Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

INTRODUCTION: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that ß-hydroxy ß-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. METHODS AND ANALYSIS: In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. ETHICS AND DISSEMINATION: This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: NCT05525039.

Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review / 中国医学科学院学报

Since end-stage renal disease leads to a variety of problems such as disability,reduced quality of life,and mental and psychological disorders,it has become a serious public health problem around the globe.Renal palliative care integrates palliative care philosophy in the care for patients with end-stage renal disease.As a planned,comprehensive,patient-centered care,renal palliative care focuses on the patient's symptoms and needs,aiming to reduce the suffering throughout the course of the disease,including but not limited to end-of-life care.This study reports the palliative care practice for a patient on maintenance dialysis in the Blood Purification Center of Peking Union Medical College Hospital and reviews the present situation of palliative care in end-stage renal disease.

A triple-source CT system for micro-scale investigation of geological materials: A simulation study.

A triple-source CT system is proposed for micro-scale testing of geological materials. This study aims at reducing the projection acquisition time by two-thirds compared to a conventional single-source CT system. The proposed system with different positioning errors in the source-to-object distance (SOD) was simulated and tested using the Shepp-Logan phantom model, as well as slices of sand, glass beads, and concrete samples. Furthermore, the imaging quality of a single-source and the triple-source CT system with different dead detector pixels was compared. The results showed that within the maximum allowable positioning error, the pixel differences between the simulated and the original images are close to zero, and the structural similarities are greater than 0.96. In the presence of dead detector pixels, the quality of the simulated images in the triple-source CT system is superior to that of a single-source CT system. The presented triple-source CT system performs well in high-quality image reconstruction.

The role of osteocytes-specific molecular mechanism in regulation of mechanotransduction - A systematic review.

Background: Osteocytes, composing over 90% of bone cells, are well known for their mechanosensing abilities. Aged osteocytes with impaired morphology and function are less efficient in mechanotransduction which will disrupt bone turnover leading to osteoporosis. The aim of this systematic review is to delineate the mechanotransduction mechanism at different stages in order to explore potential target for therapeutic drugs. Methods: A systematic literature search was performed in PubMed and Web of Science. Original animal, cell and clinical studies with available English full-text were included. Information was extracted from the included studies for review. Results: The 26 studies included in this review provided evidence that mechanical loading are sensed by osteocytes via various sensing proteins and transduced to different signaling molecules which later initiate various biochemical responses. Studies have shown that osteocyte plasma membrane and cytoskeletons are emerging key players in initiating mechanotransduction. Bone regulating genes expressions are altered in response to load sensed by osteocytes, but the genes involved different signaling pathways and the spatiotemporal expression pattern had made mechanotransduction mechanism complicated. Most of the included studies described the important role of osteocytes in pathways that regulate mechanosensing and bone remodeling. Conclusions: This systematic review provides an up-to-date insight to different steps of mechanotransduction. A better understanding of the mechanotransduction mechanism is beneficial in search of new potential treatment for osteoporotic patients. By delineating the unique morphology of osteocytes and their interconnected signaling network new targets can be discovered for drug development. Translational potential of this article: This systematic review provides an up-to-date sequential overview and highlights the different osteocyte-related pathways and signaling molecules during mechanotransduction. This allows a better understanding of mechanotransduction for future development of new therapeutic interventions to treat patients with impaired mechanosensitivity.

Fibrinolysis as a target to enhance osteoporotic fracture healing by vibration therapy in a metaphyseal fracture model.

AIMS: Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. METHODS: A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. RESULTS: All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. CONCLUSION: Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article: Bone Joint Res 2021;10(1):41-50.

Simple Turn-On Fluorescent Sensor for Discriminating Cys/Hcy and GSH from Different Fluorescent Signals.

