Imaging the Iodine Sorption-Induced Synchronous Skeleton-Pore Interactions of Single Covalent Organic Framework Particles.

Covalent organic frameworks (COFs) are promising iodine adsorbents. For improved performances, it is critical and essential to fundamentally understand the underlying mechanism. Here, using the operando dark-field optical microscopy (DFM) imaging technique, the observation of an extraordinary structure shrinkage of 2D triphenylbenzene (TPB)-dimethoxyterephthaldehyde (DMTP)-COF upon the adsorption of I2 vapor at the single-particle resolution is reported. Combining single-particle DFM imaging with other experimental and theoretical methods, it is revealed that the shrinkage mechanism of the TPB-DMTP-COF is attributed to the I2 sorption-induced synchronous skeleton-pore interactions. The redox reaction of I2 and TPB-DMTP-COF yields some cationic skeletons and I3 - species, which triggers the multi-directional halogen-bonding interactions of I2 and I3 - as well as strong cation-π interactions between neutral and cationic skeletons, accompanying the synchronous in-plane skeleton shrinking in the xy plane and compact out-of-plane layer packing in the z-direction. This understanding of the synchronous action between the skeleton and pore breaks the perspective on the structure robustness of 2D COFs with excellent stability during the I2 uptake, which offers pivotal guidance for the rational design and creation of advanced microporous adsorbents.

Dual-RPA assay for rapid detection and differentiation of E.granulosus and E.multilocularis.

Echinococcus granulosus (Eg) and Echinococcus multilocularis (Em) are the two most widely prevalent types of echinococcosis. Several diagnostic methods have been developed for detecting Eg and Em. However, some limitations, such as being time-consuming, needing expensive instruments, or exhibiting low sensitivity, make these methods unsuitable for on-site detection. In this study, a dual-RPA assay was established to detect and differentiate Eg and Em. The primer concentration ratio, reaction time, and reaction temperature of the dual-RPA were optimized. The result showed that the primer concentration ratio of Eg:Em was 400 nM:400 nM, and the best amplification efficiency was obtained by reacting at 38 °C for 20 min. The sensitivity, specificity, and repeatability of the assay were also tested. The assay's detection limit for both Eg and Em was 10 copies/µL. The assay showed reasonable specificity by testing ten parasitic nucleic acids. The assay's intra- and inter-batch coefficients of variation were below 10%, which indicates robust reproducibility of the assay. Finally, to validate the performance of the dual-RPA assay, it was compared with real-time PCR by using 86 clinical nucleic acid samples. The coincidence rate of Eg between dual-RPA and TaqMan real-time PCR was 96.51%, and the coincidence rate of Em between dual-RPA and TaqMan real-time PCR was 98.84%, indicating its potential for accurate clinical diagnosis. Therefore, this study established a rapid and sensitive dual-RPA assay that can rapidly detect and differentiate Eg and Em in one reaction tube and provided a new assay for the detection of echinococcosis in the field.

Development of a quantum dots based immunochromatographic strip for rapid and on-site detection of African swine fever virus.

African swine fever (ASF) is a lethal disease caused by ASF virus (ASFV), severely impacting the global swine industry. Though nuclear acid-based detection methods are reliable, they are laboratory-dependent. In this study, we developed a device-independent, user friendly and cost-effective quantum dots based immunochromatographic strip (QDs-ICS) with high specificity and sensitivity for the rapid and on-site detection of ASFV antigen. For the preparation of the QDs-ICS, we generated a monoclonal antibody (mAb) mAb-8G8 and polyclonal antibody (pAb) against ASFV-p72 protein. The pAb was labelled with QDs to be used as the detection probe and the mAb-8G8 was coated on the nitrocellulose membrane as the test line. Our results proved that the strip displayed no cross-reactivity with other swine viruses and detection limit of the QDs-ICS was down to 1 ng/mL for the ASFV-p72 protein with great reproducibility. The strip also exhibited high stability with a storage period up to 12 months under room temperature. Twenty blind samples and one hundred clinical samples were examined by the QDs-ICS, conventional PCR and real-time PCR method, respectively. Results showed that the agreement rate between the QDs-ICS and PCR method was 100%, and the agreement rate between the strip and real-time PCR was 94%. The novel QDs-ICS developed here would be an effective tool for on-site detection of ASFV.

