STnc1280, a trans-coding sRNA is involved in virulence modulation via targeting gldA mRNA in Salmonella Typhimurium.

Introduction. Salmonella Typhimurium (STM) is a food-borne Gram-negative bacterium, which can infect humans and a wide range of livestock and poultry, causing a variety of diseases such as septicaemia, enteritis and abortion.Hypothesis/Gap Statement. We will decipher the impacts of sRNA STnc1280 on STM virulence and provide a theoretical basis to reveal the regulatory role and molecular mechanism of STnc1280.Aim. The main objective of this study was to clarify whether sRNA STnc1280 exerts regulatory roles on STM pathogenicity.Methodology. The STnc1280 gene was amplified and its molecular characteristics were analysed in this study. Then, STnc1280 gene deletion strain (STM-ΔSTnc1280) and the complementary strain (ΔSTnc1280/STnc1280) were constructed by λ-Red homologous recombination method, respectively, to analyse of adhesion and invasive ability and pathogenicity of different strains. Subsequently, the potential target gene regulated by STnc1280 was predicted using target RNA2 software, followed by the verification of the interaction between STnc1280 and target mRNA using the dual plasmid reporter system (DPRS). Furthermore, the mRNA and protein level of target gene was determined using qRT-PCR and Western blot, respectively.Results. The results revealed that the cell adhesion and invasive ability and pathogenicity of STM-ΔSTnc1280 were significantly reduced compared to STM-SL1344 strain, indicating that the deficiency of STnc1280 gene significantly influenced STM pathogenicity. The DPRS results showed that STnc1280 can interact with the mRNA of target gene gldA, thus suppressing the expression of lacZ gene. Furthermore, the level of gldA mRNA was not influenced in STM-ΔSTnc1280, but the expression of GldA protein decreased significantly.Conclusion. Combining the bioinformatic analysis, these findings suggested that STnc1280 may bind to the SD sequence of gldA mRNA, hindering the binding of ribosomes to gldA mRNA, thereby inhibiting the expression of GldA protein to modulate the virulence of STM.

Influencing factors of falls among older adults in Chinese retirement institutions: A systematic review and meta-analysis.

BACKGROUND: The incidence of falling has always been high among the elderly, and it was easy to cause injuries to the elderly and seriously affect their quality of life. There were many studies have been conducted on risk factors affecting the fall of the elderly, but the results widely, retirement institutions as a gathering place for the elderly, there was currently no comprehensive analysis of the factors related to elderly falls in pension institutions. This study aimed to explore the influencing factors of falls among older adults in Chinese nursing homes. METHODS: Chinese and English databases were searched for literature published from database inception to 5 April 2023 on the influencing factors of falls among older adults in Chinese nursing homes. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Eleven studies involving 3503 participants were included in the meta-analysis. The pooled estimate of falls among older adults in Chinese nursing homes was 32% [95% confidence interval (95%CI) (24.0%, 39.0%)]. The main influencing factors for falls among older adults in Chinese nursing homes were age (Odds Ratio (OR) = 1.53), gender (OR = 5.50), visual impairment (OR = 2.30), sedative-hypnotics (OR = 2.36), fear of falling (OR = 2.95), hypertension (OR = 3.72), static balance (OR = 2.02), three or more chronic diseases (OR = 5.63), cognitive status (OR = 2.64), walking aid use (OR = 1.98), fall-related chronic diseases (OR = 2.48), self-awareness of abilities (OR = 2.43), and frequent reminders for fall prevention (OR = 0.10). CONCLUSION: Falls among older adults in Chinese nursing homes were common, and there were many influencing factors. Timely screening and intervention should be implemented to reduce the adverse consequences of falls on older adults. TRIAL REGISTRATION: Registration number: CRD42023421099.

Chinese expert consensus on the management of patients with hematologic malignancies infected with SARS-CoV-2.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir.

