Eight-Membered Palladacycle Intermediate Enabled Synthesis of Cyclic Biarylphosphonates.

Transition-metal-catalyzed coupling reactions that involve the direct functionalization of insert C-H bond represent one of the most efficient strategies for forming carbon-carbon bonds. Herein, a palladium-catalyzed intramolecular C-H bond arylation of triaryl phosphates is reported to access seven-membered cyclic biarylphosphonate targets. The reaction is achieved via a unique eight-membered palladacyclic intermediate and shows good functional group compatibility. Meanwhile, the product can be readily converted into other valuable phosphate compounds.

Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations.

BACKGROUND: The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized. OBJECTIVE: We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA). STUDY DESIGN: 27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis. RESULTS: The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-5-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04). CONCLUSIONS: Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging. METHODS: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies. RESULTS: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I2 = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I2 = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I2 = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I2 = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study. CONCLUSIONS: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

Disseminated intravascular coagulation in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. OBJECTIVE: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. METHODS: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. RESULTS: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). LIMITATIONS: The study limitations include small sample size and a single hospital system. CONCLUSION: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis. METHODS: Fifty-six patients aged 39-75 years were assigned into two groups to receive either probiotic sachets (n = 28) or a placebo (n = 28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1 × 1011 cfu/day) for 6 months. RESULTS: A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6 months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study. CONCLUSION: Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6 months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.

Change in body weight and body mass index in psoriasis patients receiving biologics: A systematic review and network meta-analysis.

BACKGROUND: Previous studies have suggested that biologic therapy for psoriasis might relate to body weight gain. OBJECTIVE: To assess the changes in body weight and body mass index (BMI) in psoriasis patients after receiving various biologics. METHODS: We conducted a systematic review and network meta-analysis to evaluate the changes in body weight and BMI in psoriasis patients receiving biologics. On March 1, 2019, we searched Medline, Embase, and Cochrane Central Register of Controlled Trials for relevant studies. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: We included 6 studies with 862 psoriasis patients. Compared with conventional systemic treatments, treatment with tumor necrosis factor α inhibitors was associated with a significant increase in body weight (mean difference 1.40 kg, 95% confidence interval 0.88-1.93 kg) and BMI (0.39 kg/m2, 95% confidence interval 0.24-0.54 kg/m2). In contrast, no significant increase in body weight or BMI was found among patients receiving anti-interleukin (IL)-12/23 or anti-IL-17 biologics. LIMITATIONS: Only 1 study reported body weight and BMI for patients receiving the anti-IL-17 biologic. CONCLUSION: Tumor necrosis factor α inhibitor treatment appears to be associated with an increase in body weight and BMI, and treatment with anti-IL-12/23 and anti-IL-17 biologics do not. This association should be considered before initiating biologics for overweight and obese patients.

[HMGB1 neutralizing antibody attenuates hemorrhagic shock-induced cardiac injury and modulates apoptotic gene expression in murine heart].