Development of a double antibody sandwich ELISA method for the quantitative detection of serum C-reactive protein based on nanobody.

In this study, we successfully developed a nanobody-based double antibody sandwich ELISA kit for the detection of clinical serum C-reactive protein (CRP) by using two novel CRP specific nanobodies. The developed method exhibited a linear detection range of approximately 6-200 ng/mL, with a detection limit of 1 ng/mL. Furthermore, the method demonstrated excellent specificity, as there was no cross-reactivity with interfering substances such as total bilirubin and hemoglobin and so on. To assess reproducibility, independent measurements of the samples were conducted under experimental conditions, resulting in intra- and inter-batch coefficients of variation below 10% and a recovery rate of 93%-102%. These results indicate robust reproducibility of the method. To evaluate the performance of the developed kit, we collected 90 clinical samples for correlation analysis with commercial kits. The results showed a high correlation coefficient value (R2) of 0.98, indicating accurate concordance between the developed and commercial kits. In conclusion, our study successfully developed a nanobody-based double antibody sandwich ELISA kit to detect clinical serum CRP. The utilization of nanobodies represents a significant advancement in the field of CRP immunoassay development. The developed kit demonstrates excellent performance characteristics and holds promise for clinical applications.

Development and characterization of a novel nanobody with SRMV neutralizing activity.

Peste des petits ruminants (PPR) is an acute, contact infectious disease caused by the small ruminant morbillivirus (SRMV), and its morbidity in goats and sheep can be up to 100% with significant mortality. Nanobody generated from camelid animals such as alpaca has attracted wide attention because of its unique advantages compared with conventional antibodies. The main objective of this study was to produce specific nanobodies against SRMV and identify its characteristics. To obtain the coding gene of SRMV-specific nanobodies, we first constructed an immune phage-displayed library from the VHH repertoire of alpaca that was immunized with SRMV-F and -H proteins. By using phage display technology, the target antigen-specific VHHs can be obtained after four consecutive rounds of biopanning. Results showed that the size of this VHH library was 2.26 × 1010 CFU/mL and the SRMV-F and -H specific phage particles were greatly enriched after four rounds of biopanning. The positive phage clones were selected and sequenced, and total of five independent different sequences of SRMV-specific nanobodies were identified. Subsequently, the DNA fragments of the five nanobodies were cloned into E. coli BL21(DE3), respectively, and three of them were successfully expressed and purified. Specificity and affinity towards inactivated SRMV of these purified nanobodies were then evaluated using the ELISA method. Results demonstrated that NbSRMV-1-1, NbSRMV-2-10, and NbSRMV-1-21 showed no cross-reactivity with other antigens, such as inactivated BTV, inactivated FMDV, His-tag labeled protein, and BSA. The ELISA titer of these three nanobodies against inactivated SRMV was up to 1:1000. However, only NbSRMV-1-21 displayed SRMV neutralizing activity at a maximum dilution of 1:4. The results indicate that the nanobodies against SRMV generated in this study could be useful in future applications. This study provided a novel antibody tool and laid a foundation for the treatment and detection of SRMV.

Transformer-Based Multilabel Deep Learning Model Is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on Magnetic Resonance Imaging and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and externally validated on retrospectively collected ankle magnetic resonance imaging (MRI) between April 2016 and March 2022 respectively at 3 centers. Included patients had confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multilabel paradigm. A transformer-based multilabel DL model (AnkleNet) was developed and compared with 4 convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUCs of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which were significantly higher than those of CNN-based models (all P < .001). In terms of further CAI diagnosis, there was a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = .042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSIONS: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially patients with RCAI. CLINICAL RELEVANCE: Developing such an algorithm can improve the diagnostic performance of clinicians, aiding in identifying patients who would benefit from arthroscopy, such as patients with RCAI.