The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CLpro) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in combination with ritonavir for the treatment of COVID-19. The structure-based optimization of boceprevir, an approved HCV protease inhibitor, leads to identification of simnotrelvir that covalently inhibits SARS-CoV-2 3CLpro with an enthalpy-driven thermodynamic binding signature. Multiple enzymatic assays reveal that simnotrelvir is a potent pan-CoV 3CLpro inhibitor but has high selectivity. It effectively blocks replications of SARS-CoV-2 variants in cell-based assays and exhibits good pharmacokinetic and safety profiles in male and female rats and monkeys, leading to robust oral efficacy in a male mouse model of SARS-CoV-2 Delta infection in which it not only significantly reduces lung viral loads but also eliminates the virus from brains. The discovery of simnotrelvir thereby highlights the utility of structure-based development of marked protease inhibitors for providing a small molecule therapeutic effectively combatting human coronaviruses.

A Novel Clinical Tool to Detect Severe Obstructive Sleep Apnea.

Purpose: Obstructive sleep apnea (OSA) is a disease with high morbidity and is associated with adverse health outcomes. Screening potential severe OSA patients will improve the quality of patient management and prognosis, while the accuracy and feasibility of existing screening tools are not so satisfactory. The purpose of this study is to develop and validate a well-feasible clinical predictive model for screening potential severe OSA patients. Patients and Methods: We performed a retrospective cohort study including 1920 adults with overnight polysomnography among which 979 cases were diagnosed with severe OSA. Based on demography, symptoms, and hematological data, a multivariate logistic regression model was constructed and cross-validated and then a nomogram was developed to identify severe OSA. Moreover, we compared the performance of our model with the most commonly used screening tool, Stop-Bang Questionnaire (SBQ), among patients who completed the questionnaires. Results: Severe OSA was associated with male, BMI≥ 28 kg/m2, high blood pressure, choke, sleepiness, apnea, white blood cell count ≥9.5×109/L, hemoglobin ≥175g/L, triglycerides ≥1.7 mmol/L. The AUC of the final model was 0.76 (95% CI: 0.74-0.78), with sensitivity and specificity under the optimal threshold selected by maximizing Youden Index of 73% and 66%. Among patients having the information of SBQ, the AUC of our model was statistically significantly greater than that of SBQ (0.78 vs 0.66, P = 0.002). Conclusion: Based on common clinical examination of admission, we develop a novel model and a nomogram for identifying severe OSA from inpatient with suspected OSA, which provides physicians with a visual and easy-to-use tool for screening severe OSA.

Therapeutic Drug Monitoring of Imatinib and N-Desmethyl Imatinib in Chronic Myeloid Leukemia Patients Using LC-MS/MS in a Cohort Study.

Imatinib is an oral tyrosine kinase inhibitor (TKI) and first-line therapy for patients with chronic myeloid leukemia (CML). There is a positive correlation between serum imatinib concentrations and treatment response. However, the specific relationship between the blood concentration of imatinib and its influencing factors remains unclear. This study collected basic information from 102 patients using imatinib as first-line treatment for CML. Further, we analyzed the individual differences in imatinib concentration and explored its influencing factors. Through intra-day and inter-day precision studies, we found that the precision for the imatinib assay methodology was within ±13% and that the recovery rate was above 85%. There is notable individual variation in the blood concentration of imatinib; the recommended treatment concentration is 860-1500 ng/mL, with only 41.40% of patients achieving this concentration. Also, there was a negative correlation between age and imatinib trough concentration (Ctrough ), as is observed between age and N-desmethyl imatinib. Moreover, compared with the adolescent group, the serum imatinib Ctrough for groups aged 17-47 and 48-68 years was significantly reduced. Further analysis shows that imatinib Ctrough values reaching therapeutic concentrations (59%) increased dramatically for patients with CML aged 17-47 years. Moreover, groups dosed with 400 mg/day resulted in therapeutic imatinib concentrations for 68% of patients with CML, which was the best performance. The established method was validated, with acceptable accuracy, precision, linearity, and stability, as required, and then successfully applied to the therapeutic drug monitoring of imatinib. Age, dose, and metabolites can influence the imatinib concentration and its therapeutic effect in patients with CML.

