Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Enantioselective Construction of Anthracenylidene-Based Axial Chirality by Asymmetric Heck Reaction.

Anthracenylidene is an intriguing structural unit with potential in various fields. The study presents a novel approach to introducing axial chirality into this all-carbon core skeleton through a remotely controlled desymmetrization strategy. A palladium-catalyzed enantioselective Heck arylation of exocyclic double bond of anthracene with two distinct substituents at the C10 position is harnessed to realize such a transformation. The judicious identification of the P-centrally chiral ligand is pivotal to ensure the competitive competence in reactivity and stereocontrol when the heteroatom handle is absent from the anthracenylidene skeleton. Both C10 mono- and disubstituted substrates were compatible for the established catalytic system, and structurally diverse anthracenylidene-based frameworks were forged with good-to-high enantiocontrol. The subsequent derivatization of the obtained products yielded a valuable array of centrally and axially chiral molecules, thus emphasizing the practicality of this chemistry. DFT calculations shed light on the catalytic mechanism and provided insights into the origin of the experimentally observed enantioselectivity for this reaction.

Application of real-time PCR-based multicolor melting curve with automatic analysis system in pregestational and prenatal thalassemia diagnoses.

BACKGROUND: To evaluate the value of the real-time PCR-based multicolor melting curve analysis (MMCA) with an automatic analysis system used in a mass thalassemia screening and prenatal diagnosis program. METHODS: A total of 18,912 peripheral blood samples from 9456 couples and 1150 prenatal samples were detected by MMCA assay. All prenatal samples were also tested by a conventional method. Samples with unknown melting peaks, unusual peak height ratios between a wild allele and a mutant allele, or a discordant phenotype-genotype match were further studied by using multiplex ligation-dependent probe amplification (MLPA) or Sanger sequencing. All MMCA results were automatically analyzed and manually checked. The consistency between MMCA assay and conventional methods among prenatal samples was investigated. RESULTS: Except for initiation codon (T > G) (HBB:c.2T > G), all genotypes of thalassemia inside the scope of conventional methods were detected by MMCA assay. Additionally, 27 carriers with 10 rare HBB variants, 13 with α fusion gene, 1 with a rare deletion in α globin gene, and 1 with rare HBA variant were detected by using MMCA assay. CONCLUSION: MMCA can be an alternative approach used in routine thalassemia carrier screening and prenatal diagnosis for its high throughput, sufficient stability, low cost, and easy operation.

Hb Lepore-Hong Kong: First Report of a Novel δ/ß-Globin Gene Fusion in a Chinese Family.

We describe a new δ/ß fusion gene causing ß-thalassemia (ß-thal) trait and its formation mechanism. The proband was a 39-year-old woman who presented with persistent microcytic microcytosis without iron deficiency. Molecular diagnoses revealed a 뫧 configuration within a 54 bp region between the Cap site (+22) and codon 8, causing a deletion (NG_000007.3: g.63154_70565del). This results in a variant that has been named Hb Lepore-Hong Kong and shows a decreased ß-globin mRNA in carriers compared to that of normal subjects. It is assumed that combination of this variant with ß-thal may cause severe ß-thal syndrome.

Hb Westmead (HBA2: c.369C>G): Hematological Characteristics in Heterozygotes with and without α0-Thalassemia.

Hb Westmead (α122(H5)His>Gln) (HBA2: c.369C>G) is a common α-globin variant causing α-thalassemia (α-thal) in Mainland China. In this study, we report the hematological characteristics in Hb Westmead carriers in a Chinese population. There were 546 individuals carrying Hb Westmead based on their molecular diagnosis: 514 Hb Westmead heterozygotes and 32 compound heterozygotes for Hb Westmead and α0-thal. Compared to common deletional α+-thal, Hb Westmead was associated with higher mean corpuscular hemoglobin (Hb) (MCH) values. Compound heterozygotes for Hb Westmead and α0-thal showed significantly higher Hb, mean corpuscular volume (MCV) and MCH values than subjects with deletional Hb H disease. When compared to α0-thal carriers, compound heterozygotes for Hb Westmead and α0-thal showed similar Hb values, but significantly lower MCV and MCH values. Our results indicate that Hb Westmead is a silent nondeletional α+-thal, with a deficiency of α-globin chain milder than deletional α+-thal, and compound heterozygotes for Hb Westmead/α0-thal have a phenotype similar to simple α0-thal.

Hematological Characteristics of Hb Constant Spring (HBA2: c.427T>C) Carriers in Mainland China.

