Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Comparing coronary artery cross-sectional area among asymptomatic South Asian, White, and Black participants: the MASALA and CARDIA studies.

BACKGROUND: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. METHODS: We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. RESULTS: Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 - 20.9]) and men (22.3 mm2, 95% CI [21.4 - 23.2]; White women (20.0 mm2, 95% CI [19.4-20.5]) and men (23.6 mm2, 95% CI [23.0-24.2]); and Black women (21.6 mm2, 95% CI [21.0 - 22.2]) and men (26.0 mm2, 95% CI [25.3 - 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. CONCLUSIONS: South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

[Interpretation of Chinese guideline for the clinical management of patients with ruptured intracranial aneurysms (2024)].

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurological emergency with high mortality, and even patients receiving optimal medical care may develop long-term disability, which seriously affects their quality of life and increases the heavy medical burden on society and families. To provide comprehensive clinical management advice, the Society of Neurosurgery of the Chinese Medical Association, the Society of the Chinese Stroke Association of the National Medical Center for Neurological Diseases, and the National Clinical Research Center for Neurological Diseases jointly formulate "Chinese Guidelines for the Clinical Management of Patients With Ruptured Intracranial Aneurysms in 2024". The evidence sources are divided into the Chinese population and other populations, using a modular format to provide recommendations, summaries of relevant opinions, and future research directions on epidemiology, clinical imaging diagnosis, prognosis evaluation, treatment strategies and choices, anesthesia management, perioperative care, and recommendations for the management of aSAH in special populations. It provides practical clinical guidance and recommendations for doctors and related professionals.

[A case of hematogenous disseminated tuberculosis in a patient with contradictory reactions treated with thalidomide].

Here we reported a case of a 52-year-old male with a 13-year history of Crohn's disease who developed disseminated tuberculosis after 2 injections of infliximab. The patient was admitted with a chief complaint of fever with headache of 1 month's duration. Mycobacterium tuberculosis DNA was found positive in cerebrospinal fluid and lavage fluid by lumbar puncture and bronchoscopy. He was diagnosed with tuberculous meningitis, pulmonary tuberculosis, tracheobronchial tuberculosis and lymph node tuberculosis. After treatment with anti-tuberculosis and glucocorticoids, the symptoms did not improve, the lesions progressed, and granulomas were formed in the tracheobronchial lumen. These were considered to be contradictory reactions and thalidomide was given together with glucocorticoids. The patient's clinical condition has improved significantly. Treatment was successfully completed after 18 months with 1 HREZLfxLzd/8 HEZCsLzd/1 HEZCs/8 HZCs.

Endothelial phosphoinositide 3-kinase-ß inactivation confers protection from immune-mediated vascular injury.

Heart transplant and recipient survival are limited by immune cell-mediated injury of the graft vasculature. We examined the role of the phosphoinositide 3-kinase-ß (PI3Kß) isoform in endothelial cells (EC) during coronary vascular immune injury and repair in mice. In minor histocompatibility-antigen mismatched allogeneic heart grafts, a robust immune response was mounted to each wild-type, PI3Kß inhibitor-treated, or endothelial-selective PI3Kß knockout (ECßKO) graft transplanted to wild-type recipients. However, microvascular EC loss and progressive occlusive vasculopathy only developed in control, but not PI3Kß-inactivated hearts. We observed a delay in inflammatory cell infiltration of the ECßKO grafts, particularly in the coronary arteries. Surprisingly, this was accompanied by an impaired display of proinflammatory chemokine and adhesion molecules by the ECßKO ECs. In vitro, tumor necrosis factor α-stimulated endothelial ICAM1 and VCAM1 expression was blocked by PI3Kß inhibition or RNA interference. Selective PI3Kß inhibition also blocked tumor necrosis factor α-stimulated degradation of inhibitor of nuclear factor kappa Bα and nuclear translocation of nuclear factor kappa B p65 in EC. These data identify PI3Kß as a therapeutic target to reduce vascular inflammation and injury.

Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

BACKGROUND: Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. OBJECTIVE: We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). METHODS: We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. RESULTS: Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). DISCUSSION: Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10 months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

Discrepant serological findings in SARS-CoV-2 PCR-negative hospitalized patients with fever and acute respiratory symptoms during the pandemic.