As a kind of bioactive sulfur species, biothiols (Cys, Hcy, and GSH) play an irreplaceable role in regulating the redox balance of life processes. Because of their similar chemical structures and properties, a sulfydryl group, and an amino group, it is an important challenge to distinguish two or more of them at the same time. Herein, a fluorescent sensor (NTPC) based on the coumarin structure was developed to discriminate Cys/Hcy and GSH simultaneously. The sensor has no fluorescence due to the d-PET effect but displays strong fluorescence after its reaction with biothiols. There are two potential reaction sites (nitrophenyl sulfide group and aldehyde group) in the structure of NTPC, resulting in different fluorescent signal changes after reacting with biothiols (green for Cys and Hcy and red for GSH). Under double-wavelength excitation, the sensor shows low background fluorescence, high selectivity, and low detection limits toward biothiols. Moreover, the sensor can be used to discriminate different biothiols (Cys/Hcy and GSH) in cells and zebra fish by different fluorescence signals with low toxicity and might provide a promising tool for studying the roles of different biothiols in various physiological and pathological processes.

Enhancement of osteoporotic fracture healing by vibration treatment: The role of osteocytes.

The prevalence of osteoporotic fracture is high due to global aging problem. Delayed and impaired healing in osteoporotic fractures increase the socioeconomic burden significantly. Through intensive animal and clinical research in recent years, the pathogenesis of osteoporotic fracture healing is unveiled, including decreased inflammatory response, reduced mesenchymal stem cells and deteriorated angiogenesis, etc. The enhancement of osteoporotic fracture healing is important in shortening hospitalization, thus reducing related complications. Mechanical stimulation is currently the most well-accepted approach for rehabilitation of osteoporotic fracture patients. Some new interventions providing mechanical signals were explored extensively in recent years, including vibration treatment, and osteoporotic fracture healing was found to respond very well to these signals. Vibration treatment could accelerate osteoporotic fracture healing with improved callus formation, mineralization and remodeling. However, the mechanism of how osteoporotic fracture bones sense mechanical signals and relay to bone formation remains unanswered. Osteocytes are the most abundant cells in bone tissues. Cumulative evidence confirm that osteocyte is a type of mechanosensory cell and shows altered morphology and reduced cell density during aging. Meanwhile, osteocytes serve as endocrine cells to regulate bone and mineral homeostasis. However, the contribution of osteocytes in osteoporotic fracture healing is largely unknown. A recent in vivo study was conducted to examine the morphological and functional changes of osteocytes after vibration treatment in an osteoporotic metaphyseal fracture rat model. The findings demonstrated that vibration treatment induced significant outgrowth of canaliculi and altered expression of various proteins (E11, DMP1, FGF23 and sclerostin), particularly osteocyte-specific dentin matrix protein 1 (DMP1) which was greatly increased. DMP1 may play a major role in relaying mechanical signals to bone formation, which may require further experiments to consolidate. Most importantly, vibration treatment significantly increased the mineralization and accelerated the osteoporotic fracture healing in metaphyseal fracture model. In summary, osteocyte is the major cell type to sense mechanical signals and facilitate downstream healing in osteoporotic fracture bone. Vibration treatment has good potential to be translated for clinical application to benefit osteoporotic fracture patients, while randomized controlled trials are required to validate its efficacy.

Scoliosis and associated factors among middle school students in Guangzhou City / 中国学校卫生

Objective@#To investigate the general situation of scoliosis and influencing factors among middle school students in Guangzhou, so as to provide evidence for behavioral intervention measures.@*Methods@#By stratified cluster random sampling method, 2 121 students from 8 middle schools of Guangzhou were selected to conduct questionnaire survey and physical examination.@*Results@#The detection rate of scoliosis among middle school students in Guangzhou was 8.20%, girls (9.50%)＞boys (7.00%), urban area (10.45%)＞suburb area (4.77%), senior high school (10.08%)＞junior school (6.39%) ( P ＜0.05). Among the most of the 174 positive students were found to have large thoracic curve, right lateral bending, being girls with medium scoliosis. Multivariate Logistic regression analysis showed that students in urban area ( OR=2.56, 95%CI =1.71-3.82), with mobile electronic devices usage time≥3 h/d( OR=1.59, 95%CI =1.12-2.27), prolonged near vision work ≥1 h ( OR=1.40, 95%CI =1.00-1.95), outdoor activity time＜2 h/d( OR=1.82, 95%CI =1.24-2.67) had a higher detection rate of scoliosis ( P <0.05).@*Conclusion@#The detection rate of scoliosis among middle school students in Guangzhou is much higher, which might be related to district, mobile electronic devices usage, prolonged near vision work and insufficient outdoor activity. Health education regarding spinal knowledge should be strengthened.

