Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections.

Lipocalin 2 (LCN2) plays a pivotal role in iron metabolism, particularly in the context of microbial infection resistance (e.g., viruses, bacteria, parasites, etc.). LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron, inducing immune cells to secrete various cytokines to enhance systemic immune responses, or recruiting neutrophils to infectious sites. The liver serves as the primary organ for LCN2 secretion during microbial infections. This review encapsulates recent advances in dynamic changes, clinical values, and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

Molecular Insights into Water-Chloride and Water-Water Interactions in the Supramolecular Architecture of Aconine Hydrochloride Dihydrate.

Despite the previous preparation of aconine hydrochloride monohydrate (AHM), accurate determination of the crystal's composition was hindered by severely disordered water molecules within the crystal. In this study, we successfully prepared a new dihydrate form of the aconine hydrochloride [C25H42NO9+Cl-·2(H2O), aconine hydrochloride dihydrate (AHD)] and accurately refined all water molecules within the AHD crystal. Our objective is to elucidate both water-chloride and water-water interactions in the AHD crystal. The crystal structure of AHD was determined at 136 K using X-ray diffraction and a multipolar atom model was constructed by transferring charge-density parameters to explore the topological features of key short contacts. By comparing the crystal structures of dihydrate and monohydrate forms, we have observed that both AHD and AHM exhibit identical aconine cations, except for variations in the number of water molecules present. In the AHD crystal, chloride anions and water molecules serve as pivotal connecting hubs to establish three-dimensional hydrogen bonding networks and one-dimensional hydrogen bonding chain; both water-chloride and water-water interactions assemble supramolecular architectures. The crystal packing of AHD exhibits a complete reversal in the stacking order compared to AHM, thereby emphasizing distinct disparities between them. Hirshfeld surface analysis reveals that H···Cl- and H···O contacts play a significant role in constructing the hydrogen bonding network and chain within these supramolecular architectures. Furthermore, topological analysis and electrostatic interaction energy confirm that both water-chloride and water-water interactions stabilize supramolecular architectures through electrostatic attraction facilitated by H···Cl- and H···O contacts. Importantly, these findings are strongly supported by the existing literature evidence. Consequently, navigating these water-chloride and water-water interactions is imperative for ensuring storage and safe processing of this pharmaceutical compound.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System.

Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, NMN biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, and efficiency, positioning it as a primary avenue for future NMN synthesis. Enzymatic NMN synthesis encompasses the nicotinamide-initial route and nicotinamide ribose-initial routes. Key among these is nicotinamide riboside kinase (NRK), pivotal in the latter route. The NRK-mediated biosynthesis is emerging as a prominent trend due to its streamlined route, simplicity, and precise specificity. The essential aspect is to obtain an engineered NRK that exhibits elevated activity and robust stability. This review comprehensively assesses diverse NMN synthesis methods, offering valuable insights into efficient, sustainable, and economical production routes. It spotlights the emerging NRK-mediated biosynthesis pathway and its significance. The establishment of an adenosine triphosphate (ATP) regeneration system plays a pivotal role in enhancing NMN synthesis efficiency through NRK-catalyzed routes. The review aims to be a reference for researchers developing green and sustainable NMN synthesis, as well as those optimizing NMN production.

Single-port insufflation endoscopic nipple-sparing mastectomy in early breast cancer: a retrospective cohort study.