An Aggregation-induced Emission Probe to Detect the Viscosity Change in Lipid Droplets during Ferroptosis.

Ferroptosis is a recently identified form of cell death characterized by iron-dependent lipid peroxidation. Understanding the effects of lipid peroxidation on cellular processes during ferroptosis requires insights into lipid droplets (LDs) and their viscosity changes. To gain further insights into the intricacies of ferroptosis, it is crucial to have a fluorescent probe that targets LDs and responds to changes in viscosity. In this study, we introduce a novel LD-targeting viscosity fluorescent probe named TQE, based on the principles of aggregation-induced emission (AIE). The probe displayed AIE characteristics in tetrahydrofuran, possessing a partition coefficient (logP) of 5.87. With increased viscosity, intramolecular rotation was restricted, leading to a remarkable 3.3-fold enhancement in emission. Notably, TQE exhibited robust resistance to photo-bleaching during cellular imaging, maintaining approximately 75% of its emission intensity even after 30 min of laser irradiation. Importantly, the AIEgen could not generate hydroxyl radicals when exposed to light for up to 3 h, suggesting the low photo-toxicity of TQE to cells. Leveraging these properties, we successfully employed the probe for fluorescent imaging of the viscosity change in LDs during ferroptosis.

[Finite element analysis of the effect of knee movable unicompartmental prosthesis insertion shape and mounting position on stress distribution in the knee joint after replacement].

In unicompartmental replacement surgery, there are a wide variety of commercially available unicompartmental prostheses, and the consistency of the contact surface between the common liner and the femoral prosthesis could impact the stress distribution in the knee after replacement in different ways. Medial tibial plateau fracture and liner dislocation are two common forms of failure after unicompartmental replacement. One of the reasons is the mismatch in the mounting position of the unicompartmental prosthesis in the knee joint, which may lead to failure. Therefore, this paper focuses on the influence of the shape of the contact surface between the liner and the femoral prosthesis and the mounting position of the unicompartmental prosthesis on the stress distribution in the knee joint after replacement. Firstly, a finite element model of the normal human knee joint was established, and the validity of the model was verified by both stress and displacement. Secondly, two different shapes of padded knee prosthesis models (type A and type B) were developed to simulate and analyze the stress distribution in the knee joint under single-leg stance with five internal or external rotation mounting positions of the two pads. The results showed that under a 1 kN axial load, the peak contact pressure of the liner, the peak ACL equivalent force, and the peak contact pressure of the lateral meniscus were smaller for type A than for type B. The liner displacement, peak contact pressure of the liner, peak tibial equivalent force, and peak ACL equivalent force were the smallest for type A at 3° of internal rotation in all five internal or external rotation mounting positions. For unicompartmental replacement, it is recommended that the choice of type A or type B liner for prosthetic internal rotation up to 6° should be combined with other factors of the patient for comprehensive analysis. In conclusion, the results of this paper may reduce the risk of liner dislocation and medial tibial plateau fracture after unicompartmental replacement, providing a biomechanical reference for unicompartmental prosthesis design.

Polymorphic membrane protein 20G: A promising diagnostic biomarker for specific detection of Chlamydia psittaci infection.

