Objective To investigate the effects of long non-coding RNA 00894(LINC00894)gene on prolifera-tion and metastasis of human gastric cancer cells,and to verify the regulatory relationship of LINC00894,miR-205-5p and ZEB1 in gastric cancer.Methods The expression level of LINC00894 in gastric cancer cell lines,normal gastric lines,clinical gastric cancer and normal gastric tissue samples were determined by RT-qPCR.Through fol-low-up,the relationship between the expression level of LINC00894 and the prognosis of gastric cancer patients was explored.LINC00894 knockdown cell lines and overexpression cell lines were constructed,and the knockdown and overexpression efficiency was detected by RT-qPCR.Cell proliferation and metastatic capacity were determined by CCK 8,clone formation and Transwell assays.Dual-luciferase reporter assays,RT-qPCR assays and Western blot assays were used to examine the targeted regulatory relationships of LINC00894,miR-205-5p and ZEB1.Results The expression of LINC00894 gene in gastric cancer tissues or cells was significantly higher than that in normal gas-tric tissues or cells,moreover,gastric cancer patients with high LINC00894 gene expression had a worse prognosis.The knockdown of LINC00894 inhibited the viability,clonogenesis,migration and invasion ability of gastric cancer cells,and conversely,the overexpression of LINC00894 obtained the opposite results.LINC00894 promoted ZEB1 expression by targeted downregulation of miR-205-5p expression.LINC00894 promoted the expression of ZEB1 by targeting miR-205-5p and down-regulating its expression.Conclusion LINC00894 serves as an oncogene in gastric cancer and may promote proliferation and metastasis of gastric cancer cells via regulating miR-205-5p/ZEB1 axis.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals ; Mice ; Male ; Cell Line ; Rats ; Kidney/physiology* ; Fibrosis/drug therapy* ; Renal Insufficiency, Chronic/drug therapy* ; Adenine ; Epithelial-Mesenchymal Transition ; Aquaporin 1/metabolism*

Objective:To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas (SPT) and non-metastatic SPT, and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods:Twelve metastatic SPT patients admitted to Peking University People's Hospital, Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively, including 3 males and 9 females, with a median age of 47 years old, ranging from 21 to 73 years old. Thirty non-metastatic SPT patients with clear diagnosis, clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group, including 12 males and 18 females, with a median age of 42 years old, ranging from 34 to 69 years old. Clinical data such as gender, age and pathological data were collected. Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results:There was no significant difference in general data between the two groups (all P>0.05). Among the 12 metastatic SPT patients, 4 cases metastasized to liver, 2 to spleen, 2 to lung, 2 to lymph nodes, 1 to mediastinum, and 1 to sacrum. Compared with the non-metastatic tissue, the MLH1 protein deletion in metastatic pancreatic lesions (metastatic SPT-P) and metastatic lesions (metastatic SPT-M) were increased [both 33.3%(4/12)], and the difference was statistically significant (both Chi square=5.00, both P=0.041). Compared with 0 (0/30) MLH1 gene methylation rate in non-metastatic SPT tissues, the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues [both 30% (3/10)] were higher, with statistical significance (both Chi square=0.96, both P=0.032). Conclusion:Compared with non-metastatic SPT, the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT. MLH1 methylation may occur before metastasis, which can be used as a predictor of SPT metastasis.

Cardiotoxicity is a serious complication of antineoplastic drugs. With the continuous development of antineoplastic drugs, immune checkpoint inhibitors have been used in the treatment of a variety of cancers. PD-1/PD-L1 immune checkpoint inhibitors have been widely concerned in recent years. This article reviews the manifestations and possible mechanisms of cardiotoxicity induced by PD-1/PD-L1 immune checkpoint inhibitors, and the detection methods and treatment of cardiotoxicity.

OBJECTIVE：To initially evaluate the safety of ceritinib after it is marketed ，and to provide reference for the rational use of drug. METHODS The report odd ratio method and proportional reporting ratio method were used to mine the signals of ceritinib-related adverse events from FDA adverse event reporting system （FAERS）during the second quarter of 2014 to the third quarter of 2019. The patients ’gender，age，body weight ，daily dose and course of treatment were collected. SPSS 26.0 software was used to test the number of ADR cases of this system group and other system groups by chi square test. RESULTS ：A total of 10 318 ADR reports with ceritinib as the first suspicious drug were collected ， and 236 ADR signals of seretinib were excavated. After excluding the ineffective treatment ，187 ADR signals were obtained ，involving 16 systems. Inaddition to those mentioned in the drug instructions ，the signals also included various nervous disease ，blood and lymph system disease ，infections and infectious disease ，etc.，such as hand-foot-genital syndrome ，mutation of anaplatic lymphoma kinase gene. Among them ，the ADR reports of gastrointestinal diseases were the most （576 cases）. Compared with ADR of other systems ，gender，age，body weight，daily dose and treatment course had significant effects on ADR of gastrointestinal diseases （P＜0.05）. Most of the patient with gastrointestinal ADR after using ceritinih were female （59.9％），45 years old and above （70.3％），body weight ≤65 kg （68.1％），daily dose 451-750 mg/d（50.2％），and medication duration less than 3 months（75.7％）. CONCLUSIONS ：The risk of gastrointestinal ADR in female patients over 45 years old and with body weight less than 65 kg after using seretinib is relatively high. This kind of ADRs are also related to daily dose ，and most of which occur within 3 months. Therefore ，great importance should be attached to drug monitoring during clinical use.

