A preliminary exploration on the mechanism of the carbapenem-resistance transformation of Serratia marcescens in vivo.

BACKGROUND: The infection of carbapenem-resistant organisms was a huge threat to human health due to their global spread. Dealing with a carbapenem-resistant Serratia marcescens (CRSM) infection poses a significant challenge in clinical settings. This study aims to provide insights into strategies for controlling CRSM infection by exploring the transformation mechanism of carbapenem-resistance. METHODS: We used whole genome sequencing (WGS) to investigate the mechanism of carbapenem resistance in 14 S. marcescens isolates in vivo. The expression level of related genes and the minimum inhibitory concentration of meropenem (MICMEM) were also evaluated to confirm the mechanism of carbapenem resistance. RESULTS: Seven groups of S. marcescens, each consisting of two strains, were collected from a hospital and displayed a shift in MICMEM from low to high levels. Homology analysis revealed that the isolates in five groups were significantly different from the remaining two. WGS and experimental evidence indicated that four groups of strains developed carbapenem resistance by acquiring the blaKPC (obtaining group), while two groups (persisting group) increased the expression level of the blaKPC. In contrast, isolates in the last group (missing group) did not carry the blaKPC. All strains possessed multiple ß-lactamase genes, including blaCTX-M-14, blaSRT-1, and blaSRT-2. However, only in the missing group, the carbapenem-resistant strain lost an outer membrane protein-encoding gene, leading to increased blaCTX-M-14 expression compared to the carbapenem-susceptible strain. CONCLUSION: The study findings suggest that S. marcescens strains developed diverse carbapenem resistance in vivo through the evolution of drug resistance, rather than through clone replacement. We hypothesize that carbapenem resistance in S. marcescens was due to certain clonal types with a distinct mechanism.

Dorsomedial hypothalamus-raphe pallidus-cardiac sympathetic pathway mediates electroacupuncture intervention of stress-induced tachycardia.

Electroacupuncture at Neiguan point (PC6) effectively ameliorates tachycardia. However, very little is known about the neural pathway mechanism underlying the effect of electroacupuncture at PC6 in stress-induced tachycardia. Here, we investigate whether there exists a dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-heart pathway to mediate the effect of electroacupuncture at PC6. The virus tracing results show that the heart is innervated by the neurons in DMH and RP, and the neurons of DMH project to RP. Chemogenetic inhibition of RP projecting DMH neurons reverses the cardiac autonomic imbalance and tachycardia induced by stress. Of note, immunofluorescence results show that the neural activity of DMH and RP is inhibited by electroacupuncture at PC6 accompanied with improved cardiac autonomic imbalance and tachycardia under stress. Moreover, chemogenetic inhibition of RP projecting DMH neurons cannot affect autonomic nervous activity and heart rate of stress rats after administrating electroacupuncture at PC6.NEW & NOTEWORTHY Our study suggests that this dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-cardiac sympathetic pathway involves in the improvement of cardiac dysfunction associated with stress by administrating electroacupuncture at PC6, thus providing beneficial information for the development of therapeutic strategies to prevent stress-induced cardiovascular diseases, and insight into neural pathway basis for electroacupuncture at PC6 intervention of cardiac dysfunction.

Genomic and immunocyte characterisation of bloodstream infection caused by Klebsiella pneumoniae.

OBJECTIVES: The aim of this study was to evaluate the characteristics of immunocyte associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn). METHODS: Patients with BSI-Kpn were included from 2015 to 2022 in our hospital. Immunocyte subpopulations of enrolled BSI-Kpn patients were tested on the same day of blood culture using multicolor flow cytometry analysis. Antibiotic susceptibility test was determined by agar dilution or broth dilution method. All included isolates were subjected to whole genome sequencing and comparative genomics analysis. Clinical and genetic data were integrated to investigate the risk factors associated with clinical outcome. RESULTS: There were 173 patients with non-duplicate BSI-Kpn, including 81 carbapenem-resistant Kpn (CRKP), 30 extended-spectrum ß-lactamases producing Kpn (ESBL-Kpn), 62 none CRKP or ESBL-Kpn (S-Kpn). Among 68 ST11-CRKP isolates, ST11-O2v1:KL64 was the most common serotypes cluster (77.9%, 53/68), followed by ST11-OL101: KL47 (13.2%, 9/68). Compared with CSKP group, subpopulations of immunocyte in patients with CRKP were significantly lower (P < 0.01). In patients with ST11-O2v1:KL64 BSI-Kpn, the level of cytotoxic T lymphocytes (CD3 + CD8 +) is the highest, while the B lymphocytes (CD3-CD19 +) was the least. In addition, the level of immunocyte in patients with Kpn co-harbored clpV-ybtQ-qacE were lower than that in patients with Kpn harbored one of clpV, ybtQ or qacE and without these three genes. Furthermore, co-existence of clpV-ybtQ-qacE was independently associated with a higher risk for 30-day mortality. CONCLUSIONS: The results demonstrate that patients with BSI-CRKP, especially for ST11-O2v1:KL64, exhibit lower leukomonocyte counts. In addition, BSI-Kpn co-harbored clpV-ybtQ-qacE is correlated to higher 30-day mortality.

