H2S Donor GYY4137 Mitigates sFlt-1-Induced Hypertension and Vascular Dysfunction in Pregnant Rats.

BACKGROUND: Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. OBJECTIVE: This study aimed to investigate the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats and examine the underlying mechanisms. METHODS: Pregnant rats were administered sFlt-1 (6 µg/kg/day, intravenously) or vehicle from gestation day (GD) 12 to 20. A subset of these groups received GYY4137 (an H2S donor, 50 mg/kg/day, subcutaneously) from GD 16 to 20. Serum H2S levels, mean arterial blood pressure (CODA tail-cuff), uterine artery blood flow (ultrasonography), vascular reactivity to vasopressors and endothelial-dependent relaxation (myography), endothelial nitric oxide synthase (eNOS) protein expression in uterine arteries (Western blotting) were assessed. In addition, maternal weight gain, as well as fetal and placental weights, were measured. RESULTS: Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. CONCLUSION: sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.

Research on the Construction of a Series of Transition Metal-Substituted Keggin-Type TMSPOMs@PCN-224 Composites through the Encapsulation Method and Their Electron Transfer Mechanism in CO2RR.

In order to take advantage of the distinct reversible multielectron transfer properties of polyoxometalates (POMs) and increase the electron density at the active sites during the electrochemical reduction of CO2 (CO2RR), a range of transition metal-doped polyoxometalates (TMSPOMs) was entrapped within the porphyrin-based framework of PCN-224 via an encapsulation method, known as TMSPOMs@PCN-224 (TMSPOMs = [XW11O39MII(H2O)]n-, [XW11O40VIV]n-, M = CoII, MnII; X = Si, n = 6; X = P, n = 5). The central elements (Si, P) and the incorporated transition metals (VIV, CoII, and MnII) both play a role in adjusting the electronic structure and electron transfer during the CO2RR process. Remarkably, the composite material with cobalt substitution displayed significantly improved performance. Through fine-tuning the POM loading, the electrocatalytic activity was optimized, leading to an impressive Faradaic efficiency for CO production (FECO) of 89.9% for SiW11Co@PCN-224, a significant improvement compared to the 12.1% FECO of PCN-224. Furthermore, the electrochemical stability of this catalyst was demonstrated over 20 h. Comparative analyses involving six composite materials indicated a relationship between the negative charge of the polyanions and their ability to facilitate effective electron transfer, ultimately enhancing the catalyst's performance. Meanwhile, these findings were supported by density functional theory (DFT) calculations.

Green preparation of CaO-based CO2 adsorbent by calcium-induced hydrogenation of shell wastes at room/moderate temperature.

Capturing CO2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes.

RhoA Promotes Synovial Proliferation and Bone Erosion in Rheumatoid Arthritis through Wnt/PCP Pathway.

Ras homolog gene family member A (RhoA) plays a major role in the Wnt/planar cell polarity (PCP) pathway, which is significantly activated in patients with rheumatoid arthritis (RA). The function of RhoA in RA synovitis and bone erosion is still elusive. Here, we not only explored the impact of RhoA on the proliferation and invasion of RA fibroblast-like synoviocytes (FLSs) but also elucidated its effect on mouse osteoclast and a mouse model of collagen-induced arthritis (CIA). Results showed that RhoA was overexpressed in RA and CIA synovial tissues. Lentivirus-mediated silencing of RhoA increased apoptosis, attenuated invasion, and dramatically upregulated osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) ratio in RA-FLSs. Additionally, the silencing of RhoA inhibited mouse osteoclast differentiation in vitro and alleviated synovial hyperplasia and bone erosion in the CIA mouse model. These effects in RA-FLSs and osteoclasts were all regulated by RhoA/Rho-associated protein kinase 2 (ROCK2) and might interact with Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways.

Indole-3-acetonitrile Is a Critical Molecule with Weed Allopathic Suppression Function in Broccoli (Brassica oleracea var. italica).

