Objective To explore the effects of Tepp-46, a pyruvate kinase M2 (PKM2) agonist, on the skin fibrosis of patients with systemic scleroderma (SSc) and its therapeutic effect on the SSc mouse models. Methods Full-thickness skin tissues of SSc patients and healthy controls were taken, and the expression levels of PKM2 and α-smooth muscle actin (α-SMA) were detected using immunohistochemical staining. The skin primary fibroblasts were isolated from the tissues, and the PKM2 protein expression was detected using Western blotting. SSc fibroblasts were stimulated with Tepp-46 of different concentrations, and Western blotting was used to measure the expression of PKM2, collagen type Ⅰα1 (ColⅠα1) and α-SMA protein after the stimulation. The C57BL/6 mice were randomly divided into three groups: control group, bleomycin (BLM) group and Tepp-46 group. BLM was injected subcutaneously to establish the SSc mouse model, at the same time, Tepp-46 treatment initiated in the Tepp-46 group. At 21 d after modeling, the mice were executed and their skins were taken. HE staining and Masson staining were used to analyze morphological changes of the skin. The immunohistochemical staining was used to examine the expression of PKM2 and α-SMA protein in the mouse skin. Western blotting was used to analyze the expression of ColⅠα1 and PKM2 in the mouse skin. Results Compared with the healthy controls, α-SMA protein expression in the dermis of SSc patients was higher, and PKM2 protein expression in the epidermis and dermis of SSc patients increased (P＜0.000 1). PKM2 protein expression in primary fibroblasts of SSc skin was higher than that of healthy controls (P＜0.01); after Tepp-46 stimulation, the levels of ColⅠα1 and α-SMA in SSc fibroblasts decreased (P＜0.01), but PKM2 protein was not affected. In the mice, HE and Masson stainings showed that compared with BLM group, the pathological changes of skin were alleviated in the Tepp-46 group. The immunohistochemical staining results showed the levels of PKM2 and α-SMA in the skin of Tepp-46 group were lower than those of the BLM group (P＜0.000 1). Western blotting results showed the level of ColⅠα1 in the Tepp-46 group was lower than that in the BLM group (P＜0.001). Conclusions The expression of PKM2 protein in SSc skin tissue and primary fibroblasts is up-regulated, and PKM2 agonist Tepp-46 can inhibit SSc skin fibrosis.

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.

Objective::This study aimed to evaluate the major adverse cardiovascular and cerebrovascular events (MACCEs) and overall safety profile associated with iodixanol in Chinese patients undergoing percutaneous coronary intervention (PCI).Methods::Patients at 30 centers in China registered in the OpenClinic v3.6 database from October 30, 2013, to October 7, 2015, were included in the study. The primary endpoint was in-hospital MACCEs including target lesion revascularization (TLR), stroke, stent thrombosis, cardiac death, and PCI-related myocardial infarction (MI) within 72 h post-PCI. Secondary endpoints were MACCEs from 72 h to 30 d post-PCI and other safety events within 30 d post-PCI.Results::A total of 3,042 patients were enrolled. The incidence of MACCEs within 72 h post-PCI was 2.33% ( n = 71), including cardiac death (0.03%, n = 1) and PCI-related MI (2.30%, n = 70). The incidence of MACCEs from 72 h to 30 d post-PCI was 0.16% ( n = 5), including cardiac death (0.10%, n = 3), PCI-related MI (0.03%, n = 1), and TLR for stent thrombosis (0.03%, n = 1). The incidence of composite angiographic or procedural complications was 2.86% ( n = 87); 233 (7.86%) patients had results suggesting contrast-induced acute kidney injury. Conclusions::These findings indicate that the use of iodixanol in Chinese patients undergoing PCI is associated with a low incidence of MACCEs, confirming its safety in this population.

Objective::This study aimed to evaluate the major adverse cardiovascular and cerebrovascular events (MACCEs) and overall safety profile associated with iodixanol in Chinese patients undergoing percutaneous coronary intervention (PCI).Methods::Patients at 30 centers in China registered in the OpenClinic v3.6 database from October 30, 2013, to October 7, 2015, were included in the study. The primary endpoint was in-hospital MACCEs including target lesion revascularization (TLR), stroke, stent thrombosis, cardiac death, and PCI-related myocardial infarction (MI) within 72 h post-PCI. Secondary endpoints were MACCEs from 72 h to 30 d post-PCI and other safety events within 30 d post-PCI.Results::A total of 3,042 patients were enrolled. The incidence of MACCEs within 72 h post-PCI was 2.33% ( n = 71), including cardiac death (0.03%, n = 1) and PCI-related MI (2.30%, n = 70). The incidence of MACCEs from 72 h to 30 d post-PCI was 0.16% ( n = 5), including cardiac death (0.10%, n = 3), PCI-related MI (0.03%, n = 1), and TLR for stent thrombosis (0.03%, n = 1). The incidence of composite angiographic or procedural complications was 2.86% ( n = 87); 233 (7.86%) patients had results suggesting contrast-induced acute kidney injury. Conclusions::These findings indicate that the use of iodixanol in Chinese patients undergoing PCI is associated with a low incidence of MACCEs, confirming its safety in this population.

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.

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]. CONCLUSIONS 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.
Blood Glucose ; Creatinine ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Humans ; Prospective Studies

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 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.