[Exploring the Causal Relationship Between Coagulation Function and Gestational Diabetes Mellitus Through Mendelian Randomization]. / å­Ÿå¾·å°”éšæœºåŒ–æŽ¢ç´¢å‡è¡€åŠŸèƒ½ä¸Žå¦Šå¨ æœŸç³–å°¿ç— çš„å› æžœå ³ç³».

Objective: To explore the causal association between coagulation function, including von Willebrand factor (vWF), a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), activated partial thromboplastin time (aPTT), coagulation factor Ⅷ (FⅧ), coagulation factor Ⅺ (FⅪ), coagulation factor Ⅶ (FⅦ), coagulation factor Ⅹ (FⅩ), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), protein C, and plasmin, and gestational diabetes mellitus (GDM) using two-sample two-way Mendelian randomization (MR), and to provide genetic evidence for the association between coagulation function and the pathogenesis of GDM. Methods: The IEU OpenGWAS database was accessed using the R package TwoSampleMR (v 0.5.6) to obtain the statistical data of the genome-wide association study (GWAS) summary of GDM. MR analysis of the causal association between 11 coagulation function and GDM was performed by the inverse-variance weighted method (IVW), the MR-Egger method, and the weighted median method (WM). Results: In this study, the GWAS summary statistics of GDM (covering 5 687 cases and 117 892 controls) were used for MR analysis. It was found that there was a causal relationship between the predicted plasma FⅧ level and the risk for GDM (IVW: [odds ratio, OR]=0.28, 95% confidence interval [CI]: 0.10-0.75, P<0.001; WM: OR=0.30, 95% CI: 0.09-0.98, P<0.001). There was no causal relationship between other coagulation function and the risk for GDM (P>0.05). Conclusion: There is a significant causal relationship between the plasma FⅧ level and the risk for GDM. This finding highlights the complex interaction between coagulation function and glucose metabolism during pregnancy, but further research on this finding is warranted.

Molecular epidemiology and change trend of methicillin-resistant Staphylococcus aureus from invasive infections of a hospital in Hangzhou from 2012 to 2018.

The disease caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global public health challenge that threatens society and patients seriously. Therefore, the molecular epidemiology and change trend of MRSA is essential for the control and treatment of diseases caused by the pathogen in their regions. To explore molecular epidemiology of MRSA in Hangzhou, we collected 162 MRSA isolates from 2012 to 2018, conducted the antimicrobial susceptibility and used polymerase chain reaction(PCR) to test the molecular typing including multilocus sequence typing (MLST), staphylococcal chromosome cassette mec (SCCmec), staphylococcal protein A (spa A) and Panton-Valentine leucocidin (PVL). All the strains was divided into community-associated MRSA (CA-MRSA) or hospital-associated MRSA (HA-MRSA). 162 MRSA isolates were divided into 16 STs and 30 spa types. The major ST type was ST5 (96/162, 59.3%) and the predominant spa type was t311 (83/162, 51.2%). Five SCCmec types were found and the most common SCCmec type was type II (101/162, 61.7%). ST5-II-t311 was the predominant MRSA clone. And the prevalence of ST5 MRSA gradually declined from 2014 to 2018 but the prevalence of ST59 MRSA significantly increased. At the same time, livestock-associated methicillin-resistant Staphylococcus aureus(LA-MRSA) ST398 and ST9 were detected. Twenty-eight isolates were PVL gene positive (28/162, 17.3%). The most prevalent PVL-positive clone was ST59-IVa-t437. Comparing with HA-MRSA, CA-MRSA had a lower probability of ST5 (9.1% vs 67.1%, P=0.000) but a higher probability of ST59 (63.6% vs 11.4%, P=0.000), not only that, it was more likely to carrying PVL-positive gene (36.4% vs 14.3%, P=0.028). In summary, the molecular types of MRSA were getting complex over time. ST5-II-t311 was the predominant clone of MRSA isolate with a downward incidence from 2014 to 2018. ST59 MRSA strains, which is thought community related strain are spreading into hospitals and has an upward incidence from 2014 to 2018.