Cruciferous plants are frequently used for ecologically benign weed control in agricultural production. Most effective Broccoli varieties were screened using the entropy method-based topsis model at first. Result showed that varieties of Lvwawa and Lvbaoshiwere most effective in allelopathic suppression on radishes. Column and thin-layer chromatography were used to extract the allelopathic compounds from broccoli residues, which contained various herbicidal active substances; among them, purified single-molecule indole-3-acetonitrile has a stronger inhibitory effect than pendimethalin (commercial herbicide). The weed inhibition rate increased with increasing broccoli residue dosage, with a 40 g/m2 broccoli residue dose yielding the highest suppression rate. Its effect was similar to that of indole-3-acetic acid. Too much of this substance leads to the plant's death. Moreover, broccoli residues had effective control effect on weeds in natural soils in greenhouse and field trials. The results demonstrated that broccoli residue could be used for weed management in field for abundant allopathic suppression molecules to weeds, and that Indole-3-acetonitrile is one of the most important allopathic molecule.

Combined crystal-storing histiocytosis, light chain proximal tubulopathy, and light chain crystalline podocytopathy in a patient with multiple myeloma: a case report and literature review.

BACKGROUND: Crystal-storing histiocytosis (CSH), light chain proximal tubulopathy (LCPT), and light chain crystalline podocytopathy (LCCP) are rare complications of multiple myeloma (MM) or monoclonal gammopathy of renal significance, and their diagnoses are challenging. CASE PRESENTATION: In this case, a 69-year-old Chinese woman presented with suspicious Fanconi syndrome with renal insufficiency. Immunofixation electrophoresis of both serum and urine revealed elevated immunoglobulin G kappa (IgGkappa) and kappa light chain. Bone marrow aspirate revealed 15% plasma cells with considerable cytoplasmic granular inclusions and needle-shaped crystals. Renal biopsy confirmed the final pathologic diagnosis of kappa-restricted CSH, combined LCPT and LCCP by immunoelectron microscopy. A number of special casts were present which could easily be misdiagnosed as light chain cast nephropathy. Immunofluorescence on frozen tissue presented false negative for kappa light chain, as ultimately proven by paraffin-embedded tissue after pronase digestion. MM and CSH were diagnosed, and two cycles of chemotherapy were given. The patient subsequently refused further chemotherapy, and her renal function remained relatively stable during a 2.5-year follow-up period. CONCLUSIONS: In conclusion, we report a rare case of generalized kappa-restricted CSH involving bone marrow and kidney, combined with LCPT and LCCP, provide a comprehensive summary of renal CSH, and propose a new nomenclature of monoclonal immunoglobulin-induced crystalline nephrology. The presentation of monoclonal immunoglobulin and Fanconi syndrome should suggest the presence of monoclonal immunoglobulin-induced crystalline nephrology. Use of paraffin-embedded tissue after pronase digestion and immunoelectron microscopy is beneficial to improve the sensitivity of diagnosis.

Streptothiazolidine B, a new cytotoxic alkaloid produced by Streptomyces violaceoruber.

A new cytotoxic alkaloid, named streptothiazolidine B (1), together with three known compounds (2-4), were isolated from Streptomyces violaceoruber. The structure of the undescribed compound was established using 1D and 2D NMR, and HRESIMS. Streptothiazolidine B was isolated and identified as an amide alkaloid with a unique thiazolidine side chain and its absolute configuration was determined by a combination of NOESY experiment and ECD analysis. Streptothiazolidine B exhibited significant cytotoxic activities against two human tumor cell lines, Li-7 and A2780, with IC50 values of 7.8, and 9.1 µM. Meanwhile, compound 4 showed obvious cytotoxic activities against four human tumor cell lines, THP-1, HT29, Li-7 and A2780, with IC50 values ranging from 3.1 to 10.2 µM.

ICI 182,780 Attenuates Selective Upregulation of Uterine Artery Cystathionine ß-Synthase Expression in Rat Pregnancy.

Endogenous hydrogen sulfide (H2S) produced by cystathionine ß-synthase (CBS) and cystathionine-γ lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H2S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E2ß (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E2ß tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 µM) completely attenuated E2ß-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H2S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.

[Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea].

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

[Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation].

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(ß-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

A Deep Learning-Based Approach for Glomeruli Instance Segmentation from Multistained Renal Biopsy Pathologic Images.

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.

A heat shock protein protects against oxidative stress induced by lambda-cyhalothrin in the green peach aphid Myzus persicae.

