Abstract Background With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. Methods A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into 3 disease severity groups (nonsevere, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. Results Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age >65 years (P < .001), smoking (P = .001), critical disease status (P = .002), diabetes (P = .025), high hypersensitive troponin I (>0.04 pg/mL, P = .02), leukocytosis (>10 × 109/L, P < .001), and neutrophilia (>75 × 109/L, P < .001) predicted unfavorable clinical outcomes. In contrast, the administration of hypnotics was significantly associated with favorable outcomes (P < .001), which was confirmed by survival analysis. Conclusions Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.
Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.
Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy.36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance.BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005].This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
In Brief Study Design. Retrospective clinical study. Objective. To retrospectively evaluate the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and progressive congenital scoliosis (CS) associated with split spinal cord malformation (SSCM). Summary of Background Data. For severe and rigid spinal deformity, spinal osteotomies are often advocated for correcting the deformity. However, the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and rigid CS with SSCM have been unclear thus far. Methods. Patients were treated by one-stage spinal osteotomy between September 2007 and June 2011 in our hospital. The clinical records were reviewed for demographic and radiographical data, operative time, intraoperative blood loss, blood transfusion, perioperative complications, and functional outcomes. Results. There were 18 females and 11 males with an average age of 15.5 ± 3.6 years (range, 12–28 yr). Spinal cord was longitudinally split by a bony spur in 11 patients (type I SSCM) and by a fibrous band in 18 patients (type II SSCM). Patients were observed for a minimum of 24 months after initial surgical treatment with an average follow-up of 43.0 ± 17.1 months (range 24–68 mo) from September 2007 to June 2013. The mean operative time and average blood loss of type ISSCM was significantly greater than those of type II SSCM (P < 0.05). The major curve was corrected from an average of 97.2°± 17.8° to 35.7°± 15.9°, a mean correction rate of 64.3% ± 11.0%. The average loss of correction at final follow-up was 2.9% for major curves. The overall complication rate was 24.1%, including transient neurological deterioration in 3 patients, cerebrospinal fluid leakage in 2 patients, urinary tract infection in 1 patient and pleural rupture in 1 patient. Conclusion. Relative to multistage corrective surgery, one-stage spinal osteotomy is effective for the correction of severe CS and SSCM without increasing the rate of surgical complications. However, surgical treatment of type I SSCM does require more operating time and blood loss. Level of Evidence: 4 To retrospectively evaluate the safety and efficacy of one-stage spinal osteotomy in the treatment of 29 patients, who had severe and progressive congenital scoliosis associated with split spinal cord malformation. Clinical and radiographical results of at least 2 years of follow-up show that it is effective for congenital scoliosis and split spinal cord malformation without increasing the rate of complications.
Cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) has been implicated in the poor prognosis of CA survivors. This study was designed to evaluate the impact of melatonin on postresuscitation neurological outcomes and to explore the underlying mechanism. Sprague-Dawley rats were randomly assigned to four groups: sham group, CPR group, melatonin pretreatment group (Pre-M) and posttreatment group (Post-M). For the last 2 groups, daily melatonin gavage was performed for 12 consecutive days before or 24 hours after rat survival from CA/CPR. No statistical differences were observed in heart rate (HR), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) at baseline and after restoration of spontaneous circulation (ROSC) among groups. However, melatonin pretreatment or posttreatment significantly improved neurological deficit score and memory and spatial learning ability after CA/CPR. Further studies demonstrated that the complex I- and complex-II supported mitochondrial respiration were greatly increased under melatonin treatment. In addition, melatonin treatment preserved the mitochondrial-binding hexokinase II (HKII) and ATP levels and suppressed the upregulated protein lysine acetylation in hippocampus after CA/CPR. In conclusion, using a rat asphyxial CA model we have demonstrated that treatment with melatonin either before or after CA/CPR provides a promising neuroprotective effect, and this protection was mediated by increasing mitochondrial HKII expression, suppressing protein acetylation and improving mitochondrial function in hippocampus.
To explore the therapeutic effect of the temperature-controlled radiofrequency technology in female sexual dysfunction (FSD).From July 2020 to June 2021, patients with FSD who visited the Gynecology Clinic of Peking University Shenzhen Hospital were treated with the temperature-controlled radiofrequency technology once every two weeks, for a total of five times. The therapeutic effect was objectively evaluated with pelvic floor dysfunction (PFD) indicators (FSFI score, pelvic floor muscles surface electromyography, sexual function test). The pre- and post-treatment (2 weeks)/follow-up (3 months) results were compared to evaluate the feasibility of this technology for treating FSD, as well as using PFD-related indicators in objective evaluation of FSD patients.Fifty patients completed treatment; 31 patients completed follow-up. The mean FSFI score for post-treatment/follow-up was significantly higher than pre-treatment (p < 0.05). There were no significant changes in the mean pelvic floor resting surface myoelectric potential and its variability and mean myoelectric potential of sexual function test between pre- and post-treatment/follow-up. The mean surface myoelectric potential of the patients' type I and II muscle fibers of the pelvic floor for post-treatment/follow-up was significantly higher than pre-treatment (p < 0.05). The mean peak myoelectric potential for post-treatment was significantly higher than pre-treatment (p < 0.05).Temperature-controlled radiofrequency technology has a certain therapeutic effect on FSD. Pelvic floor surface electromyography and sexual function test can be used as an objective indicator for PFD in FSD patients. Subsequent studies may involve a larger size sample and evaluate the effect over a consecutive time-point, to develop a better therapeutic approach.
Adventitious root (AR) formation is a bottleneck for vegetative proliferation. In this study, 13 AHP genes (MdAHPs) were identified in the apple genome. Phylogenetic analysis grouped them into 3 clusters (I, II, III), with 4, 4, and 5 genes respectively. The 13 MdAHPs family members were named MdAHP1 to MdAHP13 by chromosome positions. The physicochemical properties, phylogenetic relationship, motifs, and elements of their proteins were also analyzed. The amino acid quantity varied from 60~189 aa, isoelectric point lay between 4.10 and 8.93, and there were 3~7 protein-conserving motifs. Excluding MdAHP6, other members' promoter sequences behaved 2-4 CTK response elements. Additionally, the expression characteristics of MdAHPs family members at key stages of AR formation and in different tissues were also examined with exogenous 6-BA and Lov treatments. The results showed that MdAHP3 might be a key member in AR formation. GUS staining indicated that the activity of the MdAHP3 promoter was also significantly enhanced by CTK treatment. The protein interactions of MdAHP3/MdAHP1 and MdAHP3/MdAHP6 were verified. Compared with WT, 35S::MdAHP3 transgenic poplars inhibited AR formation. The above experimental results suggested that MdAHP3, as a key family member, interacts with MdAHP1 and MdAHP6 proteins to jointly mediate AR formation in apple rootstocks.
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