STGIC: A graph and image convolution-based method for spatial transcriptomic clustering.

Spatial transcriptomic (ST) clustering employs spatial and transcription information to group spots spatially coherent and transcriptionally similar together into the same spatial domain. Graph convolution network (GCN) and graph attention network (GAT), fed with spatial coordinates derived adjacency and transcription profile derived feature matrix are often used to solve the problem. Our proposed method STGIC (spatial transcriptomic clustering with graph and image convolution) is designed for techniques with regular lattices on chips. It utilizes an adaptive graph convolution (AGC) to get high quality pseudo-labels and then resorts to dilated convolution framework (DCF) for virtual image converted from gene expression information and spatial coordinates of spots. The dilation rates and kernel sizes are set appropriately and updating of weight values in the kernels is made to be subject to the spatial distance from the position of corresponding elements to kernel centers so that feature extraction of each spot is better guided by spatial distance to neighbor spots. Self-supervision realized by Kullback-Leibler (KL) divergence, spatial continuity loss and cross entropy calculated among spots with high confidence pseudo-labels make up the training objective of DCF. STGIC attains state-of-the-art (SOTA) clustering performance on the benchmark dataset of 10x Visium human dorsolateral prefrontal cortex (DLPFC). Besides, it's capable of depicting fine structures of other tissues from other species as well as guiding the identification of marker genes. Also, STGIC is expandable to Stereo-seq data with high spatial resolution.

Assessment of Dynamic Cerebral Autoregulation During Long-Term Exposure to High Altitude in Normal Subjects by Ultrasonography.

PURPOSE: To evaluate changes in dynamic cerebral autoregulation (CA) during short-term and long-term exposure to high altitude with ultrasonography, and also study the sex differences in the response of CA to altitude. METHODS: We assessed the differences in dynamic CA and measured with Doppler ultrasound of the bilateral internal carotid artery (ICA), vertebral artery (VA), and middle cerebral artery (MCA) and the values of basic information within 48 hours and at 2 years after arrival at Tibet in 65 healthy Han young Chinese volunteers, meanwhile, we compared the resistance index (RI) and pulsatility index (PI) of the right MCA at inhale oxygen 8 minutes when a newcomer with 2 years after arrival at Tibet. RESULTS: With 2 years of altitude exposure, the SaO2 of all subjects was above 90%, the mean PEF, DAP, and HR values decreased, HGB increased compared within 48 hours in same-gender groups. Comparisons of cerebral hemodynamics between before 2 years and after 2 years within male and female groups, the mean RI and PI values of bilateral MCA after 2 years were significantly higher than before 2 years, at the same time, the mean RI and PI values of bilateral ICA were significant differences (P < .05) between male groups, with regard to female groups, showed that the mean RI and PI values of bilateral VA were significant differences (P < .05). Comparisons of Right MCA hemodynamics between after oxygen uptake 8 minutes and 2 years, the mean RI and PI values were no significant difference within male and female groups (P > .05). CONCLUSIONS: Acute mountain sickness could result from an alteration of dynamic autoregulation of cerebral blood flow, but the impaired autoregulation may be corrected with the extension of time, furthermore, the response of CA to altitude in males and females are different.

CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play important roles in cancers. Here, we characterized circVMP1 (hsa_circ_0006508), an important circRNA which promoted glycolysis and disease progression in colorectal cancer (CRC). In this study, we aimed to explore the mechanism by which circVMP1 regulated tumor glycolysis and its related pathways in promoting CRC cell proliferation and metastasis. METHODS: The expression level of circVMP1 in CRC tissues and adjacent normal tissues was detected using quantitative PCR. In vitro and in vivo functional experiments were used to evaluate the effects of circVMP1 in the regulation of CRC cell proliferation and migration. Mitochondrial stress tests and glycolysis stress tests were conducted to detect the effect of circVMP1 on oxidative phosphorylation and glycolysis. Dual-luciferase reporter and RNA immunoprecipitation assays were used to evaluate the interaction between circVMP1, miR-3167, and HKDC1. RESULTS: We demonstrated that the level of circVMP1 was significantly upregulated in CRC tissues compared with normal tissues. In HCT116 and SW480 cells, overexpression of circVMP1 promoted proliferation, metastasis, and glycolysis. In vivo analysis indicated that circVMP1 accelerated the proliferation of xenograft tumors. As for the mechanism, overexpression of circVMP1 increased the levels of hexokinase domain component 1 (HKDC1) through competitive binding with miR-3167. CONCLUSION: Our study reported that circVMP1 was one of the tumor driver genes that promoted CRC malignant progression and glycolysis by upregulating HKDC1. CircVMP1/miR-3167/HKDC1 was a signaling axis that might be a target for CRC therapy.

