Prediction of 6-month poststroke spasticity in patients with acute first-ever stroke by machine learning.

OBJECTIVE: Poststroke spasticity (PSS) reduces arm function and leads to low levels of independence. This study suggested applying machine learning (ML) from routinely available data to support the clinical management of PSS. DESIGN: 172 patients with acute first-ever stroke were included in this prospective cohort study. Twenty clinical information and rehabilitation assessments were obtained to train various ML algorithms for predicting 6-month PSS defined by a modified Ashworth scale (MAS) score ≥ 1. Factors significantly relevant were also defined. RESULTS: The study results indicated that multivariate adaptive regression spline (area under the curve (AUC) value: 0.916; 95% confidence interval (CI): 0.906-0.923), adaptive boosting (AUC: 0.962; 95% CI: 0.952-0.973), random forest (RF) (AUC: 0.975; 95% CI: 0.968-0.981), support vector machine (SVM) (AUC: 0.980; 95% CI: 0.970-0.989) outperformed the traditional logistic model (AUC: 0.897; 95% CI: 0.884-0.910) (P < 0.05). Among all of the algorithms, the RF and SVM models outperformed the others (P < 0.05). FMA score, days in hospital, age, stroke location, and paretic side were the most important features. CONCLUSION: These findings suggest that ML algorithms can help augment clinical decision-making processes for the assessment of PSS occurrence, which may enhance the efficacy of management for patients with PSS in the future.

Epicoccum sorghinum Causing Leaf Spot on Polygonatum cyrtonema in China.

Polygonatum cyrtonema Hua (family Asparagaceae) is a traditional Chinese medicinal plant that is widely cultivated in various parts of China, including Hunan Province. In summer 2022, a leaf spot disease was observed in 10% of the P. cyrtonema plants (Huang jing) in 18 hectares of this crop in the Hongjiang District (27°18'4″N, 110°11'1″E) of Hunan Province. The initial symptoms of the disease were brown spots on young leaves, and adjacent tissues gradually changed from green to yellow. The entire leaf then became yellow, withered, and eventually exhibited a thn and black appearance. In total, 12 diseased plants from four sampling sites (three plants per site) were collected for laboratory analysis to address the concerns of P. cyrtonema growers. Symptomatic leaf samples were selected, and the leaf fragments containing infected parts of the plants were disinfected with 75% ethanol for 1 min, then immersed in 2.5% hypochlorite for 45 s. After disinfection, symptomatic leaf samples were rinsed three times with sterile water, placed on potato saccharose agar containing 50 µg/ml kanamycin and incubated at 25°C for 2 days. Subsequently, 12 fungal isolates were isolated from various leaf samples through hyphal tip transferring. Ten of the 12 fungal isolates had similar morphological features, and one of them (isolate hjh) was used as the representative isolate for the study. With a growth rate of 6.3 mm per day, its white colonies transformed into red concentric rings in five days; they gradually became black after 10 days of growth. The chlamydospores were round (4.0-9.9 × 3.1-9.3 µm, n = 30), whereas the conidia were ovate (8.0-12.1 × 3.2-6.5 µm, n = 30). The morphological features of the isolate hjh were similar to the features of Epicoccum spp. (Aveskamp et al. 2010). The internal transcribed spacer (ITS) region (including the partial ITS1 sequence and the 5.8S and ITS2 complete sequences), ß-tubulin (tub) gene, and large subunit (LSU) rRNA gene, were amplified from the isolate hjh using the primer pairs ITS5/ITS4, Bt2a/Bt2b, and LROR/LR5, respectively (Taguiam et al. 2021). BLASTn analysis showed that the ITS (OR253745), tub (OR253764), and LSU (OR253746) sequences generated from the isolate hjh were 98-99% similar to the sequences of E. sorghinum strains CBS 179.80 and CBS 627.68. Subsequently, the ITS, tub, and LSU sequences were combined using Sequence Matrix software; phylogenetic analysis via Bayesian and maximum likelihood methods (Vaidya et al. 2011; Li et al. 2021) classified the isolate hjh into the E. sorghinum clade. To fulfill Koch's postulates, pathogenicity tests were conducted on healthy (lesion-free and disease-free) 2-year-old P. cyrtonema plants. Three healthy plants were inoculated by spraying whole plant until run-off with a spore suspension of the isolate hjh (1 × 106 conidia/ml); Three other healthy plants were sprayed with sterile water as controls. The inoculated plants were incubated in a growth chamber at 25 ± 2°C with 85% humidity for 28 days(Chen et al. 2021). Leaves from the inoculated plants gradually became brown within 15 days. Finally, the plants died 28 days after inoculation. The control plants showed no symptoms throughout the experimental period. Isolates (isolate hjh1, hjh2 and hjh3) that were reisolated from the inoculated plants exhibited morphologically similar characteristics and molecularly identical to the original isolate hjh. To our knowledge, this is the first report of E. sorghinum causing leaf spot disease on P. cyrtonema. The results of this study may facilitate the production of P. cyrtonema in China.