Hb Constant Spring (Hb CS) (HBA2: c.427T>C) is a common α-globin variant causing α-thalassemia (α-thal) phenotypes in mainland China. In this study, we evaluated the efficiency of erythrocyte parameters and capillary electrophoresis (CE) in the determination of Hb CS in blood samples from Hb CS carriers. Based on molecular diagnosis, there were 462 patients carrying Hb CS: 411 Hb CS heterozygotes, seven carried Hb H-Hb CS disease, 18 compound heterozygotes for Hb CS/α+-thal, and 26 double heterozygotes for Hb CS and ß-thalassemia (ß-thal). Forty-three cases had no Hb CS peak visible on CE, including all 26 cases of double heterozygotes for Hb CS and ß-thal, and 17 cases of heterozygotes carrying only Hb CS. Hb CS heterozygotes, those without a Hb CS peak, presented with lower hemoglobin (Hb), mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values than those with a Hb CS peak. The MCV <80.0 fL yielded a detection rate of 87.8% for screening individuals carrying Hb CS. Therefore, we emphasize that if one partner of a couple has tested positive for α0-thal, the other should be subjected to detailed screening for this nondeletional allele using molecular analysis, regardless of his/her red cell indices and electrophoretic chromatogram.

[Correlation of age, body mass index and obesity-related biochemical indexes with semen quality in males intending for a second child].

OBJECTIVE: To explore the influence of age, body mass index (BMI) and obesity-related biochemical indexes on semen quality in adult males intending to have a second child in Guangzhou. METHODS: We conducted a questionnaire investigation among 632 adult males seeking medical advice on their intention for a second child at Guangzhou Women and Children's Medical Center from August 2017 to July 2018. We obtained their lipid metabolism indicators and semen parameters, and analyzed the correlation of semen quality with age, BMI, obesity-related biochemical indexes, living environment and occupation. RESULTS: Age, BMI, season of sperm extraction, living environment and occupation all influenced the semen quality of the males. Age was correlated negatively with the percentage of progressively motile sperm (PMS) (r = －0.109, P < 0.05), BMI positively with the semen volume (r = 0.103, P < 0.05) but negatively with the percentage of morphologically normal sperm (MNS) (r = －0.138, P < 0.05), high-density lipoprotein (HDL) negatively with PMS (r = －0.168, P < 0.01) and the percentage of immotile sperm (IM) (r = －0.135, P < 0.05), low-density lipoprotein (LDL) negatively with the semen volume (r = －0.124, P < 0.01), PMS (r = －0.127, P < 0.05), sperm concentration (r = －0.121, P < 0.05) and total sperm count (r = －0.210, P < 0.01) but positively with IM (r = 0.140, P < 0.01). Multivariate regression analysis showed BMI and LDL to be independent factors influencing the semen volume, uric acid to be an independent factor influencing semen liquefaction time, age, HDL and LDL to be independent factors influencing PMS, age, and HDL to be independent factors influencing IM, LDL to be independent factors influencing total sperm count, while BMI and TG to be independent factors influencing MNS. CONCLUSIONS: Age, BMI, season of sperm extraction, living environment and occupation may affect the semen quality of the males in Guangzhou.

KFL1 Gene Variants in α-Thalassemia Individuals with Increased Fetal Hemoglobin in a Chinese Population.

Krüppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that is a regulator of definitive erythropoiesis. The aim of this study was to detect KLF1 gene variants in α-thalassemia (α-thal) carriers with an increased Hb F level in a Chinese population, and determine the changes of hematological parameters as a result of interactions between KLF1 gene mutations and α-thal. Subjects with α-thal and Hb F levels of ≥1.0% were selected for further investigation. Direct sequencing was used to detect KLF1 gene mutations. Hematological parameters of subjects with α-thal and concomitant KLF1 gene mutations and those with α-thal alone were compared. The KLF1 gene variants were detected in 46 of 275 (16.7%) individuals with α-thal and Hb F levels of ≥1.0%. The detection rate of KLF1 gene mutations rose correspondingly when the Hb F level increased. For α0-thal carriers, significantly lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values were observed in KLF1 gene mutation-positive carriers than that in KLF1 gene mutation-free carriers; conversely, significantly higher Hb A2 and Hb F levels were observed in the former condition rather than in the latter condition. The results of this study indicate that KLF1 gene variants are common in Chinese subjects with α-thal and increased Hb F levels, and KLF1 gene mutations decreased the red blood cell (RBC) indices in α-thal carriers as that in normal adults.