Coronavirus Disease 2019 (COVID-19) serology has an evolving role in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, its use in hospitalized patients with acute respiratory symptoms remains unclear. Hospitalized patients with acute respiratory illness admitted to an isolation ward were recruited. All patients had negative nasopharyngeal swab polymerase chain reaction (PCR) for SARS-CoV-2. Serological studies using four separate assays (cPass: surrogate neutralizing enzyme-linked immunosorbent assay [ELISA]; Elecsys: N-antigen based chemiluminescent assay; SFB: S protein flow-based; epitope peptide-based ELISA) were performed on stored plasma collected from patients during the initial hospital stay, and a convalescent visit 4-12 weeks later. Of the 51 patients studied (aged 54, interquartile range 21-84; 62.7% male), no patients tested positive on the Elecsys or cPass assays. Out of 51 patients, 5 had antibodies detected on B-cell Epitope Assay and 3/51 had antibodies detected on SFB assay. These 8 patients with positive serological test to COVID-19 were more likely to have a high-risk occupation (p = 0.039), bacterial infection (p = 0.028), and neutrophilia (p = 0.013) during their initial hospital admission. Discrepant COVID-19 serological findings were observed among those with recent hospital admissions and bacterial infections. The positive serological findings within our cohort raise important questions about the interpretation of sero-epidemiology during the current pandemic.

Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia.

INTRODUCTION: The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia. OBJECTIVES: Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction. METHODS: Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n [Formula: see text] 5) or LPS (0.375 [Formula: see text]g of LPS/kg of body weight; n [Formula: see text] 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics. RESULTS: Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes. CONCLUSION: Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Preeclampsia has two phenotypes which require different treatment strategies.

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

ToTEM: A software for fast TEM image simulation.

ToTEM, a multislice-based image simulation software is developed for transmission electron microscope (TEM). This software implements the following major features: (i) capability of assigning three-dimensional potentials of atom into multiple slices and precise introduction of phase shift caused by the sub-pixel atomic position, (ii) employing CUDA coding and graphical processing units (GPU) with multithreading parallel algorithm based on the powerful batch (inverse) fast Fourier transform (FFT), which is especially beneficial for image simulation of scanning transmission electron microscopy (STEM) or (integrated) differential phase contrast (I)DPC, (iii) design for efficiently generating large batch of data set of high-resolution transmission electron microscopy (HRTEM) images. Image simulation acceleration for STEM has been verified by simulating a large-scale SrTiO3 . Additionally, iDPC image of MFI-type zeolites with xylene molecules encapsulated in straight channels demonstrates the advantage of iDPC in detecting light molecules.

Assessing Bias in Cognitive Testing for Older Adults with Sensory Impairment: An Analysis of Differential Item Functioning in the Baltimore Longitudinal Study on Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVES: Vision and hearing impairments affect 55% of people aged 60+ years and are associated with lower cognitive test performance; however, tests rely on vision, hearing, or both. We hypothesized that scores on tests that depend on vision or hearing are different among those with vision or hearing impairments, respectively, controlling for underlying cognition. METHODS: Leveraging cross-sectional data from the Baltimore Longitudinal Study of Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), we used item response theory to test for differential item functioning (DIF) by vision impairment (better eye presenting visual acuity worse than 20/40) and hearing impairment (better ear .5-4 kHz pure-tone average > 25 decibels). RESULTS: We identified DIF by vision impairment for tests whose administrations do not rely on vision [e.g., Delayed Word Recall both in ARIC-NCS: .50 logit difference between impaired and unimpaired (p = .04) and in BLSA: .62 logits (p = .02)] and DIF by hearing impairment for tests whose administrations do not rely on hearing [Digit Symbol Substitution test in BLSA: 1.25 logits (p = .001) and Incidental Learning test in ARIC-NCS: .35 logits (p = .001)]. However, no individuals had differences between unadjusted and DIF-adjusted measures of greater than the standard error of measurement. CONCLUSIONS: DIF by sensory impairment in cognitive tests was independent of administration characteristics, which could indicate that elevated cognitive load among persons with sensory impairment plays a larger role in test performance than previously acknowledged. While these results were unexpected, neither of these samples are nationally representative and each has unique selection factors; thus, replication is critical.

The effect of missing data and imputation on the detection of bias in cognitive testing using differential item functioning methods.

BACKGROUND: Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. METHODS: We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. RESULTS: When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. CONCLUSIONS: Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.

[Artificial intelligence for medical information departments : construction and evaluation of a decision-making tool to identify and prioritize stays of which the PMSI coding could be optimized, and to ensure the revenues generated by activity-based pricing]. / L'intelligence artificielle au service des départements d'information médicale : construction et évaluation d'un outil d'aide à la décision pour cibler et prioriser les séjours à contrôler et fiabiliser les recettes hospitalières générées par la tarification à l'activité.

