The relationship between copper-related protein and neurobehavioral function in individuals with occupational exposure to low-level lead / 中国职业医学

OBJECTIVE: To analyze the relationship between the neurobehavioral functions of individuals exposed to low-level lead and the levels of serum copper-related proteins glutathione S-transferase M1(GSTM1), hypoxia inducible factor-1 alpha(HIF1α), cyclooxygenase 1(COX1) and metallothionein(MT), and to screen biomarkers for changes in neurobehavioral function caused by occupational lead exposure. METHODS: A total of 194 workers who exposed to low-level lead(lead-exposed group) and 120 workers without lead exposure(control group) were selected from a battery factory as the research subjects by judgment sampling method. The inductively coupled plasma-mass spectrometry was used to determine blood lead levels of the two groups, and the State of Mood Scale(POMS) was investigated to assess the emotional state. The computerized neurobehavioral evaluation system in Chinese version 3(NES-C3) was used to test the neurobehavioral ability index(NAI) of related indicators of learning memory and mental activity. Enzyme-linked immunosorbent assay was used to detect the levels of copper-related protein in serum. After using principal component analysis to extract the principal components of emotional state, learning memory and mental activity, multiple linear regression was used to analyze the influencing factors of neurobehavioral function. RESULTS: The blood lead level of the lead-exposed group was increased [(57.15±11.12) vs(177.86±80.04) μg/L, P<0.01], and the incidence of symptoms such as dizziness, memory loss, sleep disturbance, fatigue, weakness, cold sweats in extremities, cold extremities, tingling of extremities, tingling sensation in the distal extremities, tetany, instability of holding things, metallic taste in the mouth, nausea and vomiting, anorexia, constipation, abdominal distension, abdominal pain, toothache/tooth loosening were increased(all P<0.01) compared with the control group. Meanwhile, the scores of tension-anxiety, depression-dejection, fatigue-inertia, anger-hostility, confusion-bewilderment of POMS were increased(all P<0.01), and the scores of vigor-activity were decreased(P<0.01). The NAI of the lead-exposed individuals in the NES-C3 test of 6 indicators(series addition and subtraction, visual retention, memory scanning, listening to digital breadth, visual simple reaction time, target tracking) were lower than that of the control group(all P<0.01). The serum levels of GSTM1 and HIF1α of the lead-exposed group decreased(all P<0.01), and the COX1 and MT levels increased(all P<0.01) compared with the control group. The serum GSTM1, HIF1α, COX1 and MT of the lead-exposed group were correlated with their emotional state, learning and memory and mental activity to varying degrees(all P<0.05). The results of multiple stepwise linear regression showed that serum COX1 level was an independent influencing factor of emotional state(P<0.01), serum GSTM1, COX1 and lead working years were independent influencing factor of learning and memory(all P<0.05), and work length with lead exposure and alcohol consumption was an independent influencing factor of mental activity(all P<0.05). CONCLUSION: Low-level lead exposure can cause central nervous system symptoms in workers, and the change in neurobehavioral function and serum levels of copper-related proteins GSTM1, HIF1α, COX1 and MT. Serum levels of GSTM1 and COX1 can be used as candidate biomarkers for indicating neurobehavioral function caused by lead exposure.

Clinicopathological features and prognosis of colorectal stromal tumor / 北京大学学报(医学版)

OBJECTIVE@#The incidence of colorectal stromal tumor is low among digestive tract tumors, therefore the literatures about clinicopathological features and prognosis of colorectal stromal tumor are few at home and abroad. In this study, we performed survival analyses for colorectal stromal tumor. The nomogram made by prognostic factors provided basis for evaluation of prognosis.@*METHODS@#The clinico-pathological and prognostic data of colorectal stromal tumor between January 1992 and December 2015 were collected from the surveillance, epidemiology, and end results (SEER) database. The survival analyses were made by SPSS 24.0 software. The nomogram and calibration curve were made by RMS package in R 3.5.2 software.@*RESULTS@#In the study, 546 patients with colorectal stromal tumor were included. The median age of onset was 64 years. The regional lymph node metastasis (LNM) rate was 9.4%. The multivariate Cox regression analyses of the 546 cases showed that the older age of onset (>64 years), single or divorce, colon tumor (compared with rectal tumor), non-surgery, high histological grade, LNM and distant metastasis were associated with worse cancer specific survival (CSS) and overall survival (OS), P < 0.05 for all. The treatment district was independent prognostic factor of OS (P = 0.027). The C-index of independent prognostic factors predicting CSS and OS probability were 0.76 (95%CI: 0.72-0.80) and 0.75 (95%CI: 0.72-0.78), respectively. Multivariate analyses were further carried out in the 174 patients with definite histological grade and tumor location, which revealed that the age of onset, histological grade, surgery or not were independent prognostic factors of CSS and OS (P < 0.05 for all). Tumor location was associated with CSS (P = 0.041) but not OS (P = 0.057) among the 174 cases. Four independent prognostic factors influencing the 174 patients' prognosis were used to make nomogram for predicting survival probability of 546 cases. The C-index of four prognostic factors predicting probability of CSS and OS of the 546 cases were separately 0.71 (95%CI: 0.66-0.75) and 0.73 (95%CI: 0.70-0.77). The nomogram had more accuracy for predicting OS probability of colorectal stromal tumors.@*CONCLUSION@#The prognosis of colorectal stromal tumor was affected by multiple clinicopathological factors. The nomogram provided the basis for predicting the survival probability of patients with colorectal stromal tumor.

