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In this study, a facile fluorescence-scattering ratiometric sensor was designed for visual and selective detection of levodopa (LD) via a clever physicochemical modulation scheme. The alkalized products of LD can rapidly react with polyethyleneimine (PEI) to exhibit an intense blue fluorescence and decrease the second-order scattering (SOS) signal of PEI. As the concentration of LD increased, the fluorescence intensity at 420 nm increased and the SOS intensity at 675 nm decreased synchronously. Thus the fluorescence-scattering ratiometric sensor was constructed by virtue of the two simultaneously changed signals. Furthermore, red light-emitting Au nanoclusters (AuNCs) were added into the above mixture solution to enlarge the SOS signal and provide a stable red background fluorescence. The intensity ratio of fluorescence to SOS (F/(S/S blank )) is linear dependent on C LD in the wide range of 50.0---30000.0 nM, and LD as low as 50.0 nM can be identified with the naked eye via change of fluorescence color. The developed ratiometric sensor is smart, simple and efficient, and has been applied to the convenient assay of LD in real samples. The proposed physicochemical modulation strategy provides a new and facile path for selectively and visually identifying the target from its analogues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C 0 ) and steady-state area-under-curve (AUC 0-24 ) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions., Methods: C 0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC 0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C 0 and AUC 0-24 . An external dataset was used for predictive performance evaluation., Results: Before starting treatment, C 0 can be predicted a priori using the Catboost-based C 0 -ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C 0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C 0 ) in patients have been obtained, AUC 0-24 can be further predicted using the Catboost-based AUC-ML model combined with C 0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%., Conclusion: C 0 -based and AUC 0-24 -based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients., Methods: A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model., Results: XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation., Conclusion: In this study, models based on machine learning technology were established to predict CsA levels 3-4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.

Background: Alzheimer's disease (AD) is a persistent neuropathological injury that manifests via neuronal/synaptic death, age spot development, tau hyperphosphorylation, neuroinflammation, and apoptosis. Synapsin 1 (SYN1), a neuronal phosphoprotein, is believed to be responsible for the pathology of AD., Objective: This study aimed to elucidate the exact role of SYN1 in ameliorating AD and its potential regulatory mechanisms., Methods: The AD dataset GSE48350 was downloaded from the GEO database, and SYN1 was focused on differential expression analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. After establishing an AD rat model, they were treated with RNAi lentivirus to trigger SYN1 overexpression. The amelioration of SYN1 in AD-associated behavior was validated using multiple experiments (water maze test and object recognition test). SYN1's repairing effect on the important factors in AD was confirmed by detecting the concentration of inflammatory factors (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α), neurotransmitters (acetylcholine (ACh), dopamine (DA), and 5-hydroxytryptophan (5-HT)) and markers of oxidative stress (glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS)). Molecular biology experiments (qRT-PCR and western blot) were performed to examine AD-related signaling pathways after SYN1 overexpression., Results: Differential expression analysis yielded a total of 545 differentially expressed genes, of which four were upregulated and 541 were downregulated. The enriched pathways were basically focused on synaptic functions, and the analysis of the protein- protein interaction network focused on the key genes in SYN1. SYN1 significantly improved the spatial learning and memory abilities of AD rats. This enhancement was reflected in the reduced escape latency of the rats in the water maze, the significantly extended dwell time in the third quadrant, and the increased number of crossings. Furthermore, the results of the object recognition test revealed reduced time for rats to explore familiar and new objects. After SYN1 overexpression, the cAMP signaling pathway was activated, the phosphorylation levels of the CREB and PKA proteins were elevated, and the secretion of neurotransmitters such as ACh, DA, and 5-HT was promoted. Furthermore, oxidative stress was suppressed, as supported by decreased levels of MDA and ROS. Regarding inflammatory factors, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in AD rats with SYN1 overexpression., Conclusion: SYN1 overexpression improves cognitive function and promotes the release of various neurotransmitters in AD rats by inhibiting oxidative stress and inflammatory responses through cAMP signaling pathway activation. These findings may provide a theoretical basis for the targeted diagnosis and treatment of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery., Methods: ML models for the prediction of postoperative VTE were trained on a cohort of 11 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots., Results: The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots., Conclusions: A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.