The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells.

Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-κB signaling pathway.

Association between fibrinogen-to-albumin ratio and functional prognosis of 3 months in patients with acute ischemic stroke after intravenous thrombolysis.

BACKGROUND: The presence of high fibrinogen and low albumin levels in serum is associated with a negative prognosis in acute ischemic stroke (AIS). Fibrinogen-to-albumin ratio (FAR), a new inflammatory biomarker, may provide better prognostic insights in patients with AIS than separate evaluation of fibrinogen or albumin. The objective of this investigation is to examine the correlation between FAR and 3-month functional prognosis after intravenous thrombolysis (IVT) in AIS patients. METHODS: The retrospective study recruited AIS patients who received IVT from June 2014 to December 2021. The 3-month functional prognosis was assessed using the Modified Rankin Scale (mRS). A mRS score of ≤2 indicated a good outcome, whereas a mRS score of >2 suggested a poor outcome. RESULTS: A total of 591 AIS patients who underwent IVT were included and 147 patients (24.9 %) had a poor outcome. Among the 102 pairs of patients after propensity score matching, there was a significant association between FAR and 3-month prognosis (adjusted OR, 1.19; 95% CI, 1.03-1.38; p = .020). The optimal FAR cutoff value was found to be 7.57, and even after stratifying patients based on this value, we still observed a significant correlation between high FAR level and poor outcome (adjusted OR, 2.08; 95% CI, 1.28-3.40; p = .003). CONCLUSIONS: FAR may serve as a prospective biomarker of predicting 3-month prognosis in AIS patients after IVT.

Influence of UDP-Glucuronosyltransferase Polymorphisms on Mycophenolic Acid Metabolism in Renal Transplant Patients.

This study aimed to evaluate the effects of UDP-glucuronosyltransferase (UGT) polymorphisms on mycophenolic acid (MPA) metabolism in renal transplant patients. A total of 11 single nucleotide polymorphisms (SNPs) of UGT1A1, UGT1A7, UGT1A8, UGT1A9, UGT1A10, and UGT2B7 were genotyped in 79 renal transplant patients. The associations of SNPs and clinical factors with dose-adjusted MPA area under the plasma concentration-time curve (AUC/D), the dose-adjusted plasma concentration (C0/D) of 7-O-MPA-glucuronide (MPAG), and the dose-adjusted plasma concentration (C0/D) of acyl MPAG (AcMPAG) were analyzed. In the univariate analysis, UGT1A1 rs4148323, age, and anion gap were associated with MPA AUC/D. MPA AUC/D was higher in patients with the GA genotype of UGT1A1 rs4148323 compared to patients with the GG genotype. UGT1A1 rs4148323, UGT1A9 rs2741049 and clinical factors, including age, serum total bilirubin, adenosine deaminase, anion gap, urea, and creatinine, were associated with MPAG C0/D. UGT2B7 rs7438135, UGT2B7 rs7439366, and UGT2B7 rs7662029 also were associated with AcMPAG C0/D. Multiple linear regression analysis showed that UGT1A9 rs2741049 and indirect bilirubin were negatively correlated with MPAG C0/D (P = .001; P = .039), and UGT2B7 rs7662029 was positively correlated with AcMPAG C0/D (P = .008). This study demonstrates a significant influence of UGT1A9 rs2741049 and UGT2B7 rs7662029 polymorphisms on the metabolism of MPA in vivo.

Association between lower neutrophil-to-albumin ratio and early neurological improvement in patients with acute cerebral infarction after intravenous thrombolysis.

Elevated neutrophil counts and decreased albumin levels have been linked to an unfavorable prognosis in acute cerebral infarction (ACI). The objective of this study is to explore the correlation between the neutrophil-to-albumin ratio (NAR) and the early neurological improvement (ENI) of ACI patients following intravenous thrombolysis (IVT). ACI patients who underwent IVT between June 2019 and June 2023 were enrolled. The severity of ACI was assessed using the National Institutes of Health Stroke Scale (NIHSS). ENI was defined as a reduction in NIHSS score of ≥ 4 or complete resolution of neurological deficit within 24 h after IVT. Propensity score match (PSM) and logistic regression analysis were used to explore the correlation between these variables and the early neurological outcomes of patients. A total of 545 ACI patients were included, with 253 (46.4 %) experiencing ENI. Among the 193 pairs of patients after PSM, there was a significant association between NAR and ENI (OR, 0.89; 95 % CI, 0.85-0.94; p < 0.001). The restricted cubic splines analysis revealed a significant nonlinear correlation between NAR and ENI (p for nonlinear = 0.0004; p for overall = 0.0002). The optimal cutoff for predicting ENI was determined as a NAR level of 10.20, with sensitivity and specificity values of 73.6 % and 60.9 %. NAR levels are associated with ENI in ACI patients after IVT. The decreased levels of NAR indicate an increased likelihood of post-thrombolysis ENI in ACI patients.

