Abstract:Aristolochic acids (AAs) is a group of nitrophenanthrene compounds comprised of AAⅠ, AAⅡ, AAⅢ and AAⅣ, which are widely distributed in Aristolochiaceae plants. Long-term use of drugs containing AAs could lead to aristolochic acid nephropathy (AAN) and urinary tract tumors. Active metabolites of AAs could form AA-DNA adducts with DNA, which subsequently induce characteristic A-T transversion mutation known as AA mutational signature. In 2017, Sci Transl Med reported that AAs and their derivatives were widely implicated in liver cancers in Taiwan, China and throughout Asia, suggesting that additional measure should be taken for primary prevention through avoidance of AAs exposure. This report has triggered a series of worldwide discussion on whether AAs could cause liver cancer. We analyze this research focus in the present paper and mainly discuss the controversial points of the liver carcinogenicity related to AAs in the literature, so as to provide scientific and objective evidence to evaluate the association of AAs exposure with liver cancer development in Chinese population; meanwhile, the questions that need to be solved for the safety use of AAs are also presented, and some thoughts on them were put forward.

Abstract:Objective To explore the effect of rifampin on yellow fever virus (YFV) and its preliminary mechanism. Methods Indicated concentrations of rifampin (0.04, 0.2, 1, 5, 25, 125, 625 μmol/L) were incubated with human liver cancer cells Huh-7 for 24 h. The cytotoxicity of rifampin was measured by CCK-8 assay and the 50% cytotoxic concentration (CC₅₀) was calculated. When Huh-7 cells were infected with YFV, different concentrations of rifampin (0.04, 0.2, 1, 5, 25 μmol/L) were added to detect the dose-response relationship of YFV resistance and to calculate the half inhibition concentration (IC₅₀); rifampin (5 μmol/L) was added and incubated for different exposure time (2, 4, 8, 12, 24 h) to detect the time-effect relationship of YFV resistance. Huh-7 cells were infected with YFV for 2 h, and rifampin (25 μmol/L) was added at different time points (2, 4, 6, 8, 12 h) for 2 h incubation. The most significant anti-YFV stage was detected. The effect of rifampin on YFV invasion was evaluated by virus binding assay and cholera toxin B (CTB)/transferrin (TF) mediated endocytosis experiment. Results Rifampin had a robust anti-YFV effect (IC₅₀=1.868 μmol/L, P<0.01) with low cytotoxicity (CC₅₀=176.9 μmol/L). Kinetic test, binding and endocytosis experiments showed that rifampin could significantly inhibit YFV binding and invading target cells (P<0.01), but did not affect the endocytosis process of YFV. Moreover, rifampin also had inhibitory effect at late YFV replication stage (P<0.01). Conclusion Rifampin can inhibit YFV infection by blocking viral binding to the target cells at early stage of viral entry.

Abstract:Objective To screen the substrate protein of ubiquitin-conjugating enzyme E2C (UBE2C) and to explore its role in the progression of hepatocellular carcinoma. Methods An overexpression plasmid of UBE2C was constructed with Halotag and was used to infect the highly metastatic human liver cancer cell line HCCLM3. The UBE2C binding substrate protein was precipitated by Halolink resin and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. UBE2C was overexpressed in human liver cancer cell line Huh-7; the effect on the expression of its substrate protein was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunoflurescence staining, the effect on Wnt signal pathway was detected by cell nucleoplasmic separation combined with Western blotting and TOP flash/FOP flash luciferase reporter assay, and the effect on the expression of Wnt signal pathway downstream genes was further verified by qRT-PCR and Western blotting. Results The mass spectrometry analysis of the differential band of the Halotag coprecipitate obtained by SDS-PAGE and silver staining showed that the substrate protein of UBE2C was β-tubulin. Compared with the control group, overexpression of UBE2C had no effect on the expression of β-tubulin in mRNA level in Huh-7 cells (P>0.05), while it significantly decreased the expression of β-tubulin in protein level (P<0.01). Meanwhile, overexpression of promoted the entry of β-catenin into nucleus (P<0.05), increased the luciferase activity of TOP flash/FOP flash (P<0.01), and enhanced the expression of the Wnt signaling pathway downstream genes (c-Jun N-terminal kinase[JNK], cyclin D1 and matrix metallopeptidase 7) (all P<0.05). Conclusion UBE2C contributes to the progression of hepatocellular carcinoma through decreasing the expUBE2Cression of β-tubulin in hepatocellular carcinoma cells by specifically binding to β-tubulin, activating Wnt signaling pathway and promoting expression of downstream genes.