Effects of Luteolin on Proliferation and Programmed Cell Death of Human Multiple Myeloma Cell RPMI-8226 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Luteolin on proliferation and cell death of human multiple myeloma cell line RPMI-8226 and its mechanisms.</p><p><b>METHODS</b>The effect of Luteolin on the growth of human multiple myeloma cell line RPMI-8226 was detected by CCK-8, and then the minimal effective concentration was determined and was used to treat RPMI-8226 cells. The effects of luteolin and chloroquine on expression of cleaved-caspase 3 and LC3 in RPMI8826 cells was detected by Western blot.</p><p><b>RESULTS</b>The luteolin significant inhibited RPMI-8226 cell proliferation in a dose-dependent manner. Treatment with lutedin 40-80µmol/L for 24 hours and luteolin 20-80µmol/L for 48 hours inhibited RPMI-8226 cell proliferation in a dose-dependent manner (24 h, r= -0.983; 48 h, r= -0.985). After treatment with lutelin 20µmol/L for 48 h, the expression of cleaved caspase3 and LC3 Ⅱ/Ⅰ in RPMI 8826 cells significantly increased; after treatment with chloroquine at the same time, the expression of cleaved-caspase 3 and LC3 Ⅱ/Ⅰ significantly decreased.</p><p><b>CONCLUSION</b>Luteolin inhibits the proliferation of RPMI-8226 cells by inducing the pathways of both apoptosis and autophagy, moreover the actions of apoptosis and autophagy are interactive or/and promotive each other.</p>

Influence of position and radiation technique on organs at risk in radiotherapy of rectal cancer / 华中科技大学学报（医学）（英德文版）

The influence of the position and radiation technique on the organs at risk (OARs) in radiotherapy of rectal cancer was evaluated. The relationship between the volume of irradiated small bowel (VSB) and acute bowel toxicity was determined. A total of 97 cases of rectal cancer were retrospectively randomized to receive radiotherapy with the designated treatment positions and radiation plans. Among 64 patients in the supine position, 32 patients were given three-dimensional conformal radiotherapy (3DCR) and 32 patients were subjected to intensity-modulated radiation therapy (IMRT) respectively. The rest 33 patients were treated with 3DCRT in the prone position with a belly board. The VSB was calculated for doses from 5 to 45 Gy at an interval of 5 Gy. With prescription dose in planned target volume (PTV) of 50 Gy, the dose distribution, conformal index for PTV (CI), dose-volume histogram (DVH) of OARs, the correlation of VSB and the acute toxicity were compared. The results were shown as follows: (1) Among the 3 methods, there were no differences in PTV's converge including V95 and D95; (2) For IMRT under a supine position, CIwas closest to 1, the mean dose of small bowel decreased (P<0.05), and the mean VSB from V30 to V45 significantly decreased (P<0.05). (3) For 3DCRT with a belly board under a prone position, the mean dose and the mean VSB from 40 to 45 Gy were less than those for 3DCRT under a supine position (P<0.05); (4) Mean proportion of VSB was significantly greater in the patients experiencing diarrhea grade 2-4 than in those with diarrhea grade 0-1 at dose levels from V30 to V45 (P<0.05). It was concluded that for the radiotherapy of rectal cancer, IMRT technique might decrease the high-dose VSB to reduce the risk of acute injury. 3DCRT with a belly board under a prone position is superior to 3DCRT under a supine position, which could be a second choice for radiation of rectal cancer.

Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Programmed cell death 5 (PDCD5) is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis (RA) pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 (IL-17), and the assessment of disease activity in RA.</p><p><b>METHODS</b>PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis (OA) were detected using enzyme-linked immunosorbent assay (ELISA). Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and X-ray grading scale were also evaluated.</p><p><b>RESULTS</b>Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable.</p><p><b>CONCLUSIONS</b>PDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.</p>

Wilson's disease: update on integrated Chinese and Western medicine / 中国结合医学杂志

Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism caused by ATP7B gene mutation. As WD is an inherited disease of the nervous system that is not curable; early diagnosis with early and life-long treatment leads to better prognoses. Currently, the recommended treatment for WD is integrated Chinese and Western medicine. A number of studies indicate that treatment of integrative medicine can not only enforce the de-copper effect but also improve liver function, intelligence, and other factors. This article reviewed in detail the advantages of WD treated with Chinese and Western medicine together.

