Effectiveness of mRNA and viral-vector vaccines in epidemic period led by different SARS-CoV-2 variants: A systematic review and meta-analysis.

We assessed the effectiveness of mRNA and viral-vector vaccines in epidemic period led by different SARS-CoV-2 variants. Systematic search of PubMed, EMBASE, and CNKI (China National Knowledge Infrastructure) databases without language restriction for studies published before September 19, 2022. The review was registered with PROSPERO (CRD42022335430) and reported according to PRISMA guidelines. Forty studies met the inclusion criteria for this study, with 62 954 861 participants. The overall vaccine effectiveness (VE) to prevent COVID-19 infection was 0.76 (95% confidence interval [CI] 0.73-0.78), symptomatic infection was 0.87 (95% CI 0.83-0.91), hospital admissions was 0.82 (95% CI 0.75-0.87), and mortality was 0.76 (95% CI 0.48-0.89). Subgroup analysis were performed to characterize the effectiveness of different vaccines. When SARS-CoV-2 variants are taking account, the VE decreased along with the variation of the virus by clinical outcomes and vaccine types. The findings of this systematic review provide the best available evidence that BNT162b2, mRNA-1273, ChAdOx1, and Ad26. COV2.S seems to be approximately effective from predelta to omicron, but only modestly effective in participants aged 65 or older. When SARS-CoV-2 variants are taking account, VE decreased along with the variation of the virus for all mRNA and viral-vector vaccines.

Association between monoamine oxidase A promoter polymorphism and the risk of sudden infant death syndrome: a meta-analysis.

INTRODUCTION: The etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between monoamine oxidase A (MAOA) promoter variable number tandem repeat (VNTR) polymorphism and SIDS risk. METHODS: A systematic review and meta-analysis were conducted on studies from accessible electronic databases. Each VNTR variant was examined in each gender independently by comparing with the pooled results of other alleles. RESULTS: A total of six independent case-control studies including 1022 SIDS cases and 1839 controls were enrolled in this meta-analysis. In both of the whole populations and Caucasian populations, male infants with the low-MAOA-expression alleles (2R+3R) were found to exhibit a statistically significant increased risk of SIDS, whereas those with a 4R allele exhibited a reduced risk of SIDS. Besides, an increased risk of SIDS was detected in male Caucasian infants with 2R or 3R alleles. However, none of the allele or genotype variants was associated with SIDS in female victims. CONCLUSION: In male Caucasian infants, the low expression of MAOA promoter VNTR alleles (2R and 3R) is associated with an increased risk of SIDS, and the existence of the 4R allele could be regarded as a protective factor.

DNA-based eyelid trait prediction in Chinese Han population.

The eyelid folding represents one of the most distinguishing features of East Asian faces, involving the absence or presence of the eyelid crease, i.e., single vs. double eyelid. Recently, a genome-wide association study (GWAS) identified two SNPs (rs12570134 and rs1415425) showing genome-wide significant association with the double eyelid phenotype in Japanese. Here we report a confirmatory study in 697 Chinese individuals of exclusively Han origin. Only rs1415425 was statistically significant (P-value = 0.011), and the allele effect was on the same direction with that reported in Japanese. This SNP combined with gender and age explained 10.0% of the total variation in eyelid folding. DNA-based prediction model for the eyelid trait was developed and evaluated using logistic regression. The model showed mild to moderate predictive capacity (AUC = 0.69, sensitivity = 63%, and specificity = 70%). We further selected six additional SNPs by massive parallel sequencing of 19 candidate genes in 24 samples, and one SNP rs2761882 was statistically significant (P-value = 0.027). All predictors including these two SNPs (rs1415425 and rs2761882), gender, and age explained 11.2% of the total variation. The combined prediction model obtained an improved predictive capacity (AUC = 0.72, sensitivity = 62%, and specificity = 66%). Our study thus provided a confirmation of previous GWAS findings and a DNA-based prediction of the eyelid trait in Chinese Han individuals. This model may add value to forensic DNA phenotyping applications considering gender and age can be separately inferred from genetic and epigenetic markers. To further improve the prediction accuracy, future studies should focus on identifying more informative SNPs by large GWASs in East Asian populations.

Age estimation by multidetector computed tomography of cranial sutures in Chinese male adults.

