Genetics, leadership position, and well-being: An investigation with a large-scale GWAS.

SignificanceOur study presents the largest whole-genome investigation of leadership phenotypes to date. We identified genome-wide significant loci for leadership phenotypes, which are overlapped with top hits for bipolar disorder, schizophrenia, and intelligence. Our study demonstrated the polygenetic nature of leadership, the positive genetic correlations between leadership traits and a broad range of well-being indicators, and the unique association of leadership with well-being after accounting for genetic influences related to other socioeconomic status measures. Our findings offer insights into the biological underpinnings of leadership.

[Effects of α1-antitrypsin on motor function in mice with immature brain white matter injury]. / α1-æŠ—èƒ°è›‹ç™½é ¶å¯¹æœªæˆç†Ÿè„‘ç™½è´¨æŸä¼¤å°é¼ è¿åŠ¨åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To investigate the effects of α1-antitrypsin (AAT) on motor function in adult mice with immature brain white matter injury. METHODS: Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group (n=27), hypoxia-ischemia (HI) + saline group (n=27), and HI+AAT group (n=27). The HI white matter injury mouse model was established using HI methods. The HI+AAT group received intraperitoneal injections of AAT (50 mg/kg) 24 hours before HI, immediately after HI, and 72 hours after HI; the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points. Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling. At 2 months of age, adult mice were evaluated for static, dynamic, and coordination parameters using the Catwalk gait analysis system. RESULTS: Compared to the sham surgery group, mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling, indicating significant white matter injury. The white matter injury persisted at 55 days after modeling. In comparison to the sham surgery group, the HI+saline group exhibited decreased paw print area, maximum contact area, average pressure, maximum pressure, paw print width, average velocity, body velocity, stride length, swing speed, percentage of gait pattern AA, and percentage of inter-limb coordination (left hind paw → left front paw) (P<0.05). The HI+saline group showed increased inter-paw distance, percentage of gait pattern AB, and percentage of phase lag (left front paw → left hind paw) compared to the sham surgery group (P<0.05). In comparison to the HI+saline group, the HI+AAT group showed increased average velocity, body velocity, stride length, and swing speed (right front paw) (P<0.05). CONCLUSIONS: The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood, while the use of AAT can improve some aspects of their motor function.

3D Printing-guided endovascular repair of enormous twisted thoracoabdominal aortic aneurysm with branch stenosis and occlusion.

A 67-year-old male patient was admitted with an enormous twisted thoracoabdominal aortic aneurysm (TAAA) with multiple branch arteries stenosis and occlusion. Three-dimensional (3D) printing technology combined with mechanics was used for developing a transparent model of lesion to simulate the segment of diseased aorta. A stent graft was deployed in the 3D model to make a physician-modified stent graft (PMSGs) on table. The locations of the opening of branches were marked twice during operation. The PMSG was successfully deployed during the surgery and repaired the TAAA, with no endoleak and all the branched arteries patency in follow-up. This technique could offer precision individualized therapy and could simplify the procedure process greatly.

Three-Dimensional Printing to Guide Fenestrated/Branched TEVAR in Triple Aortic Arch Branch Reconstruction With a Curative Effect Analysis.

PURPOSE: To summarize experience with and the efficacy of fenestrated/branched thoracic endovascular repair (F/B-TEVAR) using physician-modified stent-grafts (PMSGs) under 3D printing guidance in triple aortic arch branch reconstruction. MATERIALS AND METHODS: From February 2018 to April 2022, 14 cases of aortic arch aneurysms and 30 cases of aortic arch dissection (22 acute aortic arch dissection and 8 long-term aortic arch dissection)were treated by F/B-TEVAR in our department, including 34 males and 10 females, with an average age of 59.84 ± 11.72 years. Three aortic arch branches were affected in all patients. A 3D-printed model was made according to computed tomography angiography images and used to guide the fabrication of PMSGs. All patients were followed up. RESULTS: A total of 132 branches were successfully reconstructed with no case of conversion to open surgery. The average operation time was 4.97 ± 1.40 hours, including a mean 44.05 ± 7.72 minutes for stent-graft customization, the mean postoperative hospitalization duration was 9.91 ± 4.47 days, the average intraoperative blood loss was 480.91 mL (100-2810 mL), and the mean postoperative intensive care unit monitoring duration was 1.02 days (0-5 days). No deaths occurred within 30 days of surgery. Postoperative neurological complications occurred in 1 case (2.3%), and retrograde type A dissection occurred in 1 case (2.3%). CONCLUSION: Compared with conventional surgery, triple aortic arch branch reconstruction under the guidance of 3D printing is a minimally invasive treatment method with the advantages of accurate positioning, rapid postoperative recovery, few complications, and reliable short- to mid-term effects. CLINICAL IMPACT: At present the PMSG usually depend on imaging data and software calculation. With the guidance of 3D printing technology, image data could be transformed into 3D model, which has improved the accuracy of the positioning of the fenestrations. The diameter reduction technique and the internal mini cuff technique have made a complement to the slimed-down fenestration selection process and the low rate of endoleak. As reproducible study, our results may provide reference for TEVAR in different cases.

Update on the genetic diversity and population structure of Echinococcus granulosus in Gansu Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region, Western China, inferred from mitochondrial cox1, nad1, and nad5 sequences.

The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.

[Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats].

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.

[Establishment of a predictive nomogram model for predicting the death of very preterm infants during hospitalization]. / 极早产儿住院期间死亡的列线图预测模型的建立.