OBJECTIVE: To explore the possible protective effects and mechanisms of neutralizing antibody of HMGB1 on hemorrhagic shock-induced cardiac injury in mice. METHODS: The KM mice of hemorrhagic shock model were divided into sham (sham), control+IgG, hemorrhagic shock (HS) and HMGB1 neutralizing antibody treatment (HS+α-HMGB1) groups (n = 8 each). After modeling, the animals were anesthetized and blood samples collected. The concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. And the serum levels of such inflammatory factors as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and HMGB1 were analyzed by enzyme-linked immunosorbent assay (ELISA). The cardiac tissues were harvested, fixed; hemotoxylin-eosin stained and observed under transmission electron microscopy. The histopathological cardiac changes were examined after hemorrhagic shock and resuscitation (HS/R). Immunohistochemical staining was performed to detect the cardiac expressions of HMGB1 and Fas/FasL after HS/R. Reverse transcription polymerase chain reaction (PCR) was performed to analyze the RNA levels of Bax, Bcl-2 and Caspase-3 in cardiac tissues. And the protein levels of HMGB1, Bax, Bcl-2 and Caspase-3 in cardiac tissues were tested by Western blot. RESULTS: Hemorrhagic shock and resuscitation resulted in significantly cardiac cell damages, enhanced inflammatory factors in sera and up-regulated the expressions of pro-apoptotic genes and proteins in murine hearts. The lowered protein level of Bcl-2 induced by HS/R was reversed by neutralizing HMGB1 antibody treatment. Neutralizing HMGB1 antibody administration obviously attenuated HS/R-induced cardiac damages and apoptosis (HS +α-HMGB1 group vs HS group, 4.5 ± 1.3 vs 8.9 ± 1.9), inhibited inflammatory responses (HS+α-HMGB1 vs HS, IL-1ß: 127.7 ± 21.2 vs 164.3 ± 30.2; IL-6: 226.7 ± 33.4 vs 402.5 ± 59.5; TNF-α:100.6 ± 10.7 vs 146.5 ± 15.4), and modulated apoptosis-associated genes (HS+α-HMGB1 group vs HS group, Bcl-2: 0.25 ± 0.02 vs 0.19 ± 0.02; Bax: 0.38 ± 0.04 vs 0.50 ± 0.03; Caspase-3: 0.38 ± 0.04 vs 0.56 ± 0.04) and proteins expression (HS+α-HMGB1 group vs HS group, Bcl-2: 0.47 ± 0.04 vs 0.3 ± 0.03; Bax: 0.11 ± 0.02 vs 0.17 ± 0.02; Caspase-3: 0.62 ± 0.04 vs 0.8 ± 0.04) in murine hearts after HS/R. CONCLUSION: Neutralizing HMGB1 antibody may protect mice from HS/R-induced cardiac damages and apoptosis. Such an effect is probably due to its anti-inflammatory responses and anti-apoptosis related gene expression.

Chiral α-Aminophosphonates as Ligands in Copper-Catalyzed Asymmetric Oxidative Coupling of 2-Naphthols.

Chiral α-aminophosphonates with adjacent carbon and phosphonate stereogenic centers have been employed as ligands in the copper-catalyzed oxidative coupling of 2-naphthols, resulting in the production of chiral BINOLs in favorable yields and moderate to good enantiomeric excess. This represents the first application of chiral P-based ligands to enable such a transformation. The synthesis of these chiral α-aminophosphonate ligands offers a significant advantage over approaches that typically necessitate elaborate synthetic processes for chiral ligand production.

Alectinib relieves ischemic strokes caused by left atrial metastasis in a NSCLC patient with a novel SLC34A2-ALK (exon 1: exon 15) fusion.

BACKGROUND: The adoption of molecular profiling in non-small cell lung cancers (NSCLC) have promoted the discoveries of novel anaplastic lymphoma kinase (ALK) mutation patterns including rare intergenic rearrangements. It is always meaningful to report the structure of these fusions and their responses to ALK-inhibitors for future reference. Reports of cerebral ischemic strokes caused by atrial metastases through lymphohematogeneous spread are scarce. CASE PRESENTATION: A 35-year-old woman with no history of astherosclerosis presented with sudden onset of diplopia and facial palsy. Brain MRI scan discovered multiple infarcts around cortical and subcortical areas supplied by bilateral middle cerebral arteries, the occlusions of which were confirmed by angiography. Echocardiogram revealed intracavity appendages in atriums. The histology following valve debridement displayed endocardial metastases from lung cancer on mitral and trucuspid valves. PET/CT found right lower lobe primary tumor and mediastinal lymphadenopathies. The histology of primary lung tumor suggested adenocarcinoma and a DNA-based next-generation sequencing (NGS) test uncovered an intergenic (FAM49A, RAD51AP2)-ALK (intergenic: A14) rearrangement. Further RNA-based NGS uncovered a novel SLC34A2-ALK (exon 1: exon 15) fusion. Strokes recurred after valve surgery and vegetations reappeared on the mitral valve. Alectinib 600 mg bid was administered based on molecular finding and achieved remarkable tumor regression. Neurologic symptoms were largely relieved. No new infarctions or cerebral metastases has ever been found since. CONCLUSIONS: We report a novel SLC34A2-ALK rearrangement responding well to alectinib in a very interesting case of peripheral lung adenocarcinoma presenting with recurrent cerebral ischemic strokes due to endocardial metastases.

Prediction of Male Coronary Artery Bypass Grafting Outcomes Using Body Surface Area Weighted Left Ventricular End-diastolic Diameter: Multicenter Retrospective Cohort Study.

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

[Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

OBJECTIVE: To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. METHODS: On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. RESULTS: After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. CONCLUSION: Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

[Cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention in Beijing].