Area prostriata is the primary limbic structure for rapid response to the visual stimuli in the far peripheral visual field. Recent studies have revealed that the prostriata receives inputs not only from the visual and auditory cortices but also from many structures critical for spatial processing and navigation. To gain insight into the functions of the prostriata in spatial learning and memory the present study examines the effects of bilateral lesions of the prostriata on motor ability, exploratory interest and spatial learning and memory using the open field, elevated plus-maze and Morris water maze tests. Our results show that the spatial learning and memory abilities of the rats with bilateral prostriata lesions are significantly reduced compared to the control and sham groups. In addition, the lesion rats are found to be less interested in space exploration and more anxious while the exercise capacity of the rats is not affected based on the first two behavioral tests. These findings suggest that the prostriata plays important roles in spatial learning and memory and may be involved in anxiety as well., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Chen, Zhang, Chen, Xiang, Cai and Ding.)

Aiming to discover novel antifungal agents, a series of 2‑substituted‑4‑amino-quinolines and -quinazoline were prepared and characterized using IR, 1 H NMR, 13 C NMR, and HRMS spectroscopic techniques. Their antifungal activities against four invasive fungi were evaluated, and the results revealed that some of the target compounds exhibited moderate to excellent inhibitory potencies. The most promising compounds III 11 , III 14 , III 15, and III 23 exhibited potent and broad-spectrum antifungal activities with MIC values of 4-32 μg/mL. The mechanism studies showed that compound III 11 (N,2-di-p-tolylquinolin-4-amine hydrochloride) did not play antifungal potency by disrupting fungal membrane, which was quite different from many traditional membrane-active antifungal drugs. Meanwhile, III 11 also demonstrated a low likelihood of inducing resistance, and excellent stability in mouse plasma. In addition, some interesting structure-activity relationships (SARs) were also discussed. These results suggest that some 4‑aminoquinolines may serve as new and promising candidates for further antifungal drug discovery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Spinal pain (SP) is a common condition that has a major negative impact on a patient's quality of life. Recent developments in ultrasound-guided injections for the treatment of SP are increasingly being used in clinical practice. This clinical expert consensus describes the purpose, significance, implementation methods, indications, contraindications, and techniques of ultrasound-guided injections. This consensus offers a practical reference point for physicians to implement successfully ultrasound-guided injections in the treatment of chronic SP., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Lumbar disc herniation is a common disease in the clinical context and does great harm to either the physical or mental health of patients suffering from this disease. Many guidelines and consensus for the diagnosis and treatment of lumbar disc herniation have been published domestically and internationally. According to the expert consensus, clinicians could adopt tailored and personalized diagnosis and treatment management strategies for lumbar disc herniation patients., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Soil erosion will cause a degradation in soil nitrogen supplying capacity (SNSC) and manure amendment is an effective way to restored eroded soils. Both labile fractions of soil organic N (SON) and N transformation enzymes are indicators for SNSC, but the effect of manure amendments on labile SON fractions and the relationship between labile SON fractions and enzyme activities remains unclear. In this study, five degrees of erosion were simulated in Mollisols (removal of 0, 5, 10, 20 and 30 cm of topsoil) to analyse the changes in labile SON fractions and nitrogen transformation enzyme activities after 8-year manure amendment. We found that soil total N (TN), labile SON fractions and enzyme activities all increased after manure amendments. The largest labile SON fraction was particle organic nitrogen (POM-N) and the second was light fraction organic nitrogen (LFOM-N), which accounted >60% for TN in total. Correlation analysis showed that both urease and protease activities were significantly correlated with POM-N, LFOM-N, microbial biomass N and dissolvable organic N, indicating that both urease and protease activities can be used to predict labile SON pools and enzyme activities worked similarly in indicating SNSC with labile SON fractions. Altogether, 8-year manure amendment could recover SNSC of lightly eroded Mollisols to natural levels, i.e. erosion depths at 5 cm and 10 cm; however, it is not able to recover SNSC in Mollisols suffering severe erosion.

Gold(i) phosphinopyridyl clusters [Au 9 (PNC) 6 ](BF 4 ) 3 (1) and [Au 11 (PNC) 6 (PPh 3 ) 2 ](BF 4 ) 5 (2) (PNC = 2-diphenylphosphinopyridyl monoion) are assembled. In contrast to the green luminescence of 1, 2 is brightly orange emissive in CH 2 Cl 2 , which shows the presence of unsupported Au I -Au I interactions in solution. Besides, 1 and 2 can selectively light up the mitochondria of living cells.