Background: Breast cancer is the most common malignancy in female patients. In recent years, more and more studies have focused on how to improve the appearance and the quality of life for patients. This study aimed to compare the oncologic safety, aesthetic results, and upper extremity function between single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) and conventional open mastectomy (C-OM) in early-stage breast cancer treatment. Methods: In our retrospective cohort, 285 patients with stage I and II breast cancer were categorized into the SIE-NSM group (n=71) and the C-OM group (n=214). We assessed local recurrence, distant metastasis, and upper extremity function across the two groups. The BREAST-Q scale was employed to analyze differences in aesthetic results, psychosocial well-being, and sexual health. The risk of local recurrence was evaluated using multivariable binary logistic regression, while a multivariable linear regression model gauged upper extremity function and aesthetic outcomes. Results: Local recurrence rates between the two groups were statistically similar (1/71, 1.4% for SIE-NSM vs. 2/214, 0.9% for C-OM, P=0.735), as confirmed by the multivariable binary logistic regression analysis. Neither group exhibited distant metastases. The SIE-NSM group demonstrated higher scores in satisfaction with breasts, chest wellness, psychosocial health, and sexual well-being (P<0.001). The SIE-NSM group also exhibited superior outcomes regarding chest wall/breast pain, shoulder mobility, and daily arm usage (P<0.001). No subcutaneous effusion was reported in the SIE-NSM group, whereas the C-OM group had a 10.7% incidence rate (P=0.004). Conclusions: SIE-NSM offers comparable oncologic safety to C-OM but provides enhanced satisfaction regarding breast appearance, physical comfort, psychosocial health, sexual health, and improved upper extremity functionality. Consequently, this innovative approach is a suitable surgical alternative for treating early-stage breast cancer.

Impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation: a retrospective cohort study.

BACKGROUND: Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). The authors aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early post-transplant period on LAF. METHODS: A retrospective study was conducted on pediatric LT recipients with at least 1-year of follow-up. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of IS level on LAF. Longitudinal analysis was also conducted in patients with paired biopsies. RESULTS: A total of 139 patients involving 174 liver biopsies were included. With 2.3 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (7.9% were significant), up to 88.2% of whom showed normal liver function. Episodes of acute rejection, biliary complications, cytomegalovirus infection, and prolonged cold ischemia time were independent risk factors. Besides, the risk of LAF in patients with relatively low IS levels at postoperative 1-3, 3-6, 6-12, and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS levels (mean tacrolimus trough concentration ≥5.1 ng/ml) during postoperative 12-36 months, the risk of LAF was 67% lower in the short future ( P =0.006). In paired analysis, patients with increased IS levels were more likely to achieve fibrosis-reduction (HR=7.53, P =0.025). CONCLUSIONS: Mild to moderate LAF is common among pediatric LT recipients and can appear early and silently. Maintaining adequate levels of IS during 1-3 years after LT seems crucial to ensure protection against LAF.

Single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles in breast cancer.

BACKGROUND: In order to explore the surgical safety and the reliability of axillary staging of single-port endoscopic-sentinel lymph node biopsy, we combined it with indocyanine green that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles as a tracer and compared this method to conventional open sentinel lymph node biopsy. METHODS: This is a retrospective and observational study, there were 20 patients in each group and the total sample size was 60: Group 1, single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles; Group 2, single-port endoscopic-sentinel lymph node biopsy with carbon nanoparticles only; Group 3, conventional sentinel lymph node biopsy with indocyanine green and carbon nanoparticles. Sentinel lymph node detection and upper extremity function were determined to measure the safety and efficacy of the novel single-port endoscopic-sentinel lymph node biopsy (SPE-SLNB) technique to the standard conventional sentinel lymph node biopsy technique. RESULTS: The detection rate of sentinel lymph nodes was 100% in Group 1, 100% in Group 2, and 95% in Group 3. There were no significant differences in upper arm function and pain scores between the three groups. CONCLUSION: The novel technique of combining indocyanine green and carbon nanoparticles with single-port endoscopic-sentinel lymph node biopsy achieved a similar detection rate and mean number of sentinel lymph nodes as conventional sentinel lymph node biopsy. Traditional open surgery requires two different incisions for breast surgery and SLNB. While the most important advantage of SPE-SLNB is that two procedures can be effectively performed through a single-port in the axilla Therefore, for patients who meet the indications, single-port endoscopic-sentinel lymph node biopsy is as safe and reliable as conventional sentinel lymph node biopsy but has the aesthetic advantage of only one incision.