Genomic basis of environmental adaptation in the widespread poly-extremophilic Exiguobacterium group.

Delineating cohesive ecological units and determining the genetic basis for their environmental adaptation are among the most important objectives in microbiology. In the last decade, many studies have been devoted to characterizing the genetic diversity in microbial populations to address these issues. However, the impact of extreme environmental conditions, such as temperature and salinity, on microbial ecology and evolution remains unclear so far. In order to better understand the mechanisms of adaptation, we studied the (pan)genome of Exiguobacterium, a poly-extremophile bacterium able to grow in a wide range of environments, from permafrost to hot springs. To have the genome for all known Exiguobacterium type strains, we first sequenced those that were not yet available. Using a reverse-ecology approach, we showed how the integration of phylogenomic information, genomic features, gene and pathway enrichment data, regulatory element analyses, protein amino acid composition, and protein structure analyses of the entire Exiguobacterium pangenome allows to sharply delineate ecological units consisting of mesophilic, psychrophilic, halophilic-mesophilic, and halophilic-thermophilic ecotypes. This in-depth study clarified the genetic basis of the defined ecotypes and identified some key mechanisms driving the environmental adaptation to extreme environments. Our study points the way to organizing the vast microbial diversity into meaningful ecologically units, which, in turn, provides insight into how microbial communities adapt and respond to different environmental conditions in a changing world.

Target-activated multicolor fluorescent dyes for 3D imaging of plasma membranes and tracking of apoptosis.

Real-time tracking of dynamic changes in the three-dimensional morphology of the cell plasma membrane is of great importance for a deeper understanding of physiological processes related to the cell plasma membrane. However, there is a lack of imaging dyes that can specifically be used for a long term labelling of plasma membranes, especially for plant cells. Here, we have used molecular engineering strategies to develop a series of target-activated multicolour fluorescent dyes that can be used for long-term and three-dimensional imaging of plant cell plasma membranes. By combining different electron acceptors and donors, four molecular backbones with different emission colours from green to NIR have been obtained. In the designed styrene-based dyes, referred to as the SD dyes, several functional groups were introduced into the backbones to achieve the properties of target-activated fluorescence, rapid and wash-free staining, high plasma membrane targeting ability and long-term imaging function. Using onion epidermal cells as a platform, these dye molecules can provide high-quality imaging of the plasma membrane for up to 6 hours, providing a powerful tool for long-term monitoring of plasma membrane-related biological events. Calcium-mediated apoptosis of plant cells has been tracked for the first time by monitoring the morphological changes of the plasma membrane in real time using SD dyes. These dyes also exhibit excellent 3D imaging performance of the plasma membrane and were further used to track in real time the 3D morphological changes of the plasma membrane during plasmolysis of plant cells, providing a powerful imaging tool for three-dimensional (3D) biology. This work provides a set of multi-colour dye tools for long-term and three-dimensional imaging of plant cell plasma membranes, and also provides molecular design principles for guiding the transmembrane transport of small molecules.

Temporal and spatial differences in the vaginal microbiome of Chinese healthy women.

Background: Up the reproductive tract, there are large differences in the composition of vaginal microbes. Throughout the menstrual cycle, the structure of the vaginal microbiome shifts. Few studies have examined both in combination. Our study was designed to explore trends in the microbiome of different parts of the vagina in healthy women over the menstrual cycle. Methods: We performed metagenomic sequencing to characterize the microbiome differences between the cervical orifice and mid-vagina throughout the menstrual cycle. Results: Our results showed the vaginal microbiome of healthy women in the cervical orifice and the mid-vagina was similar during the periovulatory and luteal phases, with Lactobacillus being the dominant bacteria. In the follicular phase, Acinetobacter was detected in the cervical orifice. From the follicular phase to the luteal phase, the community state types (all five community status types were defined as CSTs) in samples No. 10 and No. 11 changed from CST III to CST I. In addition, the composition of the vaginal microbiome in healthy women from different regions of China was significantly different. We also detected viruses including Human alphaherpesvirus 1 (HSV-1) during periovulatory phase. Conclusion: This study is valuable for understanding whether the microbial composition of the vagina is consistent in different parts of the menstrual cycle.