Seroprevalence and Risk Factors of Toxoplasma gondii Infection of Cattle and Goats in Farms of Hunan Province, China.

Background: Toxoplasmosis is one of the most widespread foodborne parasitic zoonoses caused by the obligate intracellular protozoan Toxoplasma gondii. Although a number of studies have reported on the seroprevalence and risk factors of T. gondii infection in ruminants in China, information about T. gondii infection in cattle in Hunan province of China is not available. Material and Methods: Sera of 985 cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using the indirect hemagglutination test. Some risk factors related to the presence of cats, herd size, gender, age, and geographical origin were determined using a binary logistic regression. Results: Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) of the cattle and goats, respectively. Based on statistical analysis, the presence of cats and gender were considered important risk factors for T. gondii infection in cattle and goats in the farms in this study (P < 0.05). Conclusion: Our results provide a baseline for future prevention and control of T. gondii infection in cattle and goats in Hunan province, subtropical China. This is the first report of T. gondii seroprevalence in cattle in Hunan province, China.

[Subjective and objective comparative analysis of nasal ventilation function before and after nasal septoplasty].

Objective:To investigate the changes of nasal ventilation before and after septoplasty by using NOSE scoring scale and nasal function examination, and to explore the correlation between subjective nasal obstruction and nasal function examination and its clinical application value. Methods:A total of 129 cases of nasal septum deviation from December 2021 to April 2023 in our hospital were selected for study. All patients underwent septoplasty. Nasal obstruction symptom evaluation（NOSE） was performed in all patients before surgery and 3 months after surgery. nasal minimal cross-sectional area（MCA） and nasal cavity volume（NCV） were recorded by nasal acoustic reflex, nasal resistance meter and nasal respiration apparatus, nasal resistance（NR）, distance between the nostril to minimum cross-sectional area,（the distance between the nostril to minimum cross-sectional area, MD）, nasal inspiratory volume（IV）, nasal expiratory volume（EV）, the nasal partitioning ratio, NPR includes objective indicators such as inspiratory volume difference ratio（NPRi） and expiratory volume difference ratio（NPRe）. Paired test was used to compare and analyze the changes of various indicators before and after surgery, and the difference（P<0.05） was statistically significant, and Pearson correlation linear analysis was used to analyze the correlation between subjective and objective indicators. Results:There were statistically significant differences in NOSE score, NCV, NR, MD, EV, IV, NPRe and NPRi of 129 patients before and after surgery（P<0.05）, while there was no statistically significant difference between MCA before and after surgery（P>0.05）. Preoperative NOSE score was correlated with NR, NCV, EV, IV, NPRe and NPRi（P<0.05）, but not with MD and MCA（P>0.05）. There was correlation between NOSE score and NR, MCA, NCV, EV, IV, NPRe and NPRi（P<0.05）, but no correlation between nose score and MD（P>0.05）. Conclusion:The subjective NOSE scale combined with nasal function test has certain clinical reference value in evaluating the surgical effect of patients with deviated nasal septum.

From apparent pseudoprogression to durable complete remission of expansile destructive sinonasal mucosal melanoma under pembrolizumab after primary endoscopic resection: A case report.

Head and neck mucosal melanoma is a rare but highly aggressive malignant tumor that usually has a poor prognosis. We describe a 53-year-old male patient, having no any medical history, with left maxillary sinus mucosal melanoma causing bilateral lung metastasis. Rapid tumor regrowth was observed on the 49th day after radical tumor resection. Subsequent pembrolizumab immunotherapy initially elicited pseudoprogression, for which add-on radiation therapy was carried out during maintenance pembrolizumab. A gradual decrease in tumor volume and complete remission were observed by a series of magnetic resonance imaging scans and lung windows of a computer tomography scan of chest. At the 29-month follow-up, the patient was rendered disease-free. In conclusion, head and neck mucosal melanoma may regrow rapidly after surgical resection and pseudoprogression could be frightening during immunotherapy. Subsequent single-agent pembrolizumab plus localized radiation therapy aiming to release more tumor antigens may offer the possibility of long-term remission.