New Insights into the Impact of Ecological Factor on Bioactivities and Phytochemical Composition of Paeonia veitchii.

Paeonia veitchii has been widely distributed in China under different ecological types. Its roots contain diverse phytochemical constituents, which possess very high bioactivities. However, the influence of ecological factors on activities and ingredients of P. veitchii roots still remains unknown. The purpose of this research was to analyze the variation in bioactivities and phytochemical composition of P. veitchii roots upon exposure to various ecological factors. Seven P. veitchii populations collected from different regions in China were evaluated. The results of correlation analysis suggested that four major ecological factors, including average annual temperature, elevation, total potassium, and organic matter, had a strong correlation with the bioactivities of P. veitchii roots. Further, the major ecological factors were also highly correlated with the contents of naringin, gallic acid, benzoylpaeoniflorin, and paeoniflorin. The principal component analysis results supported four major metabolites as the main contributing ingredients. All populations were classified into three groups, G1, G2, and G3, through hierarchical cluster analysis. G1 showed more significant advantages in the above-mentioned four ecological factors, four active ingredients, and bioactivities compared to the other two groups. P. veitchii roots growing at lower average annual temperature, high elevation, rich total potassium and organic matter in the soils were presumed to have relatively higher bioactivities. These data expand the study on the bioactivities and phytochemical composition of P. veitchii roots and have a guiding significance for the ecological factor selection during the cultivation process of this herbaceous peony species.

How much do we know about the role of osteocytes in different phases of fracture healing? A systematic review.

BACKGROUND: Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the mechanistic pathway, cellular events and expression of markers at different phases of healing. METHODS: This systematic review describes the role of osteocytes in fracture healing from early to late phase. Literature search was performed in PubMed and Embase. Original animal and clinical studies with available English full-text were included. Information was retrieved from the selected studies. RESULTS: A total of 23 articles were selected in this systematic review. Most of the studies investigated changes of various genes and proteins expression patterns related to osteocytes. Several studies have described a constant expression of osteocyte-specific marker genes throughout the fracture healing cascade followed by decline phase with the progress of healing, denoting the important physiological role of the osteocyte and the osteocyte lacuno-canalicular network in fracture healing. The reports of various markers suggested that osteocytes could trigger coordinated bone healing responses from cell death and expression of proinflammatory markers cyclooxygenase-2 and interleukin 6 at early phase of fracture healing. This is followed by the expression of growth factors bone morphogenetic protein-2 and cysteine-rich angiogenic inducer 61 that matched with the neo-angiogenesis, chondrogenesis and callus formation during the intermediate phase. Tightly controlled regulation of osteocyte-specific markers E11/Podoplanin (E11), dentin matrix protein 1 and sclerostin modulate and promote osteogenesis, mineralisation and remodelling across different phases of fracture healing. Stabilised fixation was associated with the finding of higher number of osteocytes with little detectable bone morphogenetic proteins expressions in osteocytes. Sclerostin-antibody treatment was found to result in improvement in bone mass, bone strength and mineralisation. CONCLUSION: To further illustrate the function of osteocytes, additional longitudinal studies with appropriate clinically relevant model to study osteoporotic fractures are crucial. Future investigations on the morphological changes of osteocyte lacuno-canalicular network during healing, osteocyte-mediated signalling molecules in the transforming growth factor-beta-Smad3 pathway, perilacunar remodelling, type of fixation and putative biomarkers to monitor fracture healing are highly desirable to bridge the current gaps of knowledge.The translational potential of this article: This systematic review provides an up-to-date chronological overview and highlights the osteocyte-regulated events at gene, protein, cellular and tissue levels throughout the fracture healing cascade, with the hope of informing and developing potential new therapeutic strategies that could improve the timing and quality of fracture healing in the future.