Abstract:Objective To investigate the effect of methylprednisolone (METH) pretreatment on the incidence of urosepsis post percutaneous nephrolithotomy (PCNL) in patients with high-risk factors. Methods Eighty patients who underwent PCNL with high-risk factors of postoperative urosepsis were prospectively selected in this study. They were stratified by gender and randomized into METH or control groups (n=40 in each group). After induction of general anesthesia, 40 mg METH was intravenously administered in METH group before operation, while the equal volume of normal saline was done in the control group. The primary outcome was the incidence of postoperative urosepsis (according to Sepsis 3.0 definition). The secondary outcomes included the incidences of uroseptic shock and system inflammatory response syndrome (SIRS), and the changes of plasma levels of inflammatory markers (C reactive protein[CRP], procalcitonin, tumor necrosis factor α[TNF-α], interleukin[IL]-1β, IL-6, and IL-10) at 2 h and 24 h after operation. Results Six out of 80 patients were excluded. There was no significant difference in the baseline characteristics between the two groups before operation (P>0.05). The incidences of postoperative urosepsis, uroseptic shock and SIRS were 5.4% (2/37), 0 and 18.9% (7/37) in METH group (n=37), and 24.3% (9/37), 10.8% (4/37) and 51.4% (19/37) in the control group (n=37), respectively, with no significant difference in the incidence of uroseptic shock (P>0.05), but with significant differences in the incidences of urinary sepsis and SIRS between the two groups (P<0.05, P<0.01). The plasma level of IL-10 in METH group was higher than that in the control group at 2 h after operation (26.3[149.5] pg/mL vs 5.0[3.6]pg/mL, P<0.01), but lower than that in the control group at 24 h after operation (<5.0[1.5] pg/mL vs 5.9[13.8]pg/mL, P<0.05). The plasma level of IL-6 in the control group was higher than that in METH group at 24 h after operation (34.4[46.5]pg/mL vs 20.7[15.8]pg/mL, P<0.01). No significant difference was found in the levels of other inflammatory markers between the two groups (all P>0.05). Conclusion METH pretreatment can decrease the incidences of urosepsis and SIRS in high-risk patients undergoing PCNL. This protective effect may be attributed to METH pretreatment facilitating the release of IL-10 at the initial stage of inflammatory response, and then inhibiting the subsequent excessive inflammatory response.