Specific targeting of angiogenesis in lung cancer with RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a 4.7T magnetic resonance scanner / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avβ3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avβ3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer.</p><p><b>METHODS</b>USPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avβ3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avβ3 integrin expression and vessel distribution in A549 tumor xenografts.</p><p><b>RESULTS</b>HUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avβ3 integrin expression.</p><p><b>CONCLUSIONS</b>RGD-USPIO could specifically label avβ3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.</p>

Combined anti-tumor therapeutic effect of targeted gene, hyperthermia, radionuclide brachytherapy in breast carcinoma / 中华核医学杂志

Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P＜0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P ＜0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P ＜ 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.

Functional neuroimagings' investigation based on clinical neuropsychology / 上海第二医科大学学报

Neuropsychology, as well as cognitive neuroscience investigates the process of human cognition using several in vivo systemic approaches in order to explore neural mechanism. Besides the routine clinical neuropsychological assessments, up to date the latest neuroimaging techniques based on acoustics, optics, electricity and magnetism, have been applied to construct three-dimensional neuroimaging representations through mathematic models, and to identify functional areas or lesions in the brain. Presently, the combined use of functional MRI (fMRI) and event related potential (ERP) techniques is pioneering, especially when integrated synchronously.

Effect of gushen pelyuan recipe on Bcl-2 and Bax mRNA expressions in cochlea tissue of rats with Shen-yang deficiency syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Gushen Peiyuan Recipe (GPR) on the expression of Bcl-2 and Bax mRNA in Shen-yang-deficiency (SYD) rats suffering from cochlea apoptosis, thus providing a theoretical basis to the treatment and prevention of sensorineural hearing loss and fill Chinese medine's theory of kidney-ear-correlation with new substance.</p><p><b>METHODS</b>Rats were induced into experimental SYD animal models by injecting cetacort into their buttocks. Rats in the blank and model groups were given 10 mL/kg normal saline by gastrogavage, and 31 g/kg, 15.5 g/kg and 7.5 g/kg GPR were given to the rats in the high, medium and low dose groups by gastrogavage respectively. RT-PCR was adopted to detect the mRNA expressions of Bcl-2 and Bax.</p><p><b>RESULTS</b>Levels of Bcl-2 mRNA expression and Bcl-2/Bax enhanced, and mRNA expression of Bax attenuated in the model rats after GPR treatment, the Bcl-2/Bax ratio increased, showing insignificant difference when compared with the blank control group (P > 0.05).</p><p><b>CONCLUSION</b>GPR plays a significant role in regulating the mRNA expressions of Bcl-2 and Bax, therefore improving the hearing of SYD rats and protecting the structure and function of cochlea.</p>

Repair and re-establishment to traumatic upper cervical instability / 中国骨伤

<p><b>OBJECTIVE</b>To summarize and analyze the therapeutic effect of traumatic upper cervical instability and investigate therapeutic methods and effect.</p><p><b>METHODS</b>There were 19 patients with traumatic upper cervical instability (male 16, female 3), aged from 21 to 56 years,included 3 cases of atlas fracture, 10 cases of dens fracture, 3 cases of axis pedicle fracture, 3 cases of atlanto-axial subluxation. Among them, 6 cases included 1 case of dens fracture, 1 case of dens fracture affiliated with atlas fracture, 1 case of axis pedicle fracture, 3 cases of atlanto-axial subluxation were treated conservatively and the other 13 cases were treated by operations.</p><p><b>RESULTS</b>Nineteen cases were followed up for 1.8 years in average (6 months to 6 years). According to JOA standard for evaluation, the rate of improvement was 42.5% and 87.0% for conservative treatment and operation respectively.</p><p><b>CONCLUSION</b>Traumatic super cervical unsteadiness should be diagnosed and treated early. Under the condition of upper cervical vertebra being completely fixed,the function of cervical vertebra to maximum extent could be reserved when choosing operation method. Especially, the precise fusion of upper cervical vertebra plays a vital role of long-term efficacy.</p>

Expression and significance of HIF-1? and CXCR4 protein in tissues of breast cancer / 上海第二医科大学学报

Objective To investigate the expression of hypoxia-inducible factor-1?(HIF-1?) and chemokine receptor 4(CXCR4) protein in tissues of breast cancer and its association with clinicopathological features.MethodsThe expression of HIF-1? and CXCR4 protein in 60 breast cancer,30 breast fibroadenoma and 20 normal breast samples were detected by immunohistochemistry,and the relationship between the expression of HIF-1? and CXCR4 protein in the tissues of breast cancer and its association with clinicopathological factors were analysed.ResultsThere was no positive expression of HIF-1? and CXCR4 protein in normal breast tissues.The positive expression rates of HIF-1? protein in tissues of breast cancer and breast fibroadenoma were 65.0% and 26.7%,respectively(P