Remarkable Second Harmonic Generation Response in (C5H6NO)+(CH3SO3)-: Unraveling the Role of Hydrogen Bond in Thermal Driven Nonlinear Optical Switch.

Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5 cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (∆n(Zeiss) = 0.216 vs ∆n(cal.) = 0.202 at 546 nm; Δn(Immersion) = 0.210 vs ∆n(cal.) = 0.198 at 589.3 nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.

[Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. / å­¦é¾„å‰å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è¡€æ¸ å¶é ¸ã€ç»´ç”Ÿç´ B12æ°´å¹³åŠå ¶ä¸Žç¥žç»å‘è‚²ç‰¹å¾çš„å ³è”.

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.

BACKGROUND: The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). METHODS: A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. RESULTS: For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively. CONCLUSION: The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.

DIMBOA-induced gene expression, activity profiles of detoxification enzymes, multi-resistance mechanisms, and increased resistance to indoxacarb in tobacco cutworm, Spodoptera litura (Fabricius).

Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is one of the most destructive insect pests owned strong resistance to different insecticides. Indoxacarb as a novel oxadiazine insecticide becomes the main pesticide against S. litura. DIMBOA [2,4-dihydroxy-7-methoxy-2 H-1,4-benz-oxazin-3(4 H)-one] is involved in important chemical defense processes in corn plants. However, the insects' adaptation mechanism to insecticides when exposed to defensive allelochemicals in their host plants remains unclear. Here, we assessed multi-resistance, and resistance mechanisms based on S. litura life history traits. After 18 generations of selection, indoxacarb resistance was increased by 61.95-fold (Ind-Sel) and 86.06-fold (Dim-Sel) as compared to the Lab-Sus. Also, DIMBOA-pretreated larvae developed high resistance to beta-cypermethrin, chlorpyrifos, phoxim, chlorantraniliprole, and emamectin benzoate. Meanwhile, indoxacarb (LC50) was applied to detect its impact on thirty-eight detoxification-related genes expression. The transcripts of SlituCOE073, SlituCOE009, SlituCOE074, and SlituCOE111 as well as SlGSTs5, SlGSTu1, and SlGSTe13 were considerably raised in the Ind-Sel strain. Among the twenty-three P450s, CYP6AE68, CYP321B1, CYP6B50, CYP9A39, CYP4L10, and CYP4S9v1 transcripts denoted significantly higher levels in the Ind-Sel strain, suggesting that CarEs, GSTs and P450s genes may be engaged in indoxacarb resistance. These outcomes further highlighted the importance of detoxification enzymes for S. litura gene expression and their role in responses to insecticides and pest management approaches.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

The α-Subunit of the Chloroplast ATP Synthase of Tomato Reinforces Resistance to Gray Mold and Broad-Spectrum Resistance in Transgenic Tobacco.

Chloroplast ATP synthase (cpATPase) is responsible for ATP production during photosynthesis. Our previous studies showed that the cpATPase CF1 α subunit (AtpA) is a key protein involved in Clonostachys rosea-induced resistance to the fungus Botrytis cinerea in tomato. Here, we show that expression of the tomato atpA gene was upregulated by B. cinerea and Clonostachys rosea. The tomato atpA gene was then isolated, and transgenic tobacco lines were obtained. Compared with untransformed plants, atpA-overexpressing tobacco showed increased resistance to B. cinerea, characterized by reduced disease incidence, defense-associated hypersensitive response-like reactions, balanced reactive oxygen species, alleviated damage to the chloroplast ultrastructure of leaf cells, elevated levels of ATP content and cpATPase activity, and enhanced expression of genes related to carbon metabolism, photosynthesis, and defense. Incremental Ca2+ efflux and steady H+ efflux were observed in transgenic tobacco after inoculation with B. cinerea. In addition, overexpression of atpA conferred enhanced tolerance to salinity and resistance to the fungus Cladosporium fulvum. Thus, AtpA is a key regulator that links signaling to cellular redox homeostasis, ATP biosynthesis, and gene expression of resistance traits to modulate immunity to pathogen infection and provides broad-spectrum resistance in plants in the process.

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases.