Transglutaminase-Catalyzed Glycosylation Improved Physicochemical and Functional Properties of Lentinus edodes Protein Fraction.

Lentinula edodes has high nutritional value and abundant protein. In order to develop and utilize edible mushroom protein, this study was designed to investigate the effects of TGase-catalyzed glycosylation and cross-linking on the physicochemical and functional properties of Lentinus edodes protein fraction. The results showed that within a certain time, glycosylation and TGase-catalyzed glycosylation decreased the total sulfydryl, free sulfydryl, disulfide bond, surface hydrophobicity, ß-fold and α-helix, but increased the fluorescence intensity, random coil, ß-turn, particle size and thermal stability. The apparent viscosity and the shear stress of the protein with an increase in shear rate were increased, indicating that TGase-catalyzed glycosylation promoted the generation of cross-linked polymers. In addition, the TGase-catalyzed glycosylated proteins showed a compact texture structure similar to the glycosylated proteins at the beginning, indicating that they formed a stable three-dimensional network structure. The flaky structure of proteins became more and more obvious with time. Moreover, the solubility, emulsification, stability and oil-holding capacity of enzymatic glycosylated Lentinus edodes protein fraction were significantly improved because of the proper TGase effects of glycosylation grafting and cross-linking. These results showed that glycosylation and TGase-catalyzed glycosylation could improve the processing characteristics of the Lentinula edodes protein fraction to varying degrees.

Single-port nipple-sparing subcutaneous mastectomy with immediate prosthetic breast reconstruction for breast cancer.

INTRODUCTION: This study compares the perioperative results, aesthetic outcome and oncologic safety of single-port insufflation endoscopic nipple-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (SIE-NSM-IRPI) with those of conventional open-nipple and areola-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (C-NSM-IRPI). METHODS: In this retrospective cohort study, 64 early-stage breast cancer patients were divided into SIE-NSM-IRPI (n = 38) and C-NSM-IRPI (n = 26) groups. Perioperative results (operation time, intraoperative blood loss, incision length, drainage duration, and recent complications) were then compared between the two groups. Differences in satisfaction with the breasts, psychosocial well-being, physical well-being (chest) and sexual well-being were analyzed according to the BREAST-Q scale, and survival outcomes were also compared. RESULTS: The median follow-up time was 51.5 months. The incision length of SIE-NSM-IRPI was shorter than that of C-NSM-IRPI (P < 0.001). SIE-NSM-IRPI achieved the same detection rate and median number of sentinel lymph nodes as C-NSM-IRPI (3.00vs. 4.00, P = 0.780). The incidence of prosthesis removal due to infection or prosthesis exposure in the SIE-NSM-IRPI group was lower than that in the C-NSM-IRPI group (P = 0.015). Satisfaction with breasts (82.00vs.59.00, P < 0.001), psychosocial well-being (93.00vs.77.00, P = 0.001) and physical well-being (chest) (89.00vs.82.00, P < 0.001) scores were higher in the SIE-NSM-IRPI group. There were no significant differences between the two groups in disease-free survival (hazard ratio = 0.829, 95% confidence interval = 0.182-3.779) and overall survival (hazard ratio = 1.919, 95% confidence interval = 0.169-21.842). CONCLUSION: In this selected cohort of patients with early breast cancer, SIE-NSM-IRPI was comparable to C-NSM-IRPI, considering oncologic safety and detection of sentinel lymph nodes. It had a lower incidence of prosthesis removal, shorter incision length, and was associated with better patient satisfaction with the breasts. More random clinical trials of this novel approach in a larger cohort of Chinese patients with an extended follow-up period are needed in the future.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer.

BACKGROUND: In the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients' quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called 'single-port insufflation endoscopic breast-conserving surgery' (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer. METHODS: A total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale. RESULTS: The mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis. CONCLUSION: The novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients' postoperative comfort and psychological well-being, as compared to the conventional technique.