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

Effect of Glucocorticoid Pulse Therapy on Short-term Prognosis of Anti-neutrophil Cytoplasmic Antibodies-associated Glomerulonephritis / 中国医学科学院学报

Objective To investigate the prognosis predictors of anti-neutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis treated with glucocorticoid(GC).Methods The clinicopathological data of patients with biopsy-confirmed ANCA-associated glomerulonephritis were retrospective analyzed by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015. Pathological categories were re-classified. Renal remission rates,infection rates,and death events were compared between intravenous glucocorticoid(GC)pulse therapy group and non-pulse group. Logistic regression analysis was performed to analyze factors influencing the short-term prognosis.Results Among the 81 patients with ANCA-associated glomerulonephritis,49(60.5%)received GC pulse therapy and 32(39.5%)did not. The GC pulse group had significantly lower estimated glomerular filtration rate at baseline(eGFR0)than the non-pulse group(t=3.003,P=0.015)but significantly higher 24-hour urinary protein(24 hUP)(t=2.394,P=0.002)and Birmingham Systemic Vasculitis Activity Score(BVAS)(t=0.049,P=0.013). There was no significant difference in the cumulative amount of cyclophosphamide(CTX)(t=1.336,P=0.245)between these two groups. The overall renal remission rate of GC pulse group in the 6 month was significantly lower(48.7% vs. 79.3%;χ =6.591,P=0.024). Univariate analysis showed that baseline 24 hUP(t=6.222,P=0.017),eGFR0(t=3.727,P=0.046),and pathological category(χ =7.654,P=0.045)were associated with the overall renal remission rate in the 6 month. Multivariate analysis showed the crescent category was an independent factor(OR=20.63,95%CI:2.217-191.973,P=0.008;compared with sclerotic category)for overall renal remission rate in the 6 month,while GC pulse therapy was not an predictor(OR=0.271,95%CI:0.062-1.179,P=0.082). A total of 37 patients experienced infections within 6 months. The infection rate in GC pulse group(55.1%,27/49)was significantly higher than that of non-pulse group(31.3%,10/32)(P=0.042). Univariate regression analysis showed that eGFR0(t=1.912,P=0.049),baseline BVAS(t=-3.360,P=0.001)and GC pulse(χ =6.249,P=0.014)were associated with infection events within 6 months. Multivariate analysis showed that the baseline BVAS was the only predictor with 1.089 times for every 1 point increase in BVAS(OR=1.089,95%CI:1.006-1.179,P=0.034). Conclusions Crescentic category favors renal remission independently compared with sclerotic category. Patients with crescentic category may benefit more from intensive treatment. BVAS acts as an independent risk factor of infection.

Effect of Hope on Self-efficacy and Self-management in Patients with Chronic Kidney Disease(Stages 1-3) / 中国医学科学院学报

Objective To describe the status of hope,self-efficacy,and self-management in patients with chronic kidney disease(CKD)(stages 1-3)and to explore the interactions between these three variables.Methods Herth Hope Index,self-efficacy scale,and CKD self-management instrument were used to evaluate the patients with CKD(stages 1-3)in PUMC Hospital(=153). Structural equation modeling was used to establish the structural equation model of hope,self-efficacy,and self-management.Results The median score of hope was 40.0(36.0,44.5),and 85.0% of patients were in higher level of hope. The median score of self-efficacy was 8.3(7.1,9.4)and the overall score of self-management was 89.0±13.4. There were no significant differences in level of hope and self-management among patients with different age,gender,marital status,educational level,course of disease,and CKD stages(all >0.05). Age and marriage status were significantly associated with self-efficacy. Self-efficacy was significantly higher in >65 years group than in other age groups(<0.05)and was significantly higher in married group than in single group(<0.05).The level of hope had direct effect on self-efficacy(=0.67,<0.05)and self-management(=0.46,<0.05).Conclusions The levels of hope,self-efficacy,and self-management are high in patients with CKD(stages 1-3). Hope directly affects the self-efficacy and self-management of these patients.

