Objective To investigate the impaired characteristics of working memory in Parkinson's disease patients with depression and the recovery status of working memory after antidepressant treatment.methods Totally 60 cases were enrolled in this study and divided into three groups:30 Parkinson's disease patients with depression (PD-D),15 Parkinson's disease patients without depression (PD) and 15 persons without Parkinson's disease as normal controls.All subjects were evaluated with Wechsler Memory Scale (WMS-R) audio-visual span,Tower of Hanoi (TOH) and Wisconsin Card Sorting Test (WCST).30 PD-D patients were randomly divided into two subgroups:routine treatment subgroup (8 weeks levodopa therapy) and antidepressant combined treatment subgroup (8 weeks levodopa + citalopram therapy).The evaluation of Hamilton Depression Scale (HAMD),WMS-R audio-visual span,TOH and WCST were performed on these two groups before and after treatment.Result s① There were significant differences comparing PD-D and PD groups with the normal control group in scores of WMS-R,TOH and WCST indicators (P<0.05).There were significant differences in WMS-R visual span,accuracy rate and speed of TOH,as well as the percent errors and percent perseverative responses of WCST comparing PD-D group(11.88±5.91,0.420±0.345,0.408±0.334,0.882±0.253,0.565±0.229) with PD group (15.87±5.21,0.768±0.167,0.634±0.232,0.493±0.161,0.327±0.122) (P<0.05).② Before and after treatment in PD-D routine treatment subgroup,there were significant differences in digital memory and audio-visual memory of WMS-R((6.73±3.72,5.95±3.13) vs (3.77±2.16,1.91±1.58)),accuracy rate of TOH(0.45±0.26 vs 0.23±0.13),as well as percent errors((-0.58±0.17) vs (-0.37±0.14)),percent perseverative responses((-0.32±0.15) vs (-0.14±0.09)),percent conceptual level responses(0.38±0.09 vs 0.13±0.07) and number of categories completed(3.27±1.56 vs 1.06±0.91) of WCST(P<0.05).③ After 4-week treatment and 8-week treatment,there were significant differences in HAMD score comparing PD-D antidepressant combined treatment group(16.33±2.72,10.27±2.66) with PD-D routine treatment group(21.73±2.28,18.4±2.47) (P<0.05).Conclusion Comparing Parkinson's disease patients without depression,the impaired working memory is more serious and extensive in Parkinson's disease patients with depression.Antidepressant treatment can improve the working memory of Parkinson's disease patients with depression.

Objective To study the relationship between serum cystatin C(Cys C)level and the development of insulin resistance(IR)in elderly patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional survey research involving 757 elderly patients with T2DM was performed and patients were divided into groups according to Cys C and IR levels.Serum 1evels of fasting insulin (FBI),fasting blood glucose(FPG),fasting C-peptide (FCP),glycosylated hemoglobin A1 c (H bA1 c),homeostasis model assessment of insulin resistance (IR) (HOMA2 IR-C),homeostasis model assessment of insulin secretion,homeostasis model assessment of insulin sensitivity(HOMA2-％ S-C),micro-albuminuria(mALB)and serum lipid were measured and compared among the groups.Possible influence factors were adjusted,and the correlation between Cys C levels and IR was analyzed.The influencing factors on IR were also analyzed.Results There were statistically significant differences in ages,course of T2 DM,FBI,FCP,HbA1c,urinary mALB,IR,insulin secretion,insulin sensitivity,morbidity rate of coronary heart disease,hypertension and diabetic nephropathy among the three groups(allP＜0.05).Insulin sensitivity was decreased with the increase of Cys C level,while others were increased.Among 757 patients,the level of serum Cys C was positively correlated with FCP,HOMA2-IR C levels,and was negatively correlated with HOMA2-％ S-C levels(P＜0.05).Multiple logistic regression analysis showed that the higher level of Cys C was independent risk factors for IR in elderly T2DM patients(OR=3.41,95％CI:2.22-5.22,P＜0.05).Conclusions Serum Cys C level is closely related with IR in elderly T2DM,and the elevated level of serum Cys C is one of independent risk factors for elderly T2DM.

