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Objective: To assess the effects of Yi Qi Jie Du Formula (YQJDF) combined with salinomycin (SAL) on nasopharyngeal carcinoma stem cells (NPC-SCs) and investigate the underlying molecular mechanisms. Methods: Cell counting methods, the CCK-8 assay, transwell migration assay and JC-1 staining, were used to observe the effects of the combination on the proliferation, migration and apoptosis of NPC stem cells, respectively. Western blot was used to detect the levels of protein in NPC-SCs. Results: YQJDF combined with SAL had a synergistic effect on the inhibition of proliferation and migration and induction of NPC-SC apoptosis. Mechanistically, YQJDF combined with SAL synergistically upregulated the levels of apoptotic proteins, including cleaved Caspase-3, cleaved Caspase-7 and cleaved Caspase-9. Moreover, YQJDF combined with SAL synergistically decreased the levels of CD44, p-c-Src, Ras, p-PKCδ, p-MEK, p-c-Raf, p-ERK1/2 and p-AKT proteins. Conclusions: The combination of YQJDF and SAL has a synergistic effect on the inhibition of NPC-SC proliferation and migration and induction of apoptosis, which may be closely related to the downregulation of the CD44/Ras signaling pathway.

Objective: This aim of this study was to analyze the correlations between clinical manifestations, treatment strategies, and the prognosis in cryptococcal meningitis (CM) in China. Methods: This was a retrospective analysis of the clinical data of CM patients treated during the years 2002–2019. The clinical features and supplementary examinations, treatment strategies, and prognosis were summarized and then a correlation analysis was performed. Results: Fifty patients were enrolled. The most common symptoms were fever, headache, and vomiting. Five of these patients died and five had visual impairment sequelae; nine of these patients were treated before 2010. Correlation analysis suggested that cerebral hernia, consciousness disorder, visual impairment, hydrocephalus, and an intracranial pressure >300 mmH2O in cerebrospinal fluid (CSF) were associated with a poor prognosis. Whether or not the application of intrathecal administration had little effect on prognosis. Early surgical intervention with internal drainage helped to reduce the mortality and incidence of visual impairment sequelae, whether or not Cryptococcus was present in the CSF before surgery. Conclusions: Clinically, the presence of a cerebral hernia, consciousness disorder, hydrocephalus, visual impairment, or intracranial pressure >300 mmH2O often indicates a poor prognosis in patients with CM. The prognosis improved significantly after 2010, following an adjustment of the treatment strategy. Early internal drainage is the key factor, and CSF positive for Cryptococcus before surgery is not a contraindication.

ObjectiveTo explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.MethodsIn the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.ResultsA total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia.SignificanceThe most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.

ObjectiveThe limitations of adrenocorticotrophic hormone (ACTH) treatment for infantile spasms (ISs), such as high costs, limited availability, and adverse effects (AEs), make it necessary to explore whether corticosteroids are optimal alternatives. Many other compelling treatments have gone through trials due to the suboptimal effectiveness of hormonal therapy. A systematic review and meta-analysis were performed to evaluate the effectiveness and safety of hormonal therapy for patients with ISs.MethodsEMBASE, Ovid MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and online registers were searched through April 2021 for randomized controlled trials (RCTs).ResultsA total of 19 RCTs (N = 1,279) were included. There was no significant difference in the effectiveness of oral corticosteroids and ACTH in electro-clinical response (risk ratio [RR] = 0.85, 95% CI 0.41–1.76). Low-dose ACTH had similar effectiveness in electro-clinical response compared to usual-dose group (RR = 0.94, 95% CI 0.60–1.47) but conferred a lower risk of AEs (RR = 1.71, 95% CI 1.08–2.71). ACTH was more beneficial in controlling spasms than vigabatrin (VGB) (RR = 1.31, 95% CI 1.05–1.64) for patients without tuberous sclerosis complex (TSC). All RCTs were connected through network meta-analysis, and we found that ketogenic diet (KD), zonisamide, methylprednisolone, or combined treatment of hormonal therapy with topiramate (TPM) or pyridoxine was not different in electro-clinical response compared to usual-dose ACTH.ConclusionOur analysis showed that oral corticosteroids could be optional alternatives when ACTH is not applicable, and ACTH is more beneficial for patients without TSC. Moreover, low-dose ACTH is recommended due to comparative effectiveness but lower risk of AEs. However, due to the high heterogeneity of included patients and treatment protocols, these results must be interpreted with caution. RCTs with multicentric involvement and larger sample size are needed for solid evaluation of other alternative treatments.

Executing code containing side-channel vulnerabilities exhibits different non-functional behaviors related to inputs.Attackers can obtain these behaviors by leveraging micro architecture side-channel attacks and then analyze the pattern between the behaviors and the inputs to access sensitive data.Vulnerability repairing at the software layer brings low overheads to a program’s execution.Besides, it does not require modifying hardware or system, which enables fast patching and widespread deployment.It becomes the mainstream strategy applied to the current cryptographic implementations.However, existing solutions are deeply bound to the program’s implementation and requires manual intervention.This brings challenge to implement and is not versatile enough.A general patching method was proposed for side-channel vulnerabilities that combined dynamic obfuscated execution with hardware atomic transaction.To hide the real accesses of the side-channel vulnerabilities of a program, the proposed method inserted dynamic confusing accesses into the vulnerabilities.To avoid an attacker using fine-grained side-channel attack to distinguish the real access and the confusing access, both of them were encapsulated as transactions and they were guaranteed to be uninterrupted during the running period.In addition, a prototype system called SC-Patcher was implemented based on the LLVM compiler.Various optimization strategies were supported, including secure springboard and transaction aggregation, to further improve system security and performance.Experimental results show that the proposed method makes it impossible for an attacker to restore accurate sensitive data through side-channel attack, and it also brings almost no additional performance overhead to the program.