Childhood neglect and problematic smartphone use among chinese young adults: the mediating roles of peer attachment and fear of missing out.

BACKGROUND: Research has revealed that childhood neglect may be a risk factor for problematic smartphone use among young adults in China. However, few studies have examined the mediating roles of peer attachment and the fear of missing out in the relationship between childhood neglect and problematic smartphone use. To fill this gap, the present study proposes a multiple mediation model to understand the relationships among childhood neglect, peer attachment, fear of missing out, and problematic smartphone use among young adults. METHODS: A total of 869 young adults in China completed questionnaires for evaluating different levels of the relationships between childhood neglect, peer attachment, the fear of missing out, and problematic smartphone use. The collected data were analyzed using SPSS 23.0 and MPLUS8.3. RESULTS: The results showed that childhood neglect was positively associated with problematic smartphone use among young adults in China. Moreover, peer attachment and the fear of missing out had partial mediating effects as well as sequential mediating effects in the relationship between childhood neglect and problematic smartphone use among young adults. CONCLUSION: Based on these findings, peer attachment and the fear of missing out, as mediators, could be considered proximal factors affecting problematic smartphone use among young adults. These findings broaden our understanding of the psychological processes that underlie the association between childhood neglect and problematic smartphone use and afford practical guidance on reducing the risks associated with problematic smartphone use.

Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans.

SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.

Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol.

BACKGROUND: Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. METHODS: We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children's Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. DISCUSSION: The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. TRIAL REGISTRATION: This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection.

Objectives: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. Methods: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. Results: IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. Conclusion: Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.

Methods of postoperative void trial management after urogynecologic surgery: a systematic review and meta-analysis.

BACKGROUND: Voiding trials are used to identify women at risk for postoperative urinary retention while performing optimal voiding trial management with minimal burden to the patient and medical service team. We performed a systematic review and meta-analysis of postoperative void trials following urogynecologic surgery to investigate (1) the optimal postoperative void trial methodology and (2) the optimal criteria for assessing void trial. METHOD: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant reference lists of eligible articles from inception to April 2022. We identified any randomized controlled trials (RCTs) in English that studied void trials in patients undergoing urogynecologic surgery. Study selection (title/abstract and full text), data extraction, and risk of bias assessment were conducted by two independent reviewers. Extracted study outcomes included the following: the correct passing rate, time to discharge, discharge rate without a catheter after the initial void trial, postoperative urinary tract infection, and patient satisfaction. RESULTS: Void trial methodology included backfill-assisted and autofill studies (2 RCTs, n = 95). Backfill assistance was more likely to be successful than autofill (RR 2.12, 95% CI 1.29, 3.47, P = 0.00); however, no significant difference was found in the time to discharge (WMDs = - 29.11 min, 95% CI - 57.45, 1.23, P = 0.06). The criteria for passing void trial included subjective assessment of the urinary force of stream and objective assessment of the standard voiding trial (3 RCTs, n = 377). No significant differences were found in the correct passing rate (RR 0.97, 95% CI 0.93, 1.01, P = 0.14) or void trial failure rate (RR 0.78, 95% CI 0.52, 1.18, P = 0.24). Moreover, no significant differences were found in the complication rates or patient satisfaction between the two criteria. CONCLUSION: Bladder backfilling was associated with a lower rate of catheter discharge after urogynecologic surgery. The subjective assessment of FOS is a reliable and safe method for assessing postoperative voiding because it is less invasive. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022313397.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.

Modulation of Crystal Growth of an Energetic Metal-Organic Framework on the Surfaces of Graphene Derivatives for Improved Detonation Performance.