Gut microbiota and metabolomic profile changes play critical roles in tacrolimus-induced diabetes in rats.

Aims: Hyperglycemia is one of the adverse effects of tacrolimus (TAC), but the underlying mechanism is not fully identified. We used multi-omics analysis to evaluate the changes in the gut microbiota and metabolic profile of rats with TAC-induced diabetes. Methods: To establish a diabetic animal model, Sprague Dawley rats were divided randomly into two groups. Those in the TAC group received intraperitoneal injections of TAC (3 mg/kg) for 8 weeks, and those in the CON group served as the control. 16S rRNA sequencing was used to analyze fecal microbiota. The metabolites of the two groups were detected and analyzed by nontargeted and targeted metabolomics, including amino acids (AAs), bile acids (BAs), and short-chain fatty acids (SCFAs). Results: The rats treated with TAC exhibited hyperglycemia as well as changes in the gut microbiota and metabolites. Specifically, their gut microbiota had significantly higher abundances of Escherichia-Shigella, Enterococcus, and Allobaculum, and significantly lower abundances of Ruminococcus, Akkermansia, and Roseburia. In addition, they had significantly reduced serum levels of AAs including asparagine, aspartic acid, glutamic acid, and methionine. With respect to BAs, they had significantly higher serum levels of taurocholic acid (TCA), and glycochenodeoxycholic acid (GCDCA), but significantly lower levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). There were no differences in the levels of SCFAs between the two groups. Correlations existed among glucose metabolism indexes (fasting blood glucose and fasting insulin), gut microbiota (Ruminococcus and Akkermansia), and metabolites (glutamic acid, hydroxyproline, GCDCA, TDCA, and TUDCA). Conclusions: Both AAs and BAs may play crucial roles as signaling molecules in the regulation of TAC-induced diabetes.

Does Antibiotic Use Increase the Risk of Post-Transplantation Diabetes Mellitus? A Retrospective Study of Renal Transplant Patients.

BACKGROUND This study aimed to investigate the incidence of post-transplant diabetes mellitus (PTDM) in renal transplant (RT) patients at our center and to explore new risk factors for PTDM. MATERIAL AND METHODS This retrospective study included RT patients from 2010 to 2022. Clinic data on RT patients were obtained from hospital electronic medical records. CYP3A5*3, POR*28, ABCB1 (3435 C>T), and ABCB1 (1236 C>T) were genotyped in RT patients. The associations between age, BMI, concentration of tacrolimus (TAC), polymorphism of genes, antibiotics (eg, penicillins, cephalosporins, oxazolidinones, quinolones), numbers and days of antibiotic use, and PTDM were analyzed. RESULTS In this study, 409 patients with RT were included. The cumulative incidence of PTDM in the first year after RT was 9.05%. The numbers and days of antibiotic use in PTDM patients were significantly higher than those in non-PTDM patients. Multivariate logistic regression analysis identified age (OR=1.047, P=0.014), body mass index (BMI) (OR=1.178, P=0.007), dose-adjusted trough concentration of TAC (TAC C0/D) at 7 days after RT (OR=1.159, P=0.042), trough concentration of TAC (TAC C0) at 28 days after RT (OR=1.094, P=0.042), and levofloxacin (OR=5.975, P=0.003) as independent risk factors for PTDM. CONCLUSIONS In addition to age, BMI, and TAC concentration after RT, antibiotic use may be a novel factor affecting PTDM. The use of antibiotics may influence the development of PTDM.

Diagnostic value of whole-brain computed tomographic perfusion imaging for suspected large artery occlusion stroke patients in emergency department.

