1.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
2.Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer
Meirong ZHOU ; Jiayue WANG ; Yulin PENG ; Xiangge TIAN ; Wen ZHANG ; Junlin CHEN ; Yue WANG ; Yu WANG ; Youjian YANG ; Yongwei ZHANG ; Xiaokui HUO ; Yuzhuo WU ; Zhenlong YU ; Tian XIE ; Xiaochi MA
Journal of Pharmaceutical Analysis 2025;15(3):585-598
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
3.Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer.
Meirong ZHOU ; Jiayue WANG ; Yulin PENG ; Xiangge TIAN ; Wen ZHANG ; Junlin CHEN ; Yue WANG ; Yu WANG ; Youjian YANG ; Yongwei ZHANG ; Xiaokui HUO ; Yuzhuo WU ; Zhenlong YU ; Tian XIE ; Xiaochi MA
Journal of Pharmaceutical Analysis 2025;15(3):101118-101118
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
4.Effects of diverse influencing factors in clinical dental photography on depth-of-field sharpness and distortion: a comparative study
Wei ZHAO ; Xuhan WANG ; Wei LI ; Ruonan CHEN ; Xiangge ZHUO ; Jiang CHEN
Chinese Journal of Stomatology 2025;60(4):381-387
Objective:To evaluate the effects of different combinations of digital single-lens reflex cameras and macro lenses, aperture settings, and focusing points on depth-of-field sharpness and image distortion in dental clinical photography, and to provide evidence-based guidance for standardizing dental clinical photography.Methods:Full-frame and advanced photo system type-C (APS-C) digital single-lens reflex cameras were paired with 105 mm and 60 mm macro lenses. Photography was performed under eight preset aperture values (F16, F18, F20, F22, F25, F29, F32, and F36) on a standard oral model, focusing separately on three points simulating the central incisor, canine, and first molar. Five attending physicians, who had completed standardized training in dental esthetic clinical photography and calibration training (with over 5 years of dental clinical photography experience), evaluated the depth-of-field sharpness of the photographs using a double-blind method. Image distortion was assessed by measuring the width-to-length ratio of the central incisor.Results:Photographs taken with the APS-C digital single-lens reflex camera combined with the 105 mm macro lens showed significantly higher depth-of-field sharpness scores (2.756±0.357) compared to other camera-lens combinations ( P<0.05). Photographs taken at aperture settings of F25, F29, F32, and F36 demonstrated significantly higher depth-of-field sharpness scores than those taken at F16, F18, F20, and F22 ( P<0.05). Images focused on the simulated canine achieved the highest depth-of-field sharpness scores, followed by the central incisor, with the first molar showing the lowest scores ( P<0.05). Main effect and interaction effect tests revealed that camera-lens combinations significantly affected image distortion ( F=2.79, P=0.042), while focusing points and aperture settings showed no significant effect on image distortion ( F=0.40, P=0.671; F=1.27, P=0.270). Conclusion:Based on experimental data analysis, using an APS-C digital single-lens reflex camera with a 105 mm macro lens, setting the aperture value between F25 and F36, and focusing on the canine can ensure sufficient depth-of-field sharpness while avoiding image distortion, thereby achieving optimal results in dental clinical photography.