Objective To investigate the effects of trimebutine maleate (TM) on the expression of large conductance calcium-activated potassium channel (BKCa) and ryanodine receptors (RyR)channels at mRNA and protein level in colonic smooth muscle cell of cold restraint stress(CRS)induced rats.Methods A total of 24 Wistar rats were divided into CRS group,CRS with TM group and control group equally.The rats of CRS group were gavaged with 0.9％NaCl (6 ml/kg) daily; the rats of CRS with TM group were gavaged with 15 g/L TM (6 ml/kg) daily and activity was restricted in wire cage at 4 ℃ for two hours,continuously for five days.The rats of control group were gavaged with 0.9 ％ NaCl (6 ml/kg) once without CRS.The amount and characteristics of stool of rats in each group were observed.The colonic smooth muscle was isolated to detect the expression of BKCa and RyR at mRNA and protein level by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results The median of rats defecation particles of CRS group was six,control group was one and CRS with TM group was five.Compared with control group,the defecation appearance of CRS group and CRS with TM group was looser and wetter observed by naked eyes.Compared with control group,there was no obvious pathological changes in CRS and CRS with TM group.There was no significant difference in the mRNA expression of BKCa and RyR channels between control group and CRS group.Compared with control group,the BKCa expression at mRNA level of CRS with TM group increased 1.45 fold.Compared with control group,the RyR2 expression at mRNA level of CRS with TM group increased 1.32 fold.Compared with control group,the BKCa expression at protein level of CRS with TM group increased 1.39 fold,and there was no RyR2 expression band at protein level.Conclusion TM might affect colonic smooth muscle contraction through the upregulation of BKCa expression at mRNA and protein level and RyR expression at mRNA level.

Objective To investigate proliferation and apoptosis of colonic epithelial cells from ulcerative colitis (UC)patients with active new-onset,remission and active recurrent stages,and to study the effects of 5-aminosalicylic acid (5-ASA)on proliferation and apoptosis of colonic epithelial cells during the treatment of inducing remission and maintanence remission. Methods From January 2002 to December 2012,twelve patients with mild-to-moderate UC who received treatment and long-term follow-up and achieved remission with 5-ASA and received long-term maintanence treatment with it were assigned to UC group.At the same period,10 healthy individuals with negative endoscopy results or solitary colonic polyp were assigned to control group.The biopsy tissues from colonoscopy for pathological examination of patients in UC group at new-onset active stage,remission stage and recurrence stage were obtained.Levels of proliferation marker Ki-67 and apoptosis of colonic epithelial cells were determined by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)assay,respectively.Data were expressed by median(lower quartile,upper quartile).Kruskal-Wallis test and Mann-Whitney test were performed to compare the differences between groups and Bonferroni method was used for correction.Results The median proliferation indexes (PI)of colonic epithelial cells of UC patients at new-onset active period,remission period and recurrent active period were 31 .65 % (19.14%,39.66%), 12.30% (11 .11 %,14.10%) and 44.15 % (33.65 %,52.45 %), respectively,which were all higher than those of control group (7.89% (6.54%,8.86%))there were statistically significant differentes among four groups (H =30.033,P <0.01 );those of new onset active period and recurrent active period were both higher than remission period,and the differences were statistically significant (all P <0.05/6).The median apoptosis indexes (AI)of colonic epithelial cells in UC patients at new-onset active period,remission period and recurrent active period were 24.18%(17.81 %,27.16%),44.19% (43.41 %,50.55 %),41 .24% (33.78%,46.24%),respectively,which were all higher than those of control group (2.65 %(2.48%,2.98%)),there were statistically significant differences among four groups (H =31 .563,P <0.01);and those of remission and recurrent active period were both higher than new-onset active period (all P <0.05/6).The median apoptosis/proliferation ratios of control group,new onset active period,remission period and recurrent active period were 0.320 0 (0.275 5 ,0.425 0),0.749 9 (0.634 9,1 .115 8 ),3.282 8 (3.133 1 ,4.406 8 )and 1 .008 2 (0.801 9, 1 .099 2),respectively,there were statically significant differences among four groups (H =29.441 ,P <0.01);those of new onset active period and recurrent active period were both lower than that of remission period and the differnces were statistically significant (both P <0.05/6 ).Conclusions Proliferation and apoptosis imbalance in colonic epithelial cells of UC patients is one of the important mechanisms for the pathgensis of UC.5-ASA does not promote the proliferation of epithelial cells during UC remission period.