Energetic materials are a special class of energy materials composed of C, H, O, and N. Their safety always deteriorates with increasing energy. Regulating the properties of energetic materials to meet application requirements is one of the focuses of research in this field. Energetic metal-organic frameworks (EMOFs) are good candidates as primary explosives to replace lead azide (LA) and other explosives containing toxic metal elements. However, safety remains the biggest concern in applications. In this paper, crystal morphology modulation of EMOF was carried out by stepwise coordination of metal ions and energetic ligands on surfaces of graphene oxide (GO) and amino-functionalized graphene oxide (AGO). Two energetic composite materials, Cu-AFTO@GO and Cu-AFTO@AGO, were successfully synthesized and also the EMOF (Cu-AFTO). The structures and morphologies of these materials were fully characterized. The thermal decomposition behaviors, mechanical sensitivity, and electrostatic discharge sensitivity were investigated in detail. The electric ignition ability of EMOF and two composite materials was tested. This study shows that it is possible to reduce the diameter of EMOF crystals from hundreds of microns to tens of nanometers by a stepwise coordination method. The high electrical conductivity and sensitivity-reducing effect of GO and/or AGO allow the nanosized EMOF crystals to have a lower ignition threshold and lower sensitivity.

TREM2 drives microglia response to amyloid-ß via SYK-dependent and -independent pathways.

Genetic studies have highlighted microglia as pivotal in orchestrating Alzheimer's disease (AD). Microglia that adhere to Aß plaques acquire a transcriptional signature, "disease-associated microglia" (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK. The human TREM2R47H variant associated with high AD risk fails to activate microglia via SYK. We found that SYK-deficient microglia cannot encase Aß plaques, accelerating brain pathology and behavioral deficits. SYK deficiency impaired the PI3K-AKT-GSK-3ß-mTOR pathway, incapacitating anabolic support required for attaining the DAM profile. However, SYK-deficient microglia proliferated and advanced to an Apoe-expressing prodromal stage of DAM; this pathway relied on the adapter DAP10, which also binds TREM2. Thus, microglial responses to Aß involve non-redundant SYK- and DAP10-pathways. Systemic administration of an antibody against CLEC7A, a receptor that directly activates SYK, rescued microglia activation in mice expressing the TREM2R47H allele, unveiling new options for AD immunotherapy.

Human-Machine Interaction Methods for Minimally Invasive Surgical Robotic Arms.

Minimally invasive surgery has a smaller incision area than traditional open surgery, which can greatly reduce damage to the human body and improve the utilization of medical devices. However, minimally invasive surgery also has disadvantages such as limited flexibility and operational characteristics. The interactive minimally invasive surgical robot system not only improves the stability, safety, and accuracy of minimally invasive surgery but also introduces force feedback in controlling the surgical robot, which is a new development direction in the field of minimally invasive surgery. This paper reviews the development status of interactive minimally invasive surgical robotic systems and key technologies to achieve human-robot interaction and finally provides an outlook and summary of its development. Fuzzy theory and reinforcement learning are introduced into the parameter adjustment process of the variable guide control model, and a human-robot interaction method for minimally invasive surgical robot posture adjustment is proposed.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones 1-4 . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) 5-9 . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants. Here, we show that boosting with the original SARS- CoV-2 spike vaccine (mRNA-1273) or a B.1.351/B.1.617.2 (Beta/Delta) bivalent vaccine (mRNA-1273.213) induces robust spike-specific GC B cell responses in humans. The GC response persisted for at least eight weeks, leading to significantly more mutated antigen-specific MBC and bone marrow plasma cell compartments. Interrogation of MBC-derived spike-binding monoclonal antibodies (mAbs) isolated from individuals boosted with either mRNA-1273, mRNA-1273.213, or a monovalent Omicron BA.1-based vaccine (mRNA-1273.529) revealed a striking imprinting effect by the primary vaccination series, with all mAbs (n=769) recognizing the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted approach, we isolated mAbs that recognized the spike protein of the SARS-CoV-2 Omicron (BA.1) but not the original SARS-CoV-2 spike from the mRNA-1273.529 boosted individuals. The latter mAbs were less mutated and recognized novel epitopes within the spike protein, suggesting a naïve B cell origin. Thus, SARS-CoV-2 boosting in humans induce robust GC B cell responses, and immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.

Oral supramolecular nanovectors for dual natural medicine codelivery to prevent gastric mucosal lesion.

