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Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT.

Some functional microorganisms in the soil immobilize heavy metals by adsorption and precipitation, prevent the absorption of heavy metals by crops, and play an important role in the passivation and remediation of medium and mild heavy metal-contaminated soil. A pot experiment was conducted to study the effects of the exogenous polyamine-producing bacterium

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis. In addition, COX2 in tumor cells and tumor-associated macrophages (TAMs) facilitates lymphangiogenesis. We recently reported that aiphanol, a natural stilbenolignan, attenuates tumor angiogenesis by repressing VEGFR2 and COX2. In this study, we evaluated the antilymphangiogenic and antimetastatic potency of aiphanol using in vitro, ex vivo and in vivo systems. We first demonstrated that aiphanol directly bound to VEGFR3 and blocked its kinase activity with an half-maximal inhibitory concentration (IC

BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Additional file 3. Figure S2. The expression of 8-FIRLs in normal and OC samples. (a) The expression of AC138904.1; (b)The expression of AP005205.2; (c) The expression of AC007114.1; (d) The expression of LINC00665; (e) The expression of UBXN10-AS1; (f) The expression of AC083880.1; (g) The expression of LINC01558; (h) The expression of AL023583.1; *P < 0.05; **P < 0.01; ***P < 0.001.

Additional file 1. Table S1. A list of FIRGs

Additional file 2. Figure S1. Calibration curve of nomogram. (a-b) Calibration curve of nomogram based on FIRLs signature for OS prediction at 1 year (a), 3 year (b) , and 5 year (c) in the training set; (d-f) Calibration curve of nomogram based on FIRLs signature for OS prediction at 1 year (d), 3 year (e), and 5 year (f) in the testing set.

Highlights Two-dimensional black phosphorus (2D BP) possesses huge potential in electrochemical energy storage field owing to its unique electronic structure, high charge carrier mobility, and large interlayer spacing.Comparison on the different preparation methods and processes, characteristics, and applications of few-layer BP is presented.The applications of 2D BP in electrochemical energy storage devices in these years are well reviewed., Two-dimensional black phosphorus (2D BP), well known as phosphorene, has triggered tremendous attention since the first discovery in 2014. The unique puckered monolayer structure endows 2D BP intriguing properties, which facilitate its potential applications in various fields, such as catalyst, energy storage, sensor, etc. Owing to the large surface area, good electric conductivity, and high theoretical specific capacity, 2D BP has been widely studied as electrode materials and significantly enhanced the performance of energy storage devices. With the rapid development of energy storage devices based on 2D BP, a timely review on this topic is in demand to further extend the application of 2D BP in energy storage. In this review, recent advances in experimental and theoretical development of 2D BP are presented along with its structures, properties, and synthetic methods. Particularly, their emerging applications in electrochemical energy storage, including Li−/K−/Mg−/Na-ion, Li–S batteries, and supercapacitors, are systematically summarized with milestones as well as the challenges. Benefited from the fast-growing dynamic investigation of 2D BP, some possible improvements and constructive perspectives are provided to guide the design of 2D BP-based energy storage devices with high performance.

CRISPR-Cas provides bacteria and archaea with immunity against invading phages and foreign plasmid DNA and has been successfully adapted for gene editing in a variety of species. The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Here we report the repurposing of CRISPR-Cas13a to inhibit human immunodeficiency virus type 1 (HIV-1) infection through targeting HIV-1 RNA and diminishing viral gene expression. We observed strong inhibition of HIV-1 infection by CRISPR-Cas13a in human cells. We showed that CRISPR-Cas13a not only diminishes the level of newly synthesized viral RNA, either from the transfected plasmid DNA or from the viral DNA, which is integrated into cellular DNA, but it also targets and destroys the viral RNA that enters cells within viral capsid, leading to strong inhibition of HIV-1 infection. Together, our results suggest that CRISPR-Cas13a provides a potential novel tool to treat viral diseases in humans., Graphical Abstract, The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Yin et al. demonstrate that CRISPR-Cas13a targets and cleaves the HIV RNA genome and mRNA, leading to strong inhibition of HIV-1 infection.

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505-527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515-519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.

Asian countries face various developmental issues such as natural disasters, water concerns, urbanization, healthcare, and climate change, and there is the need to develop infrastructure to resolve these issues. This paper first introduces the system of Taiwan's infrastructure quality management and then provides a study on the countermeasures to improve quality management. The findings of the discussions will be collected as an infrastructure maintenance and management reference.

2D transition metal carbides or nitrides, known as MXenes, are a new family of 2D materials with close to 30 members experimentally synthesized and dozens more theoretically investigated. Because o...

