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.

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.

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.

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.

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.

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 P<0.05), and the expression of TTF-1, CK7 and NapsinA in AC had statistically significant differences compared with those in SCC (all P<0.05). Conclusion CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA are of great significance in the differential diagnosis of SCC and AC in small biopsy specimens of NSCLC.

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.

Objective To evaluate the effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung injury ( VILI ) and the relationship with phosphatidylinositol 3-kinase∕serine-threonine protein kinase ( PI3K∕Akt) signaling pathway. Methods One hundred clean-grade male Sprague-Dawley rats, aged 4-5 months, weighing 270-320 g, were divided into 5 groups ( n=20 each) using a random number table method: control group ( C group) , VILI group ( V group) and different doses of methylprednisolone groups ( M1-3 groups) . Group C received no mechanical ventilation and kept spontane-ous breathing for 4 h. Rats were mechanically ventilated ( tidal volume 40 ml∕kg, respiratory rate 15-17 breaths∕min, inspiratory∕expiratory ratio 1 : 1, positive end-expiratory pressure 0, fraction of inspired oxy-gen 21％ during OLV) in group V. Methylprednisolone 2, 10 and 30 mg∕kg were intravenously injected at 20 min before mechanical ventilation in M1-3 groups, respectively, and the equal volume of normal saline was given in group V. Blood samples and lung tissues were taken at 4 h of ventilation for measurement of the lung permeability index ( LPI) and wet∕dry lung weight ratio ( W∕D ratio) , for examination of pathological changes, and for determination of apoptosis index ( AI) in lung tissues ( by TUNEL) , expression of Akt, phosphorylated Akt (p-Akt), glucose-regulated protein 78 (GRP78), CCAAT∕enhancer-binding protein homologous protein (CHOP) and caspase-12 in lung tissues (by Western blot). Injured alveoli rate (IAR) was calculated. Results Compared with group C, the W∕D ratio, LPI, IAR and AI were significantly in-creased, the expression of p-Akt was down-regulated, and the expression of GRP78, CHOP and caspase-12 was up-regulated in V and M1 groups ( P<0. 05) , and no significant change was found in the indexes mentioned above in M2 and M3 groups ( P>0. 05) . Compared with group V, the W∕D ratio, LPI, IAR and AI were significantly decreased, p-Akt expression was up-regulated, and the expression of GRP78, CHOP and caspase-12 was down-regulated in M2 and M3 groups ( P<0. 05) . Conclusion Methylprednisolone in-hibits endoplasmic reticulum stress, thus inhibiting cell apoptosis, and the mechanism is related to activa-ting PI3K∕Akt signaling pathway in rats with VILI.

Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLC-PDA, HPLC-VWD and UHPLC-MS , combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated . PLSR analysis revealed significant positive correlations ( = 0.5795) between the contents of triterpenes , , , and and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.