Objective: To assess the value of multi-parametric MRI in mammographically detected breast imaging reporting and data systems (BI-RADS) 3 to 4 exclusive microcalcifications. Methods: A retrospective analysis was performed in 152 patients with mammographically detected BI-RADS 3 to 4 exclusive microcalcifications from January 2013 to December 2017. All patients underwent bilateral breast multi-parametric MRI before surgical biopsy. Microcalcifications were classified according to BI-RADS by two radiologists with more than 10 years′ experience in breast imaging. The area under the curve (AUC), sensitivity and specificity of BI-RADS 3 to 4 exclusive microcalcifications diagnosis by mammography and mammography plus MRI were calculated and compared using pathology as the gold standard. Results: A total of 152 lesions (93 benign lesionsand 59 malignant lesions) were assessed in this study. The positive predictive value (PPV) of mammography for BI-RADS 3, 4A, 4B and 4C microcalcifications diagnosis were 22.2%(16/72), 5.0%(1/20), 48.5%(17/35) and 100.0%(25/25) respectively. The PPV of MRI for BI-RADS 2, 3, 4, 5 microcalcifications diagnosis were 1.6%(1/62), 7.1%(2/28), 72.2%(13/18) and 97.7%(43/44).The area under curve, sensitivity and specificity of mammography for BI-RADS 3 to 4 microcalcifications diagnosis were 0.676,72.9% and 60.2%. The area under curve, sensitivity and specificity of mammography plus MRI for BI-RADS 3 to 4 microcalcifications diagnosis were 0.982, 94.9% and 93.6%. Conclusions Multi-parametric MRI can improve the diagnostic accuracy in mammographically detected BI-RADS 3 to 4 exclusive microcalcifications, which is helpful to differentiate benign and malignant breast lesions with microcalcifications and avoid unnecessary biopsies.

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Animals ; Computational Biology ; Constriction ; Down-Regulation ; Hyperalgesia ; Inflammation ; Injections, Spinal ; Mice ; MicroRNAs ; Neuralgia ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Rats ; Sciatic Nerve ; Spinal Cord ; Up-Regulation

Background and purpose: The technique of dynamic contrast-enhanced MRI (DCE-MRI) is widely applied in differential diagnosis between benign and malignant tumor and therapeutic estimation of neoadjuvant chemotherapy in clinic. However, there is no standard quantitative measurement method. This study aimed to assess the variability of different region of interest (ROI) selections for tumor bed of breast cancer using DCE-MRI, and to ascertain the optimal ROI delineation. Methods: We retrospectively analyzed DCE-MRI of 30 patients diagnosed with breast cancer by pathology. The ROIs were delineated by 2 different observers using iCAD software with 4 methods, including whole tumor (Whole), the slice containing the most enhancing voxels (SliceMax), 3 slices centered in SliceMax (Partial) and the 5％ most enhancing contiguous voxels within SliceMax (5Max), to generate the volume transfer constant (Ktrans), the extracellular volume fraction (Ve) and rate constant (Kep). And the reproducibilities of the measurements were assessed using the Bland-Altman method. Results: In the analysis of ROIs delineation, the Ktrans, Ve and Kep reported by different observers were 1.26±0.54 vs 1.25±0.53, 0.75±0.23 vs 0.73±0.22 and 1.93±1.46 vs 1.95±1.51 (P＞0.05) using the method of Whole, and 1.28±0.43 vs 1.26±0.43, 0.74±0.21 vs 0.80±0.27, 1.95±1.53 vs 1.93±1.43 (P＞0.05) using the method of Partial, and 1.30±0.33 vs 1.32±0.33, 0.77±0.20 vs 0.73±0.24, 1.82±1.53 vs 1.87±1.45 (P＞0.05) using the method of SliceMax, and 1.31±0.35 vs 1.35±0.33, 0.77±0.20 vs 0.98±0.25, 1.97±1.36 vs 1.73±1.55 using the method of 5Max (P＜0.05). Using the methods of ROI delineation except 5Max, there was no significant difference between Ktrans, Ve and Kep reported by different observers. The bias vs limits of agreement were 0.002 vs-0.013 to 0.012,-0.003 vs-0.023 to 0.017, 0.006 vs-0.018 to 0.029,-0.035 vs-0.054 to 0.018 measured with Whole method, SliceMax, Partial and 5Max respectively using the Bland-Altman method. Conclusion: It may be reliable to measure functional parameters of primary tumors in breast cancer using DCE-MRI according to the methods of Whole, Partial and SliceMax.