Abstract:Objective To explore the clinical features, imaging features and treatment outcomes of renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion (Xp11.2/TFE3 RCC) in adult patients. Methods The clinical data of 43 adult patients with Xp11.2/TFE3 RCC confirmed by pathology from Sep. 2014 to Jul. 2019 in Changhai Hospital of Naval Medical University (Second Military Medical University) were collected. The general information, clinical symptoms, imaging data, surgical approaches, pathological data and prognosis of the patients were retrospectively analyzed. Results Among the 43 Xp11.2/TFE3 RCC cases, there were 24 males and 19 females, aged from 25 to 77 years, with an average age of (47.5±15.2) years. The main clinical manifestations included gross hematuria (five cases), lumbar and abdominal discomfort (six cases), and the symptom caused by tumor metastasis (one case); the other 31 cases were found during physical examination without obvious symptoms. The diameter of the tumor was 1.1-9.5 cm (average[5.1±2.7] cm). The lesions were round-like in 29 cases and irregular in 14 cases, and 37 cases had distinct borders and pseudocapsules around the tumors, six cases with poorly-defined borders. Most of the lesions showed heterogeneous changes in density or signal, mainly manifested as hemorrhage (21 cases), cystic degeneration or necrosis (24 cases) and calcification (11 cases). There were moderate to marked enhancement in 30 cases, mild enhancement in 13 cases, including papillary enhancement in 23 cases. Perirenal invasion appeared in 10 cases and distant metastases in eight cases. Among the 43 patients, 15 patients underwent laparoscopic radical nephrectomy, 13 patients underwent laparoscopic partial nephrectomy, seven patients underwent intelligent arm-assisted laparoscopic partial nephrectomy, five patients underwent open radical nephrectomy, one patient underwent open partial nephrectomy, one patient underwent renal biopsy, and one patient underwent resection of metastatic spinal canal tumor. The results of immunohistochemistry in 43 patients and fluorescence in situ hybridization in three patients were all positive for TFE3. High positive expression rates of carbonic anhydrase Ⅸ (CAⅨ; 74.4%, 32/43), avidin-biotin-peroxidase complex (ABC; 93.0%, 40/43), CD10 (93.0%, 40/43), von Hippel-Lindau (VHL; 72.1%, 31/43) and low-molecular-weight cytokeratin (CAM5.2; 83.7%, 36/43) were found through immunohistochemistry staining. The positive expression rate of Ki-67 ranged from 1% to 60%, with an average of 9.7%. Except for six patients who were lost to follow-up, the other 37 patients were followed up for 11-68 months, with an average of (47.4±17.5) months. During the follow-up period, five patients had multiple metastases, of which three patients died, and two patients had no significant progress after treatment with targeted drugs and were still alive; one patient had postoperative recurrence. Conclusion The main clinical manifestations of adult Xp11.2/TFE3 RCC patients are hematuria and umbar and abdominal discomfort. More patients are asymptomatic and found in physical examination. Imaging manifestations are diverse. The final confirmed diagnosis of Xp11.2/TFE3 RCC relies on pathological examination. Surgery, especially radical nephrectomy, is the first choice for Xp11.2/TFE3 RCC patients. Most patients have ideal prognosis, and a few patients have recurrence or metastasis after surgery.

Abstract:Objective To investigate the monitoring efficacy of the BigThumb^® electrocardiogram (ECG) monitor for the recurrence of atrial fibrillation (AF) after ablation and the advantages of artificial intelligence algorithm in the diagnosis of AF. Methods A total of 185 eligible patients with nonvalvular AF who underwent interventional ablation in our hospital from Mar. 2019 to Aug. 2019 were prospectively selected and randomly divided into two groups:BigThumb^® group (BT group, n=94) and traditional follow-up group (TF group, n=91). The AF-free survival rates of the two groups were followed up and compared, and the sensitivity and specificity of artificial intelligence algorithm and traditional ECG algorithm in the diagnosis of AF were also analyzed. Results The patients in BT group and TF group were followed up for 98-263 (157.0±38.4) d and 91-268 (158.8±54.7) d, respectively. Log-rank test results showed that the AF-free survival rates were 79.8% (75/94) and 92.3% (84/91), respectively (P<0.05). Three months after ablation the proportion of patients who changed treatment strategy in BT group was higher than that in TF group (P<0.05). A total of 18 981 ECGs were recorded in BT group, of which 1 520 (8.0%) were diagnosed as AF by electrocardiographists. The sensitivity and specificity of the artificial intelligence algorithm were 96.5% (1 467/1 520) and 99.6% (17 391/17 461), respectively, which were significantly higher than those of the traditional ECG algorithm (89.7%[1 363/1 520] and 97.2%[16 972/17 461]), respectively (both P<0.05). Conclusion The BigThumb^® ECG monitor improves the detection of AF recurrence after ablation, which is helpful to change the treatment strategy in time. Artificial intelligence algorithm can improve the accuracy of AF diagnosis and the BigThumb^® ECG monitor based on this algorithm is reliable in the follow-up for AF after ablation.