PURPOSE: To evaluate the diagnostic value of whole-brain computed tomographic perfusion (WB-CTP) in emergency department for suspected large artery occlusion stroke. METHODS: Suspected large artery occlusion (LAO) stroke patients had initial WB-CTP in the neurological emergency department from August 2016 to August 2018 were retrospectively reviewed for analysis. The sensitivity and specificity of non-contrast computed tomographic scan (NCCT) or WB-CTP for diagnosis of cerebral infarction was compared between the anterior circulation and posterior circulation. The imaging characteristics of WB-CTP in patients with stroke-mimics were described. RESULTS: Among the 300 included patients, 259 patients (86.3%) were finally diagnosed as cerebral infarction, 16 (5.3%) were transient ischemic attack, 10 (3.3%) were epileptic seizure and 3 (1%) were cerebral venous sinus thrombosis (CVST). For patients with final diagnosis of cerebral infarction, WB-CTP found abnormality in 206 cases (79.5%). NCCT had poor sensitivity (4.6%) but high specificity (100%) for cerebral infarction. The CTP imaging had a sensitivity of 81.2% in anterior circulation and 59.6% in posterior circulation stroke, both with good specificity (57.1% and 92.6%, respectively). 60% (6/10) of epileptic patients showed abnormal perfusion in CTP maps, which was inconsistent with cerebral arterial supply territories. Hypoperfusion manifestations were discovered in areas adjacent to occlusion sinus of all 3 CVST cases. CONCLUSION: This retrospective study indicates WB-CTP can be useful in identifying acute ischemic stroke in emergency department, especially for patients with acute LAO stroke. Moreover, WB-CTP may have a value in differentiating stroke mimics such as epilepsy and CVST.

Improving the Prehospital Identification and Acute Care of Acute Stroke Patients: A Quality Improvement Project.

BACKGROUND: There are a large number of stroke patients in China, and there is currently a lack of prehospital acute stroke care training programs. AIM: To develop a prehospital emergency medical service (PEMS) training program to improve the prehospital identification and acute care of acute stroke. METHODS: Forty prehospital emergency doctors whose service stations are located within a 10 km radius from Shanghai Pudong New Area Medical Emergency Service Center took this course on November 13, 2014. A questionnaire was designed to evaluate the PEMS personnel's knowledge in stroke and acute stroke care and was conducted before and after training as an assessment of the effectiveness of training. The patient population in this study included a baseline cohort before training and a prospective cohort after training, each composed of patients who were sent to Shanghai East Hospital South Stoke Center within one year. The transit time, final diagnosis, administration of thrombolysis, and door-to-needle time (DNT) were collected and analyzed. RESULTS: After the training, 100% of the PEMS personnel were competent to identify stroke cases using the Cincinnati prehospital stroke scale (CPSS). All participants realized that intravenous thrombolysis therapy in a time-sensitive manner is the most effective way to treat acute ischemic stroke. Although there was no difference in first-aid transit time before and after training, the stroke diagnosis rate improved by 6.5% after training (P=0.03). The thrombolysis rate increased to 29.6% from 24.3% but did not reach statistical significance. Compared to 84.0 minutes (standard deviation: 23.1 minutes) before the training, the average DNT after training was 53 minutes (standard deviation: 15.0 minutes), demonstrating a remarkable reduction (P < 0.01). CONCLUSION: The training program effectively improved the PEMS personnel's knowledge in stroke and stroke acute care.

Detection of rare thalassemia mutations using long-read single-molecule real-time sequencing.

Gap- polymerase chain reaction (PCR), reverse dot-blot assay (RDB), real-time PCR based multicolor melting curve analysis (MMCA assay), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing are conventional methods to diagnose thalassemia but all of them have limitations. In this study, we applied single-molecule real-time (SMRT) sequencing following multiplex long-range PCR to uncover rare mutations in nine patients and their family members. The patients with different results between Gap-PCR and MMCA assay or with phenotype not matching genotype were included. Using SMRT sequencing, we first identified the carriers with αααanti3.7/HKαα, -α762bpα/αα (chr16:172,648-173,409), ααfusion/αQSα (in a trans configuration), two cases with novel gene rearrangements and another case with a novel 341 bp insertion in α-globin gene cluster, respectively. One carrier with --SEA/αααanti4.2, and two carriers with the coexistence of globin variant and an α-globin gene duplication were also found. Most importantly, we could determine two defects in α-globin gene cluster being a cis or trans configuration in a single test. Our results showed that SMRT has great advantages in detection of α-globin gene triplications, rare deletions and determination of a cis or trans configuration. SMRT is a comprehensive and one-step method for thalassemia screening and diagnosis, especially for detection of rare thalassemia mutations.

Mild-to-moderate neurogenic pyrexia in acute cerebral infarction.

