Efficacy of Different Pharmacological Interventions for Cervical High-risk HPV Infection: Bayesian Network Meta-analysis / 肿瘤防治研究

Objective To compare the efficacy of common clinical interventions in the treatment of cervical high-risk (HR) HPV infection based on Bayesian network meta-analysis. Methods Randomized controlled trials (RCTs) about common clinical interventions for cervical HR-HPV infection were searched in PubMed, Web of Science, Embase, The Cochrane Library, CBM, CNKI, Wanfang Data, and VIP databases from inception to July 31, 2021 using specific inclusion and exclusion criteria. The quality of the included studies was evaluated in accordance with the Cochrane systematic review manual. Meta-analysis was performed with Stata16 and RevMan5.3 software. Results Seventy-three RCTs were included, involving 3642 patients and eight treatment methods. Network meta-analysis showed that in the three months after treatment, the negative conversion rate was in the order: PTL > anti-HPV BPD > ALA-PDT > Nr-CWS > BFKS > CSJZS > rhIFNα-2b > FUO. In the six months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > PTL > anti-HPV BPD > BFKS > rhIFNα-2b > FUO > CSJZS. In the nine months after treatment, the negative conversion rate was in the order: PTL > ALA-PDT > BFKS > anti-HPV BPD > rhIFNα-2b > FUO. IN the 12 months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > anti-HPV BPD > PTL > BFKS > rhIFNα-2b > FUO > CSJZS. Conclusion In terms of HPV negative conversion rate, Nr-CWS and PTL are more effective and currently ideal compared with the other treatments. Owing to the quality of the evidence, the above conclusions must be confirmed by future high-quality studies.

Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI

Single-cell RNA-seq and V(D)J profiling of immune cells in COVID-19 patients

Coronavirus disease 2019 (COVID-19) has caused over 220,000 deaths so far and is still an ongoing global health problem. However, the immunopathological changes of key types of immune cells during and after virus infection remain unclear. Here, we enriched CD3+ and CD19+ lymphocytes from peripheral blood mononuclear cells of COVID-19 patients (severe patients and recovered patients at early or late stages) and healthy people (SARS-CoV-2 negative) and revealed transcriptional profiles and changes in these lymphocytes by comprehensive single-cell transcriptome and V(D)J recombination analyses. We found that although the T lymphocytes were decreased in the blood of patients with virus infection, the remaining T cells still highly expressed inflammatory genes and persisted for a while after recovery in patients. We also observed the potential transition from effector CD8 T cells to central memory T cells in recovered patients at the late stage. Among B lymphocytes, we analyzed the expansion trajectory of a subtype of plasma cells in severe COVID-19 patients and traced the source as atypical memory B cells (AMBCs). Additional BCR and TCR analyses revealed a high level of clonal expansion in patients with severe COVID-19, especially of B lymphocytes, and the clonally expanded B cells highly expressed genes related to inflammatory responses and lymphocyte activation. V-J gene usage and clonal types of higher frequency in COVID-19 patients were also summarized. Taken together, our results provide crucial insights into the immune response against patients with severe COVID-19 and recovered patients and valuable information for the development of vaccines and therapeutic strategies.

Comparison of the efficacy of chloroprocaine and ropivacaine for epidural labor analgesia / 中国基层医药