The Small Non-coding RNA rli106 Contributes to the Environmental Adaptation and Pathogenicity of Listeria Monocytogenes.

Introduction: Listeria monocytogenes (LM) is an important food-borne pathogen, and the risk of its ingestion is a serious public health issue. The better its environmental adaptation mechanisms and pathogenicity are understood, the better the risk it poses can be countered. The regulatory role of the small non-coding RNA (sRNA) rli106 in the environmental adaptation and pathogenicity of LM is still unclear and this study investigated that role through its biological function. Material and Methods: An LM-Δrli106 gene deletion strain and an LM-Δrli106/rli106 gene complementation strain were constructed using the homologous recombination technique. Then, the adaptation of these strains to temperature, alkalinity, acidity, salinity, ethanol and oxidative stressors, their biofilm-forming ability and their pathogenicity in mice were investigated to show the regulatory roles of sRNA rli106 in LM. The target gene of rli106 was also predicted, and the interaction between it and rli106 was verified by a two-plasmid co-expressing system based on E.coli and Western blot analysis. Results: The adaptation of LM-Δrli106 to environmental stressors of pH 9, 5% NaCl and 8% NaCl, 3.8% ethanol and 5 mM H2O2 was significantly reduced when compared to the parental (LM EGD-e) and complementation strains. Also, the biofilm formation, cell adhesion, invasion, intracellular proliferation and pathogenicity of LM-Δrli106 in mice were significantly reduced. The results of two-plasmid co-expression and Western blot showed that rli106 can interact with the mRNA of the predicted DegU target gene. Conclusion: The sRNA rli106 may positively regulate the expression of the DegU gene in LM. This study sheds light on its regulatory roles in environmental adaptation and pathogenicity, providing new insights into the molecular mechanism of sRNA mediation in LM .

Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.

Human alpha-2-macroglobulin is a well-known inhibitor of a broad spectrum of proteases and plays important roles in immunity, inflammation, and infections. Here, we report the cryo-EM structures of human alpha-2-macroglobulin in its native state, induced state transformed by its authentic substrate, human trypsin, and serial intermediate states between the native and fully induced states. These structures exhibit distinct conformations, which reveal the dynamic transformation of alpha-2-macro-globulin that acts as a protease inhibitor. The results shed light on the molecular mechanism of alpha-2-macroglobulin in entrapping substrates.

Community Bargaining with Urban Growth: The Case of J Village in Guangzhou.

The past several decades have seen China undergo a rapid urbanization process. During periods of economic prosperity, cities expropriate outlying lands, often villages, for economic development with the support of various local and national government programs designed to encourage urban expansion. However, the autonomy of the villages has not been paid enough attention. How does incorporation into an urban development zone affect the community identity and autonomy of a village? How does the village bargain with external urban institutions? This research is based on ethnographic research and interviews conducted in 2013, 2014, 2017, and 2021. The results reveal that villagers are generally willing to accept the loss of their collective land in exchange for a larger share of the promised prosperity of industrialization, but over time they tend to find that the immediate benefits of expropriation are outweighed by long-term costs. They lose the support of the state and are exposed to new vulnerabilities, such as pollution and economic instability. Indeed, they agree to undertake unknown future risks in exchange for short-term gains. They cannot gain the right to the city, but gradually lose control of the village.

Association of admission blood glucose level and clinical outcomes in elderly community-acquired pneumonia patients with or without diabetes.