BACKGROUND: Pyrexia is often associated with unfavorable stroke outcomes. However, limited information is available on the relationship between the causes of poststroke hyperthermia and stroke prognosis, especially for mild-to-moderate neurogenic pyrexia in acute cerebral infarction. AIMS: To compare the differences in the clinical features and characteristics of pyrexia as well as its prognosis among acute cerebral infarction patients with mild-to-moderate neurogenic pyrexia, with infectious pyrexia, and without pyrexia. The focus was on mild-to-moderate neurogenic pyrexia. METHODS: A total of 709 patients with acute cerebral infarction were prospectively recruited and their clinical data were analyzed. RESULTS: No significant difference was detected in age, gender, history of smoking, hypertension, or diabetes among the 3 groups (p > 0.05). Patients with mild-to-moderate neurogenic pyrexia and those with infectious pyrexia had higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (15.1 ± 6.7, p = 0.003; 14.3 ± 8.1, p = 0.002, respectively), lower 3-month Barthel index (BI) values (64.2 ± 40.7, p < 0.001; 61.9 ± 49.3, p < 0.001, respectively) and higher 3-month mortality rates (13%, p = 0.026; 16%, p < 0.001, respectively) than patients without pyrexia (NIHSS score 11.4 ± 7.9; BI 82.6 ± 39.8, and mortality rate 6%, respectively). No difference existed in these parameters between the 2 pyrexia groups (p > 0.05), but mild-to-moderate neurogenic pyrexia had an earlier onset and a shorter duration than infectious pyrexia (p < 0.001). CONCLUSIONS: Acute cerebral infarction patients with mild-to-moderate neurogenic pyrexia had a similar prognosis compared to those with infectious pyrexia. Mild-to-moderate neurogenic pyrexia is possibly associated with stroke severity.

Effect of rt-PA intravenous thrombolysis on the prognosis of patients with minor ischemic stroke.

AIMS: The evidence of rt-PA intravenous thrombolysis in patients with minor ischemic stroke (MIS) is still controversial. This study aims to investigate the effect of rt-PA intravenous thrombolysis on the prognosis of patients with MIS. METHODS: We continuously enrolled and analyzed patients with MIS admitted into our hospital within 24 h after symptom onset between January 2016 and December 2018, including 96 patients received intravenous thrombolysis within 4.5 h after symptom onset and 84 patients not received intravenous thrombolysis. A favorable long-term outcome was a 90-day mRS score of 0-1. Good short-term outcome was a 7-day NIHSS score of 0 or less than NIHSS onset. RESULTS: There were no statistical differences between two groups of patients' age, gender, history of hypertension, coronary heart disease, atrial fibrillation, smoking, drinking, and baseline NIHSS score. Patients with history of stroke (22.62% vs. 10.42%, p < 0.05) and diabetes (46.43% vs. 22.92%, p = 0.01) were higher in group of non-thrombolysis. The difference of NIHSS score after 7 days was statistically different between the two groups (p < 0.05), while there was no significant difference in 90-day mRS score. Logistic regression analysis indicated that the prognosis of patients was correlated with neutrophil ratio and CRP at admission. CONCLUSION: Patients with MIS received intravenous thrombolysis may be associated with earlier neurological improvement, but might has no significant effect on long-term prognosis. The level of neutrophil ratio and CRP at admission are risk factors determining the prognosis, which requires further research.

Mechanical Thrombectomy for Acute Stroke Due to Large-Vessel Occlusion Presenting With Mild Symptoms.

Purpose: To evaluate the safety and efficacy of mechanical thrombectomy (MT) for acute stroke due to large vessel occlusion (LVO), presenting with mild symptoms. Methods: A prospective cohort study of patients with mild ischemic stroke and LVO was conducted. Patients were divided into two groups: MT group or best medical management (MM) group. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups. The primary outcome was functional independence at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with outcomes. Results: Among the 105 included patients, 43 were in the MT group and 62 in the MM group. Forty-three pairs of patients were generated after PSM. There were no significant differences in sICH rates between two groups (p = 1.000). The MT group had a higher proportion of independent outcomes (83.7% MT vs. 67.4% MM; OR 2.483; 95% CI 0.886-6.959; p = 0.079) and excellent outcomes (76.7% MT vs. 51.2% MM; OR 3.150; 95% CI 1.247-7.954; p = 0.013) compared to the MM group, especially in patients with stroke of the anterior circulation (p < 0.05). Multivariate logistic regression analysis showed that small infarct core volume (p = 0.015) and MT treatment (p = 0.013) were independently associated with excellent outcomes. Conclusions: Our results suggest that MT in stroke patients, presenting with mild symptoms, due to acute LVO in the anterior circulation may be associated with satisfactory clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04526756.