OBJECTIVES: This study aimed to explore whether computed tomography (CT) images of cranial sutures can contribute to adult age estimation in Chinese Han individuals. MATERIALS AND METHODS: This study was based on cranial CT scans of 230 Chinese Han males aged 23.33-76.93 years. A total of 160 images from 16 suture segments were scored after volume reformation and multiplanar reconstruction in each individual. Decision tree regression, linear support vector regression, Bayesian ridge regression, and gradient boosting regression were developed for adult age estimation by a training set using leave-one-out cross-validation and further evaluated by the test set. The inaccuracy and bias were calculated to evaluate the four models and the previously used models from the literature. RESULTS: The degree of suture closure was associated with adult age. The minimum inaccuracy of the test set was 7.73 years obtained by linear support vector regression, while the inaccuracy of previous simple linear regression models was 13.09 and 10.97 years. The accuracy was higher in the age group from 40.00 to 59.99 years compared to the other age groups. DISCUSSION: The accuracy of our models for adult age estimation was superior to those in previous studies based on cranial sutures. Hence, the application of novel statistical data mining tools helps to improve aging issues. Nevertheless, age estimation of adults should be combined with other methods, since the accuracy level is still not satisfactory.

Increased expression of phosphoenolpyruvate carboxykinase cytoplasmic isoform by hepatitis B virus X protein affects hepatitis B virus replication.

Hepatitis B virus X protein (HBx) can stimulate the transcription of phosphoenolpyruvate carboxykinase (PEPCK), a rate-determining enzyme in gluconeogenic pathway. Two isoforms of PEPCK exist, a cytoplasmic form (PCK1) and a mitochondrial isoform (PCK2). The current study investigated the direct effect of HBx-stimulated PEPCK on hepatitis B virus (HBV) replication. We showed that PCK1 rather than PCK2 was upregulated by HBx. We also demonstrated that overexpression of PCK1 decreased HBV replication, whereas inhibition of PCK1-enhanced HBV replication. Furthermore, we found overexpression of PCK1 led to reduced expression of peroxisome proliferator-activated receptor-coactivator 1α (PGC-1α) and peroxisome proliferator-activated receptor γ (PPAR-γ), whereas knocking down PCK1 resulted in an increased expression of PGC-1α and PPAR-γ. When PPAR-γ was inhibited, knocking down PCK1 could not induce the apparent enhanced HBV replication. Our data suggested that PCK1 induced by HBx led to decreased HBV replication through the downregulation of PGC-1α and PPAR-γ. Thus, our study demonstrates a negative-feedback loop involving PCK1 and HBV may provide a balanced cell environment for HBV persistent infection.

Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.

Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.

[Research progress of mitochondrial fission and fusion related proteins].

Mitochondria are an essential component of multicellular life and play important roles in the health of the cells and the body. Mitochondria can produce energy by oxidative phosphorylation, mediate calcium and reactive oxygen signal transduction, and regulate cell apoptosis. Recent studies indicate that mitochondria continually change their shapes and distribution by fission and fusion, which are collectively termed mitochondrial dynamics. Mitochondrial dynamics play critical roles in maintaining mitochondrial function. This review focuses on the structure and biological functions of mitochondrial fission and fusion related proteins in mammal cells.

TAGLN2, a novel regulator involved in Hepatitis B virus transcription and replication.

Hepatitis B virus (HBV) infection is one of the major health problems in the world. Transgelin-2 (TAGLN2) expression has been revealed to be significantly altered in previous studies concerning HBV-host interaction. The present study investigated TAGLN2 expression patterns in HBV related hepatocellular carcinoma (HCC) tissues and its role in HBV transcription and replication. We collected 59 HBV related HCC tissue samples, their adjacent non-tumoral tissues and 16 normal livers to make the tissue microarray. TAGLN2 protein was detected by immunohistochemistry and the transcriptional levels of TAGLN2, HBc, HBs and HBx were detected by qRT-PCR. Then we investigated the function of TAGLN2 on HBV transcription and replication in vitro by ectopic expressing or knocking down TAGLN2 in HepG2 and HepG2.2.15 cell lines. We further studied the effect of HBx on TAGLN2 expression with a Tet-on HBx expressing cell line. TAGLN2 protein expression was lower in normal livers and HBV-HCC tissues comparing to adjacent non-tumoral tissues. The transcriptional levels of TAGLN2 in HBV-HCC tissues and their adjacent tissues were positively related to that of HBc, HBs and HBx (P < 0.05). Ectopic expression of TAGLN2 in vitro could enhance HBV transcription and replication while suppressing TAGLN2 had the contrary effect. TAGLN2 could be induced by HBx in a dose-dependent manner. Our data demonstrated that TAGLN2 might be an HBx induced positive host factor involved in HBV transcription and replication and HBx related liver fibrosis and tumorigenesis.

