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This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9–11) vs. 11 (95% CI 10–12) vs. 9 (95% CI 8–12) days, P  = 0.15], time from administration to NANC [median, 9 (95% CI 8–10) vs. 10 (95% CI 9.48–11) vs. 8.708 (95% CI 7.51–11) days, P  = 0.50], or hospital stay [median, 11 (95% CI 11–13) vs. 13 (95% CI 12–14) vs. 12 (95% CI 10–14) days, P  = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 ( P  = 0.858), 34.8%/21.5%/32.0% at day 7 ( P  = 0.226), 66.7%/52.3%/60.0% at 10 days ( P  = 0.246), and 86.4%/86.2%/80.0% at day 14 ( P  = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs.

In automatic and accurate reading recognition of analog meters based on machine vision, one of important issues is the detection of pointer features, which includes the meter center and pointer image processing. The current automatic-recognition approaches to reading analog meters often consist in locating the meter center based on the dial region or its border. The located center is not coincident with the rotation center of pointer which leads to inevitable reading errors. In the paper, the centripetalism of annular scale lines is used to calculate the position of the pointer rotation center. First, it uses the region growing method to locate the dial region and uses the eccentricity measure to extract annular scale lines. Second, the parameters of these scale lines are estimated with the Hough transform method. Then, the common intersection of a group of lines, i.e., the meter rotation center, is determined with the maximum probability criterion. Finally, the pointer centerline and direction are detected through the calculated center and the Hough transform results. The simulated and experimental results demonstrate that the proposed method can accurately locate the pointer rotation center and obtain pointer centerline. Moreover, it is applicable to the meter image captured under a slant camera view or with uneven light illumination.

Objective： To observe effect of acupuncture for acute facial paralysis patients with ocular skin blood perfusion, and to explore the safety and effectiveness of acupuncture in treating acute facial paralysis. Methods： Thirty patients with acute facial paralysis were enrolled and acupunctured in facial points and bilateral Hegu （LI 14）, and the PeriCam laser speckle flow video monitoring system was used not only for recording ocular skin blood perfusion condition in both normal and affected sides before acupuncture, at 15 min after acupuncture and after removing needles immediately, but also for calculating reduction ratio of ocular skin average perfusion in the affected side face compared with the healthy side. Results： Compared with the healthy side of face, the ocular skin blood perfusion of the affected side after acupuncture was significantly different from that before intervention. The blood perfusion levels after 1S-minute acupuncture and at the time of remaining needles were significantly different from the basic line （all P〈0.01）. Conclusion： Acupuncture can significantly improve eve blood perfusion of the acute facial paralysis, enhance metabolic activity of the affected facial tissues, and promote the recovery of facial nerve function.

A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune‐related gene (IRG)‐based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF‐related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow‐up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG‐based signature from the specific module. Risk plot analyses, Kaplan‐Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell’s concordance index were used to assess the prognostic value and predictive accuracy of the IRG‐based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG‐based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG‐based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low‐risk and high‐risk groups in PRAD. We identified a novel IRG‐based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD. This study aimed to identify a novel immune‐related gene (IRG)‐based signature for risk stratification and prognosis of biochemical failure in prostatic adenocarcinoma (PRAD). We identified an IRG‐based signature using weighted gene coexpression network analysis and random forest and multivariable stepwise Cox regression analyses and assessed the prognostic value and predictive accuracy of the IRG‐based signature in both internal and external cohorts. This novel IRG‐based signature could function as an index for assessing tumor immune status and risk stratification in PRAD. In addition, we analyzed the immune microenvironment of PRAD and identified immune cell changes associated with high‐risk PRAD.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid-polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- - -hexadecyl (mPEG- - -C ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.

The aim of the present study was to investigate the role and potential regulatory mechanisms of cyclin B1 (CCNB1) in the proliferation, apoptosis and epithelial-to-mesenchymal transition (EMT) in pituitary adenomas. A total of 24 specimens were included in the present study. The expression levels of CCNB1 protein in two normal pituitary and 22 pituitary adenoma tissues were determined by western blotting. CCNB1 was knocked-down by lentiviral-mediated infection of short hairpin RNA (shRNA) in GH3 and MMQ cell lines. The proliferation, cell cycle and apoptosis of GH3 and MMQ cell lines were detected using a Cell Counting Kit-8 and flow cytometer. Reverse transcription-quantitative PCR was utilized to detect the expression level of CCNB1 gene and EMT markers. In the present study, resveratrol (RES) was used as an inhibitor of CCNB1. The protein expression level of CCNB1 in pituitary adenomas was higher than that in normal pituitary tissue, as assessed by western blot analysis. In addition, the expression level of CCNB1 in invasive pituitary adenomas was higher when comparing invasive pituitary adenomas and non-invasive pituitary adenomas. Knockdown of CCNB1 resulted in significant decreases in cell viability and proliferation, arrested cell cycle at the G2/M phase and increased apoptosis. In addition, knockdown of CCNB1 significantly decreased the expression levels of the mesothelial cell marker N-cadherin (P<0.001), but significantly increased the expression levels of the epithelial cell markers E-cadherin (P<0.01) and p120-catenin (P<0.001). Further analyses identified that RES inhibited the expression level of CCNB1, and RES treatment exhibited a similar effect as CCNB1 shRNA infection. The present study suggested that suppressing the expression level of CCNB1 could regulate the proliferation and apoptosis of pituitary tumor cells and alter the expression level of various EMT markers. In addition, RES treatment could be used as an inhibitor of CCNB1. The present study also identified the molecular mechanisms underlying CCNB1 role in EMT.

Background Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. Methods The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. Results Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. Conclusion Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling. Our study identified two novel pathogenic variants of TCOF1 gene, clarified the etiology of Treacher Collins syndrome, enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Background Plastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS. Methods We conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021. Results A total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression. Conclusions Children with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.