Objective To explore the effect of total flavonoids of astragalus (TFA) on the apoptosis of endothelial cells induced by serum of uremia patient .Methods The serum of 22 healthy volunteers and 25 uremia patients receiving regularly hemodialysis were enrolled in the study .HUVECs were used as research objects ,which were divided into control group(adding serum of healthy people when cell synchronized) and uremia group (adding serum of uremia patient when cell synchronized ) .Low dose ,moderate dose and high dose group were prepared by adding 0 .5 ,1 .0 ,2 .0 mg/mL TFA respectively 6 h before cell synchronization .After 24 hours′culture since the serum were added ,the morphological change of endothelial cells were observed by microscopy ,proliferation activities were tested by using MTT ,SOD activities were tested by using xanthine oxidase method ,NO levels were measured by u-sing nitrate reductase colorimetric method ,DNA damage was detected by using comet assay ,the morphological change of apoptosis was observed by using TUNEL method .Results Compared with the control group ,the proliferation activity ,SOD activity ,NO lev-els were lower in uremia group(P< 0 .01) ,DNA tailing rate ,apoptosis index(AI) significantly increased (P<0 .01) .Compared with cells of uremia group ,cell proliferation activity of all the TFA intervention groups increased (P<0 .05) ,NO levels also in-creased (P<0 .01) .Compared with uremia group ,moderate and high dose group′s SOD activity increased (P<0 .05) ,DNA damage tailing rate decreased (P<0 .05) .Conclusion Total flavonoids of astragalus reduces apoptosis of HUVECs induced by serum of uremia patient ,the possible mechanism is associated with the decrease of oxidative stress .

Aim To construct a eukaryotic expression vector of human MCHR2 and to analyze the stable expression and signal transduction pathways of MCHR2 in CHO cells. Methods The full-length MCHR2 cDNA fragment was amplified by PCR from the human fetal brain cDNA library and inserted into eukaryotic expres-sion vector pcDNA3.1(+), resulted in the recombinant expression vector pcDNA3.1-MCHR2. The recombinant plasmid was confirmed by the restriction enzymatic digestion and DNA sequencing analysis, and then transfected into CHO cells by lipofectamine. A stably-transfected cell line was obtained by the dominant G418 selection, and the expression of the MCHR2 gene on transcription and translation levels were identified by RT-PCR and Western blot. Signal transduction pathways mediated by MCHR2 were analyzed by measurement of intracellular cAMP and calcium. Results The eukaryotic expression vector pcDNA3.1-MCHR2 was successfully constructed and the MCHR2 gene was stably transfected into CHO cells. A stably-transfected cell line was established and the MCHR2 gene was efficiently transcribed and translated. MCH stimulation had no effect on the production of cAMP, however, it could induce a clear and transient increase of intracellular calcium, suggesting that MCHR2 was only coupled to Gq protein. Conclusion The stable expression of MCHR2 and analysis of its signal transduction pathways in CHO cell line provided a solid experimental foundation for further studies on the function of the MCHR2 gene in vitro.

Palliative and hospice care is an emerging medical care model for the development of modern medicine,and its emergence is not only a sign of social demand and the development of human civilization,but also an important manifestation of the change in the modern medical model.Hospice care is the final stage of palliative care,which is of great significance for the end-of-life treatment of incurable diseases.Palliative and hospice care has become an independent discipline in many countries,and its development has been rapid.However,the develop-ment of hospice and palliative care in China is not satisfactory,and the lack of money and human resources are the main reasons limiting its development.Many scholars have carried out a lot of useful practices in this regard.How to explore a road of hospice and palliative care development suitable for China′s national conditions is an urgent problem to be solved.By reviewing domestic and foreign literature,this paper summarizes the development mode and payment method of palliative and hospice care abroad,identifies the challenges encountered in the practice of hospice care in China,and draws on the development experience of palliative and hospice care in foreign countries.We aimed to identify pain points and difficulties faced in developing palliative and hospice care in China,so as to better serve patients at the end of life,gradually promote the concept of palliative and hospice care,and contribute to the sustainable development of palliative and hospice care in China.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