AIM: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). METHODS: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01-2.68; female: HR, 1.68; 95% CI, 1.02-2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97-2.64; female: HR, 1.58; 95% CI, 0.95-2.61) in the fully adjusted model. CONCLUSIONS: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.

Synchronized fractionation and phase separation in binary colloids.

Fractionation is necessary for self-assembly in multicomponent mixtures. Here, reversible fractionation and crystallization are realized and studied in two-dimensional binary colloids which are supersaturated by enhancing the attraction between colloidal particles. As a deep and fast supersaturation results in gels with a uniform distribution of binary particles, a gradual quasistatic supersaturation process leads to a two-step crystallization in which small particles and large particles are fractionated as coexisting crystal and liquid phases respectively. Fractionation occurs as well in the quasistatic melting of gels. We show that the synchronized fractionation and phase separation arises from the competition between the size-dependent repulsion and the tunable attraction. The results in this study demonstrate a robust mechanism of fractionation via phase separation, and have important implication in understanding the reversible formation of membraneless organelles in living cells.

Comprehensive Understanding of Polyester Stereocomplexation.

We report a comprehensive understanding of the stereoselective interaction between two opposite enantiomeric polyesters prepared from the regioselective copolymerization of chiral terminal epoxides and cyclic anhydrides. For many of the resultant polyesters, the interactions between polymer chains of opposite chirality are stronger than those of polymer chains with the same chirality, resulting in the formation of a stereocomplex with an enhanced melting point (Tm) and crystallinity. The backbone, tacticity, steric hindrance of the pendant group, and molecular weight of the polyesters have significant effects on stereocomplex formation. Bulky substituent groups favor stereocomplexation, resulting in a greater rise in Tm in comparison to the component enantiomeric polymers. The stereocomplex assembly of discrete (R)- and (S)-poly(phenyl glycidyl ether-alt-phthalic anhydride)s oligomers revealed that the minimum degree of polymerization required for stereocomplex formation is five. Raman spectroscopy and solid-state NMR studies indicate that stereocomplex formation significantly restricts the local mobilities of C═O and C-H groups along the backbone of chains. The reduced mobility results in the enhanced spin-lattice relaxation time and both 1H and 13C downfield shifts due to the strong intermolecular interactions between R- and S-chains.

Carbon nanotube computer.

The miniaturization of electronic devices has been the principal driving force behind the semiconductor industry, and has brought about major improvements in computational power and energy efficiency. Although advances with silicon-based electronics continue to be made, alternative technologies are being explored. Digital circuits based on transistors fabricated from carbon nanotubes (CNTs) have the potential to outperform silicon by improving the energy-delay product, a metric of energy efficiency, by more than an order of magnitude. Hence, CNTs are an exciting complement to existing semiconductor technologies. Owing to substantial fundamental imperfections inherent in CNTs, however, only very basic circuit blocks have been demonstrated. Here we show how these imperfections can be overcome, and demonstrate the first computer built entirely using CNT-based transistors. The CNT computer runs an operating system that is capable of multitasking: as a demonstration, we perform counting and integer-sorting simultaneously. In addition, we implement 20 different instructions from the commercial MIPS instruction set to demonstrate the generality of our CNT computer. This experimental demonstration is the most complex carbon-based electronic system yet realized. It is a considerable advance because CNTs are prominent among a variety of emerging technologies that are being considered for the next generation of highly energy-efficient electronic systems.

Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort Study of 1965 Cases.

BACKGROUND: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. METHODS: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m2, and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52-3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62-4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07-1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08-1.27), respectively, in the fully adjusted model. The multivariate -logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. CONCLUSIONS: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.

Expression of inflammatory cytokines in serum and peritoneal fluid from patients with different stages of endometriosis.