Objective To observe and compare the efficacy and safety of chloroprocaine and ropivacaine for epidural labor analgesia.Methods 86 cases of voluntary acceptance of maternal painless natural childbirth were selected in the study.43 cases were given chloroprocaine epidural analgesia (chloroprocaine group),and the other 43 cases were given ropivacaine epidural analgesia (ropivacaine group).The pain (VAS score),lower limb motor block degree(MBS score),fetal heart rate(FHR) and contractions duration of maternal prenatal and medication immediately after 10min,20min,40min,80min were compared between two groups.The first,second and third stage of labor and fetal output after 1 min,5min,10min Apgar score were compared.The incidence of adverse events were observed.Results In the chloroprocaine group,the 10min VAS score was (2.10 ± 1.02),which was significantly lower than (4.31 ± 1.13) in the ropivacaine group (t =4.565,P ＜ 0.05).In the chloroprocaine group,analgesia 20min MBS score was (0.24 ± 0.03),which was significantly higher than (0.11 ± 0.04) in the ropivacaine group (t =4.126,P ＜ 0.05).In the chloroprocaine group,4 cases occurred nerve injury,which was more than the ropivacaine group (1 case),the difference was statistically significant (x2 =4.263,P ＜ 0.05).Conclusion Chloroprocaine and ropivacaine for epidural labor analgesia have superior efficacy and the clinical efficacy is similar.Chloroprocaine has the advantage of quick results,but the medication about 20min time period that the drug might lead to a greater degree of lower limb motor block,and has the risk of nerve injury,pregnant women can choose according to their medication.

The pneumococcal surface adhesin A (PsaA) protein and its application in conjugate vaccine / 中华微生物学和免疫学杂志

Objective To express and purify the pneumococcal surface adhesin A(PsaA) protein,discuss its application as a protein carrier in conjugates vaccine. Methods The gene encoding for the PsaA protein was amplified from the genomic DNA of Streptococcus pneumoniae using PCR. The PCR product was then cloned into the prokaryotic expression vector pET-28a and the recombinant was transformed into host cell E. coli BL21 (DE3). The expression of the recombinant protein(rPsaA) was induced by IPTG and purifled by using DEAE anion-exchange chromatography. The rPsaA was successfully conjugated with group A meningococcal polysaccharide(GAMP). The mice were immunized subcutaneously with the conjugate and the immune responses against GAMP and PsaA were detected by ELISA. Results The recombinant PsaA was expressed as a 37 × 103 soluble protein without His-Tag. The rPsaA was successfully conjugated with GAMP. In addition to the immune response against PsaA, The antibody response against GAMP was significant improved in the mice immunized with conjugate vaccine in comparison with those immunized with GAMP alone. Conclusion The recombinant protein PsaA without His-Tag was obtained and conjugated with GAMP. The strong antibody responses against PsaA and CAMP were obtained in the immunized mice at the same time which may provide the protection against pneumonia and meningitis simultaneously.

Correlation between MRI and clinical profiles of periventricular leukomalacia in children / 中华放射学杂志

Objective To study the relationship between MRI and clinical profiles of periventricular leukomalacia (PVL) in children Methods The clinical and MRI findings in 34 cases with PVL were retrospectively analyzed Results (1) Periventricular hyperintensity on T 2WI was more prominent in the preterm group than that in the term group, and P value was 0 000; (2) Cortical lesion and subcortical leukomalacia was seen in 9 of 19 cases in the children with PVL born at term, but detected in only 1/15 in the preterm group P value was 0 020; (3)Seizure was common in term children P value was 0 036; (4) The degree of reduction of periventricular white matter correlated with motor impairment and mental retardation in all children, and P values were 0 002 and 0 000, respectively The thinning of the corpus callosum also correlated with mental retardation and P value was 0 012 The degree of reduction of periventricular white matter correlated with visual impairment in preterm group Conclusion The end stage PVL can been clearly displayed by MRI, and gestational age and clinical manifestation were closely related to the findings of MRI

MRI and Clinical Profiles of Malformations of Cortical Organization / 实用放射学杂志

Objective To perform the MR findings and clinic characteristics of a series cases with malformations of cortical organization and to have a better understanding of malformations of cortical organization.Methods The clinical records and MRI studies of 5 cases with malformations of cortical organization were retrospectively reviewed.Results (1) 3 of 5 cases were polymicrogyria and 2 cases were schizencephaly. (2) Most patients with malformations of cortical organization suffered from epilepsy.Conclusion Malformations of cortical organization were recognized as the important causes of developmental delay and epilepsy and should be paid more attentions to them.