INTRODUCTION: Community-acquired pneumonia (CAP) is the major cause of infection-related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia. OBJECTIVES: The aim of this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes. METHODS: In this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30-day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed. RESULTS: Of the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30-day mortality both in non-diabetic and diabetic patients. Furthermore, Kaplan-Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30-day mortality in patients with CAP (P < 0.001). CONCLUSION: Admission blood glucose is correlated with 30-day hospital mortality, ICU admission, and IMV of CAP in elderly patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L was a significant risk factor for 30-day hospital mortality.

AI-2 Induces Urease Expression Through Downregulation of Orphan Response Regulator HP1021 in Helicobacter pylori.

Helicobacter pylori causes gastric infections in more than half of the world's population. The bacterium's survival in the stomach is mediated by the abundant production of urease to enable acid acclimation. In this study, our transcriptomic analysis demonstrated that the expression of urease structural proteins, UreA and UreB, is induced by the autoinducer AI-2 in H. pylori. We also found that the orphan response regulator HP1021 is downregulated by AI-2, resulting in the induction of urease expression. HP1021 represses the expression of urease by directly binding to the promoter region of ureAB, ranging from -47 to +3 with respect to the transcriptional start site. The study findings suggest that quorum sensing via AI-2 enhances acid acclimation when bacterial density increases, and might enable bacterial dispersal to other sites when entering gastric acid.

A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC.

More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement. However, most patients inevitably develop crizotinib resistance due to acquired secondary mutations in the ALK kinase domain, such as the gatekeeper mutation L1196M and the most refractory mutation, G1202R. Here, we develop XMU-MP-5 as a new-generation ALK inhibitor to overcome crizotinib resistance mutations, including L1196M and G1202R. XMU-MP-5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild-type or mutant EML4-ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo. Structural analysis provides insights into the mode of action of XMU-MP-5. In addition, XMU-MP-5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models, further demonstrating its pharmacological efficacy and potential for clinical application. These preclinical data support XMU-MP-5 as a novel selective ALK inhibitor with high potency and selectivity. XMU-MP-5 holds great promise as a new therapeutic against clinically relevant secondary ALK mutations.

Prevalences and Characteristics of Trichuris Spp. Infection in Sheep in Pastoral Areas of the Tianshan, Xinjiang, China.

Introduction: Nematodes of the Trichuris genus are commonly reported parasites that can cause trichuriasis in many animals, which leads to inflammation, intestinal bleeding and reductions of productivity in livestock. Knowledge of the prevalence of Trichuris infestation in the Tianshan ovine population and of the nematode species parasitising the population is not exhaustive, and this study aimed to expand the knowledge. Material and Methods: A total of 1,216 sheep slaughtered in five pasture areas in the Tianshan Mountains of Xinjiang were investigated and a phylogenetic analysis based on the mitochondrial cox1 gene was performed to clarify the genetic relationships of the various Trichuris species. Results: Sheep totalling 1,047 were infected with Trichuris spp. establishing the rate at 86.1%. Using a morphological protocol, six documented and one undefined species were identified, namely T. gazellae, T. lani, T. ovina, T. longispiculus, T. concolor, T. discolor and Trichuris sp. Among them, T. gazellae and T. lani were the dominant species, accounting for 34.5% and 31.0% of Trichuris spp., respectively. Phylogenetic analysis divided the detected species of Trichuris spp. into two genetic clades (clade I and clade II). The six documented species that can infect sheep and the undefined species were clustered into clade I, with inter- and intra-species genetic diversity apparent. Conclusion: This survey described in detail the morphological characteristics of six known and one undefined species of Trichuris, which not only enriched the taxonomic information on record regarding Trichuris spp., but also provided valuable epidemiological data for the prevention and control of trichuriasis in sheep.

Effects of Basic Psychological Needs on Resilience: A Human Agency Model.