Lambda-cyhalothrin (LCT) is a pyrethroid insecticide widely used to control insect pests. Insect exposure to LCT may cause abnormal accumulation of reactive oxygen species (ROS) and result in oxidative damage. Heat shock proteins (HSPs) may help protect against oxidative stress. However, little is known about the role of HSPs in response to LCT in the green peach aphid, Myzus persicae. This insect is an important agricultural pest causing severe yield losses in crops. In this study, we characterized a cDNA sequence (MpHsp70) encoding a member of the HSP70 family in M. persicae. MpHsp70 encoded a 623 amino acid protein putatively localized in the cytosol. The highest expression level of MpHsp70 occurred in fourth-instar nymphs. Treatment of M. persicae with LCT resulted in oxidative stress and significantly increased H2O2 and malondialdehyde levels. This led to an elevated transcription level of MpHsp70. Injection of H2O2 into M. persicae also upregulated the MpHsp70 expression level, suggesting that MpHsp70 is responsive to ROS, particularly H2O2, induced by LCT. Recombinant MpHSP70 protein was expressed in Escherichia coli. E. coli cells overexpressing MpHSP70 exhibited significant tolerance to H2O2 and the ROS generators, cumene hydroperoxide and paraquat. This indicated that MpHSP70 protects against oxidative stress. Furthermore, knockdown of MpHsp70 by RNA interference resulted in increased susceptibility in apterous adults of M. persicae to LCT. These findings indicate that MpHsp70 plays an important role in defense against LCT-induced oxidative stress and insecticide susceptibility in M. persicae.

Association of serum mannose-binding lectin, anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study.

OBJECTIVES: Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a 'full-house' on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN. METHODS: We conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested. RESULTS: Finally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (-) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (-) patients (p = .045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups. CONCLUSIONS: The complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.

Synthesis and antitumor activity of benzophenone compound.

Seven benzophenone compounds were synthesized in one or two steps, then their antitumor activity was evaluated. The total yields ranged from 9% to 44%. Compounds 3c-5c exhibited obvious antitumor activity. Among them, compounds 3c and 4c exhibited excellent and broad-spectrum antitumor activity. Compound 3c exhibited much stronger inhibitory activities against fourteen cancer cells than cisplatin. In particular, compound 3c exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than Taxol, with a half maximal inhibitory concentration (IC50) of approximately 0.111 µM. These results demonstrated that compounds 3c, 4c and 5c were very promising antitumor leads for further structural modification.

One-pot preparation of H2-mixed CH4 fuel and CaO-based CO2 sorbent by the hydrogenation of waste clamshell/eggshell at room temperature.

The preparation of clean fuel or CO2 adsorbents using industrial and domestic garbage is an alternative way of meeting global energy needs and alleviating environmental problems. Herein, H2-mixed CH4 fuel and CaO-based CO2 sorbent were first prepared in one pot by the mechanochemical reaction of pretreated clamshell or eggshell wastes (carbon and calcium source) with calcium hydride (hydrogen source) at room temperature. In the above reactions, CH4 was the sole hydrocarbon product, and its yield reached 78.23%. The H2/CH4 ratio of the produced H2-mixed CH4 fuel was tunable according to the need by changing the reaction conditions. It is inspiring that the simultaneously formed solid CaO/carbon products were efficient CaO-based sorbents, which possessed a higher CO2 adsorption capacity (49.81-58.74 wt.%) at 650 °C and could maintain good adsorption stability in 30 carbonation/calcination cycles (average activity loss per cycle of only 1.6%). The three achievements of the idea are that it can simultaneously eliminate clamshell or eggshell wastes, obtain valuable clean fuel, and acquire efficient CaO-based sorbents.

A new sesquineolignan and four new neolignans isolated from the leaves of Piper betle, a traditional medicinal plant in Myanmar.

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B-E (2-5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 µM, respectively, compared with the positive control NG-monomethyl-l-arginine (l-NMMA, IC50 = 33.84 µM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity.

Renal outcomes of idiopathic and atypical membranous nephropathy in adult Chinese patients: a single center retrospective cohort study.

BACKGROUND: Membranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows "full house" in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared. METHODS: iMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients' demographics, laboratory values, induction regimens and patients' responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN. RESULTS: There were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399). CONCLUSIONS: The proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.