Abstract:Objective To explore the predictive value of monocyte count to high-density lipoprotein-cholesterol ratio (MHR) for new atrial high-rate episodes (AHREs) in patients with bradycardiac arrhythmia after dual-chamber pacemaker implantation. Methods The data of patients implanted with dual-chamber pacemaker in the First Hospital of Hebei Medical University from Jun. 2013 to Jun. 2018 were retrospectively analyzed. According to the inclusion and exclusion criteria, 140 patients were finally included. The patients were followed up for 12 months, and then divided into AHREs group and non-AHREs group according to whether AHREs occurred during the follow-up period. The general characteristics and the laboratory indexes were compared between the two groups. Furthermore, all patients were divided into MHR<3.26 group, MHR 3.26-5.00 group and MHR>5.00 group. Cox proportional hazards regression analysis was used to analyze the risk of AHREs. Results The median age of the patients was 70.00 (61.00, 75.00) years. AHREs were detected in 28 patients during the follow-up. There were significant differences in white blood cell count, neutrophil count, monocyte count, high-density lipoprotein-cholesterol and MHR in the patients with AHREs compared with the non-AHREs group during the follow-up (all P<0.05). Multivariate Cox proportional hazards regression analysis showed that MHR (HR=1.537, 95% CI 1.209-1.955, P<0.001) increased the risks of new AHREs after dual-chamber pacemaker implantation. Compared with the MHR<3.26 group, the risk of AHREs in the MHR 3.26-5.00 group (HR=1.811, 95% CI 0.366-8.958, P=0.467) had no significant change, while the risk of AHREs in the MHR>5.00 group (HR=10.128, 95% CI 2.051-50.003, P=0.004) was increased significantly. Conclusion As a new marker of inflammation and oxidative stress in blood, high MHR increases the risk of new AHREs in patients with bradycardiac arrhythmia after dual-chamber pacemaker implantation.

Abstract:Objective To evaluate coronary artery stenosis based on coronary computed tomography angiograpy (CCTA), and to explore the influence of generalized anxiety disorder (GAD) on coronary artery disease (CAD) and the influence of gender on CAD risk factors and clinical characteristics. Methods Altogether 1 117 patients who underwent CCTA in Tianjin Medical University General Hospital from Apr. 2018 to Jun. 2019 were evaluated with Duke CAD index and generalized anxiety disorder 7 (GAD-7). The relationships between GAD, gender and high-risk CAD were analyzed by binary logistic regression. Results A total of 1 099 patients were enrolled, including 460 males (41.9%) and 639 females (58.1%). GAD was a risk factor for high-risk CAD (odds ratio[OR]=1.071, 95% confidence interval[CI] 1.013-1.134, P=0.017). Compared with men, women had higher prevalence of GAD (20.3%[130/639]vs 7.0%[32/460], P<0.01), but GAD was not a risk factor of high-risk CAD in women (OR=1.037, 95% CI 0.954-1.129, P=0.392). Age, GAD, diabetes mellitus, hyperlipidemia and smoking were the risk factors of high-risk CAD in men (all P<0.05), while only age and hypertension were risk factors in women (both P<0.05). Conclusion Women are more likely to suffer from GAD, but it is not a risk factor of high-risk CAD in women. For women with suspected CAD symptoms, the symptoms may be caused by GAD rather than CAD, so more attention should be paid to the influence of psychological factors; for men with GAD, we should focus on screening of high-risk CAD in clinic.