Objectives: This study seeks to examine the characteristics and health-related quality of life (HRQL) of patients with uremic peripheral neuropathy., Methods: Uremic patients undergoing maintenance hemodialysis (MHD) at our hospital were enrolled in this study. Data collection began in January 2011 and ended in June 2011. The patients were divided into two groups, the lesion group (110 cases) and the non-lesion group (168 cases), based on the presence or absence of peripheral neuropathy. To examine continuous changes in signs and symptoms in the lesion group, electromyography (EMG) was performed to measure sensory nerve conduction velocity (SCV), motor nerve conduction velocity (MCV), and distal latency (DL). Furthermore, HRQL was analyzed using the generic Short Form-36 (SF-36) questionnaire., Results: Numbness and a burning sensation in the distal limbs were observed in the lesion group; in particular, these phenomena occurred in the upper limbs and the lower limbs in 3.6% (4/110) and 48.2% (53/110) of patients, respectively. With respect to motor symptoms, upper and lower limb weakness was observed in 1.8% (2/110) and 11.8% (13/110) of patients, respectively. Changes in physical signs were mainly evidenced by tendon reflexes, for example, areflexia, or tendon reflex loss was detected in the upper extremities, the knee tendon, and the Achilles tendon in 9.09% (10/110), 55.45% (61/110), and 35.5% (39/110) of patients, respectively. Relative to the non-lesion group, the lesion group had significantly slower average SCV and MCV as well as a longer average DL (p < 0.01 for all comparisons). Based on a clinical statistical analysis of SF-36 reports, scores on each scale were lower in the lesion group than in the non-lesion group. However, compared with the non-lesion group, the lesion group did not significantly differ with respect to overall SF-36 score (t = 1.896, p = 0.060) but did significantly differ with respect to bodily pain score (t = 5.301, p < 0.001)., Conclusions: Typical symptoms of uremic peripheral neuropathy include numbness of the limbs and changes in tendon reflexes. In this study, sensory nerves were damaged more severely than motor nerves, and lower extremity lesions were more frequent than upper limb lesions. Clinicians should devote greater attention to patients with uremic peripheral neuropathy and strive to continuously improve these patients' quality of life.
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A red-near-IR dual-emissive nanocluster with the composition [Au10 Ag2 (2-py-C≡C)3 (dppy)6 ](BF4 )5 (1; 2-py-C≡C is 2-pyridylethynyl, dppy=2-pyridyldiphenylphosphine) has been synthesized. Single-crystal X-ray structural analysis reveals that 1 has a trigonal bipyramidal Au10 Ag2 core that contains a planar Au4 (2-py-C≡C)3 unit sandwiched by two Au3 Ag(dppy)3 motifs. Cluster 1 shows intense red-NIR dual emission in solution. The visible emission originates from metal-to-ligand charge transfer (MLCT) from silver atoms to phosphine ligands in the Au3 Ag(dppy)3 motifs, and the intense NIR emission is associated with the participation of 2-pyridylethynyl in the frontier orbitals of the cluster, which is confirmed by a time-dependent density functional theory (TD-DFT) calculation., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18-75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χtrend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11-12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure., Competing Interests: The authors have no conflicts of interest to disclose.

Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI.

Background: A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage., Methods: Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices., Results: Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that., Conclusions: The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Background: An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease. However, very few researches have examined the skeletal muscle quantity and quality in clinical patients. This study investigated the muscle morphologic changes by magnetic resonance imaging (MRI) and analyzed the related factors in hemodialysis patients., Methods: Fifty-eight patients receiving maintenance hemodialysis (HD) were investigated and 28 healthy adults with gender and age matched were used as controls (Control). Anthropometry, cytokine factors, and laboratory data were measured. The muscle and intermuscular adipose tissues (IMAT) were analyzed via a Thigh MRI. The bicep samples were observed after HE staining. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured and their association with muscle wasting was analyzed., Results: HD patients tended to have a lower protein diet, anthropometry data, and serum albumin, but the C reactive protein and interleukin-6 increased significantly. The MRI showed that HD patients had less muscle mass and a lower muscle/total ratio, but the fat/muscle and IMAT was higher when compared to the Control group. The muscle fiber showed atrophy and fat accumulation in the biceps samples come from the HD patients. Moreover, we found that the HD patients presented with a high level of plasma fasting insulin and increased HOMA-IR which negatively correlated with the muscle/total ratio, but positively with the fat/muscle ratio., Conclusions: Muscle wasting presented early before an obvious malnutrition condition emerged in HD patients. The main morphological change was muscle atrophy along with intermuscular lipid accumulation. Insulin resistance was associated with muscle wasting in dialysis patients.