5.Effects of diverse influencing factors in clinical dental photography on depth-of-field sharpness and distortion: a comparative study
Wei ZHAO ; Xuhan WANG ; Wei LI ; Ruonan CHEN ; Xiangge ZHUO ; Jiang CHEN
Chinese Journal of Stomatology 2025;60(4):381-387
Objective:To evaluate the effects of different combinations of digital single-lens reflex cameras and macro lenses, aperture settings, and focusing points on depth-of-field sharpness and image distortion in dental clinical photography, and to provide evidence-based guidance for standardizing dental clinical photography.Methods:Full-frame and advanced photo system type-C (APS-C) digital single-lens reflex cameras were paired with 105 mm and 60 mm macro lenses. Photography was performed under eight preset aperture values (F16, F18, F20, F22, F25, F29, F32, and F36) on a standard oral model, focusing separately on three points simulating the central incisor, canine, and first molar. Five attending physicians, who had completed standardized training in dental esthetic clinical photography and calibration training (with over 5 years of dental clinical photography experience), evaluated the depth-of-field sharpness of the photographs using a double-blind method. Image distortion was assessed by measuring the width-to-length ratio of the central incisor.Results:Photographs taken with the APS-C digital single-lens reflex camera combined with the 105 mm macro lens showed significantly higher depth-of-field sharpness scores (2.756±0.357) compared to other camera-lens combinations ( P<0.05). Photographs taken at aperture settings of F25, F29, F32, and F36 demonstrated significantly higher depth-of-field sharpness scores than those taken at F16, F18, F20, and F22 ( P<0.05). Images focused on the simulated canine achieved the highest depth-of-field sharpness scores, followed by the central incisor, with the first molar showing the lowest scores ( P<0.05). Main effect and interaction effect tests revealed that camera-lens combinations significantly affected image distortion ( F=2.79, P=0.042), while focusing points and aperture settings showed no significant effect on image distortion ( F=0.40, P=0.671; F=1.27, P=0.270). Conclusion:Based on experimental data analysis, using an APS-C digital single-lens reflex camera with a 105 mm macro lens, setting the aperture value between F25 and F36, and focusing on the canine can ensure sufficient depth-of-field sharpness while avoiding image distortion, thereby achieving optimal results in dental clinical photography.
6.Expression of PD-L1 and CD8 in HER2 positive breast cancer and its clinicopathological significance
Tiantian ZHAO ; Chao DUAN ; Xuwen ZHAO ; Qirong MAN ; Xiangge WANG
China Modern Doctor 2024;62(29):45-49
Objective To determine the role of programmed cell death-ligand l(PD-L1)and cluster of differentiation 8(CD8)in judging the prognosis of human epidermal growth factor receptor 2(HER2)positive breast cancer patients,through evaluating the expression of PD-L1 and CD8 in the tumor microenvironment,and their correlation with clinicopathological data.Methods A total of 65 HER2 positive breast cancer patients were collected admitted to Tengzhou Central People's Hospital in Shandong Province from October 2016 to October 2018,all of whom were women.Theparaffin slices of cancer tissue were labeled with PD-L1 and CD8 using immunohistochemical methods.Collect clinicopathological data of patients,including 7 prognostic parameters,such as age,histological grade,P53,KI-67,estrogen receptor,progesterone receptor and tumor node metastasis classification(TNM)staging.Statistical analysis was conducted to determine whether the expression of PD-L1 and CD8 were correlated with the above clinicopathological data.Results PD-L1 positive rate was 21.5%,the positive expression of PD-L1 was correlated with histological grading and TNM staging,and the difference in results was statistically significant(x2=6.250,P=0.044;x2=13.730,P=0.001);CD8 positive rate was 32.3%,the expression of CD8 cells was correlated with histological grading and TNM staging,and the difference in results was statistically significant(x2=8.023,P=0.018;x2=6.117,P=0.047).Conclusion PD-L1 and CD8 expression are correlated with breast cancer histological grade and TNM stage.PD-L1 and CD8 expression may be important prognostic markers for HER2 positive breast cancer patients.
