Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

ObjectiveTo investigate the mechanisms by which Jianpi Yangzheng Xiaozheng prescription （JPYZXZ） treats poorly cohesive gastric carcinoma （PC-GC） through regulation of ubiquitin-specific peptidase 51 （USP51）. MethodsIn vitro experiments： Cell viability and proliferation of PC-GC cell lines （MKN-45 and HGC-27） treated with different concentrations of JPYZXZ （2， 4， 6 g·L^-1） were assessed using Cell Counting Kit-8 （CCK-8） and colony formation assays. Cell migration was evaluated by wound healing （scratch） and Transwell assays. The mRNA and protein expression levels of USP51， zinc finger E-box-binding homeobox 1 （ZEB1）， and epithelial-mesenchymal transition （EMT）-related markers （e.g.， E-cadherin） were detected by quantitative real-time PCR （Real-time PCR） and Western blot， respectively. Subsequently， stable MKN-45 and HGC-27 cell lines with USP51 knockdown （sh-USP51） and overexpression （oe-USP51） were constructed. Their migration ability and EMT-related protein expression were further evaluated by scratch assay， Transwell assay， and Western blot. In vivo experiments： A subcutaneous xenograft model of MKN-45 human gastric cancer was established in BALB/c nude mice. Thirty mice were randomly divided into six groups （NC， NC + JPYZXZ， sh-USP51， sh-USP51 + JPYZXZ， oe-USP51， and oe-USP51 + JPYZXZ）， with five mice in each group. After successful modeling， mice in the treatment groups were administered JPYZXZ （30 g·kg^-1） by gavage for 28 days. Body weight and tumor volume were monitored during the experiment. The expression levels of USP51 and EMT-related proteins in tumor tissues were detected by Western blot and immunohistochemistry （IHC）. ResultsCompared with the blank group， the colony formation rate， wound healing rate， and number of migrated cells in MKN-45 and HGC-27 cells were significantly reduced in all JPYZXZ groups and the 5-fluorouracil （5-FU） group （P<0.05）. The mRNA and protein expression levels of USP51 were decreased （P<0.05）. The expression of ZEB1 and mesenchymal phenotype proteins （e.g.， N-cadherin and vimentin） was reduced （P<0.05）， whereas the expression of the epithelial marker E-cadherin was increased （P<0.05）. Compared with the control group， USP51 expression was decreased in the sh-USP51 group and increased in the oe-USP51 group （P<0.05）. Compared with the NC group， USP51 knockdown significantly reduced the migration and proliferation of gastric cancer cells （P<0.01）， decreased the expression of ZEB1 and EMT-related proteins， and increased E-cadherin expression （P<0.05）. In vivo results showed that JPYZXZ significantly inhibited the growth of xenograft tumors in nude mice （P<0.05） and markedly reversed the abnormal expression of EMT-related proteins in tumor tissues （P<0.05）. ConclusionThe therapeutic mechanisms of JPYZXZ in PC-GC may be associated with inhibition of the EMT process via regulation of the USP51-ZEB1 signaling pathway.

Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

To effectively carry out community health education and prevention and control of chronic obstructive pulmonary disease(COPD),we conducted a questionnaire survey on the awareness of COPD knowledge among residents aged 40 and above in Jiading District of Shanghai by using two-stage sampling method.We included 1 783 permanent residents in 4 districts and collected 1 666 valid questionnaires.The awareness rates of COPD name,pulmonary function test and related knowledge were 15.9%,11.9%and 17.2%,respectively.For the main symptoms of COPD,the awareness rate of sputum was the lowest(65.2%),of shortness of breath and dyspnea was the highest(78.4%).For the risk factors,the awareness rate of severe respiratory tract infection in childhood was the lowest(67.3%),of smoking was the highest(86.8%).Multiple response analysis showed that mobile phones and computers accounted for the highest proportion of acquiring knowledge of COPD(66.7%).Multivariate logistic regression analysis showed that low educational level,low monthly income,engaged in production and manufacturing,never or less exercise,no use of indoor air improvement measures,no wearing of masks in public places and no vaccination of influenza vaccine per year were associated with lower awareness rate of COPD.The community should improve the way and ability of health science popularization,and carry out health education for key groups.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Allergic rhinitis(AR)affects 10%-40%of the population in the world.Because CLOCK genes regulate the circadian rhythms of AR,the symptoms in parts of the patients are aggravated in the morning and evening and relieved at moon.Although lots of studies showed that traditional Chinese medicine is effective for AR,further explores are still needed to analyze the circadian rhythm of AR based on Chinese Chronological Medicine for controlling the circadian outbreak point of symptoms of AR in daily cycle.We supposed that Weiyang might play an important role for controlling the circadian rhythm of AR with closed similarities with the tidal variation of the expressions of CLOCK genes.Thus based on Weiyang theory,we tried to clarify the mechanism of circadian rhythm of AR and explore the relationship between Weiyang and the CLOCK genes so as to further expand the treatment methods of adjusting the circadian cycle of AR with TCM and improve the corresponding therapeutic efficacy.

