Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems in the world. Pharmaceutical industry is an important part of China's national economy. At present, there are few related studies reported at home and abroad. Objective To investigate the status and influencing factors of WMSDs in chemical pharmaceutical industry. Methods A cross-sectional epidemiological survey was conducted among all workers from three chemical pharmaceutical enterprises in Guangzhou. The Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, symptoms of musculoskeletal disorders, types of work, work organization, and and work postures. Multiple logistic regression method was used to analyze the risk factors of WMSDs in chemical pharmaceutical workers. Results In this study, 563 workers were selected as subjects. The total prevalence rate of WMSDs symptoms in the chemical pharmaceutical workers was 43.9% (247/563), and the leading body part-specific prevalence rate from high to low was 34.3% in the lower back, 24.3% in the upper back, 24.0% in the shoulders, and 23.8% in the neck. The prevalence rate of WMSDs symptoms in multiple body parts (30.0%) was 2.16 times higher than that in single body part (13.9%), and the prevalence rate of WMSDs symptoms in four body parts was the highest (11.4%). The results of multiple logistic regression analysis showed that age ≥50 years (reference age <30 years) (OR=2.140, 95%CI: 1.054-4.345), often or very often (reference never/rarely) long-time head rotating (OR=2.695, 95%CI: 1.753-4.142) and long-time keeping arms above shoulders (OR=1.902, 95%CI: 1.108-3.265) increased the risk of reporting WMSDs symptoms (P<0.05). Regarding education level, workers with high school and technical secondary school (OR=0.333, 95%CI: 0.175-0.636) or college and above (OR=0.413, 95%CI: 0.216-0.790) education had a lower risk of reporting WMSDs symptoms than those with middle school or below (P<0.05). Conclusion The prevalence rate of reporting WMSDs symptoms in chemical pharmaceutical industry is high, the involving body parts are lower back, upper back, shoulders, and neck, and reporting simultaneous occurrence of WMSDs symptoms in multiple body parts is common. The chemical pharmaceutical manufacturers can reduce the risk of WMSDs by strengthening the training on workers' ergonomics knowledge, paying attention to the less educated personnel, protecting the elderly workers, and avoiding awkward work postures, like rotating head for a long time and raising arms over shoulders.

{L-End}Objective To analyze the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) and their influencing factors among workers in the chemical pharmaceutical industry. {L-End}Methods A total of 563 workers from three chemical pharmaceutical factories in Guangzhou City were selected as the research subjects using the judgment sampling method. The prevalence of multi-site WMSDs in the past 12 months was investigated using the electronic questionnaire of Chinese Version of Musculoskeletal Disorders Questionnaire. {L-End}Results The prevalence of multi-site WMSDs in the research subjects was 30.0% (169/563). The results of multivariable logistic regression analysis showed that workers who smoked regularly/frequently and those who had their hands above shoulder level for long periods of time had a lower risk of multi-site WMSDs than those who never/occasionally smoked (all P≤0.05). Workers with a high school, secondary specialty, college degree, or above had a lower risk of multi-site WMSDs than those with a middle school education or below (all P<0.05). The longer the daily working hours, the higher the risk of multiple WMSDs (all P<0.05). Workers with regular/frequently work shifts had a lower risk of multi-site WMSDs than those with none/occasional work shifts (P<0.05). {L-End}Conclusion The prevalence of multi-site WMSDs among workers in the chemical pharmaceutical industry is relatively high. The influencing factors are individual factors, unreasonable work organization and poor ergonomics factors.

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

OBJECTIVE: To improve the standard detection method for acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace. METHODS: Acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace were collected using silica gel tube, desorbed with 45.0% ethanol, separated by a capillary column and detected by a flame ionization detector. RESULTS: The linear range of this method for detecting acetaldehyde, butyraldehyde and isobutyraldehyde were 1.57-1 568.00, 1.60-1 600.00 and 1.59-1 588.00 mg/L, respectively. All the correlation coefficients were greater than 0.999. The detection limits were 0.52, 0.46 and 0.54 mg/L, respectively. The desorption efficiency was 91.0%-103.0%. The within-run relative standard deviation(RSD) was 0.7%-1.7%.The between-run RSD was 2.0%-3.7%. The samples could be stored for at least 10 days at room temperature. CONCLUSION: This method can be used for simultaneous detection of acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace.