Objective: To explore the effects of erythropoietin (EPO) on the differentiation and secretion of cultured bone marrow-derived mesenchymal stem cells (BM-MSC) in the microenvironment of acute kidney injury (AKI)., Methods: C57BL/6 murine BM-MSC (mBM-MSC) were successfully isolated by the methods of Percoll density gradient centrifugation and adherence cultivation. The AKI murine model was induced by ischemia/reperfusion (I/R). The homogenate supernatants were prepared for normal and I/R murine kidney. P3-mBM-MSC were treated differently: Group A: low glucose DMEM medium with 10% fetal bovine serum, Group B: normal murine kidney homogenate supernatant intervention, Group C: I/R kidney homogenate supernatant intervention, Group D: I/R kidney homogenate supernatant plus different concentrations of EPO (1, 5, 10, 50 U/ml). Each group was incubated for 1, 3, 5 and 7 days. Inverted microscope was used to observe the morphological changes of these cells and their ultrastructural changes were observed by transmission electron microscope. Cytokeratin-18 was detected by flow cytometry. The levels of bone morphogenetic protein-7 (BMP-7), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were detected by ELISA in culture medium., Results: The cells yielded a high expression of CD29 and CD44 and a low expression of CD34 and CD45. Compared with Groups A and B, the cells of Group C presented oval and short fusiform shapes. After the intervention of EPO, Group D showed a cobble appearance. More organelles were also found. A trace expression of CK18 was found in Groups A and B. A positive expression of CK18 was significantly higher in Groups C and D than Groups A and B (P < 0.01). The expression of EPO 50 U/ml at Day 5 and 7 was higher than Group C of the same time (5 d: 35.22 ± 4.04 vs 8.72 ± 0.38, 7 d: 42.00 ± 5.39 vs 13.20 ± 1.14, both P < 0.01). The results of ELISA showed that the levels of BMP-7, HGF and VEGF in Group C decreased significantly (P < 0.01 or P < 0.05)., Conclusion: The intervention of EPO may boost the differentiation of mBM-MSC but reverse its low secretion.

Background: To identify the risk factors for early kidney damage in hospitalized Chinese patients with chronic kidney disease (CKD)., Methods: A total of 12 multicenter cross-sectional studies were conducted between January 2005 and January 2006 in Chinese CKD patients with estimated glomerular filtration rate (eGFR) equal to or more than 30 mL/min/1.73 m2 in Shanghai. CKD was defined according to the K/DOQI guideline. GFR was estimated by the simplified modification of diet in renal disease equation. The demographic, clinical, and laboratory data were collected through a questionnaire and analyzed among eligible patients stratified by three different CKD groups (CKD stages 1, 2, and 3). The relevant clinical and laboratory risk factors for early kidney damage with a GFR < 90 mL/min/1.73 m2 were determined by logistic regression., Results: A total of 822 CKD patients were enrolled in this study. There were significant differences in age and gender among patients with CKD stages 1, 2, and 3. The prevalence of hypertension, cardiovascular disease, cerebral vascular disease, anemia, and hyperuricemia increases when the eGFR declines. Logistic analysis showed that age, hypertension, anemia, and hyperuricemia were independently associated with early kidney damage., Conclusions: In CKD patients, we have identified only age, hypertension, anemia, and hyperuricemia as the risk factors for early kidney damage. Risk factors should be managed to prevent accelerated kidney damage in CKD patients.

Objective: To study the prevalence, treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control., Methods: We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female. Hypertension was defined as systolic blood pressure (SBP)≥140 and/or diastolic blood pressure (DBP)≥90 mm Hg (1 mm Hg=0.133 kPa). Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey. Hypertension control was defined as blood pressure<140/90 mm Hg before each dialysis session., Results: The prevalence of hypertension in the hemodialysis patients was 86.3%. The treatment rate and control rate in those patients were 96.8% and 25.5% respectively. More than half (50.4%) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more. Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin II receptor blockers (56.4%), centrally acting anti-hypertensive agent (26.4%), beta blockers and alpha, beta-blockers (14.0%). The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease. The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension. The hypertension control rate elevated significantly with the adequate hemodialysis., Conclusions: There is a very high prevalence of hypertension in maintenance hemodialysis patients. Although the treatment rate is high, the control rate is unsatisfactory. So the control of hypertension in hemodialysis patient is still a clinical challenge. Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.