Abstract:Objective To investigate the effect of individualized nutritional therapy on the clinical outcome of perioperative patients with nutritional risks in digestive system diseases. Methods A prospective, randomized controlled clinical trial was conducted in 217 patients with digestive system diseases undergoing elective surgery, including 112 patients in the study group (receiving individualized nutritional therapy) and 105 patients in the control group (receiving non-individualized nutritional therapy). The baseline data, postoperative complications, hospital stay, hospital costs, postoperative mortality and improvement of the quality of life were recorded and compared. Results There were no differences in gender, age, education level, place of residence, payment method of medical expenses or nutritional risk screening (NRS) 2002 score between the two groups (all P>0.05). The incidence of postoperative infectious complications in the study group was lower than that in the control group (8.0%[9/112] vs 17.1%[18/105], P=0.042), while there were no differences in the incidence of total complications or non-infectious complications between the study group and the control group (15.2%[17/112] vs 22.9%[24/105], 7.1%[8/112] vs 5.7%[6/105], both P>0.05). The total hospital stay, postoperative hospital stay and total hospital costs of the study group were all lower than those of the control group (all P<0.05). There was no difference in postoperative mortality between the two groups (P=0.286). Multivariate logistic regression analysis showed that gender, NRS 2002 score and nutritional mode were the influencing factors of postoperative infectious complications (all P<0.05). Multiple stepwise regression analysis showed that the surgery type, NRS 2002 score and nutritional mode were the influencing factors of total hospital stay (all P<0.01), and age, nutritional mode and infectious complications were the influencing factors of postoperative hospital stay (all P<0.05). Surgical type, nutritional costs and total hospital stay were the influencing factors of total hospital costs (all P<0.05). Nutritional mode and total hospital stay were the influencing factors of nutritional costs (both P<0.01). There was no significant difference in European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire-core 30 (QLQ-C30) scores between the two groups before discharge (58.9±17.1 vs 56.3±18.5) (P=0.631), but the scores of physical function, emotional function, fatigue and financial difficulty in the study group were all better than those in the control group (all P<0.05), and the score of nausea and vomiting was worse than that in the control group (P<0.05). Conclusion Individualized nutritional therapy can decrease the incidence of postoperative infectious complications, shorten the length of hospital stay, reduce the hospital costs, and improve the quality of life of perioperative patients with digestive system diseases.

Abstract:Objective To explore the correlation between ⁶⁸Gallium-prostate-specific membrane antigen (⁶⁸Ga-PSMA)-11 positron emission tomography-computed tomography (PET-CT)-derived metabolic volume parameters and clinical indicators of patients with newly diagnosed prostate cancer (PCa). Methods The imaging and clinical data of untreated 85 patients with PCa diagnosed by prostate biopsy who underwent ⁶⁸Ga-PSMA-11 PET-CT in Changhai Hospital, Naval Medical University (Second Military Medical University) from Jan. to Dec. 2019 were retrospectively analyzed; 46 patients without tumor metastasis were included in the non-metastasis group and 39 with tumor metastasis in the metastasis group. Spearman rank correlation test was performed to analyze the correlation between metabolic volume parameters (primary tumor maximum standardized uptake value[SUV_max], mean standardized uptake value[SUV_mean] of primary tumor, total lesion of prostate-specific membrane antigen[TL-PSMA]) and clinical indicators (age, body mass index, Gleason score[GS], and prostate-specific antigen[PSA]) of the two groups. Results In the non-metastasis group, PSA was moderately positively correlated with primary tumor SUV_max and primary tumor TL-PSMA (r_s=0.409, P=0.005; r_s=0.587, P<0.001), while GS was not correlated with primary tumor SUV_max and primary tumor TL-PSMA (r_s=0.181, P=0.229; r_s=0.101, P=0.505). In the metastasis group, PSA was moderately positively correlated with primary tumor TL-PSMA, metastasic tumor TL-PSMA and whole-body TL-PSMA (r_s=0.439, P=0.005; r_s=0.588, P<0.001; r_s=0.569, P<0.001), but not correlated with primary tumor SUV_max (r_s=0.255, P=0.117); while GS was not correlated with primary tumor SUV_max, primary tumor TL-PSMA, metastasic tumor TL-PSMA and whole-body TL-PSMA (r_s=0.069, P=0.675; r_s=0.194, P=0.237; r_s=0.299, P=0.064; r_s=0.300, P=0.063). Conclusion The metabolic volume parameter TL-PSMA, which reflects the systemic tumor burden in patients with newly diagnosed PCa, is positively correlated with serum PSA, but not with GS, which reflects the differentiation degree of primary tumor.