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage. Wendan Decoction (WDD) is a traditional Chinese herbal formula used to treat various gastrointestinal disorders, such as gastritis, functional dyspepsia, and irritable bowel syndrome. Mosapride, a prokinetic agent, functions as a selective 5-hydroxytryptamine 4 agonist, enhancing gastrointestinal motility. AIM: To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery. METHODS: Eighty patients with GERD were randomly divided into treatment (receiving WDD combined with mosapride) and control (receiving mosapride alone) groups. The treatment was conducted from January 2021 to January 2023. The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire (RDQ). The secondary outcomes were improved esophageal motility (measured using esophageal manometry), gastric emptying (measured using gastric scintigraphy), and quality of life [measured via the Short Form-36 (SF-36) Health Survey]. RESULTS: The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters, such as lower esophageal sphincter pressure, peristaltic amplitude, and peristaltic velocity compared to the control group. The treatment group showed significantly higher gastric emptying rates and SF-36 scores (in both physical and mental domains) compared to the control group. No serious adverse effects were observed in either group. CONCLUSION: WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery. It can improve GERD symptoms, esophageal motility, gastric emptying, and the quality of life of patients. Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

Immune-related LncRNAs scores predicts chemotherapeutic responses and prognosis in cervical cancer patients.

BACKGROUND: Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients. METHODS: CC patients' relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm. RESULTS: Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746-0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine. CONCLUSIONS: An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.

A comparative study of two pelvimetry methods: 3D models based on CT and MRI.

INTRODUCTION AND HYPOTHESIS: To compare 3D models based on magnetic resonance imaging (MRI) and 3D models based on computed tomography (CT) in pelvimetry. METHODS: A retrospective analysis of 141 patients who underwent both pelvic 3D MRI and 3D CT pelvimetry for gynecological diseases from December 2009 to October 2020 was performed. The two pelvimetry methods were compared by paired Student's t test, Pearson's correlation coefficient, Bland-Altman analysis and intraclass correlation coefficient (ICC). RESULTS: The differences between methods for each diameter were statistically significant, except for those of the posterior sagittal diameter of the pelvic inlet (t:-0.71, P = 0.5) and the anteroposterior pelvic outlet diameter (t:0.02, P = 0.98). 3D MRI and 3D CT pelvimetry strongly correlated with each other (r: min 0.7, max: 0.96, P < 0.01). The Bland-Altman results indicate that the difference points of each pelvic diameter line greater than 95 % are within the 95 % limits of agreement. The ICC was good to very good for all pelvimetric measurements using either MRI-3D (ICC: 0.64-0.98) or CT-3D (ICC: 0.72-0.98) between the two readers. CONCLUSIONS: 3D MRI and 3D CT pelvimetry have good agreement and reproducibility, indicating that 3D MRI is reliable for pelvimetry.

Meta Learning with Attention Based FP-GNNs for Few-Shot Molecular Property Prediction.

Molecular property prediction holds significant importance in drug discovery, enabling the identification of biologically active compounds with favorable drug-like properties. However, the low data problem, arising from the scarcity of labeled data in drug discovery, poses a substantial obstacle for accurate predictions. To address this challenge, we introduce a novel architecture, AttFPGNN-MAML, for few-shot molecular property prediction. The proposed approach incorporates a hybrid feature representation to enrich molecular representations and model intermolecular relationships specific to the task. By leveraging ProtoMAML, a meta-learning strategy, our model is trained and adapted to new tasks. Evaluation on two few-shot data sets, MoleculeNet and FS-Mol, demonstrates our method's superior performance in three out of four tasks and across various support set sizes. These results convincingly validate the effectiveness of our method in the realm of few-shot molecular property prediction. The source code is publicly available at https://github.com/sanomics-lab/AttFPGNN-MAML.

Development and application of a machine learning-based predictive model for obstructive sleep apnea screening.