BACKGROUND: Medical Information Departments help to optimize the hospital revenues generated by activity-based pricing. A review of medical files, selected after the targeting of coding summaries, is organized. The aim is to make any corrections to the diagnoses or coded procedures with a potential impact on the pricing of the stay. Targeting is of major importance as a means of concentrating resources on the files for which coding can be effectively improved. The tools available for targeting can be optimized. We have developed a decision-making support tool to make targeting more efficient. The objective of our study was to evaluate the performance of this tool. METHODS: The tool combines an artificial intelligence module with a rule-based expert module. A predictive score is assigned to each coding summary that reflects the probability of a revalued stay. Evaluation of the performance of this tool was based on a sample of 400 stays of at least 3 nights of patients hospitalized at the Paris Saint-Joseph Hospital from 1st November to 31st December 2019. Each stay was reviewed by a coding expert, without knowledge of the score assigned and without help from expert queries. Two main assessment criteria were used: area under the ROC curve and positive predictive value (PPV). RESULTS: The area under the ROC curve was 0.70 (CI 95% [0.64-0.76]). With a revalued coding rate of 32%, PPV was 41% for scores above 5, 65% for scores above 8, 88% for scores above 9. CONCLUSION: The study made it possible to validate the performance of the tool. The implementation of new variables could further increase its performance. This is an area of development to be considered, particularly with in view of generalizing individual invoicing in hospitals.

[Effects of one-stop hybrid operation on the risk and prognosis of brain arteriovenous malformations with posterior feeding artery].

Objective: To explore the effect of the combination of posterior circulation embolization and micro-resection on the risk and prognosis in patients with brain arteriovenous malformations (bAVMs) supplied by posterior circulation in a one-stop hybrid operation setting. Methods: Patients with bAVMs supplied by posterior circulation who received surgical treatment in Beijing Tiantan Hospital, Capital Medical University, were enrolled from January 2016 to December 2019 from a prospective, multicentral cohort (NCT03209804). The patients were divided into the posterior circulation embolization group and the non-posterior circulation embolization group. Propensity score matching (PSM) (1∶1) was performed according to the baseline information, the morphology of bAVMs, vascular architecture, and Spetzler-Martin grade of brain lesions. The primary endpoint was the deterioration of neurological function. The secondary endpoints were perioperative complications. The differences in surgical risk and clinical prognosis between the two groups were compared. Results: Five hundred and forty-five patients were enrolled in the cohort, and 38.3% met the included criteria (n=209 cases), with 42 cases in the posterior circulation embolization group and 167 cases in the non-posterior circulation embolization group. Depending on whether the patients were posterior circulation embolized, 39 patients in the posterior circulation embolization group and 39 patients in the non-posterior circulation embolization group were finally included after performing PSM. There were 50 males and 28 females, aged 5-58 (30±13) years. The exacerbation rate of neurological dysfunction in the posterior circulation embolization group was higher than that in the non-posterior circulation embolization group three months after surgery, however there was no statistically significant difference between the two groups [15.4% (6/39) vs 2.6% (1/39), P=0.107]. The intraoperative blood loss in the embolization group was significantly less than that in the non-embolization group [650 (500, 1 500) ml vs 1 200 (800, 2 000) ml, P=0.002]. There was no significant difference in microsurgery time between the two groups [437 (374, 521) min vs 424 (359, 601) min, P=0.865]. Likewise, there were no statistically significant differences in the incidence of postoperative complications and aggravation of neurological dysfunction, including postoperative bAVMs residual [5.1%(2/39) vs 7.7%(3/39), P=1.000], hemorrhagic complications [5.1%(2/39) vs 0(0), P=0.494], postoperative ischemic complications [10.3%(4/39) vs 5.1%(2/39), P=0.675], neurological dysfunction at discharge (17.9% vs 15.4%, P=0.755), and one-year neurological dysfunction [5.1%(2/39) vs 2.6%(1/39), P=1.000]. Conclusions: Posterior circulation embolization of bAVMs in a one-stop hybrid operation can effectively reduce intraoperative bleeding and surgical risk. Embolization of the feeding artery has no significant impact on the perioperative complications and neurological outcomes.

[Safety and efficacy of TIPS combined with iodine-125 seed strands in the treatment of patients with hepatocellular carcinoma combined with portal vein tumor thrombosis].