Abstract:In recent years many studies have found that epilepsy patients had a new form of forgetting-accelerated long-term forgetting (ALF), with normal initial learning and memory, becoming abnormal in the following days or weeks. Although it has been nearly 30 years since ALF's discovery, there are still many problems to be understood. This paper reviews the definition, neurobiological basis, influencing factors, involvement in other diseases and current evaluation methods of ALF.

Abstract:The harm of sun exposure to human body is often neglected, especially due to the limited sun protection knowledge of military officers and soldiers and the low application rate of sun protection products. With the progression of the PLA strategic transformation, military training is becoming gradually diversified. The long-term sun exposure has seriously affected the combat capability of the army and disturbed their work, life and study and even led to non-combat depletion of strength. Based on the different resident environments and training characteristics of naval and plateau forces, this paper analyzes the demands of officers and soldiers in different positions for sun protection products, reviews the composition design of the sun protection products for individual soldiers, and puts forward suggestions and ideas for the research and development of military sun protection products.

Abstract:After diving decompression, bubbles will generate in diver's body even the decompression schedule is not violated, and they may increase the risk for venous gas embolism (VGE). Due to the small number of bubbles or the absence of obvious symptoms and signs of decompression sickness, most divers could not feel the presence of VGE. However, the amount, location, and duration of bubbles in the body after decompression are closely related to the risk of decompression sickness after diving. Therefore, increasingly more studies have evaluated the degree of decompression stress and the risk of decompression sickness by detecting the related parameters of bubbles in the body after decompression. Herein, we briefly reviewed the application of ultrasonic bubble detection in diving decompression researches.

Abstract:Objective To investigate the status quo of combat casualty care capability in Chinese peacekeeping military doctors before deployment, and analyze the problems in the training of combat casualty care, so as to provide reference for improving the training content. Methods The cluster sampling was used to recruit the peacekeeping military doctors from Chinese peacekeeping LevelⅠhospitals before deployment. A total of 35 peacekeeping military doctors who completed the training of combat casualty care were investigated through questionnaire, test, desktop simulation and practical training (including on-site assessment, triage and closed thoracic drainage). Likert 5-grade scoring method was used to evaluate the questionnaire items. The error rates of knowledge points and reasonable deduction rates were used to evaluate the test and the desktop simulation, respectively. The on-site assessment and the triage were assessed with five-point method of medical simulation training of the United Nations medical team, and the closed thoracic drainage was graded using percentage. Results The results of the questionnaire on the 35 peacekeeping military doctors showed that the average score of mastery level (3.99±0.68), teaching quality (4.48±0.64), task demand (4.55±0.54) and personal demand (4.41±0.60) were significantly different (F=26.65, P<0.01), with the average score of mastery level being the lowest. The test results showed that the error rates of seven knowledge points were significantly different (χ²=167.65, P<0.001), and the error rate of the basic skill (hemostasis principle) of combat casualty first aid was the highest, and the error rate of injury ticket and injury label was the lowest. The results of the desktop simulation indicated that all the 35 participants were able to complete the deduction of the 21 items, the reasonable rates of two items were 100.00%, the reasonable rates of six items were less than 60%, and three items had inappropriate deduction measures. The average scores of on-site assessment were as follows:3.00 points for the equipment preparation, on-site treatment and casualty evacuation; 2.89 points for the safety awareness; 2.78 points for the sequence and key points of physical examination of casualty; and 2.67 points for the contents of physical examination of casualty. The average scores of triage were as follows:3.00 points for the overall classification concept; 2.89 points for the treatment classification (secondary assessment) and the sequence and key points of physical examination of casualty; 2.11 points for the physical examination contents of casualty; 1.00 point for the injury severity and treatment order, surgical methods and casualty flow; and 77-97 (91.33±5.84) points for the closed thoracic drainage. Conclusion There are still some weaknesses in overall casualty treatment capacity of peacekeeping military doctors before deployment. In the future, the training of combat casualty care should be strengthened in weapon wound treatment, damage control surgery and mass casualty treatment; the proportion of practical training courses should be increased, and comprehensive ability training courses should be added.