Objective: To investigate the incidence and prognosis of drug-induced acute renal failure (ARF) in Shanghai., Methods: The registration forms of ARF patients admitted in 17 hospitals of and over the middle class in Shanghai from January 1, 2004 to December 31, 2006 were screened prospectively. The data, such as epidemiology, survival, mortality, and morbidity were analyzed., Results: 347 of the 1200 ARF patients (28.9%), 224 males and 123 females, aged (58+/-20), suffered from drug-induced ARF. 51.0% of the 347 patients were older than 60. 60.2% of the drug-induced ARF in the non-surgical departments were community-acquired, while 55.7% of the drug-induced ARF in the surgical departments were hospital-acquired. Among the non-surgical departments, the incidence of hospital-acquired drug-induced ARF was the lowest in the department of nephrology (9.5%), while higher in the departments of hematology, cardiology, and neurology, and among the surgical departments, it was the lowest in department of renal surgery, while higher in the departments of liver transplantation, neurosurgery, and cardiovascular surgery. The most common complication was chronic kidney disease (CKD) (n=69, 19.9%), followed by cerebrovascular disease (n=59, 17.0%), diabetes mellitus (n=43, 12.4%), and hypertension (n=41, 11.8%). Renal biopsy showed acute tubular necrosis (18, 37.5%), acute interstitial nephritis (11, 22.9%), and acute infectious tubulo-interstitial nephritis (6, 12.5%). Antibiotics (47.8%) were the head causes of drug-induced ARF, especially aminoglycoside (17.0%) and cephalosporins (12.7%), followed by diuretics (22.2%) and radiocontrasts (13.3%). 22.5% of the drug-induced ARF patients had used two or more drugs. 119 patients (34.3%) needed renal replacement treatment. 100 of the 347 patients (28.8%) died. 188 of the surviving patients (54.2%) had their renal function recovered completely, the renal function of 42 of them (12.1%) was recovered partially, and 17 of then (4.9%) required dialysis when discharged., Conclusion: Drug-induced ARF is common with higher incidence in the patients with complications. Antibiotics, diuretic agents, and contrast medium are the main causes.

Aim: To construct the fusion gene of transmembrane programmed death ligand (PD-L1) and red fluorescent protein (DsRed2), and to study the expression and effect of the fused PD-L1/pDsRed2-N1., Methods: The cloning technology was employed to construct the PD-L1/pDsRed2-N1 fusion gene. The fusion gene was transfected into NIT cells by lipofectamine. The expression of the fusion gene was determined by flow cytometry (FCM) and inverted phase contrast microscope. The effects on allo-spleen cells proliferation were detected by single mixed lymphocyte reaction. FCM was used to detect the proliferation of spleen cells., Results: The expression of the fusion gene was observed in transiently transfected NIT cells. The fusion protein was expressed on cell membrane. These data suggested that the red fluorescent protein tag did not interfere with the natural assembly and the biological activity of PD-L1 molecule., Conclusion: The PD-L1-RFP fusion gene is constructed successfully and the fusion protein has biological activity.

Objective: To investigate the effects of glycyrrihizic acid (GA) and prednisone on renal injury in chronic aristolochic acid nephropathy (AAN) rat model., Methods: Ninety-eight male Wistar rats of SPF grade were randomly divided into 4 groups, the normal control group (n = 20), the GA group, the model group, and the prednisone group, 26 rats in each group. Rats in the latter 3 groups were made into AAN model by administration of aristolochic acid (AA, contained in extract of Caulis Aristolochiae Manshuriensis) 20 mg/(kg x d) by gastric gavage, and equal volume of drinking water was given to rats in the control group. Medication was started 2 h later, the GA group was treated with GA 25 mg/(kg x d), the prednisone group with prednisone 3.15 mg/(kg x d), and to the other two groups equal volume of drinking water was given. Body weight was measured weekly, renal function related indices and morphology of the renal tissue were examined at the 4th, 8th and 12th weekend., Results: Along with the feeding time, body weight in the control group increased steadily, while that in the treated groups increased slowly. The ratio of serum creatinine/body weight increased markedly in the model group, while it significantly lowered in the treated groups. Morphological examination showed that the structural injury in the treated groups was milder than that in the model group, and its degree of fibrosis was milder also (15% - 20% vs 30%). Electronmicroscopy showed that AA induced, injury degeneration and necrosis of renal tubular epithelial cells, and markedly injured the cell organs, such as mitochondria, and induced nuclear variation, while in the treated groups, it was mainly limited in renal tubule, with normal cell organs, few nucleolus variation and less interstitial collagen fibers., Conclusion: GA and prednisone could reduce the serum creatinine level, improve renal function, relieve the renal morphological changes, and decrease the inter stitial fibrosis, showing a definite preventing effect on chronic AAN in rats.