Objective: To study the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with iodine-125 (125Ⅰ) seed strands implantation in patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. Methods: 25 cases with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ requiring TIPS were simultaneously implanted with 125Ⅰseed strand. Tumor thrombus was controlled with 125I seed implantation brachytherapy to keep the TIPS pathway unobstructed, reduce the portal vein pressure, and observe the changes in the cause of death of the patients. During the same period, 30 cases without TIPS and seed strand implantation were used as controls. Data between groups were compared using t-test, Chi-Squared test or Fisher's exact test. Results: TIPS combined with 125Ⅰ seed strand implantation was safe in patients with diffuse hepatocellular carcinoma combined with type III/IV portal vein tumor thrombus, and 92.0% (23/25) of the patients maintained unobstructed TIPS pathway. Compared with the control group, patients in the treatment group died of fewer lead-related complications, and most died from chronic liver failure (84.0% vs. 56.7%, χ2 = 4.771, P=0.029). The incidence of upper gastrointestinal bleeding was significantly decreased (12.0% vs. 46.7%, χ2 =7.674, P=0.006) and ascites severity was significantly improved (mild 40.0% vs. 16.7%, moderate 52.0% vs. 20.0%, severe 8.0% vs. 46.7%, χ2 =13.246 , P=0.001). Conclusions: TIPS combined with 125Ⅰ seed strand implantation is safe and feasible in patients with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ. Moreover, it can effectively keep the shunt patency and reduce portal vein pressure, thereby reducing the incidence of upper gastrointestinal bleeding and improving the degree of ascites. TIPS combined with 125Ⅰ seed strand implantation may be used as a standard treatment modality for patients requiring TIPS therapy combined with tumor thrombus type Ⅲ/Ⅳ.

[Hepatitis C elimination among drug users in China: challenges, strategies and experiences].

The prevalence of hepatitis C among drug users in China is high, and thus it is one of the populations that needs attention to achieve hepatitis C elimination. However, due to the complexities of this population's situation, hepatitis C elimination still faces many challenges, such as difficult screening, low cure rate, poor compliance, and high reinfection rates. Therefore, the existing diagnostic and therapeutic system cannot meet the needs of this population. China has pledged to establish a unified system for drug users that will integrate drug treatment programs, education, medical care, and rehabilitation, creating favorable conditions for integrating hepatitis C diagnosis and treatment and improving the accessibility of drug users. Starting with the current situation and challenges of eliminating hepatitis C among drug users in China, in combination with cases from other countries, this paper discusses the strategy for eliminating hepatitis C and introduces what Hainan Province did to eliminate hepatitis C among drug users.

CodY, ComA, DegU and Spo0A controlling lipopeptides biosynthesis in Bacillus amyloliquefaciens fmbJ.

AIM: In the study, we investigated the regulatory effects of these genes (codY, comA, degU and spo0A) on the biosynthesis of three lipopeptides (bacillomycin D, fengycin and surfactin) in Bacillus amyloliquefaciens. METHODS AND RESULTS: The codY, comA, degU and spo0A genes in B. amyloliquefaciens fmbJ were knocked out. The results showed that the productions of bacillomycin D were significantly reduced compared with that of fmbJ. Their deletion induced great changes in the levels of transcripts specifying metabolic pathways, quorum sensing system and substance transport system in fmbJ. Moreover, overexpression of these genes improved the productions of bacillomycin D. In particular, the overexpression of spo0A enhanced bacillomycin D yield up to 648·9 ± 60·9 mg l-1 from 277·3 ± 30·5 mg l-1 . In addition, the yields of surfactin in fmbJΔcodY and fmbJΔdegU were significantly improved, and the regulatory factor CodY had no significant effect on the synthesis of fengycin. CONCLUSIONS: These genes positively regulated the expression of bacillomycin D and fengycin synthase genes in strain fmbJ. However, codY and degU negatively regulated surfactin biosynthesis. Moreover, it was found that CodY had a concentration dependence on bacillomycin D synthesis. Spo0A might play a direct regulatory role in the synthesis and secretion of bacillomycin D. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicated that genetic engineering of regulatory genes was an effective strategy to improve the yields of antimicrobial lipopeptides and provided promising strains for industrial production of lipopeptides.

Laboratory simulation of longitudinally cracked teeth using the step-stress cyclic loading method.

AIM: To simulate in a laboratory setting longitudinal cracking in root filled premolar teeth, using cyclic mechanical fatigue. METHODOLOGY: Mesial-occlusal-distal (MOD) cavities were prepared in twenty root filled, single-rooted, mandibular premolars restored with fibre posts and resin composites. The samples were randomly divided into two groups based on the loading approaches: static loading with a crosshead speed of 0.5 mm/min and step-stress cyclic loading (1 Hz) with increasing amplitude. The loads and numbers of cycles to failure were recorded. Micro-CT was also used to identify the fracture modes. Statistical analysis was performed using Student's t-test. The level of significance was set at 0.05. RESULTS: The mean fracture loads for the static loading and cyclic loading groups were 769 ± 171 N and 720 ± 92 N, respectively. There was no significant difference between the two groups (P > 0.05). The proportions of longitudinal, cuspal and mixed-mode fractures under cyclic loading were 50%, 20% and 30%, respectively. Longitudinal fractures occurred with larger numbers of cycles and higher average loads per cycle compared with the other fractures. Static loading produced only cuspal fractures. CONCLUSIONS: Longitudinally cracked premolar teeth with root fillings were successfully produced using the step-stress cyclic loading method. This provides a more clinically representative methodology for studying cracked teeth in a laboratory setting.