Genomic analysis of Thalassospira sp. SW-3-3 reveals its genetic potential for phthalate pollution remediation.

Thalassospira sp. SW-3-3 is a bacterial strain isolated from deep seawater of the Pacific Ocean at a water depth of 3112 m. It is a Gram-negative, aerobic, and curved rod-shaped bacterium belonging to the family Thalassospiraceae. In this study, we report the complete genome sequence of strain SW-3-3. It has a circular chromosome with a size of 4,764,478 bp and a G + C content of 54.7%. The genome contains 4296 protein-coding genes, 63 tRNA genes, and 12 rRNA genes. Genomic analysis shows that strain SW-3-3 contains genes and catalytic pathways relevant to phthalate metabolism. Phthalates are well-known emerging contaminants that are harmful to environments and human health. They are chemically stable compounds that are widely used in plastic products and are pervasive in our life. With the discharge of plastic pollutants, a huge number of phthalate compounds enter the ocean. The genetic information of strain SW-3-3 suggests that it has the potential to metabolize phthalates. There are 9 key enzymes in the metabolization pathway, and phthalates are finally catalyzed to produce succinyl-CoA which is further degraded through the tricarboxylic acid (TCA) cycle pathway. This genomic analysis will be helpful for further understanding of the applications of strain SW-3-3 in the remediation of phthalate pollution.

Network Pharmacology-Based Analysis on the Effects and Mechanism of the Wang-Bi Capsule for Rheumatoid Arthritis and Osteoarthritis.

Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herb couple Angelicae pubescentis radix (APR) and Notopterygii rhizoma et radix (NRR), composition of two traditional Chinese medicinal herbs, has been used clinically in China for the treatment of rheumatoid arthritis (RA) over years. APR and NRR contain coumarins and phenolic acids, which have been reported to have analgesic and anti-inflammatory activities. AIM OF THE STUDY: The active ingredients combination (AIC) and potential therapeutic mechanism of APR and NRR (AN) herb couple remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on RA. MATERIALS AND METHODS: Firstly, a novel strategy of in vitro experiments, computational analysis, UPLC-QTOF-MS and UPLC-QQQ-MS was established to confirm the optimum ratio of AN herb couple samples and identified the AIC. Then, the anti-arthritis effects of the optimal herb couple and AIC were studied with Collagen II induced rheumatoid arthritis (CIA) rats in vivo. Finally, an integrated model of network pharmacology, metabolomics, gut microbiota analysis and biological techniques were applied to clarify the underlying mechanism through a comprehensive perspective. RESULTS: AN7:3 herb couple was regarded as the optimal ratio of AN herbal samples, and AIC was screened as osthole, columbianadin, notopterol, isoimperatorin, psoralen, xanthotoxin, bergapten, nodakenin and bergaptol respectively. Additionally, AIC exerted similar therapeutic effects as AN 7:3 in CIA rats. Moreover, AIC ameliorated RA might via regulating MAPK signaling pathway, altering metabolic disorders and gut microbiome involved autoimmunity. CONCLUSIONS: our findings provided scientific evidence to support that AIC of AN herb couple could be used as a prebiotic agent for RA. Importantly, this research provided a systematic and feasible strategy to optimize the proportion of medicinal materials and screen AIC from multi-component traditional Chinese herb couples or Chinese medicine formulae. Moreover, it provided a comprehensive perspective to discover AIC, clarify the overall effects and understand the mechanisms for natural products through the perspective of database and multi-omics integration.

Navigation in bone-impacted premaxillary supernumerary tooth removal: a preliminary clinical trial.