Objective: To develop a robust machine learning prediction model for the automatic screening and diagnosis of obstructive sleep apnea (OSA) using five advanced algorithms, namely Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Support Vector Machine (SVM), Light Gradient Boosting Machine (LightGBM), and Random Forest (RF) to provide substantial support for early clinical diagnosis and intervention. Methods: We conducted a retrospective analysis of clinical data from 439 patients who underwent polysomnography at the Affiliated Hospital of Xuzhou Medical University between October 2019 and October 2022. Predictor variables such as demographic information [age, sex, height, weight, body mass index (BMI)], medical history, and Epworth Sleepiness Scale (ESS) were used. Univariate analysis was used to identify variables with significant differences, and the dataset was then divided into training and validation sets in a 4:1 ratio. The training set was established to predict OSA severity grading. The validation set was used to assess model performance using the area under the curve (AUC). Additionally, a separate analysis was conducted, categorizing the normal population as one group and patients with moderate-to-severe OSA as another. The same univariate analysis was applied, and the dataset was divided into training and validation sets in a 4:1 ratio. The training set was used to build a prediction model for screening moderate-to-severe OSA, while the validation set was used to verify the model's performance. Results: Among the four groups, the LightGBM model outperformed others, with the top five feature importance rankings of ESS total score, BMI, sex, hypertension, and gastroesophageal reflux (GERD), where Age, ESS total score and BMI played the most significant roles. In the dichotomous model, RF is the best performer of the five models respectively. The top five ranked feature importance of the best-performing RF models were ESS total score, BMI, GERD, age and Dry mouth, with ESS total score and BMI being particularly pivotal. Conclusion: Machine learning-based prediction models for OSA disease grading and screening prove instrumental in the early identification of patients with moderate-to-severe OSA, revealing pertinent risk factors and facilitating timely interventions to counter pathological changes induced by OSA. Notably, ESS total score and BMI emerge as the most critical features for predicting OSA, emphasizing their significance in clinical assessments. The dataset will be publicly available on my Github.

Epidemiology and clinical features of Skin and Soft Tissue Infections Caused by PVL-Positive and PVL-Negative Methicillin-Resistant Staphylococcus aureus Isolates in inpatients in China: a single-center retrospective 7-year study.

Previous studies have mainly focused on outpatient cases of skin and soft tissue infections (SSTIs), with limited attention to inpatient occurrences. Thus, we aimed to compare the clinical parameters of inpatients with SSTIs, performed genomic characterization, and determined the subtypes of Panton-Valentine leucocidin (PVL) bacteriophages of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from these patients. We found that PVL-positive patients had shorter hospital stays (mean, 9 vs. 24 days; p < 0.001) and abscess resolution durations (mean, 8 vs. 13 days; p < 0.01). PVL-positive MRSA-induced SSTIs were more frequently associated with abscesses [36/55 (65.5%) vs. 15/124 (12.1%), p < 0.001], with 52.7% undergoing incision and drainage; over 80% of PVL-negative patients received incision, drainage, and antibiotics. In PVL-positive patients receiving empirical antibiotics, anti-staphylococcal agents such as vancomycin and linezolid were administered less frequently (32.7%, 18/55) than in PVL-negative patients (74.2%, 92/124), indicating that patients with PVL-positive SSTIs are more likely to require surgical drainage rather than antimicrobial treatment. We also found that the ST59 lineage was predominant, regardless of PVL status (41.3%, 74/179). Additionally, we investigated the linear structure of the lukSF-PV gene, revealing that major clusters were associated with specific STs, suggesting independent acquisition of PVL by different strain types and indicating that significant diversity was observed even within PVL-positive strains detected in the same facility. Overall, our study provides comprehensive insights into the clinical, genetic, and phage-related aspects of MRSA-induced SSTIs in hospitalized patients and contributes to a more profound understanding of the epidemiology and evolution of these pathogens in the Chinese population.

In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA.

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole's MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians.

Compound heterozygous B3GALNT2 mutations in a fetus with encephalocele: A case report.

An encephalocele is a congenital malformation characterized by protrusion of the intracranial contents through a cranial defect. We report that a fetus of a pregnant mother who had two consecutive pregnancies with ultrasound-detected encephalocele carried compound heterozygous variants in B3GALNT2 NM_152490.5:c.[1423C > T (p.Gln475Ter)]; [261-2A > G] of maternal and paternal origins, respectively, as confirmed by exome sequencing followed by Sanger sequencing validation. The present case implies that mutations in B3GALNT2, a well-known dystroglycanopathy causative gene, may result in a phenotype of neural tube defect, providing new insights into the clinical spectrum of B3GALNT2-related disorders. Our study may contribute to prenatal screening/diagnosis and genetic counseling of congenital brain malformations.

Characteristics of Immunocytes and Cytokines in Patients with Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae in China.