Academic resilience refers to the ability to recover and achieve high academic outcomes despite environmental adversity in the academic setting. At the same time, self-determination theory (SDT) offers a human agency model to understand individuals' autonomy to achieve in various fields. The present longitudinal study explored the factors influencing resilience from the analytical framework of SDT to investigate how basic psychological needs strengthen students' resilience. A mediation model was proposed that resilience may mediate the relationship between basic psychological needs and academic performance. The results from 450 10th grade Chinese students showed that three basic psychological needs (i.e., autonomy, competence, and relatedness) facilitate academic resilience; academic resilience thus increases subsequent academic performance after controlling for previous test scores.

The Role of a Dipeptide Transporter in the Virulence of Human Pathogen, Helicobacter pylori.

Helicobacter pylori harbors a dipeptide (Dpp) transporter consisting of a substrate-binding protein (DppA), two permeases (DppB and C), and two ATPases (DppD and F). The Dpp transporter is responsible for the transportation of dipeptides and short peptides. We found that its expression is important for the growth of H. pylori. To understand the role of the Dpp transporter in the pathogenesis of H. pylori, the expression of virulence factors and H. pylori-induced IL-8 production were investigated in H. pylori wild-type and isogenic H. pylori Dpp transporter mutants. We found that expression of CagA was downregulated, while expression of type 4 secretion system (T4SS) components was upregulated in Dpp transporter mutants. The DppA mutant strain expressed higher levels of outer membrane proteins (OMPs), including BabA, HopZ, OipA, and SabA, and showed a higher adhesion level to gastric epithelial AGS cells compared with the H. pylori 26695 wild-type strain. After infection of AGS cells, H. pylori ΔdppA induced a higher level of NF-κB activation and IL-8 production compared with wild-type. These results suggested that in addition to supporting the growth of H. pylori, the Dpp transporter causes bacteria to alter the expression of virulence factors and reduces H. pylori-induced NF-κB activation and IL-8 production in gastric epithelial cells.

LMR-101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ-aminobutyric acid type A receptors.

OBJECTIVE: LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic. METHODS: Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties. RESULTS: In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR-101 also suppressed seizure behaviors evoked by (+)-bicuculline in mice in a dose-dependent manner. In the pilocarpine-induced SE model, LMR-101 significantly decreased the maximum seizure score and seizure duration in a dose-dependent manner. The median effective dose for LMR-101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR-101 primarily inhibited tert-[35 S] butylbicyclophosphorothionate binding to γ-aminobutyric acid type A (GABAA ) receptors (half-maximal inhibitory concentration = 2.06 µmol·L-1 ), but it did not affect [3 H] flunitrazepam or [3 H] muscimol binding. SIGNIFICANCE: It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABAA receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABAA receptors.

SIK2 represses AKT/GSK3ß/ß-catenin signaling and suppresses gastric cancer by inhibiting autophagic degradation of protein phosphatases.

Salt-inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial-mesenchymal transition via inhibition of AKT/GSK3ß/ß-catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3ß/ß-catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor.

Vertical transmission and kidney damage in newborns whose mothers had coronavirus disease 2019 during pregnancy.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. However, the hazard to newborns in pregnancy remains controversial. The aim of this study was to investigate the vertical transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mother to child and developmental toxicity in the fetus. METHODS: All clinical information was recorded on 22 neonates born to mothers with confirmed COVID-19 pneumonia in Tongji Hospital. RESULTS: The average birth weight of the 22 newborns (16 males and 6 females) was 2980 g, and the mean gestational week was 37W+3. The birth weight of three babies was <2500 g, and the gestational week of all three low-birth-weight neonates was less than 36W. Three newborns had minor lesions of infection in the lungs as shown by computed tomography (CT) scans. Furthermore, three newborns had elevated SARS-CoV-2-related immunoglobin M (IgM) antibodies, and 11 newborns (52.4%) had positive immunoglobin G (IgG) antibodies. Notably, both cystatin C and ß2-microglobulin were increased in all newborns. Five of the 21 tested newborns had leukocytosis, and 11 had increased neutrophil levels. In addition, the aspartate aminotransferase of 18 newborns and the γ-glutamyl transpeptidase of 19 newborns were increased. Total bilirubin was elevated in all newborns and serum albumin was reduced in 20 of 22 newborns. CONCLUSIONS: This study was the first to discover that COVID-19 infection in the third trimester of pregnancy could cause fetal kidney developmental injury, as indicated by increased cystatin C and ß2-microglobulin in all neonates. Furthermore, there is the possibility of maternal-fetal transmission of SARS-CoV-2.