Object: Perimenopause depression disorder (PDD) is a very common problem in clinical practice and is characterized by depression and autonomic nervous symptoms, including hot flashes, palpitation, and night sweating. In addition, the comorbidity of menopause depression has long been an integral component of the estradiol (E2) shortage. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of endocrine and cerebellar networks. Emerging evidence has shown that the endocrine–brain–gut–microbiota axis plays a key role in the regulation of affective disorders. Yangyin-ningshen formula (YYNS) is a traditional Chinese decoction tailored by Yijintang for menopausal depression intervention. Thus, we hypothesized that the YYNS may be involved in the menopause depression alleviation through the endocrine–brain–gut–microbiota axis. Methods: To verify this, we constructed a bilateral ovariectomy (OVX) mouse model to simulate menopausal-related depression. Subsequently, behavioral tests including the open field test (OFT) and the forced swimming test (FST) were conducted to examine the depression state post-OVX. With YYNS or E2 intervention, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum sex hormones level. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to analyze the microbiome of the colon samples collected from mice in the sham surgery group (CSH), the OVX model group (CMD), the OVX with E2 hormone intervention group (CHM), and the OVX with YYNS intervention group (CYYNS). One week after OVX, CMD, CHM, and CYYNS showed depression in OFT, FST. Three weeks post-OVX, CHM and CYYNS showed a notable relief of depression; CMD shaped the OTUs shrinkage; and OTUs were raised in the sham, CHM, and CYYNS group. The CMD group showed that the abundance of Actinobiota decreased but that of Bacteriodia increased. The relative abundance of the genus varied in each group. Moreover, functional correlation of changes in sex hormone and gut microbes between different groups showed that the PRL level was negatively correlated with Odoribacter. T level was positively correlated with Lachnospiraceae NK4A136 group and Odoribacter abundance (p < 0.05). Conclusion: Our results not only offer novel insights into the sex hormones and depression with OVX mice but also build an important basis for E2 or YYNS therapeutic efficacy on PDD, which provide for future research on this etiology through the endocrine–brain–gut–microbiota network. [ABSTRACT FROM AUTHOR]

This article discusses a case of relapsed nasal natural killer/T-cell lymphoma with an intravascular pattern in a 59-year-old woman. The patient had previously been diagnosed with stage I extranodal natural killer/T-cell lymphoma and had undergone surgery and radiotherapy. The skin involvement in this case presented as erythematous nodules, ulcerated lesions, telangiectases, and subcutaneous nodules. Laboratory tests revealed abnormalities such as mild anemia, thrombocytopenia, hypertriglyceridemia, and elevated ferritin levels. The diagnosis of cutaneous intravascular invasion by nasal extranodal natural killer/T-cell lymphoma was established based on histopathology, immunocytochemical analysis, and PET-CT findings. The article emphasizes the need for early diagnosis and treatment of these rare lymphomas. [Extracted from the article]

Geopolymer is a green substitute for Portland cement but has low tensile strength, high brittleness and easy cracking. Therefore, fibers and nanomaterials are used to strengthen and toughen geopolymer composites. The influence of nano-calcium carbonate and PVA fiber on the properties of fresh and hardened geopolymer mortar were studied herein. The hybrid of long and short fibers with small content (0.8 vol.%) is conducive to flowability, while the hybrid with large content (1.6 vol.%) and nano-calcium carbonate is conducive to flowability. The slump flow and flow rate of geopolymer mortars with low fiber factor (product of fiber volume fraction and length-diameter ratio) decrease with the growth in nano-calcium carbonate content. As the PVA fiber factor reaches 464.8%, the slump flow and flow rate values of mortars with 0, 1 wt.% and 2 wt.% nano-calcium carbonate are close to each other. About 450% is the density packing threshold of PVA fiber in geopolymer composites. The combination of 0.8 vol.% 12 mm + 0.4 vol.% 6 mm fiber + 1 wt.% nano-calcium carbonate presents the highest flexural strength and flexural to compressive strength ratio, with a compressive strength of about 36 MPa. The optimal fiber factor range of PVA fiber in cement and geopolymer mortar is about 400% and higher than 600%, respectively. PVA fibers show more effective enhancement of flexural strength and toughness in geopolymer than cement mortar. The ultrasonic wave velocity and apparent density of geopolymer mortar show a downward trend as a whole with the increase in fiber factor. The intensity rise of the hump between 17° and 38° (2 θ) in the XRD pattern is observed. The SEM indicates that the surface of PVA fiber in geopolymer mortar with nano-calcium carbonate is heavily scratched, and the fiber filaments are rolled up, demonstrating improved bonding between PVA fiber and geopolymer mortar. [ABSTRACT FROM AUTHOR]