Luteolin Inhibits Hepatitis B Virus Replication through Extracellular Signal-Regulated Kinase-Mediated Down-Regulation of Hepatocyte Nuclear Factor 4α Expression.

Whether luteolin inhibits HBV replication has not been validated and the underlying mechanism of which has never been elucidated. In this study, we show that luteolin reduces HBV DNA replication in HepG2.2.15 cells. Luteolin effectively inhibited the expression of hepatocyte nuclear factor 4α (HNF4α) and its binding to the HBV promoters in HepG2.2.15 cells. While the extracellular signal-regulated kinase (ERK) was activated by luteolin, inhibition of ERK abolished luteolin-induced HNF4α suppression. Consistently, blocking ERK attenuated the anti-HBV activity of luteolin. In a HBV replication mouse model, luteolin decreased the levels of HBsAg, HBeAg, HBV DNA replication intermediates, and the HBsAg and HBcAg expression. Taken together, our results validated the anti-HBV activity of luteolin in both in vitro and in vivo studies and established a signaling cascade consisting of ERK and HNF4α for inhibition of HBV replication by luteolin, which may be exploited for clinical application of luteolin for anti-HBV therapy.

Case report: Sudden unexpected death due to tuberculous myocarditis involving sinus node at autopsy.

Tuberculous myocarditis (TM) is an extremely rare manifestation of Mycobacterium tuberculosis (TB) infection. Although TM is a critical cause of sudden cardiac death, only a few cases have been reported. We report the case of an older patient with pulmonary TB with a history of fever, chest tightness, paroxysmal palpitations, and electrocardiographic evidence of sinus node conduction abnormalities on admission. Although emergency physicians observed these unusual clinical manifestations, no timely differential diagnosis was made nor interventions were performed. A definitive diagnosis of TM and histopathological findings compatible with sinus node involvement were made based on autopsy outcomes. Herein, we describe the clinical presentation and pathological features of a rare form of Mycobacterium TB. In addition, we provide an overview of issues related to the diagnosis of myocardial TB.

Multigenerational exposure of cadmium trans-generationally impairs locomotive and chemotactic behaviors in Caenorhabditis elegans.

Cadmium is a naturally existing heavy metal and a notorious environmental pollutant. While its toxic outcomes and underlying mechanisms remain largely elusive. To explore the behavioral change caused by multigenerational exposure of cadmium to C. elegans, we challenged the C. elegans with cadmium for six generations and observed its impact on animal behaviors. Wild-type worms were randomly divided into two groups, the control and cadmium exposure groups. Locomotive and chemotactic behaviors were observed across six generations. Head thrashing frequency, chemotaxis index, and fold change index were used to evaluate the neurotoxicity of multigenerational cadmium exposure. Multigenerational cadmium exposure can trans-generationally increase the head thrashing frequency of C. elegans during swimming, and impair the chemotactic behaviors to isoamyl alcohol, diacetyl, and 2-nonanone. Our findings proposed a trans-generationally behavioral impact induced by multigenerational cadmium exposure.

Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.

BACKGROUND: The effects of Hepatitis B virus (HBV) rtA181T/sW172* mutation on viral replication and pathogenicity was concerned recently. This study aimed to investigate the biological characteristics of rtA181T/sW172* mutant strain of HBV in animal model. METHODS: The rtA181T/sW172* mutant plasmid was constructed using the pHBV4.1 (wild type HBV) as a template. The wild and mutant HBV replication mouse models were established utilizing a hydrodynamic technique. The titers of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and HBV DNA in serum, and the levels of HBsAg, hepatitis B core antigen(HBcAg), HBV DNA replication intermediates (HBV DNA RI) and HBV RNA in liver were measured after 1, 3, 5, 7, 10, 12 and 15 days of plasmid injection. RESULTS: In wild-type HBV replication mouse model, serum HBsAg was high on day 1, 3, and 5, but became lower since day 7; while in mutant HBV mouse model, serum HBsAg was always at very low level. In liver tissues, HBV DNA RI of wild type HBV was detected on day 1 after transfection. The level subsequently peaked on day 3, gradually declined after day 5, and was almost undetectable on day 10. However, the HBV DNA RI levels of the mutant strain were always higher and lasted longer until day 15. Consistently, the expression levels of HBsAg and HBcAg in liver of the mutant group were significantly increased. CONCLUSIONS: In the case of the HBV rtA181T/sW172* mutation, the secretion of serum HBsAg was impaired, whereas HBV DNA replication and HBsAg/HBcAg expression were increased in liver. These results suggest that the mutation can impair HBsAg secretion, and may cause the accumulation of viral core particles in liver.

Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection.

Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3ß) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3ß with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3ß expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3ß was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB.

[The mechanism of HBV disruption on RIG-I signaling pathway].

Hepatitis B virus (HBV) infection disrupt the innate immunity response, which may play an important role in the chronic mechanism, while retinoic acid-induced gene I (RIG-I) mediated signaling pathway is one of the most important channel in the innate immunity. HBx and HBV polymerase may disrupt RIG-I mediated signaling pathway. The recent advances about HBV and RIG-I are reviewed in this article.

Identification and Verification of Potential Hub Genes in Amphetamine-Type Stimulant (ATS) and Opioid Dependence by Bioinformatic Analysis.

Objective: Amphetamine-type stimulant (ATS) and opioid dependencies are chronic inflammatory diseases with similar symptoms and common genomics. However, their coexpressive genes have not been thoroughly investigated. We aimed to identify and verify the coexpressive hub genes and pathway involved in the pathogenesis of ATS and opioid dependencies. Methods: The microarray of ATS- and opioid-treatment mouse models was obtained from the Gene Expression Omnibus database. GEO2R and Venn diagram were performed to identify differentially expressed genes (DEGs) and coexpressive DEGs (CDEGs). Functional annotation and protein-protein interaction network detected the potential functions. The hub genes were screened using the CytoHubba and MCODE plugin with different algorithms, and further validated by receiver operating characteristic analysis in the GSE15774 database. We also validated the hub genes mRNA levels in BV2 cells using qPCR. Result: Forty-four CDEGs were identified between ATS and opioid databases, which were prominently enriched in the PI3K/Akt signaling pathway. The top 10 hub genes were mainly enriched in apoptotic process (CD44, Dusp1, Sgk1, and Hspa1b), neuron differentiation, migration, and proliferation (Nr4a2 and Ddit4), response to external stimulation (Fos and Cdkn1a), and transcriptional regulation (Nr4a2 and Npas4). Receiver operating characteristic (ROC) analysis found that six hub genes (Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, and Nr4a2) have an area under the curve (AUC) of more than 0.70 in GSE15774. The mRNA levels of Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, PI3K, and Akt in BV2 cells and GSE15774 with METH and heroin treatments were higher than those of controls. However, the Nr4a2 mRNA levels increased in BV2 cells and decreased in the bioinformatic analysis. Conclusions: The identification of hub genes was associated with ATS and opioid dependencies, which were involved in apoptosis, neuron differentiation, migration, and proliferation. The PI3K/Akt signaling pathway might play a critical role in the pathogenesis of substance dependence.

Screening of the HBx transactivation domain interacting proteins and the function of interactor Pin1 in HBV replication.

Hepatitis B virus (HBV) X protein (HBx) has been determined to play a crucial role in the replication and transcription of HBV, and its biological functions mainly depend on the interaction with other host proteins. This study aims at screening the proteins that bind to the key functional domain of HBx by integrated proteomics. Proteins that specifically bind to the transactivation domain of HBx were selected by comparing interactors of full-length HBx and HBx-D5 truncation determined by glutathione-S-transferase (GST) pull-down assay combined with mass spectrometry (MS). The function of HBx interactor Pin1 in HBV replication was further investigated by in vitro experiments. In this study, a total of 189 proteins were identified from HepG2 cells that specifically bind to the transactivation domain of HBx by GST pull-down and subsequent MS. After gene ontology (GO) analysis, Pin1 was selected as the protein with the highest score in the largest cluster functioning in protein binding, and also classified into the cluster of proteins with the function of structural molecule activity, which is of great potential to be involved in HBV life cycle. The interaction between Pin1 and HBx has been further confirmed by Ni2+-NTA pulldown assay, co-immunoprecipitation, and immunofluorescence microscopy. HBsAg and HBeAg levels significantly decreased in Pin1 expression inhibited HepG2.2.15 cells. Besides, the inhibition of Pin1 expression in HepG2 cells impeded the restored replication of HBx-deficient HBV repaired by ectopic HBx expression. In conclusion, our study identified Pin1 as an interactor binds to the transactivation domain of HBx, and suggested the potential association between Pin1 and the function of HBx in HBV replication.