AIM: The present clinical trial aimed to preliminarily assess whether navigation could help to position impacted supernumerary teeth (STs) and reduce surgical trauma. MATERIALS AND METHODS: Subjects with an impacted supernumerary tooth (ST) in the premaxillary area were enrolled in the study and randomly distributed into a navigation group and a control group. In the navigation group, STs were positioned and extracted under real-time optic navigation. In the control group, STs were extracted depending on the surgeon's experience. Subjects were followed up for 12 to 24 weeks postsurgery. Operating time, futile bony trauma, and the positioning precision of the STs were the major outcomes assessed. Multivariate correlation analysis was performed. RESULTS: In 24 subjects, 32 STs were removed and no severe complications occurred in either group. The proportion of ST exposure at the planned access point was 100% in the navigation group and 68.75% in the control group (χ² = 5.926, P = 0.015). Futile length, futile width, and the distance between the point where the ST was initially exposed and the bony point planned for accessing it were related to both navigation/control grouping and bone thickness in the access side. For challenging STs with bone thickness of > 0.5 mm in the access side (N = 22), the futile length in the navigation group (0.0 [0.0, 4.0] mm) was significantly smaller than that in the control group (3.0 [0.0, 8.0] mm, P = 0.028). Similarly, the futile width in the navigation group (0.0 [0.0, 2.0] mm) was significantly smaller than that in the control group (2.0 [0.0, 4.0] mm, P = 0.018). CONCLUSIONS: Navigation helped to position impacted STs precisely and reduced surgical bony trauma to some extent, especially in challenging cases in which the bone in the access side was thicker than 0.5 mm.

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer's Disease.

Alzheimer's disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl3-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins.

Two Cases of Well Controlled Chronic Spontaneous Urticaria Triggered by the Moderna COVID-19 Vaccine.

Chronic spontaneous urticaria (CSU, chronic idiopathic urticaria) is a clinical diagnosis characterized by recurrent urticaria of unknown origin, with or without angioedema, that occurs for six weeks or longer. Management of CSU includes a second-generation H1 antihistamine and/or elimination of exacerbating factors. If initial treatment is unsuccessful, trials of first generation H1 antihistamine, H2 blocking antihistamine, leukotriene-receptor antagonist, anti-inflammatory or immunosuppressive agents may be administered. Exacerbating factors include stress, environmental conditions, medications, physical stimuli, and infections. We report the first two cases of a COVID-19 vaccine triggered relapse of CSU that was previously well controlled on therapy.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials.

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Jackfruit Anaphylaxis in a Latex Allergic Non-Healthcare Worker.

INTRODUCTION: Anaphylaxis to jackfruit (Artocarpus heterophyllus) is rare. Two previously reported cases have been published in two healthcare workers from jackfruit endemic regions. Latex allergy and birch pollen cross reactivity have both been associated with jackfruit anaphylaxis, providing two separate mechanisms of sensitization. We present a case of jackfruit anaphylaxis in a young latex allergic non-healthcare worker in a non-endemic region. CASE REPORT: A 21-year-old male had an anaphylactic reaction immediately after ingesting dried jackfruit. He had a history of allergic rhinitis and latex allergy. He was born premature and required neonatal intensive care and multiple surgeries in infancy, which could possibly be the source of his latex sensitization. Skin prick testing was positive for jackfruit and latex. DISCUSSION: Jackfruit anaphylaxis has only been described in conjunction with a latex allergy or a birch pollen allergy. As jackfruit becomes more available across the world, it is important for physicians and patients with these sensitivities to be aware of these possible cross reactions. Fruit sensitivities in latex allergic patients have been well established as Latex-fruit syndrome. Our case highlights the association of latex sensitization and jackfruit anaphylaxis. CONCLUSION: We present a case of Jackfruit anaphylaxis associated with latex allergy in a non-healthcare worker from Midwestern United States. As jackfruit becomes more popular in non-endemic regions, its possible cross reactivity with latex, as well as birch pollen should be recognized.

Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model.

Background: Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods: To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results: Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-ß and NMDAR2-α subtypes as well as their downstream signaling proteins ß-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of ß-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-ß association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions: These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine's lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.