Psittacosis is a zoonotic disease caused by Chlamydia psittaci (C. psittaci), leading to high risk for animal industry and human health. Lack of reliable commercial kits and effective vaccines is hampering control of C. psittaci infection. Polymorphic outer membrane protein Gs (PmpGs) are enriched in diverse C. psittaci, and its role are unclear during C. psittaci infection. In the present study, pmp20G gene was cloned into pET-28a vector and then the constructed plasmid was transferred into Escherichia coli Rossetta (DE3). After denaturation and renaturation, the recombinant Pmp20G-N was identified by SDS-PAGE and Western blot. Afterwards Pmp20G-N was used as the coating antigen to develop an indirect ELISA (I-ELISA) assay. Both the specificity and sensitivity of Pmp20G-N ELISA were 100%, while the MOMP-ELISA had 93.65% sensitivity and 98.94% specificity, respectively. The concordance between MOMP-ELISA and Pmp20G-N ELISA assay was 98.1%. Hence, Pmp20G-N ELISA has the potential to be a diagnostic antigen for detection C. psittaci antibody. However, further studies are needed to be done for differentiating C. psittaci from Chlamydia spp. and other C.psittaci-specific serovars using Pmp20G-N ELISA.

Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p.

miRNAs are a family of short, noncoding RNAs that are involved in many processes in melanoma cells. MITF acts as a master regulator of melanocyte function, development and survival by modulating various genes. Hydroxyurea (HU) is used to treat melanoma, and miRNA expression is altered after HU treatment in B16 melanoma cells. In this study, we screened for miRNAs that were upregulated after HU treatment and that targeted the MITF gene. We found that miR-7013-3p exhibited increased expression after HU treatment and could bind to MITF. miR-7013-3p inhibited melanin production, proliferation, and migration and promoted apoptosis in B16 melanoma cells. The results may provide more information on the roles of miR-7013-3p in B16 melanoma cells.

Lipopolysaccharide inhibits triglyceride synthesis in dairy cow mammary epithelial cells by upregulating miR-27a-3p, which targets the PPARG gene.

The fat content of milk determines the quality of milk, and triglycerides are the major components of milk fat. Milk fat synthesis is regulated by many factors. Lipopolysaccharide (LPS) has been shown to inhibit milk fat synthesis in bovine mammary epithelial cells, but research on the underlying mechanisms has been limited. MicroRNA (miRNA) are involved in many physiological processes, but there have been few studies on their regulation in milk fat synthesis. In this study, we aimed to investigate whether LPS upregulates miR-27a-3p, which targets PPARG, thereby inhibiting the synthesis of triglycerides in a dairy cow mammary epithelial cell line (MAC-T). After LPS stimulation of MAC-T cells, PPARG gene expression and milk fat synthesis were inhibited. TargetScan software was used to predict miRNA targeting PPARG, and miR-27a-3p was selected as a candidate. A dual luciferase reporter assay further confirmed the targeting connection between miR-27a-3p and the PPARG gene. To investigate the functions of miR-27a-3p, miR-27a-3p mimic and inhibitors were transfected into MAC-T cells. The mRNA and protein levels of PPAR-γ were negatively correlated with the expression of miR-27a-3p. Lipid droplet accumulation and triglyceride synthesis were also negatively correlated with miR-27a-3p expression. Inhibition of miR-27a-3p partially reversed the LPS-induced decreases in PPARG expression and milk fat synthesis. In summary, our results reveal that LPS can inhibit MAC-T cell milk fat synthesis by upregulating miR-27a-3p, which targets the PPARG gene.

Differentially expressed lncRNA-m433s1 regulates FSH secretion by functioning as a miRNA sponge in male rat anterior pituitary cells†.

Long noncoding RNAs (lncRNAs) are important regulators that have multiple functions in a variety of biological processes. However, the contributions of lncRNAs to follicle-stimulating hormone (FSH) secretion remain largely unknown. In this study, we first identified a novel lncRNA, lncRNA-m433s1, as an intergenic lncRNA located in the cytoplasm. We next used MS2-RIP assays to demonstrate that lncRNA-m433s1 interacted with miR-433. Furthermore, we detected the levels of lncRNA-m433s1, miR-433, and Fshß expression, FSH concentrations, and apoptosis upon overexpression and knockdown of lncRNA-m433s1, revealing that lncRNA-m433s1 upregulated Fshß expression. Globally, lncRNA-m433s1 reduced the inhibitory effect of miR-433 on Fshß and further regulated FSH secretion as a competing endogenous RNA (ceRNA) by sponging miR-433. This ceRNA model will provide novel insight into the regulatory mechanisms of lncRNAs associated with rat reproduction.

Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open-label, 2:1 randomized, treat-to-target trial.

AIMS: To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin. MATERIALS AND METHODS: We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes. RESULTS: Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified. CONCLUSIONS: The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial.

AIM: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). RESEARCH DESIGN AND METHODS: In this multicentre, double-blind, active-controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24. RESULTS: Data from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m2 ; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P < .001) or metformin plus placebo (-2.8%; P = .034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. CONCLUSIONS: Saxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naïve Chinese patients with type 2 diabetes, and was well tolerated.

Saxagliptin add-on therapy in Chinese patients with type 2 diabetes inadequately controlled by insulin with or without metformin: Results from the SUPER study, a randomized, double-blind, placebo-controlled trial.

This prospective, multicentre, phase III study (NCT02104804) evaluated the efficacy and safety of saxagliptin add-on therapy in Chinese patients with type 2 diabetes inadequately controlled by insulin ± metformin. Patients with glycated haemoglobin (HbA1c) 7.5% to 10.5% and fasting plasma glucose (FPG) <15 mmol/L (270 mg/dL) on stable insulin therapy (20-150 U/d) were randomized (1:1) to saxagliptin 5 mg once daily (N = 232) or placebo (N = 230) for 24 weeks, stratified by metformin use. The primary efficacy measure was change in HbA1c. Saxagliptin treatment resulted in a greater adjusted mean change in HbA1c from baseline to week 24 than placebo (-0.58%; P < .001), irrespective of metformin use, and a greater mean change in FPG (0.9 mmol/L [-15.9 mg/dL]; P < .001). More patients achieved HbA1c <7% with saxagliptin (11.4%) than with placebo (3.5%, P = .002). Adverse events and incidence of hypoglycaemia were similar in both groups. Overall, add-on saxagliptin 5 mg once daily significantly improved glycaemic control without increasing hypoglycaemia risk and was well tolerated in Chinese patients with type 2 diabetes inadequately controlled by insulin (± metformin).

A Quninolylthiazole Derivatives as an ICT-Based Fluorescent Probe of Hg(II) and its Application in Ratiometric Imaging in Live HeLa Cells.

As a structural analogue of pyridylthiazole, 2-(2-benzothiazoyl)-phenylethynylquinoline (QBT) was designed as a fluorescent probe for Hg(II) based on an intramolecular charge transfer (ICT) mechanism. The compound was synthesized in three steps starting from 6-bromo-2-methylquinoline, with moderate yield. Corresponding studies on the optical properties of QBT indicate that changes in the fluorescence ratio of QBT in response to Hg(II) could be quantified based on dual-emission changes. More specifically, the emission spectrum of QBT before and after interactions with Hg(II) exhibited a remarkable red shift of about 120 nm, which is rarely reported in ICT-based fluorescent sensors. Finally, QBT was applied in the two-channel imaging of Hg(II) in live HeLa cells.

[Tripterygium glycosides in treatment of henoch-schonlein purpura nephritis: a systematic review of randomized controlled trials].