OBJECTIVE: To investigate the level of inflammatory cytokines in endometriosis patients, and explore the relationship between IL-37 concentration and endometriosis stages. METHODS: Inflammatory cytokine concentrations from 27 patients with different stages of endometriosis and 52 controls without endometriosis were examined by ELISA. Then, the specificity and sensitivity of cytokines for distinguishing from controls and the different stages of endometriosis were analyzed using the ROC curve. RESULTS: The difference in serum concentrations of IL-37, IL-17A, IL-10, and IL-2 between the endometriosis and control groups was statistically significant (p < .01). Compared with controls, significantly higher levels of serum IL-37 and IL-10, and significantly lower levels of serum IL-17A and IL-2 were detected in patients with endometriosis (p < .01). Furthermore, IL-2 concentration was significantly higher in peritoneal fluid (PF) in the endometriosis group (p = .0034), IL-10 concentrations in PF were significantly lower in the early-stages of endometriosis than in the more advanced groups (p = .0439), and IL-4 concentration in PF was significantly higher in more advanced endometriosis (p = .0228). The sensitivity and specificity of serum IL-37 for distinguishing endometriosis were 81.48% and 83.33%, respectively, and the cutoff concentration was 69.84 pg/ml. For IL-17A, the sensitivity and specificity were 96.30% and 100%, respectively, and the cutoff concentration was 57.54 pg/ml. For IL-10, the sensitivity and specificity was 92.59% and 100%, respectively, and the cutoff concentration was 3.301 pg/ml. For IL-2, the sensitivity and specificity were 74.07% and 93.75%, respectively, and the cutoff concentration was 1.813 pg/ml. For PF IL-2, the sensitivity and specificity were 29.73% and 100%, respectively, and the cutoff concentration was 1.06 pg/ml. CONCLUSIONS: IL-37, IL-17A, IL-10, and IL-2 may play a significant role in immune response in endometriosis. IL-37 levels may be used as a diagnostic marker for endometriosis.

Cancer risk in patients with Peutz-Jeghers syndrome: A retrospective cohort study of 336 cases.

Peutz-Jeghers syndrome is a rare autosomal dominant inherited disorder characterized by mucocutaneous pigmentation and hamartomatous gastrointestinal polyposis. A growing body of evidence has shown that Peutz-Jeghers syndrome could cause an increased risk of various cancers, yet the range of cancer risk estimates was wide among different studies. In this retrospective cohort study, 336 patients with Peutz-Jeghers syndrome in China were enrolled. The clinical characteristics, cancer spectrum, relative cancer risks, and cumulative cancer risks were analyzed. In total, 52 patients were diagnosed of cancer in the follow-up period, at a median age of 41 years (range: 21-67). The relative risk for cancer in Peutz-Jeghers syndrome patients was 63.858 (confidence interval: 47.514-85.823), and the cumulative cancer risk at the age of 60 years was 55%. Colorectal cancer was the most common cancer for Peutz-Jeghers syndrome patients (relative risk: 237.918, confidence interval: 154.417-366.572) and the cumulative cancer risk at the age of 60 years was 28%. There was a statistically significant difference in the cumulative cancer risk between patients with family history and those without family history, as well as between patients living in rural area and those living in urban areas ( p < 0.05), while no significant effects of gender and intussusception history on the cumulative cancer risk was found ( p > 0.05). Hopefully, our study may contribute to the management of this rare disorder and establishment of related surveillance projects, especially in China.

[A Systematic Review on Safety Evaluation of Treating Cardiovascular Diseases by Shuxuening In- jection].

Objective To systematically evaluate the safety of Shuxuening Injection ( SI) for treating cardiovascular disease in line with indications. Methods Ten databases such as Cochrane Li- brary, Medline, EMBase, Web of Science, Clinical Trials, CBM, CNKI, VIP, Wangfang Data, and Chinese Clinical Trial Registry Database were retrieved in October 2015 for collecting literatures on use of SI. Data were screened by inclusion and exclusion criteria. Literatures retrieved included randomized controlled trials, non-randomized controlled trials, observational research (case control, cohort studies, case series, case reports, and so on) , and were methodologically evaluated by Cochrane Systematic Risk of Bias Manual, TREND, and SUMARI. Results A total of 185 literatures were retrieved in this systematic review. Of them, 155 randomized controlled trials( RCT) , 6 non-randomized controlled trials, 11 case series, and 13 case reports were finally identified. Among the 13 case reports, adverse drug reactions (ADRs) occurred in 15 cases. Of the 155 RCT studies, XI was used in 8 553 patients, with ADRs in 162 cases and adverse events (AEs) in 4 cases. The outcomes of ADRs mainly covered the gastrointestinal system damage, central/peripheral nervous system damage, skin and appendages injury, and so on. The degree of damage was mostly mild. It is difficult to get a clear judgment on the relationship be- tween the occurrence of these ADRs and drug dosage, drug administration, drug solvents, and combina- tion medications. Conclusions The general safety of using XI for treating cardiovascular diseases was acceptable in this systematic review. Although Xl was systematically analyzed to be safely used in case reports, mechanism studies or large sample observational studies are lack.