Pancreatic outflow tract reconstruction after pancreaticoduodenectomy: a meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the outcomes of pancreaticogastrostomy and pancreaticojejunostomy after pancreatoduodenectomy with the help of a meta-analysis. METHODS: Randomized controlled trials comparing pancreaticogastrostomy and pancreaticojejunostomy were searched electronically using PubMed, The Cochrane Library, and EMBASE. Fixed and random-effects were used to measure pooled estimates. Research indicators included pancreatic fistula, delayed gastric emptying, postoperative hemorrhage, intraperitoneal fluid collection, wound infection, overall postoperative complications, reoperation, and mortality. RESULTS: Overall, 10 randomized controlled trials were included in this meta-analysis, with a total of 1629 patients. The overall incidences of pancreatic fistula and intra-abdominal collections were lower in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=0.73, 95% CI 0.55~0.96, p=0.02; OR=0.59, 95% CI 0.37~0.96, p=0.02, respectively). The incidence of B/C grade pancreatic fistula in the pancreaticogastrostomy group was lower than that in the pancreaticojejunostomy group, but no significant difference was observed (OR=0.61, 95%CI 0.34~1.09, p=0.09). Postoperative hemorrhage was more frequent in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=1.52; 95% CI 1.08~2.14, p=0.02). No significant differences in terms of delayed gastric emptying, wound infection, reoperation, overall postoperative complications, mortality, exocrine function, and hospital readmission were observed between groups. CONCLUSION: This meta-analysis suggests that pancreaticogastrostomy reduces the incidence of postoperative pancreatic fistula and intraperitoneal fluid collection but increases the risk of postoperative hemorrhage compared with pancreaticojejunostomy.

Uterine, vaginal and placental blood flows increase with dynamic changes in serum metabolic parameters and oxidative stress across gestation in buffaloes.

The aims of the present study were to determine uterine, vaginal and placental blood flows by Doppler ultrasound cross-buffalo gestation and to evaluate the relationships among reproductive Doppler parameters and serum metabolic parameters as well as oxidative stress. Uterine (UA) and vaginal (VA) arteries were scanned every month, and placentome was scanned from month 4 till 8 in gestation. Time-averaged maximum velocity (TAMV), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (SD) and arterial diameter (AD) were used for accessing UA and VA hemodynamics. Time-averaged maximum velocity positively correlated with and AD, and both negatively correlated with their PI, RI and SD in UA and VA. TAMV and AD increased constantly in pregnancy, with maximum increase in months 4 and 9. Pulsatility index, RI and AD of UA decreased between months 4 and 9, while PI, RI and AD of VA decreased between months 5 and 9 and then increased in month 10 in pregnancy. Time-averaged maximum velocity of placentome blood flow increased exponentially from months 4 to 8, but decreased at the last two months in pregnancy. Serum lipids were significantly higher in the first month compared to all other months, while glucose was significantly lower in months 9 and 10. Malondialdehyde increased from month 3 till term, but peaked in month 5 and 10. Glutathione and catalase were highest in the first month and remained after. Time-averaged maximum velocity and AD for both UA and VA negatively correlated with serum lipids, glucose, catalase and glutathione, while positively correlated with malondialdehyde and total protein. Thus, increases in uterine blood flow (UtBF), vaginal blood flow (VaBF) and placental blood flow (PaBF) are associated with increased metabolism and oxidative stress in buffalo pregnancy.

Efficient synthesis, and antitumor and antioxidant activities of polyhydroxybenzophenone.

Five polyhydroxybenzophenones were synthesized, then their antitumor and antioxidant activities were evaluated. Compounds 1-3 and 5 exhibited obvious antitumor activity. Among them, compounds 1 and 2 exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than cisplatin, with half maximal inhibitory concentrations (IC50) of approximately 3.86 and 5.32 µM, respectively. Compounds 1, 2, and 3 exhibited stronger antioxidant activity than trolox, with IC50 values of 11.15, 10.15, and 8.91 µM, respectively, and the antioxidant mechanism and strength of all compounds were further verified using computational chemistry. These results demonstrated that compounds 1-3 and 5 were very promising leads for further structural modification.