective, novel nonsteroidal mineralocorticoid receptor antagonist(MRA), mitigates MR overactivation through anti-inflammatory and anti-fibrotic effects and by improving the immune-inflammatory environment. This significantly reduces cardiovascular and renal composite endpoints in patients with type 2 diabetes mellitus(T2DM) and chronic kidney disease(CKD), and improve cardiorenal outcomes. Based on its novel molecular structure, Finerenone exhibits a lower incidence of adverse effects compared to the previous MRAs. This article elucidates the molecular structure and pathophysiological role of MR, and explores the molecular mechanisms through which finerenone provides cardiorenal benefits. It also discusses the advantages and safety of finerenone compared to first- and second-generation MRAs from a molecular structure perspective, providing evidence for its clinical application.

OBJECTIVE To investigate the effects of polyphyllin Ⅵ（PPⅥ） on the proliferation and apoptosis of glioma cells and potential mechanism. METHODS Using human glioma LN229 cells as objects， MTT assay was used to detect the survival rate after treated with different concentrations of PPⅥ [0 （control group）， 1， 2， 4， 8， 16， 32， 64 μmol/L] for different time （24， 48， 72 h）. The clone formation experiments were adopted to detect the number of cell clones and clone formation rate after being treated with different concentrations of PPⅥ [0 （control group）， 2， 4， 8 μmol/L] for 14 days. The flow cytometry and Western blot assay were used to detect the apoptotic rate of cells， the expressions of apoptosis-related protein [B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3]， and the expressions of related proteins of Fas/Fas ligand （FasL） death receptor pathway and protein kinase B （Akt）/glycogen synthesis kinase-3β （GSK-3β） pathway after being treated with different concentrations of PPⅥ [0（control group）， 4， 8 μmol/L] for 24 h. RESULTS Compared with the control group， the survival rate of cells， the number of clones and clone formation rate， the protein expression of Bcl-2， and the phosphorylation levels of Akt and GSK-3β protein were decreased significantly in different concentration groups of PPⅥ （P＜0.05 or P＜0.01）. The apoptotic rate， the protein expressions of Bax， cleaved caspase-3， Fas， FasL and cleaved caspase-8 were increased significantly （P＜0.05 or P＜ 0.01）. CONCLUSIONS PPⅥ can inhibit the proliferation and induce the apoptosis of human glioma LN229 cells， which may be related to the activation of the Fas/FasL death receptor pathway and the inhibition of the Akt/GSK-3β pathway.

Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO₂) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO₂ exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO₂ group, 15 rats in each group. Rats in the SiO₂ group were given 1 mL of 50 mg·L⁻¹ SiO₂ suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO₂ exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO₂ group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO₂ group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO₂ group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO₂ group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO₂ group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO₂ exposure.

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

To investigate the inhibitory effect of sildenafil on Caco-2 cell proliferation and its anti-inflammatory effect on menadione-induced NCM460 cell inflammation model, MTT assay was used to determine cell proliferation. Intracellular reactive oxygen species(ROS)and nitric oxide(NO)levels were detected by fluorescent probe. Western blot was used to detect the expression of eNOS/ERK/JNK pathway related proteins in Caco-2 cells and correlated inflammatory cytokines in NCM460 cells. The effect of sildenafil on the growth of two probiotics was determined by spectrophotometry. Results showed that sildenafil signi-ficantly inhibited the proliferation of Caco-2 cells and enhanced the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins in Caco-2 cells; while after adding NG-nitro-L-arginine methyl ester(L-NAME), the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins were significantly lower than those of the sildenafil group. Compared with the menadione group, sildenafil significantly reduced ROS levels in NCM460 cells and inhibited the expression levels of IL-6, IL-1β, p62, and TNF-α. Moreover, high concentrations of sildenafil had no obvious toxic effects on Lactobacillus casei and Lactobacillus rhamnosus. Thus, the results indicated that sildenafil could effectively inhibit the intestinal inflammatory response without affecting the balance of the intestinal flora, and prevent colorectal cancer by reducing the oxidative stress responses in the intestinal cells.