Objective: To evaluate the characteristics of immunocytes and cytokines associated with bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: Patients with BSIs K. pneumoniae (BSIs-Kpn) were enrolled in our hospital between 2015 and 2022. Whole blood and serum samples were collected on the first day after diagnosis. Immunocytes and cytokines profiles were assessed using multicolor flow cytometry and multiplex immunoassays, respectively. The test cytokines included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A. Results: A total of 313 patients had BSIs-Kpn, including 145 with CRKP, 43 with extended-spectrum ß-lactamases (ESBL) producing Kpn (ESBL-Kpn) and 125 with non-CRKP or non-ESBL-Kpn (susceptible Kpn, S-Kpn). Absolute number of leukomonocyte (CD45+) in CRKP, ESBL-Kpn and S-Kpn were 280.0 (138.0-523.0) cells/µL, 354.5 (150.3-737.3) cells/µL, and 637.0 (245.0-996.5) cells/µL, respectively. Compared with S-Kpn group, the absolute numbers of leukomonocyte (including T lymphocytes, B lymphocytes and natural killer cells) in patients with CRKP were significantly lower than that in patients with S-Kpn (P < 0.01). The levels of cytokines IL-2 and IL-17A were significantly higher in patients with S-Kpn than in those patients with CRKP (P<0.05). The area under receiver operating curve (AUC) of IL-2, IL-4, and IL-17A for S-Kpn was 0.576, 0.513, and 0.561, respectively, whereas that for the combination of these three cytokines with immunocytes was 0.804. Conclusion: Patients with BSIs-CRKP had lower leukomonocyte counts. High levels of IL-2 and IL-17A combined with immunocyte subpopulations showed relatively high diagnostic value for BSIs-S-Kpn from BSIs-CRKP.

Risk evaluation for diabetic retinopathy in Chinese renal-biopsied type 2 diabetes mellitus patients.

AIM: To investigate diabetic retinopathy (DR) prevalence in Chinese renal-biopsied type 2 diabetes mellitus (T2DM) patients with kidney dysfunction, and to further evaluate its relationship with diabetic nephropathy (DN) incidence and the risk factors for DR development in this population. METHODS: A total of 84 renal-biopsied T2DM patients were included. Fundus and imaging examinations were employed for DR diagnosis. Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups. Risk factors on DR development were analyzed with multiple logistic regression. RESULTS: DR prevalence was 50% in total. The incidences of DN, non-diabetic renal disease (NDRD) and mixed-type pathology were 47.6%, 19.0% and 33.3% in the DR group respectively, while 11.9%, 83.3% and 4.8% in the non-DR group. Systolic blood pressure, ratio of urinary albumin to creatine ratio, urinary albumin, 24-hours urinary protein, the incidence and severity of DN histopathology were found statistically increased in the DR group. Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development [odds ratio (OR)=21.664, 95% confidential interval (CI) 5.588 to 83.991, P<0.001 for DN, and OR=45.475, 95%CI 6.949 to 297.611, P<0.001 for mixed-type, respectively, in reference to NDRD)], wherein DN severity positively correlated. CONCLUSION: Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

RNA polymerase stalling-derived genome instability underlies ribosomal antibiotic efficacy and resistance evolution.

Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here, we find that a broad range of ribosome-targeting antibiotics cause mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we find that the translation inhibitor causes genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis shows that the stalling is caused by the disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induce lesions to the DNA via transcription-coupled repair. While most of the bacteria are killed by genotoxicity, a small subpopulation acquires mutations via SOS-induced mutagenesis. Given that these processes are triggered shortly after antibiotic addition, resistance rapidly emerges in the population. Our work reveals a mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance.

Prolonged Disease Course Leads to Impaired Brain Function in Anxiety Disorder: A Resting State EEG Study.

Objective: Anxiety disorder (AD) is a common disabling disease. The prolonged disease course may lead to impaired cognitive performance, brain function, and a bad prognosis. Few studies have examined the effect of disease course on brain function by electroencephalogram (EEG). Methods: Resting-state EEG analysis was performed in 34 AD patients. The 34 patients with AD were divided into two groups according to the duration of their illness: anxious state (AS) and generalized anxiety disorder (GAD). Then, EEG features, including univariate power spectral density (PSD), fuzzy entropy (FE), and multivariable functional connectivity (FC), were extracted and compared between AS and GAD. These features were evaluated by three previously validated machine learning methods to test the accuracy of classification in AS and GAD. Results: Significant decreased PSD and FE in GAD were detected compared with AS, especially in the Alpha 2 band. In addition, FC analysis indicated that GAD patients' connection between the left and right hemispheres decreased. Based on machine learning, AS and GAD are classified on a six-month criterion with the highest classification accuracy of up to 0.99 ± 0.0015. Conclusion: The brain function of patients is more severely impaired in AD patients with longer illness duration. Resting-state EEG demonstrated to be a promising examination in the classification in GAD and AS using machine learning methods with better classification accuracy.