Histological changes in chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal.

The role of ALT as a predictor of liver injury has been questioned. The aim of this study is to use liver biopsy to assess the degree of liver injury in patients with chronic hepatitis B(CHB) whose ALT < 2 x upper limit of normal (ULN). A total of 49.2% of patients in this study had significant inflammation (grade >or=2) and 36.4% had significant fibrosis (stage >or=2). The frequency of serious inflammation and fibrosis was similar in patients with different ALT levels. The level of serum HBV DNA was not significantly associated with the extent of inflammation and fibrosis. Advanced age was a significant independent predictor of histological damage and the presence of more significant inflammation and fibrosis. We conclude that many CHB patients with ALT < 2 x ULN have significant liver inflammation or fibrosis and that liver biopsy is necessary to assess liver damage and should be used to assess the need for anti-viral therapy.

[Forensic pathological analysis on 23 cases of fatal pulmonary thromboembolism].

OBJECTIVE: To analyze the forensic pathological characteristics of sudden death caused by pulmonary thromboembolism and the chronological transformation of thrombus and explore the assessment method of the causal relationship between previous trauma and the following fatal PTE episode. METHODS: All the 23 cases reviewed here were collected from our institute files from the year of 1998 to 2008. RESULTS: Trauma, surgery and braking etc. were all risky factors of PTE. Of these cases, 12 cases were caused by trauma, 21 cases were caused by surgery and 22 cases died in hospitals which were often happened one or two weeks after injury or one week's postoperative time. Of all the cases, 6 cases had single attack of thrombus and the rest 17 cases had the recurrence of thrombus. The number of the leg deep vein to be the embolic source was 16 cases which were often seen in the left leg. CONCLUSION: It is important to confirm the embolic source, trauma, surgery and chronological events in determing the sudden death with PTE.

An evaluation of statistical models for age estimation and the assessment of the 18-year threshold using conventional pelvic radiographs.

The developmental patterns of the pelvic epiphyses are one of the anatomical markers used in the assessment of skeletal age and the legally relevant age threshold. In this study, four regression models and five classification models were developed for forensic age estimation and the determination of the 18-year threshold, respectively. A total of 2137 conventional pelvic radiographs (1215 males and 922 females) aged 10.00-25.99 years were analyzed, and the ossification and fusion of the iliac crest and ischial tuberosity epiphyses were scored separately. The epiphyses on both sides were used as inputs for all models. The accuracy of the regression models was compared using the mean absolute error (MAE) and root mean square error. The percentages of correct classifications were evaluated for the determination of the 18-year threshold. Support vector regression (SVR) and gradient boosting regression (GBR) showed higher accuracy for age estimation in both sexes. The lowest MAE was 1.38 years in males when using SVR and 1.16 years in females when using GBR. In the demarcation of minors and adults, the percentage of correct classification was over 92%, and the area under the receiver operating characteristic curves was over 0.91 in all models, except the Bernoulli naive Bayes classifier. This study demonstrated that the present models may be helpful for age estimation and the determination of the 18-year threshold. However, owing to the high effective dose of ionizing radiation used during conventional radiography of the pelvis, it is expected that these models will be tested with pelvic MRI for age estimation.

Establishment of cell lines using a doxycycline-inducible gene expression system to regulate expression of hepatitis B virus X protein.

The hepatitis B virus (HBV) X gene plays an important role in HBV-associated pathogenesis, especially hepatocarcinogenesis. Establishment of a stable and regulable HBx expression system will allow study of the function of this gene. Here, we describe the development of a doxycycline-inducible recombinant plasmid (pBPSTR3-FlagX) with the full-length HBV X gene and all components of the tetracycline-on ("Tet-on") gene expression system. This vector exhibited dose-dependent doxycycline-dependent induction of the Flag-HBx protein in HepG2 and Hep3B cells. We also observed dose-dependent doxycycline transactivation of HBx in HepG2 cells. After transfecting HepG2 cells with the pBPSTR3-FlagX plasmid, we isolated five puromycin-resistant cell clones with stable HBx expression, two of which exhibited stable and tight control of HBx expression by doxycycline. This new system has great potential for functional studies of the HBV X gene.