OBJECTIVES: To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization. METHODS: A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model. RESULTS: Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95%CI: 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95%CI: 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit (P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort. CONCLUSIONS: A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.

[Clinical features of very preterm infants with prelabor rupture of membranes and predictive factors for major adverse outcomes].

OBJECTIVE: To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death. METHODS: A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours (n=107), 18 hours to < 3 days (n=111), 3 days to < 14 days (n=144), and ≥ 14 days (n=37). According to the presence or absence of EOS, the infants were divided into EOS (n=42) and non-EOS groups (n=357). According to the survival state, the infants were divided into a survival group (n=359) and a death group (n=40). Clinical features were analyzed for very preterm infants with different times of PROM. A multivariate logistic regression analysis was used to investigate the predictive factors for EOS and death in very preterm infants with PROM. RESULTS: There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM (P > 0.05). Birth weight < 1 000 g (OR=4.353, P=0.042), grade Ⅲ amniotic fluid contamination (OR=4.132, P=0.032), and grade Ⅲ-Ⅳ respiratory distress syndrome (RDS) (OR=2.528, P=0.021) were predictive factors for EOS in very preterm infants with PROM. Lower birth weights (< 1 000 g or 1 000-1 499 g; OR=11.267 and 3.456 respectively; P=0.004 and 0.050 respectively), grade Ⅲ-Ⅳ RDS (OR=5.572, P < 0.001), and neonatal sepsis (OR=2.631, P=0.012) were predictive factors for death in very preterm infants with PROM. CONCLUSIONS: Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.

MiR-9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway.

Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for thrombi recanalization. However, this role of EPCs is confined by some detrimental factors. The aim of this study was to explore the role of the miR-9-5p in regulation of the proliferation, migration and angiogenesis of EPCs and the subsequent therapeutic role in thrombosis event. Wound healing, transwell assay, tube formation assay and in vivo angiogenesis assay were carried out to measure cell migration, invasion and angiogenic abilities, respectively. Western blot was performed to elucidate the relationship between miR-9-5p and TRPM7 in the autophagy pathway. It was found that miR-9-5p could promote migration, invasion and angiogenesis of EPCs by attenuating TRPM7 expression via activating PI3K/Akt/autophagy pathway. In conclusion, miR-9-5p, targets TRPM7 via the PI3K/Ak/autophagy pathway, thereby mediating cell proliferation, migration and angiogenesis in EPCs. Acting as a potential therapeutic target, miR-9-5p may play an important role in the prognosis of DVT.

A chemiluminescence immunoassay for the detection of NT-proBNP.

BACKGROUND: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. METHODS: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. RESULTS: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". CONCLUSIONS: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.

MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression.

MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non-coding RNAs that affect post-transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual-luciferase reporter assay, qRT-PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK-8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR-205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR-205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F-actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down-regulation of miR-205 played the opposite role in EPCs. Importantly, this study demonstrated that miR-205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro-angiogenesis effects of miR-205 in EPCs and established it as a potential target for DVT treatment.

LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways.

Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus-mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR-3120-5P, and MMP-1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP-1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR-3120-5P binding site. Suppression of WTAPP1 by miR-3120-5P decreased the level of MMP-1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR-3120-5p, regulates MMP-1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863-12.

Effect of oceanic turbulence on the visibility of underwater ghost imaging.

We carry out a detailed study on underwater ghost imaging (GI) in oceanic turbulence. We set up a physical model of GI through oceanic turbulence, which includes light-field transmission, and interaction between light field and oceanic turbulence without considering the effects of water absorption and scattering of light. We obtain theoretical expressions for the impulse response function and the visibility of GI in oceanic turbulence based on the power spectrum of the turbulence and the extended Huygens-Fresnel integral. The results show that the quality of GI under the effects of oceanic turbulence is related to the intensity of turbulence and the propagation distance of light. The quality of GI could be maintained at a relatively small distance in strong oceanic turbulence, whereas the quality is degraded dramatically at a relatively long distance in strong oceanic turbulence. We further analyze the quality of GI under various turbulence conditions and over different propagation distances by numerical calculation. Our results provide guidance for the realization of adaptive underwater optical GI over different length scales under the effect of oceanic turbulence.

Performance of underwater quantum key distribution with polarization encoding.

Underwater quantum key distribution (QKD) has potential applications in absolutely secure underwater communication. However, the performance of underwater QKD is limited by the optical elements, background light, and dark counts of the detector. In this paper, we propose a modified formula for the quantum bit error rate (QBER), which takes into account the effect of detector efficiency on the QBER caused by the background light. Then we calculate the QBER of the polarization encoding BB84 protocol in Jerlov-type seawater by analyzing the effect of the background light and optical components in a more realistic situation. Finally, we further analyze the final key rate and the maximum secure communication distance in three propagation modes, i.e., upward, downward, and horizontal modes. We find that secure QKD can be performed in the clearest Jerlov-type seawater at a distance of hundreds of meters, even in the worst downward propagation mode. Specifically, by optimizing the system parameters, it is possible to securely transmit information with a rate of 67 kbits/s at a distance of 100 m in the seawater channel with an attenuation coefficient of 0.03/m at night. For practical underwater QKD, the performance can also be improved by using decoy states. Our results are useful for long-distance underwater quantum communication.

[Pharmaceutics research advances in oral administration of puerarin].

Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.

The regulatory role of microRNAs in angiogenesis-related diseases.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis-related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA-based biomarkers in the diagnosis, treatment and prognosis of angiogenesis-related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1ß production.

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols.

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.