C/EBPß enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation.

Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPß, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPß, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPß can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPß may provide more precise therapeutic options in ovarian cancer.

Predictors of Short-term Outcomes of Patients with Peritoneal Dialysis-associated Peritonitis / 中国医学科学院学报

Objective To investigate the risk factors predicting the short-term outcomes of patients with peritoneal dialysis(PD)-associated peritonitis (PDAP). Methods In this retrospective cohort study,the clinical data at baseline and 0-3 months before peritonitis onset (peritonitis-free period) were collected from end-stage renal disease patients who started PD and suffered from PDAP between January 1,2004 and March 31,2017 in Peking Union Medical College Hospital. After 4 weeks of follow-up,these patients were divided into two groups according to the clinical outcomes,namely poor outcome group and good outcome group. Characteristics at baseline and before peritonitis were compared. Risk factors associated with short-term outcomes were also analyzed. Results Totally 162 PDAP patients were enrolled,among whom 55 (34.0%) experienced adverse outcomes and 107 (66.0%) had good outcome. At baseline,the proportion of clinical atherosclerotic vascular disease was significantly higher in poor outcome group than in good outcome group (49.1% vs. 31.8%;χ=4.639,P=0.031),whereas indicators were comparable (all P>0.05). During the peritonitis-free period,significantly higher level of high-sensitivity C-reactive protein (hsCRP) [9.3(2.2,16.3)mg/dl vs. 3.6(1.4,9.5)mg/dl,Z=-2.879,P=0.004],higher proportion of low transport type of peritoneum function (8.7% vs. 1.0%;Z=4.879,P=0.027),and lower creatinine clearance rate [56.7 (45.7,71.1) ml/(min·w·1.73 m)vs. 61.4 (54.5,76.4) ml/(min·w·1.73 m);Z=-2.084,P=0.037] were observed in poor outcome group. Univariate Logistic regression analysis showed the combination of clinical atherosclerotic vascular disease (OR=2.070,95%CI:1.062-4.034,P=0.033) and higher hsCRP before peritonitis (OR=1.032,95%CI:1.001-1.059,P=0.015) were the risk factors of short-term poor outcome in PDAP patients. Multivariate Logistic regression analysis showed that,after the gender,age at peritonitis,PD duration,diabetes,and serum albumin before peritonitis were adjusted,higher hsCRP before peritonitis (OR=1.026,95%CI:1.000-1.052,P=0.046) and comorbidity of clinical atherosclerotic vascular disease (OR=2.105,95% CI:1.014-4.367,P=0.046) were the independent risk factors for the poor outcomes in PDAP patients. Conclusion Higher pre-peritonitis hsCRP and comorbidity of clinical atherosclerotic vascular disease at baseline may predict poor short-term outcomes in PDAP patients.

Clinicopathological Features and Treatment of Renal Impair in Primary Sjögren Syndrome / 中国医学科学院学报

Primary Sjögren syndrome,characterized by autoimmune epithelitis,is a prevalent systemic autoimmune disease involving multiple organs,among which kidney is a major target organ.Tubulointerstitial lesion is the most frequent form,involving proximal tubule,distal tubule,or collecting duct.The disease has an occult onset and may progressively develop into renal function impairment and end-stage renal disease,which can be accompanied with low-molecular-weight proteinuria,renal tubule acidosis and electrolyte disturbance.Pathologically,it is featured by lymphocyte infiltration,renal tubule atrophy,and interstitial fibrosis.Glomerular lesion is less common and usually takes the form of membranoproliferative glomerulitis.Glucocorticoid combined with immunosuppresant is the main treatment option,and B cell-targeted therapy has been reported.Most patients respond well to these treatments.In this article we review the prevalence,clinicopathological features,and treatment of renal disease in primary Sjögren syndrome.