The oral administration of a single formulation loaded with more than one natural medicine to treat chronic diseases has advantages such as convenience, effectiveness, and economy. Here, using biomaterials approved by the drug administration, we fabricated supramolecular nanovectors containing dual natural medicines to prevent gastric mucosal lesions. Nanovectors exhibited superior intestinal absorption and bioavailability, which might be due to their high dispersion, good muco-adhesiveness, blood-lymph circulation transport, lipid sensing, and protective effects. Molecular docking results clarified the possible mechanisms in aspects of efflux pump (p-glycoprotein and multidrug resistance protein 1) inhibition effects, metabolic enzyme (cytochrome P450 3A4/1A2) blocking effects, serum albumin deposit effects, and dual drug interaction effects. Nanovectors decreased ethanol-induced gastric mucosal lesions by lowering the gastric ulcer index, preventing oxidative damage, decreasing interleukin-6, tumor necrosis factor-α and malondialdehyde, increasing glutathione, superoxide dismutase, and prostaglandin E2 levels. The interactions of inhibitor of nuclear factor-κB or κB kinase-related proteins and dual drugs or nanovector components were simulated computationally to provide an understanding of the gastro-protective action mechanism. In all, industrializable supramolecular nanovectors could effectively co-deliver dual natural medicines via the oral route by improving the pharmacokinetic behavior and exerting protective efficacy of the gastric mucosa by decreasing the oxidative stress and inflammatory level.

Laparoscopic Cholecystectomy in a Patient With Situs Inversus Totalis Presenting With Cholelithiasis: A Case Report.

Laparoscopic cholecystectomy is the standard treatment for cholelithiasis. A very rare condition named situs inversus should not be considered as a contraindication for laparoscopic cholecystectomy. Here, we reported a case of successful laparoscopic cholecystectomy in a patient with situs inversus totalis. We also described the technical advantages of this treatment and reviewed the literature.

The Effect of Chronic Rhinosinusitis on the Staging and Prognosis of Extranodal Natural Killer/T-Cell Lymphoma: A Single-Center Retrospective Analysis.

Clinically, extranodal natural killer/T-cell lymphoma (ENKTL) patients frequently had a history of chronic rhinosinusitis (CRS) before onset, and the correlation between the two diseases has not been systematically reported at present. In this study, we applied the method-retrospective analysis-to explore the relationship between CRS and ENKTL. We collected clinical data and the length of CRS history before onset in 214 patients diagnosed with ENKTL and found that the length of CRS history was correlated with the stage of 182 ENKTL patients whose primary sites were upper aerodigestive tract (UAT) (χ 2 = 21.317, p = 0.046, n = 182); the Spearman correlation coefficient was 0.162 (p = 0.029). There was no significant difference in stage of the non-UAT-ENKTL patients (χ 2 = 18.910, p = 0.091, n = 32). The COX multivariate regression analysis showed that CRS history was an independent prognostic predictor for PFS of the UAT-ENKTL patients (p = 0.004), and patients without CRS had significantly better PFS than the more than 15 years CRS history group (p = 0.001). Our findings suggested that we should not ignore the existence of chronic inflammation of the nasal cavity in ENKTL patients. It is better to treat CRS as soon as possible in clinical practice to reduce the possibility of the occurrence or progression of UAT-ENKTL.

Germinal centre-driven maturation of B cell response to mRNA vaccination.

Germinal centres (GC) are lymphoid structures in which B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells1-5 (BMPCs). SARS-CoV-2 mRNA vaccination induces a persistent GC response that lasts for at least six months in humans6-8. The fate of responding GC B cells as well as the functional consequences of such persistence remain unknown. Here, we detected SARS-CoV-2 spike protein-specific MBCs in 42 individuals who had received two doses of the SARS-CoV-2 mRNA vaccine BNT162b2 six month earlier. Spike-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of sequencing the B cell receptors of responding blood plasmablasts and MBCs, lymph node GC B cells and plasma cells and BMPCs from eight individuals and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1,540 spike-specific B cell clones. On average, early blood spike-specific plasmablasts exhibited the lowest SHM frequencies. By contrast, SHM frequencies of spike-specific GC B cells increased by 3.5-fold within six months after vaccination. Spike-specific MBCs and BMPCs accumulated high levels of SHM, which corresponded with enhanced anti-spike antibody avidity in blood and enhanced affinity as well as neutralization capacity of BMPC-derived monoclonal antibodies. We report how the notable persistence of the GC reaction induced by SARS-CoV-2 mRNA vaccination in humans culminates in affinity-matured long-term antibody responses that potently neutralize the virus.

SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans.

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.