Abstract:Objective To investigate the mediating role of depressive symptoms between sleep and suicidal ideation among navy officers and soldiers. Methods The Pittsburgh sleep quality index (PSQI), self-rating depression scale (SDS) and self-rating idea of suicide scale (SIOSS) were used to survey 849 navy officers and soldiers by random sampling and group testing. The relationship among sleep, depressive symptoms and suicidal ideation, and the mediating effect of depressive symptoms between sleep and suicidal ideation were analyzed. Results A total of 849 questionnaires were sent out, and 812 valid questionnaires were collected, with an effective rate of 95.6%. Pearson correlation analysis showed that there were positive correlations between sleep quality, sleep latency, sleep disorder and depressive symptoms (r=0.446, 0.390, and 0.394, all P<0.01) as well as suicidal ideation (r=0.498, 0.462, and 0.420, all P<0.01); and depression symptoms were also associated with suicidal ideation (r=0.706, P<0.01). There were significant differences in the path coefficients of the model (P<0.05), and all fitting indexes were good (χ²=5.380, P=0.250). The mediating effect of depressive symptoms between sleep and suicidal ideation was 0.28, accounting for 41.2% (7/17) of the total effect. Conclusion Depressive symptoms play a partial mediating role between sleep and suicidal ideation among navy officers and soldiers.

Abstract:Objective To screen microRNA (miRNA) with elevated expression in intervertebral disc degeneration (IDD) tissues, and to explore its role and possible mechanisms in IDD. Methods Two published IDD miRNA sequencing databases were compared to screen the most highly expressed miRNA-miRNA-603. Intervertebral disc tissues of 10 patients with IDD and 10 patients with lumbar spine fracture were collected, and the nucleus pulposus cells from normal intervertebral disc tissues were isolated and cultured. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miRNA-603 in the IDD and normal intervertebral disc tissues. The role of miRNA-603 in tumor necrosis factor α (TNF-α)-induced inflammation of nucleus pulposus cells was explored using miRNA-603 mimics and inhibitor factor. Sorbin and SH3 domain-containing protein 3 (SORBS3), a target gene of miRNA-603, was found by using bioinformatics website and the published IDD miRNA sequencing databases, and was verified by dual-luciferase reporter assay. The function of miRNA-603 and SORBS3 in the inflammatory response of nucleus pulposus cells was explored by the overexpression of miRNA-603 and SORBS3. Results The expression of miRNA-603 increased significantly in IDD tissues (P<0.01). Overexpression of miRNA-603 could promote the expression of interleukin (IL)-6 and IL-1β in nucleus pulposus cells (both P<0.01); inhibition of the miRNA-603 expression could reduce the TNF-α-induced expression of IL-6 and IL-1β (P<0.01, P<0.05). At the same time, the expression of cleaved caspase-1 also decreased (P<0.01). Bioinformatics prediction showed that miRNA-603 could targetedly regulate SORBS3, and the expression of SORBS3 in IDD tissues was low (P<0.01). Compared with the overexpression of miRNA-603 alone, co-overexpression of miRNA-603 and SORBS3 inhibited the TNF-α-induced expression of IL-6 and IL-1β in nucleus pulposus cells (both P<0.01). Conclusion The expression of miRNA-603 increases in human IDD tissues. miRNA-603 can induce the inflammatory response of nucleus pulposus cells by targetedly inhibiting SORBS3, which may promote the IDD process.