7.Regulatory effect of lactate on peripheral blood CD4+T cell subsets in patients with rheumatoid arthritis
Huina HUANG ; Jing ZHAO ; Xiangge ZHAO ; Ziran BAI ; Xia LI ; Guan WANG
Journal of Peking University(Health Sciences) 2024;56(3):519-525
Objective:To investigate the serum lactate level in patients with rheumatoid arthritis(RA)and its relationship with disease activity,and to analyze the effect of sodium lactate on the activation of CD4+T cells,the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients.Methods:The peripheral blood of healthy controls(HC)and RA patients was collected,and the content of lactate in the supernatant was detected by lactate detection kit,the correlation between the content of lactate and the disease score of the RA patients was analyzed;the activation level of CD4+T cells,the proportion of CD4+T cell subsets and the cytokines secreted by CD4+T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate.Results:The serum lactate level in the RA patients(n=66)was significantly higher than that in the HC(n=60,P<0.001),and there was a certain correlation with disease activity score in 28 joints(DAS28)-C-reactive protein(CRP)(r=0.273,P=0.029),The levels of rheumatoid factor[RF,197.50(26.03,783.00)IU/mL vs.29.30(0.00,102.60)IU/mL,P<0.01],CRP[37.40(11.30,72.60)mg/L vs.5.83(2.36,12.45)mg/L,P<0.001],were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L,however,there was no significant difference in the expres-sion of erythrocyte sedimentation rate[ESR,42.00(19.00,77.00)mm/h vs.25.00(12.50,45.50)mm/h,P>0.05]and anti-cyclic citrullinated peptied(CCP)antibody[82.35(17.70,137.00)RU/mL vs.68.60(25.95,119.70)RU/mL,P>0.05].Compared with the control group,the expression of PD-1(46.15%±8.54%vs.41.67%±9.98%,P<0.001),inducible costimulatory molecule(ICOS,5.77%±8.60%vs.18.65%±7.94%,P<0.01)and CD25(25.89%±5.80%vs.22.25%±4.59%,P<0.01)on the surface of CD4+T cells in the RA patients treated with sodium lactate was significantly increased.Compared with the control group,the proportion of Th17(4.62%±1.74%vs.2.93%±1.92%,P<0.05)and Tph(28.02%±6.28%vs.20.32%±5.82%,P<0.01)cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased.Compared with the con-trol group,the expression of IL-21(5.73%±1.59%vs.4.75%±1.71%,P<0.05)inCD4+Tcells was up-regulated in the RA patients treated with sodium lactate.Conclusion:The level of serum lactate in RA patients is increased,which promotes the activation of CD4+T cells and the secretion of IL-21,and up-regulates the proportion of Th 17 and Tph cells in the RA patients.
8.Efficacy of high-intensity focused ultrasound cycloplasty in glaucoma and its influencing factor
Yurong TANG ; Fuhua LI ; Xiangge HE ; Xiaohong ZHOU ; Yi ZHOU ; Wei WANG
International Eye Science 2024;24(4):618-622
AIM: To evaluate the efficacy of high-intensity focused ultrasound cyclo plasty(UCP)in the treatment of glaucoma and to investigate related influencing factors.METHODS: The study involved a total of 110 patients(134 eyes)who received UCP treatment between January 2019 and January 2022 at three medical centers: Tianjin Eye Aier Eye Hospital, Chongqing Aier Eye Hospital, and Chongqing Nanping Aier Eye Hospital. Patients were classified into three categories: primary angle-closure glaucoma, primary open-angle glaucoma, and secondary glaucoma. Best corrected visual acuity, intraocular pressure, and the usage of anti-glaucoma medications, etc., were recorded at 6 and 12 mo postoperatively.RESULTS: After 6 months of the UCP procedure, statistically significant differences in intraocular pressure were observed across all groups(all P<0.05). At 12 mo postoperatively, intraocular pressure of the primary angle-closure and primary open-angle glaucoma groups showed differences(all P<0.05). Notably, there were no significant changes in visual acuity at either the 6 or 12 mo compared to preoperative values across all patient groups(all P>0.05). Furthermore, the study identified a statistically significant correlation between the changes in intraocular pressure at 6 mo and factors such as age, history of previous glaucoma surgery, baseline white-to-white(corneal diameter), and the extent of UCP treatment(all P<0.05).CONCLUSION: The UCP procedure has been demonstrated to effectively lower intraocular pressure in patients with glaucoma. The efficacy appears to be influenced by variables including patient age, previous glaucoma surgery history, baseline white-to-white(corneal diameter), and the scope of UCP treatment. Importantly, UCP treatment did not adversely affect visual acuity, underscoring its favorable safety profile.