Objective To explore the potential diagnostic value of protocadherin 17(PCDH17)and transducer of ERBB2,(TOB1)in gastric cancer,as well as their effects on autophagy and apoptosis in gastric cancer cells,providing novel target insights for gastric canc-er diagnosis.Methods Tissue samples were collected from 120gastric cancer patients,including cancerous and adjacent normal tissues.The expression levels of PCDH17 and TOB1 were assessed via immunohistochemistry.Overexpression of PCDH17 and TOB1 in the AGS gastric cancer cell line was analyzed using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot.The effects of these overexpressions on cell proliferation,autophagy,and apoptosis were evaluated using CCK-8 assays,Western blot a-nalysis,and detection of autophagy and apoptosis-related proteins.Additionally,receiver operating characteristic(ROC)curve analysis was employed to evaluate the sensitivity and specificity of combined PCDH17 and TOB1 in diagnosing gastric cancer.Results The ex-pression levels of PCDH17 and TOB1 were significantly lower in gastric cancer tissues compared to adjacent normal tissues(P＜0.001),and their low expression was significantly correlated with clinical stage and lymph node metastasis(P＜0.001).In vitro experiments dem-onstrated that overexpression of PCDH17 and TOB1 could significantly inhibited the proliferation of gastric cancer cells(P＜0.001),and promoted autophagy and apoptosis through upregulation of autophagy markers LC3 and Beclin-1,along with pro-apoptotic protein BAX,while downregulating anti-apoptotic protein BCL-2.The combined overexpression of PCDH17 and TOB1 resulted in a more pronounced inhibitory effect on cell proliferation and enhanced levels of autophagy and apoptosis compared to individual overexpression(P＜0.001).The area under the curve for the combined diagnostic efficacy of PCDH17 and TOB1 was 0.887,with a sensitivity of 88.39％,and a spe-cificity of 87.24％,the diagnostic effect was superior to that of individual assays.Conclusion The low expression of PCDH17 and TOB1 is closely associated with the occurrence and progression of gastric cancer.Furthermore,the combined detection of these markers exhibits high sensitivity and specificity for gastric cancer diagnosis.The combined overexpression of PCDH17 and TOB1 had a significant synergistic effects on inhibiting proliferation while promoting autophagy and apoptosis of gastric cancer cells.PCDH17 and TOB1 can be used as po-tential diagnostic biomarkers and therapeutic targets for gastric cancer,providing new avenues for the diagnosis and targeted treatment of gastric cancer.

Objective To investigate the changes and clinical significance of serum C1q tumor necrosis factor-related protein 12(CTRP12),adiponectin(APN),and resistin(RETN)in patients with type 2 diabetes mellitus(T2DM)combined with different grades of hypertension.Methods A total of 156 patients with T2DM were selected and divided into the following groups:isolated T2DM group(T2DM,n=38),T2DM combined with hypertension grade 1(DH1,n=39)group,T2DM combined with hypertension grade 2(DH2,n=39)group,and T2DM combined with hypertension grade 3(DH3,n=40)group.Additionally,healthy individuals who underwent physical examinations at our hospital were selected as the normal control(NC,n=40)group.Serum levels of CTRP12,APN,and RETN were measured using ELISA.Pearson correlation analysis was used to evaluate the relationship between serum CTRP12,APN,RETN,and other indicators.Multiple linear regression analysis was performed to determine the influencing factors for the three indicators.Results In NC,T2DM,DH1,DH2 and DH3 groups,DBP increased in turn(P<0.05),while CTRP12 decreased in turn(P<0.05).SBP in T2DM,DH1,DH2 and DH3 groups increased in turn(P<0.05).In DH1,DH2 and DH3 groups,RENT increased in turn(P<0.05),while APN decreased in turn(P<0.05).Pearson correlation analysis showed that serum CTRP12 was negatively correlated with WHR,BMI,HOMA-IR,FPG,HbA1c,FIns,TC,LDL-C,SBP,and DBP(P<0.05).Serum APN was negatively correlated with BMI,FPG,HbA1c,FIns,TC,SBP,and DBP(P<0.05),and positively correlated with HDL-C(P<0.05).Serum RETN was positively correlated with WHR,HOMA-IR,FPG,HbA1c,FIns,SBP,and DBP(P<0.05).Multiple linear regression analysis indicated that SBP was an influencing factor for CTRP12 and RETN,while SBP and HbA1c were influencing factors for RETN.Conclusions In patients with T2DM combined with hypertension,serum CTRP12 and APN levels decrease,while RETN levels increase,with significant changes observed as HP grades increase,suggesting that these three factors may collectively influence the occurrence and development of T2DM combined with HP.