Objective To evaluate the efficacy of high tibial osteotomy(HTO) and unicompartmental knee arthroplasty(UKA) for knee unicompartmental osteoarthrits(KOA) using Meta analysis. Methods The controlled clinical trial literatures of HTO and UKA treating KOA were retrieved, the database including Chinese Biomedical Literature Database, Wanfang Data, CNKI, VIP Data, PubMed, Cochrane Library, EBSCO and Embase, and the search period was limited to the beginning of the database to July 2018. The literature was screened and evaluated, and Review Manager 5.3 software was used for Meta analysis. Results A total of 19 articles including 1359 knee joints were included. Meta analysis results showed that HTO was superior to UKA in range of motion (ROM) (P<0.05). For the indicators, including excellent rate, Lysholm score, visual analogue scale (VAS) score, complications, repair rate, blood loss, length of stay, ambulation time, Hospital for Special Surgery (HSS) score and femorotibial angle (FTA), UKA was superior to HTO (all P<0.05). There was no significant difference in the repair rate between open wedge HTO (OWHTO) and UKA in the sub-group analysis. There were no significant differences in the operation time and Tegner exercise score between HTO and UKA ( all P>0 . 05 ) . Conclusions Both HTO and UKA have their own advantages and disadvantages. It is necessary to properly choose the operation according to the patient's condition and psychological expectation.

Knee osteoarthritis (KOA) is the main cause of knee pain and disability in the elderly. KOA is a complex disease that is controlled by a variety of pathogenic factors, including general physical factors such as age, gender, obesity, family history, and mechanical factors, and unfavorable mechanical factors to the knee joint, such as trauma, sports injuries, and daily routines. The prevalence of KOA is related to genetic factors. Currently, conservative treatment has limited effects to this disease, and knee joint replacement is usually associated with many complications. Mesenchymal stem cells(MSCs) were first discovered in the bone marrow and subsequently found in peripheral blood, cord blood, skeletal muscle, heart and adipose tissue, which have high plasticity and pluripotency. The discovery of MSCs provides a new method for the treatment of KOA. Due to its powerful cartilage repair and regeneration function, researchers have conducted a large number of experimental studies on the efficacy, safety and mechanism of MSCs in the treatment of KOA in recent years. In this paper, the above studies presented were systematically reviewed.

Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1,2014 and June 30,2015 were collected.The specimens of HCC tissues were collected and embedded in paraffin,and then were detected by immunohistochemistry staining.Observation indicators:(1) expression of CUL4B in HCC tissues;(2) follow-up and survival;(3) prognostic factors analysis after liver transplantation;(4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation.Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018.Measurement data with normal distribution were represented as (x)±s.The comparison between groups of count data was done using the chi-square test.The survival curve drawn using the Kaplan-Meier method,and the survival analysis was done by Log-rank test.The univariate and multivariate analysis were respectively done using the COX regression model.The association analysis was done using the Pearson test.Results (1) Expression of CUL4B in HCC tissues:immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm,with a powerful brownish-yellow staining.The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients,respectively.(2) Follow-up and survival:79 patients were followed up for 38-56 months,with an average time of 46 months.During the follow-up,37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis);36 had survival and 43 died;the 1-and 3-year overall survival rates were respectively 86.84％ and 63.25％,and 1-and 3-year tumorfree survival rates were respectively 62.31％ and 51.27％.(3) Prognostic factors analysis after liver transplantation:① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR) =2.17,3.36,3.66,2.43,2.19,3.36,2.84,95％ confidence interval(CI):1.17-4.04,1.53-7.42,2.10-6.42,1.33-4.17,1.08-9.04,1.58-7.59,1.17-6.32,P＜ 0.05].The preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR =2.06,3.72,3.16,2.36,2.83,3.21,1.69,95％CI:1.34-4.85,1.72-8.63,1.79-7.31,1.46-4.86,1.19-8.63,1.19-7.92,1.06-4.87,P＜0.05).② Results of multivariate analysis showed that maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR) =3.43,3.69,2.81,95％CI:1.16-6.02,1.96-9.38,1.04-9.63,P＜0.05].The maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25,4.72,2.74,95％C1:1.16-4.02,1.98-9.47,1.03-7.10,P＜ 0.05).The 3-year overall survival rate in patients with high-and low-expressions of CUL4B was respectively 66.7％ and 32.8％,with a statistically significant difference (x2 =5.69,P＜0.05).The 3-year tumor-free survival rate in patients with high-and low-expressions of CUL4B was respectively 73.3％ and 18.6％,with a statistically significant difference (x2 =4.63,P＜0.05).(4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation:results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r =0.62,P＜0.05).The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84,P ＜ 0.05).Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation,and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation.