9. Expression and clinical significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer
Xindong ZHANG ; Jing MA ; Xiangge WANG ; Tiantian ZHAO
Chinese Journal of Primary Medicine and Pharmacy 2020;27(2):218-221
Objective:
To detect the expression and the differential significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer (NSCLC), squamous cell carcinoma (SCC) and adenocarcinoma (AC).
Methods:
Immunohistochemical SP method was used to detect the expressions of CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017, and the results were analyzed combined with the clinical characteristics of NSCLC.
Results:
The positive expression rates of CK5/6, DSG3 and P40 in lung SCC were 100.0%(56/56), 89.3%(50/56) and 96.4%(54/56), respectively, with specificity of 90.6%, 100.0% and 100.0%, respectively.The positive expression rates of NapsinA, TTF-1 and CK7 in lung AC were 81.3%(52/64), 90.6%(58/64) and 93.8%(60/64), respectively, with specificity of 100.0%, 92.9% and 96.4%, respectively.The positive expression rates of CK5/6, DSG3, P40 in SCC had statistically significant differences compared with those in AC (all
10.Efficacy and safety of pazufloxacin mesylate eye drops for bacterial conjunctivitis:a multicenter randomized, double-masked, parallel controlled clinical trial
Yueqin ZHANG ; Xiangge HE ; Zhengqin YIN ; Linnong WANG ; Longbiao LI ; Hong ZHANG ; Qinmei WANG ; Jianwei WU ; Liya WANG ; Dongqing ZHAO ; Yi HE ; Lei ZHU ; Jiachen LI ; Junjie ZHANG
Chinese Journal of Experimental Ophthalmology 2019;37(7):546-552
Objective To compare the clinical efficacy and safety following the topical application of pazufloxacin mesylate eye drops with levofloxacin eye drops (LOFX) for bacterial conjunctivitis.Methods A multicenter,randomized,investigator-masked,parallel-controlled clinical trial was performed.Five hundred and twenty eyes of 520 patients with bacterial conjunctivitis were enrolled from March to October 2008 in seven ophthalmic centers in China.The patients were randomized into trial group and control group in 3 ∶ 1 ratio with the 390 eyes in the trial group and 130 eyes in the control group.Pazufloxacin mesylate eye drops was topically used 4 times per day for consecutively 7-14 days in the trial group,and levofloxacin eye drops was used in the same way in the control group.Microbiological cultures for conjunctiva sac secretions and drug sensitive test were carried out before and at the end of the administration of eye drops.The signs and symptoms were observed and scored before treatment and 0,3,7 and 14days after treatment.The adverse events following the administration of the eye drops were evaluated and compared.Results The intention to treat analysis (ITT) showed that the cure rate was 59.38% in the trial group and 60.47% in the control group,with the effective rate 88.80% and 86.05%,respectively,with an insignificant difference between the two groups (x2 =0.12,P =0.72).The clinically evaluable analysis (CE) exhibited that the cure rates were 63.48% in the trial group and 63.87% in the control group,with the effective rate 92.46% and 88.24%,whichwas not significantly different between them (x2 =0.54,P=0.46).The modified-ITT analysis (mITT) showed that the cure rates were 60.57% in the trial group and 62.07% in the control group,with the effective rate 90.32% and 88.51%,without significant difference between the two groups (P>0.05).Based on microbiologically evaluable analysis (ME),the clinical cure rates were 63.71% and 63.41% in the trial group and control group,and the effective rates were 93.44% and 90.24%,respectively.There was no significantly difference between the both groups (P>0.05).In the trial group and control group,the bacterial eradication rate was 89.42% and 90.80% based on ITT,90.11% and 92.77% based on CE,respectively.There was no significant difference in incidences of adverse events following the administration of the drug between the trial group and control group,including ocular tolerance,burning sensation,pricking and itching (P =0.34).Conclusions The effectiveness and adverse response were resemble between Pazufloxacin mesylate eye drops and LOFV following the topical application for bacterial conjunctivitis,which indicate that Pazufloxacin mesylate eye drops is effective and safe.

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