Abstract:Objective To observe the clinical efficacy of Shugan Jianpi Jiedu recipe for treatment of liver stagnation and spleen deficiency syndrome after surgical excision of intrahepatic cholangiocarcinoma (ICC). Methods A single center, prospective, randomized controlled trial was conducted. Seventy patients with liver stagnation and spleen deficiency syndrome after surgical excision of ICC were evenly randomized into two groups (n=35):treatment group and control group. Patients with hepatitis B or hepatitis C history continued antiviral treatment and liver protection treatment if necessary. The treatment group was treated with Shugan Jianpi Jiedu recipe once a day for at least 3 months. The control group was not given oral traditional Chinese medicine. After 3 months of treatment, the clinical symptoms and Karnofsky performance score (KPS) were evaluated. The patients were followed up for 4 months to 1 year to calculate the progression-free survival. Results There were no significant differences in gender, age, clinical stage or Child-Pugh classification between the two groups (all P>0.05). After 3 months of treatment, the main clinical symptoms of the treatment group were improved significantly compared with the control group, including flank swelling, abdominal distension, anorexia and fatigue (all P<0.05), and the KPS was significantly higher than that of the control group (P<0.01). After 4 months to 1 year follow-up, the average progression-free survival was (48.20±7.34) weeks and the progression-free survival rate was 80.00% in the treatment group, while those in the control group were (38.30±16.73) weeks and 57.14%, respectively, with significant difference found in the progression-free survival rates between the two groups (P<0.05). Conclusion Shugan Jianpi Jiedu recipe can improve the clinical symptoms, quality of life and progression-free survival rate of patients with liver stagnation and spleen deficiency syndrome after surgical excision of ICC.

Abstract:Objective To establish a high-performance liquid chromatography (HPLC) method for simultaneously determining the two triterpenoid acids (schisandronic acid[SA] and coccinic acid[CA]) in Schisandra, and investigate their content differences in Schisandra from different habitats, so as to provide basis for improving the quality of medicinal materials. Methods The HPLC condition was as follows:Waters Symmetry C₁₈ column (4.6 mm×250 mm, 5 μm), the mobile phase was composed of methanol-0.1% formic acid solution (86:14), the detection wavelength was 220 nm, the flow rate was 1.0 mL/min, the column temperature was 30℃, and the injection volume was 10 μL. The contents of SA and CA were determined in Schisandra from Liaoning, Jilin, Hubei, Hunan, Shaanxi, Shanxi, and Henan. SPSS software (SPSSAU) was used to analyze the obtained data. Results There were good linear relationships in the range of 10-800 μg/mL for both SA and CA, the correlation coefficients were both 0.999 7, and the average recovery rates were 97.25% (RSD=2.04%, n=6) and 96.02% (RSD=2.03%, n=6), respectively. The contents of SA and CA in Schisandra from different habitats varied greatly. The contents of SA and CA in Schisandra sphenanthera (from Hubei, Hunan, Shaanxi, Shanxi, and Henan) were higher than those in Schisandra chinensis (from Liaoning and Jilin). The highest content of SA in Schisandra was from Henan ([0.285±0.015] mg/g) and the lowest one was from Jilin ([0.068±0.017] mg/g. The highest content of CA was from Shanxi ([0.927±0.017] mg/g) and the lowest one was from Jilin ([0.039±0.010] mg/g). Conclusion The method in this study is simple, accurate, reliable and reproducible, and it is suitable for the simultaneous quantitative analysis of the two triterpenoid acids SA and CA.

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