OBJECTIVE: To analyze the cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) in Beijing area to evoke better individualized preventive approach. METHODS: In-hospital mortality and causes were analyzed based on database from Beijing percutaneous coronary intervention registry study (BJPCI Registry) in 2010. RESULTS: A total of 4660 PPCI patients from 48 hospitals were included. In-hospital mortality was 2.4% (n = 110). Cardiogenic shock (39.1%, 43/110), mechanical complications (28.2%, 31/110) and intervention-related complications [28.2%, 31/110: procedure related (n = 28), drug related (n = 3)] were the leading causes of in-hospital death. Five deaths was attributed to comorbidity related reason (4.5%, 5/110). The in-hospital mortality had no significant difference among hospitals of different grade or total annual PCI (all P > 0.05). In-hospital mortality was slightly higher in hospital with annual PPCI < 300 than in hospitals with annual PPCI ≥ 300 (2.9% vs. 1.8%, P < 0.05). CONCLUSION: Cardiogenic shock, mechanical complications and intervention-related complications are the main causes of in-hospital death among acute myocardial infarction patients receiving PPCI.

Development and validation of a multifrequency bioimpedance spectroscopy equation to predict appendicular skeletal muscle mass in hemodialysis patients.

BACKGROUND & AIMS: The Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, has been widely used to assess body composition in hemodialysis patients because its measurement is not affected by overhydration commonly seen in chronic kidney disease. We aimed to develop and validate an equation for obtaining appendicular skeletal muscle mass (ASM) from BCM taking dual-energy X-ray absorptiometry (DXA) as the reference among hemodialysis patients. METHODS: A total of 322 consecutive body composition measurements with BCM and DXA in 263 hemodialysis patients were randomly divided at a ratio of 2:1 into development and validation groups. Stepwise multiple regression modeling was applied to develop the ASM prediction equation. We evaluated the model as a diagnostic tool for sarcopenia using cutoffs of ASM defined by the Asian Working Group for Sarcopenia (AWGS). We further explored the association between ASM predicted by the BCM equation and all-cause mortality in two independent cohorts: one with 326 stage 3-5 CKD patients and one with 629 hemodialysis patients. RESULTS: BCM yielded the following equation: ASM (kg) = -1.838 + 0.395 × total body water (L) + 0.105 × body weight (kg) + 1.231 × male sex - 0.026 × age (years) (R2 = 0.914, standard error of estimate = 1.35 kg). In the validation group, Bland-Altman reliability analysis showed no significant bias of 0.098 kg and limits of agreement ±2.440 kg. Using the AWGS criteria, the model was found to have a sensitivity of 94.1%, a specificity of 98.8%, a positive predictive value of 84.2%, and a negative predictive value of 99.6% for the diagnosis of sarcopenia. Low ASM predicted by the BCM equation was associated with significantly worse overall survival among CKD patients but not hemodialysis patients. CONCLUSIONS: The new BCM equation provides a feasible and valid option for assessing ASM in hemodialysis patients.

Engineering of dendritic mesoporous silica nanoparticles for efficient delivery of water-insoluble paclitaxel in cancer therapy.

The efficacy of hydrophobic chemotherapy drugs in cancer treatment is often hampered by their poor solubility in the physiological environment, which causes their low delivery efficiency in the body. This manuscript develops an intelligent nanocarrier (~100 nm) drug delivery system that can highly load a water-insoluble drug, and possesses desirable tumor-targeting properties for cancer therapy. In this system, highly porous silica nanoparticles (pore volume ~ 1.4 cm3 g-1) with a dendritic pore structure (denoted as DMSN) are applied as a matrix for drug loading. A facile, vacuum rotary evaporation-mediated casting method is applied to quantitatively load a high content of a hydrophobic drug (i.e., paclitaxel) in the DMSN matrix. A thiol-modified poly(methacrylic acid) (denoted as PMAsh) shell is then assembled and crosslinked via disulfide bonds on the particle surface to improve the dispersibility of the particles in an aqueous environment. After functionalization of the PMAsh shell with the targeting ligand transferrin (Tf), the nanocarriers exhibit accumulation ability on tumor cells, both in vitro and in vivo. Combining the fascinating properties of high drug-loading, excellent colloidal stability, low cytotoxicity, targeting ability and glutathione-responsive PMAsh shell deconstruction properties, the nanocarriers described here hold great promise for the efficient delivery of hydrophobic drugs and tumor treatment.