To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG for HSPN. Two researchers independently screened the literature according to inclusion criteria and exclusion criteria, extracted data, and evaluated the quality of the literature. After completion, cross-checking was performed and Meta-analysis was performed using RevMan 5.3 software. At the same time, different outcomes of the interventions were analyzed subgroupically. A total of 46 RCTs were included, with 1 659 in the experimental group and 1 596 in the control group. All the clinical studies showed a low quality. In terms of complete remission rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.82，95%CI[1.39，2.39];RR=2.03，95%CI[1.37，2.99]），the group with TG+GC performed better than the group with GC（RR=1.46，95%CI[1.32，1.60]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.35，95%CI[0.16，0.75]）. In terms of total effective rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.44，95%CI[1.19,1.74];RR=1.30，95%CI[1.16，1.46]），the group with TG+GC performed better than the group with GC（RR=1.27，95%CI[1.21，1.34]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.60，95%CI[0.43，0.85]）. No significant difference was found between the group with TG+GC and LEF+GC（RR=0.68，95%CI[0.30，1.53]）. In terms of urinary protein, urine occult blood negative time，the group with TG performed better than the group with conventional therapy（MD=-9.00，95% CI[-11.99，-6.01];MD=-12.00，95%CI[-16.13，-7.87]），the group with TG+GC performed better than the group with GC（MD=-8.86，95%CI[-10.08，-7.64];MD=-16.24，95%CI[-23.80，-8.67]）. In terms of recurrence rate, the group with TG+GC was lower than the group with GC（RR=0.13，95%CI[0.06，0.25]）, but there were no significant difference between the group with TG and conventional therapy（RR=0.43，95%CI[0.15，1.19]）. In adverse reactions, the common adverse effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and the adverse reactions are relatively safe. Due to the generally low methodological quality of the included studies, which affected the accuracy and reliability of the result. Therefore, more high-quality, large samples and multi-center randomized controlled trials are necessary for further evidence.

A case of fulminant type 1 diabetes associated with acute renal failure.

A 56-year-old man suffered from severe diabetic ketoacidosis which was complicated by acute renal failure and rhabdomyolysis. Before admission the patient had had flu-like symptoms for 5 days and had developed polyuria and polydipsia. The clinical examination on admission showed his plasma glucose level was 80.65 mmol/L while the HbA1c was 7.4%. His amylase concentration was high without any signs of pancreatitis. The islet-associated autoantibodies (GAD antibody, islet cell antibody) were absent. These data were compatible with the diagnosis of fulminant type 1 diabetes. A continuous intravenous insulin infusion therapy was given during the acute phase to control hyperglycemia and ketoacidosis. This patient remained dependent on continuous veno-venous hemofiltration (CVVHF) for 5 days, followed by regular kidney dialysis for three times, before his renal function was finally recovered. To conclude, this is a rare case of abrupt onset fulminant type 1 diabetes with the onset of acute renal failure. Hence, early detection, quick diagnosis and immediate treatment are very important. In particular, prompt CVVHF and kidney dialysis are required and useful for rescuing the renal function.

Association of the ENPP1 K121Q polymorphism with susceptibility to type 2 diabetes in different populations: evidence based on 40 studies.

The K121Q gene polymorphism of ectoenzyme nucleotide pyrophosphate phosphodiesterase 1(ENPP1) has been widely investigated, however, results have been somewhat conflicting. The aim of this meta-analysis was to establish a precise estimation of the association between ENPP1 gene polymorphisms and type 2 diabetes (T2D). A literature search in PubMed, Embase, Cochrane Library and China Biology Medicine (CBM) databases was conducted on publications published prior to November 21(st), 2013. The combined odds ratio (OR) with 95% confidence intervals (95% CI) was calculated to estimate the strength of the association using a random-effects/fixed-effects model. Statistical analyses were performed using the STATA 11.0 software. For the overall population, there was a significant association between ENPP1 gene polymorphisms and T2D when comparing the Q allele versus K allele (OR = 1.29, 95% CI 1.16-1.44, p = 0.000). Considering diverse ethnic groups, effect sizes were consistent for patients of Caucasian and Asian descent (OR = 1.20, 95% CI = 1.08-1.33 and OR = 1.47, 95% CI = 1.15-1.89, respectively); however, effect size was not consistent for those of African descent. Under other models of inheritance, significant associations were also observed. Sensitivity analyses did not leading to differing he results. In summary, the Q allele of the ENPP1 K121Q gene may contribute to the susceptibility for T2D in Caucasians and Asians.