Objective: To estimate the incidence and mortality of laryngeal cancer in China based on the cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR), and to provide support data for the control and prevention of laryngeal cancer. Methods: The incident and death data of laryngeal cancer in 2014 from 339 cancer registries met the quality criteria of NCCR, and then adopted for analysis. The incident and death number, crude rate, age standardized rate, truncated rate and proportion which stratified by areas (urban/rural) and age were calculated. The nationwide incidence and mortality of laryngeal cancer in 2014 were estimated by combining with those data on national population in 2014. Chinese population census in 2000 and Segi′s population were used for age-standardized incidence/mortality rates. Results: It was estimates that 23.4 thousand new cases of laryngeal cancer occurred in China in 2014. There were 20.8 thousand males and 2.6 thousand females. And 14.5 thousand occurred in urban areas, while 8.9 thousand in rural areas. The age standardized rates of incidence by world standard population (ASRs world) in male, female and both genders were 2.05/100, 000, 0.24/100, 000 and 1.14/100, 000, respectively, whereas those were 1.22/100, 000 and 1.03/100, 000 for urban and rural areas. The incidence was much higher in males than females, and slightly higher in urban areas than those in rural areas. Moreover, it was estimates that 13.2 thousand death cases of laryngeal cancer occurred in China in 2014. There were 11.5 thousand males and 1.7 thousand females. And 7.8 thousand occurred in urban areas, while 5.4 thousand in rural areas. The age standardized rates of mortality by ASRs world in male, female and both genders were 1.08/100, 000, 0.14/100, 000 and 0.60/100, 000, respectively, whereas those were 0.60/100, 000 and 0.59/100, 000 for urban and rural areas. The mortality was much higher in males than females, and slightly higher in urban areas than those in rural areas. In males, the age specific incidence and mortality of laryngeal cancer increased greatly from 40-44 and 45-44 years old, respectively, and peaked at age group of 75-79 and >85 years old. In females, the age specific incidence and mortality increased slowly from 50-54 and 60-64 years old, respectively, and peaked at age group of 80-84 and >85 years old. The trends remained similar in urban and rural areas, except for the different peak ages. Conclusions The incidence and mortality of laryngeal cancer in China are at middle-low levels worldwide, and there are obvious differences between urban and rural areas with distinct gender disparity. Comprehensive prevention and control strategies should be carried out according to local status and age groups.

Objective: To investigate the effects of dexmedetomidine (DEX) on oxidative stress and systemic inflammatory response syndrome(SIRS) during cardiopulmonary bypass (CPB).Methods: Totally 62 patients scheduled for mitral valve replacement surgery were enrolled in this study and randomly assigned to DEX group with constant infusion of DEX (0.5 μg·kg-1 ·h-1 , n =31) and the control group with the same amount of 0.9% sodium chloride injection(n =31).A volume of 4 ml of jugular vein blood was respectively withdrawn before the induction of anesthesia (T0), at 10 min after aortic-off clamping(T1), the end of bypass(T2), 4h after bypass(T3),12h after bypass(T4) and 24h after bypass(T5).The serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6(IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) were determined.Results: The serum CRP in both groups increased remarkably at T1-T5 , while the serum CRP in DEX group was significantly lower than those in the control group at T3-T5.The serum TNF-α increased remarkably in control group at T2-T4, while the serum TNF-α increased remarkably in DEX group at T2-T3;the serum TNF-α in DEX group was significantly lower than those in the control group at T3-T4.The serum IL-6, IL-8, IL-10 in both groups were increased remarkably at T2-T5, T1-T5,T1-T3, respectively.The serum IL-6 and IL-8 in the DEX group were significantly lower than those in the control group at T2-T4 while the serum IL-10 in the DEX group was significantly higher than that in the control group at T1-T3.The serum WBC in both groups at T3-T5 were higher than those at T0, while the serum WBC in the control group was significantly higher than that in the DEX group at T3-T5.However, the differences between the two groups at mechanical ventilation time, ICU observation time, the incidence of postoperative SIRS after 24h, hospitalization days, and the adverse reactions were not statistically significant.Conclusion: DEX has notable protective effects on systemic inflammatory response syndrome during extracorporeal circulation.