A total of 115 patients with type 2 diabetes recruited from Quanzijie Township Health Service Center were divided into integrated management group (n=54) and specialist management group (n=61). Patients in integrated management group were managed by specialists, general practitioners (GPs) and community nurses jointly; while patients in specialist management group were managed by specialists only. Subjects were followed up every 4 weeks for 24 weeks. Total 366 person/time diabetes education courses were given to subjects in integrated management group during the intervention. After intervention, the fasting glucose, 2 h postprandial glucose and glycosylated hemoglobin were decreased significantly in both groups (P<0.05), while the triglyceride level in the integrated management group was significantly lower than that in the specialist management group (P<0.05). In conclusion, patients with type 2 diabetes managed by integrated mode can achieve similar glucose control effect as specialist management mode in primary care settings and their triglyceride level can be also significantly decreased.

Objective: To explore the effect of "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" on diabetic nephropathy (DN) in primary medical institutions. Methods: Patients with type 2 diabetes admitted to Quanzijie Health Clinic of Jimusar County of Xinjiang Uygur Autonomous Region from October 2017 to March 2018 were enrolled. The Patients were divided into co-management group or specialist management group according to their administrative villages. The treatment plans of the two groups were formulated with reference to the current guidelines. The subjects of the co-management group were jointly managed by a fixed team composed of diabetes specialists from Jimusar Traditional Chinese Medicine Hospital, community general practitioners and community nurses from Quanzijie Health Clinic, and required to attend diabetes education courses every month. The diabetes specialist of Jimusar Traditional Chinese Medicine Hospital was responsible for the formulation and management of the treatment plan of the research object. Follow-up was fulfilled once every 4 weeks for 24 weeks in two groups. Before and after intervention, blood glucose, blood pressure, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) as well as the utilization rate of angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor blocker (ACEI/ARB) were collected. Results: A total of 115 patients accomplished this study with 54 patients in co-management group and 61 patients in specialist management group. After 24 weeks of intervention, fasting glucose level, postprandial glucose level 2 hours after breakfast, glycosylated hemoglobin (HbA1c), Log UACR in co-management group and specialists management group were significantly decreased compared with baseline [fasting glucose level (mmol/L): 8.06±1.92 vs. 9.16±2.83, 8.21±2.10 vs. 9.06±1.89; postprandial glucose level 2 hours after breakfast (mmol/L): 12.26±3.78 vs. 14.11±5.28, 12.47±3.63 vs. 14.00±3.88; HbA1c: 0.074±0.014 vs. 0.082±0.023, 0.076±0.014 vs. 0.081±0.016; Log UACR (mg/g): 1.63±1.56 vs. 2.25±1.44, 1.84±1.65 vs. 2.43±1.56, all P < 0.05], but there was no statistical significance between the two groups [fasting glucose level (mmol/L): -1.10±0.47 vs. -0.85±0.36, postprandial glucose level 2 hours after breakfast (mmol/L): -1.85±0.88 vs. -1.53±0.68, HbA1c: -0.008±0.004 vs. -0.006±0.003, Log UACR (mg/g): -0.61±0.29 vs. -0.59±0.29, all P < 0.05]. There were no significant changes in blood pressure, serum creatinine and eGFR in the two groups before and after intervention. There were 18 and 24 patients with hypertension in co-management group and specialist management group, respectively. The utilization rates of ACEI/ARB in both groups after intervention were significantly higher than those before intervention [88.9% (16/18) vs. 22.2% (4/18), 95.8% (23/24) vs. 29.2% (7/24), both P < 0.01]. At the end of the study, the utilization rate of ACEI/ARB was similar between the two groups [88.9% (16/18) vs. 95.8% (23/24), P > 0.05]. Conclusion Both "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" can effectively decrease glucose levels and UACR levels of patients with type 2 diabetes as well as the standard use of antihypertensive agents, which has positive effects on the prevention and treatment on DN.