A Retrospective Study on the Effects of Convalescent Plasma Therapy in 24 Patients Diagnosed with COVID-19 Pneumonia in February and March 2020 at 2 Centers in Wuhan, China.

BACKGROUND This retrospective study aimed to describe the effects of convalescent plasma therapy in 24 patients diagnosed with coronavirus disease 2019 (COVID-19) pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during February and March 2020 in Wuhan, China. MATERIAL AND METHODS The confirmation of SARS-CoV-2 infection was made by the reverse transcription-polymerase chain reaction test. We retrospectively analyzed the clinical data and laboratory test reports of patients with severe COVID-19 pneumonia who received a convalescent plasma transfusion. RESULTS A total of 24 patients with COVID-19 pneumonia who were transfused with ABO-compatible convalescent plasma were enrolled in the study. Convalescent plasma transfusion showed an effective clinical outcome in 14 of 24 patients (an effective rate of 58.3%). No patients had an adverse reaction to the transfusion. Compared with before convalescent plasma transfusion, the lymphocyte count after convalescent plasma transfusion increased to a normal level (median: 0.80×109/L vs. 1.12×109/L, P=0.004). Other laboratory indicators such as white blood cells, high-sensitivity C-reactive protein, procalcitonin, alanine aminotransferase, and aspartate transaminase showed a decreasing trend after transfusion. CONCLUSIONS This retrospective observational clinical study showed that convalescent plasma therapy could have beneficial effects on patient outcomes. Recently, regulatory authorization has been given for the use of convalescent plasma therapy, and clinical guidelines have been developed for the collection and use of convalescent plasma and hyperimmune immunoglobulin in patients with COVID-19.

Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a threat to global health. The mortality rate of severely ill patients in the early stage is 32.5%. The exacerbation of the condition and death of patients are closely associated with inflammatory cytokine storms, which are caused by excessive activation of the immune and complement systems as well as the coinfection of other pathogens. However, the immunological characteristics and the mechanisms underlying inflammatory storms have not been well elucidated. Here, we analyzed the clinical and immunological characteristics of 71 confirmed COVID-19 patients. Based on the National Health Commission of China (NHCC) guidelines, patients were stratified into mild and severe types. We compared the clinical and laboratory data obtained from electronic medical records between the two types. In regard to the hematological parameters, COVID-19 patients showed decreased erythrocyte count, hemoglobin, hematocrit, lymphocyte count, eosinophil count, and complement C1q, whereas neutrophils, C-reactive protein, and procalcitonin were significantly increased, especially in severe cases. We also found that CD3+ CD4+ T lymphocytes, CD3+ CD8+ T lymphocytes, CD19+ B lymphocytes, and CD16+ CD56+ NK cells in the peripheral blood of all patients were decreased. In addition, CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, and complement C1q in severely ill patients decreased more significantly. Additionally, interleukin 6 (IL-6) elevation was particularly prominent in all patients, especially in severe cases. These results suggest that CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6 may play critical roles in the inflammatory cytokine storm. The dysregulation of these aforementioned immune parameters, along with bacterial coinfection, were the important causes of exacerbation of the patients' condition and death. This study improves our understanding of the immune dysregulation of COVID-19 and provides potential immunotherapeutic strategies.IMPORTANCE The dysregulation of CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6, along with bacterial coinfection, were important causes of exacerbation of the patients' condition and death.