A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy / 中国医学科学杂志(英文版)

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ =18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy / 中国医学科学杂志(英文版)

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm(AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m(six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 mvs. -8.1±21.4 ml/min per 1.73 m, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 mof body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Effectiveness of Peritoneal Dialysis in Treating Adult End Stage Renal Disease Patients with Polycystic Kidney Disease / 中国医学科学院学报

Objective To observe the clinical characteristics,dialysis modalities,and outcomes of end stage renal disease(ESRD)patients with polycystic kidney disease(PKD)and to evaluate the feasibility of peritoneal dialysis in these population. Methods The clinical data of ESRD patient whose primary diagnosis was PKD in Peking Union Medical College Hospital were retrospectively collected from January 1993 to December 2015.PKD patients were divided into two groups according to dialysis modality,namely peritoneal dialysis group(PKD-PD)group and hemodialysis(PKD-HD)group.In addition,we randomly chose non-PKD patients from 622 peritoneal dialysis patients who were matched with PKD-PD patients in age,gender and dialysis time.The primary end point was death.The survival rate was calculated by Kaplan-Meier analysis and the risk factors for suivival were analyzed by Cox regression model. Results Totally 47 PKD patients were enrolled,including 33 patients in PKD-PD group and 14 patients in PKD-HD group,and 42 non-PKD patients as the control group.The average age of PKD patients was(53±11)years,of which 38.3% were women.When compared with PKD-HD group,no significant difference in age,gender,comorbidities,kidney size,and residual glomerular filtration rate were observed in PKD-PD patients at baseline(all P>0.05).The average time on dialysis of PKD-PD patients was(36.2±33.1)months.The weekly urea clearance index(Kt/V)and weekly creatinine clearance were similar to non-PKD-PD group at 3 months,1 year,3 years,and 5 years(all P>0.05).The peritonitis rate was 1 episode/84.5 months.The survival rates at 1 year,3 years,and 5 years of PKD-PD group were 85.7%,78.6%,and 78.6%,which were similar to non-PKD-PD group and PKD-HD group respectively(all P>0.05).Multivariate Cox regression analysis showed that neither PKD nor PD independently predicted the mortality. Conclusion PD can be an option for ESRD patients with PKD.

SIX1 coordinates with TGFß signals to induce epithelial-mesenchymal transition in cervical cancer.

Epithelial-mesenchymal transition (EMT) plays a critical role in promoting tumor invasion and metastasis. However, the key cofactors that modulate the signal transduction to induce EMT have note been fully explored to date. The present study reports that sine oculis homeobox homolog 1 (SIX1) is able to promote EMT of cervical cancer by coordinating with transforming growth factor (TGF)ß-SMAD signals. The expression of SIX1 was negatively correlated with the expression of the epithelial marker E-cadherin in two independent groups of cervical cancer specimens. SIX1 could promote the transition of mesenchymal phenotype in the presence of active TGFß signals in vitro and in vivo. TGFß-SMAD signals were required for the SIX1-mediated promotion of EMT and metastatic capacity of cervical cancer cells. Together, SIX1 and TGFß cooperated to induce more remarkable changes in the transition of phenotype than each of them alone, and coordinated to promote cell motility and tumor metastasis in cervical cancer. These results suggest that the coordination of SIX1 and TGFß signals may be crucial in the EMT program, and that SIX1/TGFß may be considered a valuable marker for evaluating the metastatic potential of cervical cancer cells, or a therapeutic target in the treatment of cervical cancer.