(1) Background: The COVID-19 pandemic impacted education systems globally, and numerous strategies were used to transform education into online learning. Caring is recognized as a core competency in nursing, this competency is difficult to cultivate and measure. This study aimed to explore the effect of online team-based learning (TBL) on cultivating nursing students’ caring competency. (2) Method: A mix-methods study design with convenience sampling was used for this study. The intervention was online TBL with field observation. Quantitative data were collected by the modified Peer Caring Measurement (PCM) and analyzed using descriptive and inferential statistics. Qualitative data were collected by dialog in social media and analyzed by content analysis. (3) Result: Both the quantitative and qualitative data showed a significant increase in caring competency. A paired t-test of modified PCM showed significant improvement (p &lt, 0.001), and female students had greater learning performances compared with male students in academic and affective dimensions. Three themes emerged, including that online TBL possesses remarkable benefits, students felt in charge of their learning, and changes in the students’ caring competency were revealed. (4) Conclusion: This online TBL strategy works well in teaching and fostering caring in an online environment among nursing students, which is necessary under COVID-19 restrictions.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-β-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.通过尿生物标志物进行早期诊断和无创性预测对于预防糖尿病肾病(DKD)的进展是重要的，但是，也是有争议的。既往的研究显示，尿肾小管生物标志物(UTBs)与DKD患者中医证候之间有潜在的联系。因此，我们进一步评价尿生物标志物的联合检测在无创性预测早期DKD肾气虚证患者肾损伤程度中的临床意义，并初步揭示UTBs与DKD中医证候之间的潜在生物学联系。将92例2型糖尿病患者分为以下3组，正常白蛋白尿组20例患者，微量白蛋白尿组50例患者，大量白蛋白尿组22例患者。我们发现，在各组患者中，24hUAlb和UACR呈现出逐步而明显的升高。尿胱抑素C(UCysC)、尿N-乙酰1-β-D-氨基葡萄糖苷酶(UNAG)和尿视黄醇结合蛋白(URBP)均显示出逐渐的升高，这与各组患者白蛋白尿的程度相一致。而且，24hUAlb、UACR 与 UCysC、UNAG 和 URBP 分别呈正相关。在72例伴有白蛋白尿的2型DKD患者中，UNAG与URBP呈正相关，UCysC也与UNAG、URBP分别呈正相关。此外，所有患者的中医证候分布特征均与肾气虚证的临床表现相一致。因此，UCysC、UNAG、URBP和UAlb的联合检测可作为一项无创性预测早期2型DKD肾气虚证患者肾损伤程度的实用临床技术。UTBs可能是DKD患者特定中医证候的生物学基础之一。.

Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements. Author summary Retrotransposons occupy more than 40% of human genome, and have co-evolved with humans for millions of years. Long interspersed element type 1 (LINE-1, or L1) is the only retrotransposon that is able to jump to a new locus. LINE-1 retrotransposition causes genome instability, and is associated with genetic diseases including autoimmune diseases and cancer. To suppress this genome toxicity caused by LINE-1, humans have developed multi-layered mechanisms to control LINE-1 activity. MxB has been previously shown to inhibit LINE-1 mobility, thus contributing to host restriction of LINE-1. Here, we further demonstrate that MxB effectively restricts LINE-1 retrotransposition by sequestering LINE-1 ribonucleoprotein (RNP) within the cytoplasmic stress granules, thus guards genome stability. Hence our data attribute the restriction function of MxB to sequestering LINE-1 RNP to stress granules.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

Flipped learning is an instructional model with core features of pre-class learning followed by in- class practice of knowledge through active and collaborative learning. However, non-compliance with pre-class activities is a commonly cited challenge in flipped learning, where a lack of student engagement leads to insufficient pre-class preparation, diminishing flipped learning’s intended benefits significantly as the students will then not participate well in the in-class activities. It lends consideration to the potential obstacles and solutions in increasing students’ engagement in pre-class learning, paving the way to pre-class learning compliance to achieve the full potential of flipped learning in improving students’ learning outcomes. This study uses systematic literature review with qualitative content analysis to identify three main areas, namely technological, pedagogical, and student perceptions, to instil optimal conditions to promote pre-class engagement and preparation.

Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries. Hypothesis/Gap Statement. To better understand the epidemiological trends and characteristics of CRE in the Henan province. Aim. We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China. Methodology. A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla KPC, bla NDM, bla IMP, bla VIM, bla OXA-48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP). Results. The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla KPC, 13 % bla NDM, 6 % bla IMP, and 1 % combined bla KPC/bla NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains. Conclusion. A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

Introduction Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries. Hypothesis/Gap Statement To better understand the epidemiological trends and characteristics of CRE in the Henan province. Aim We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China. Methodology A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla KPC, bla NDM, bla IMP, bla VIM, bla OXA-48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP). Results The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla KPC, 13 % bla NDM, 6 % bla IMP, and 1 % combined bla KPC/bla NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains. Conclusion A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

Initial malarial infection mostly causes symptomatic illness in humans. Infection that is not fatal induces complete protection from severe illness and death, and thus complete protection from severe illness or death is granted with sufficient exposure. However, malaria parasite immunity necessitates constant exposure. Therefore, it is important to evaluate lowered immunity and recurrent susceptibility to symptomatic disease in lower transmission areas. We aimed to investigate selection pressure based on transmission levels, antimalarial drug use, and environmental factors. We whole genome sequenced (WGS) P. falciparum clinical samples from Chinese hosts working in Ghana and compared the results with the WGS data of isolates from native Ghanaians downloaded from pf3k. The P. falciparum samples were generally clustered according to their geographic origin, and Chinese imported samples showed a clear African origin with a slightly different distribution from the native Ghanaian samples. Moreover, samples collected from two host populations showed evidence of differences in the intensity of selection. Compared with native Ghanaian samples, the China-imported isolates exhibited a higher proportion of monoclonal infections, and many genes associated with RBC invasion and immune evasion were found to be under less selection pressure. There was no significant difference in the selection of drug-resistance genes due to a similar artemisinin-based combination therapy medication profile. Local selection of malarial parasites is considered to be a result of differences in the host immunity or disparity in the transmission opportunities of the host. In China, most P. falciparum infections were imported from Africa, and under these circumstances, distinct local selective pressures may be caused by varying acquired immunity and transmission intensity. This study revealed the impact of host switching on the immune system, and it may provide a better understanding of the mechanisms that enable clinical immunity to malaria.

Additional file 3: Table S3. Logistic regression analysis of clinical characteristics associated with clinical remission at 1-year for the total population.

Additional file 2: Table S2. Absolute and percent changes in β cell function at 1-year for subgroups based on DK/DKA history. Data are shown as means ± S.D. DK, diabetic ketosis; DKA, diabetic ketoacidosis.

Additional file 1: Table S1. Absolute and percent changes in β cell function at 1-year for the total population and age-based subgroups. Data are shown as means ± S.D. FCP, fasting C-peptide; PCP, 2-h postprandial C-peptide. ΔFCP ratio was defined as the calibration of changed FCP at 1-year follow-up by its baseline level; ΔPCP ratio was defined as the calibration of changed PCP at 1-year follow-up by its baseline level.

Background: Recently, diabetic nephropathy (DN) becomes a common health problem in China as one of the major microvascular complications of diabetes mellitus. Therefore, the incipient diagnosis and noninvasive detections in clinic by the association of urinary biomarkers are important for preventing the progress of DN. However, the clinical significance of urinary biomarkers is controversial nowadays. This study thereby aimed to further evaluate the clinical significance of the association of urinary biomarkers in noninvasively predicting the renal damaged extent of the early type 2 DN patients with kidney qi deficiency syndrome in an integrated traditional and western medical center, and preliminarily confirm the correlation between urinary tubular biomarkers and the biological bases of DN patients.Methods: Ninety-two patients in an integrated traditional and western medical center of China were categorized into 3 groups, 20 patients with normo-albuminuria, 50 patients with micro-albuminuria, and 22 patients with macro-albuminuria. In addition to urinary albumin (UAlb) and urinary albumin-to-creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate and various urinary tubular biomarkers were tested respectively. Besides, clinical characteristics and kidney asthenia syndrome distribution in all patients were observed. Results: In these 3 groups, 24-h UAlb and UACR showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acety1-β-D-glucosaminidase (UNAG) and urinary retinal binding protein (URBP) synchronously showed gradual increases consistent with albuminuria degree in 3 groups. Moreover, 24-h UAlb and UACR were positively correlated with UCysC, UNAG and URBP. In the 72 DN patients with albuminuria, there was a positive correlation between UNAG and URBP, and UCysC was also positively correlated with UNAG and URBP. Additionally, TCM syndrome distributional characteristics in all patients were consistent with the clinical manifestations of kidney qi deficiency syndrome. Conclusion: In this investigation, we ulteriorly demonstrated that the association within UCysC, UNAG, URBP and UAlb may be used as practical targets in noninvasively forecasting the extent of renal injury in the early type 2 DN patients with kidney qi deficiency syndrome. More importantly, we found that urinary tubular biomarkers may be one of the biological bases of DN patients with the specific traditional Chinese medicine syndrome.