Objective To estimate the value of multi-modal guiding in transrectal ultrasound-guided prostate targeted biopsies (TB) in the biopsy naive patients.Methods From June 2016 to December 2017,178 patients with suspicious prostate cancer were retrospectively evaluated.The age of patients was 54-87 years(median 70 yesrs).Serum PSA level before biopsy was 1.5-95.0 ng/ml (median 13.2 ng/ml),in which 70 cases with PSA ＜ 10 ng/ml,58 cases 10-20 ng/ml,and 50 cases ＞ 20 ng/ml.All patients underwent transrectal ultrasound (TRUS),real-time tissue elastography (RTE) and contrast-enhanced ultrasonography(CEUS).All positive sites on imaging undergoing two-core TB and 10 core-systematic biopsy (SB).The detection rates and positive rates of biopsy for any cancer (PCa) and clinically significant prostate cancer (CsPCa) were compared between TB and SB.Pathological findings of each biopsy core was analyzed for Gleason grade and the single-core length of prostate cancer.Results The total detection rate for PCa was 48.8％ (87/178).The diagnostic accuracy of PCa did not significantly differ between TB 35.5％ (63/178) and SB 42.8％ (76/178) groups.There was no significant difference between the proportion of CsPCa in TB group and SB group [80％ (50/63) vs.66％ (50/76),P =0.21].TB had an obvious higher single-core positive rate for prostate cancer 60.6％ (449/740) and an obvious higher singlecore positive rate for high-risk prostate cancer [10.3％ (76/740)] than SB [29.7％ (530/1 780) and 5.5 ％ (98/1 780)],with statistically signficant difference (P ＜ 0.001,P =0.002).TB also had a higher single-core length of prostate cancer than SB [6.80 (0.20-15.00) mm vs.5.50 (0.06-18.00) mm,P ＜0.05].Conclusions This study revealed a similar rate of prostate cancer detection between multi-modal guiding in transrectal ultrasound-guided prostate targeted biopsies (TB) and 10 core-systematic biopsy (SB).TB maybe tend to detect higher proportion of high-risk PCa.

Objective To evaluate the effect of intrathecal oxytocin on neuropathic pain in rats.Methods Thirty-six SPF male Sprague-Dawley rats,aged 4-6 weeks,weighing 100-150 g,were divided into 4 groups (n =9 each) using a random number table:control group (group C),neuropathic pain group (group NP),neuropathic pain plus normal saline group (group NPN) and neuropathic pain plus oxytocin group (group NPO).The neuropathic pain model was made by partial sciatic nerve injury in NP,NPN and NPO groups.In group NPO,oxytocin l0 μl (0.1 μg) was intrathecally injected on the day of establishing the model and 1 and 2 days after establishing the model,and then normal saline 10 μl was given for tube sealing at 9 a.m.and 4 p.m.every day.In group NPN,normal saline 20 μl was given for tube sealing at the corresponding time points.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 1,2,3,4,5,6 and 7 days after establishing the model.The expression of the astrocyte marker glial fibrillary acidic protein (GFAP) and a specific marker of microglia ionized calcium-binding adaptor molecule 1 (IBa-1) was detected by Western blot at 1 day before establishing the model and 3 and 7 days after establishing the model.Results Compared with group C,the MWT was significantly decreased,TWL was shortened and the expression of GFAP and IBa-1 was up-regulated at each time point in NP and NPN groups (P＜0.05).There was no significant difference in MWT,TWL GFAP and IBa-1 at each time point between group NPN and group NP (P＞0.05).Compared with NP group,MWT was significantly increased at 2-4 days after establishing the model,TWL was prolonged at 1-4 days after establishing the model,the expression of IBa-1 was down-regulated on 3 days after establishing the model,and the expression of GFAP was downregulated on 3 and 7 days after establishing the model in group NPO (P＜0.05).Conclusion Oxytocin can reduce neuropathic pain,and the mechanism may be related to inhibiting activation of glial cells in the spinal cord of rats.