Attenuation of Wnt/ß-catenin signaling in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Current studies have suggested that the pathobiology of drug-mediated SJS/TEN involves a dysregulation of cellular immunity with overwhelming activation of cytotoxic T lymphocytes. The canonical Wnt signaling pathway plays important roles in T cell development and activation, which may provide potential avenues for alleviating dysregulated immunity in SJS/TEN. In this study, we aimed to assess the implication of Wnt signaling in drug-reactive T cells in SJS/TEN. We showed downregulation of Wnt signaling components, including T cell factor 1 (TCF-1)/lymphoid enhancer binding factor 1 (LEF-1) transcription factors, in SJS/TEN patients, suggesting that canonical Wnt signaling is regulated during cytotoxic T cell responses in SJS/TEN. Further analyses demonstrated that engagement of the T cell receptor by antigen encounter and treatment of a prognostic marker of SJS/TEN, IL-15, in vitro led to the downregulation of LEF-1 and TCF-1 expression in CD8+ T cells. Enhancement of Wnt signaling by adding the Wnt activators attenuated ex vivo activation of drug-specific T cells from SJS/TEN patients, indicating a functional involvement of Wnt signaling in the pathomechanism of SJS/TEN. These findings provide additional insight into the immunopathogenesis and therapeutic intervention of this devastating condition.

Increased oxidative stress in hemodialysis patients with high risk for sleep apnea syndrome.

BACKGROUND: In recent years, sleep apnea syndrome (SAS) has been widely considered to be a cardiovascular disease (CVD) risk factor. Although several plausible mechanisms have been put forth to explain such association in patients with SAS, oxidative stress has been suggested to play a major role. In patients with SAS, the repetitive ischemia-reperfusion state causes excessive production of oxygen free radicals and may subsequently lead to oxidative injury of various biomolecules. Due to the high prevalence of SAS in dialysis patients, this possible uremia-specific CVD risk factor may definitely need more medical attention. METHODS: We, therefore, performed a case control study to investigate the relationship between oxidative stress and SAS in a group of dialysis patients, using some well-established oxidative biomarkers. RESULTS: Our results showed that plasma nitrotyrosine, protein carbonyl and malonaldehyde levels were significantly elevated in patients with SAS. Markers of endothelial activation such as soluble CD40 ligand were also increased in this subgroup of patients. However, there was no significant difference in serum C-reactive protein levels between these groups. CONCLUSIONS: Our results indicate that patients with SAS manifest evidence for higher oxidative stress and endothelial activation. Thus, intermittent hypoxia represents a form of oxidative stress and low-grade chronic inflammatory state that may be associated with increased cardiovascular disease in these patients.

Development of SSR markers for Astragalus lehmannianus, a vulnerable species from northwestern China.

PREMISE: Astragalus lehmannianus (Fabaceae) is a vulnerable species found in the cold deserts of northwestern China. We aimed to characterize polymorphic microsatellite loci for A. lehmannianus to support future studies of population genetic dynamics and conservation management of the species. METHODS AND RESULTS: We used next-generation sequencing to detect polymorphic microsatellites. Twenty-five potential microsatellite loci were identified, 12 of which were polymorphic and present in the three study populations of A. lehmannianus. Levels of observed and expected heterozygosities were 0.000-1.000 and 0.000-0.827, respectively. Furthermore, two and five of the 12 developed primers were successfully amplified in two congeneric species, A. arpilobus and A. oxyglottis, respectively. CONCLUSIONS: These newly developed microsatellite markers can be used to determine population diversity and to develop conservation strategies in A. lehmannianus.

Psoriasiform drug eruption secondary to sorafenib: case series and review of the literature.

The expanding use of novel targeted anticancer agents such as sorafenib has led to an increasing number of dermatologic adverse events. Although cutaneous adverse events are commonly described in patients taking sorafenib, there are few reports describing psoriasis secondary to this medication. In this report, we describe 3 patients with sorafenib-induced psoriasiform drug eruption and review the available literature of similar patient cases. Our findings highlight shared characteristics among affected patients and potential treatment options for patients in whom sorafenib cannot be discontinued. Increased awareness of such drug eruptions and management options is critical to prevent suboptimal dosing and decreased quality of life.