Cerebrospinal fluid metabolomic and proteomic characterization of neurologic post-acute sequelae of SARS-CoV-2 infection.

The mechanism by which SARS-CoV-2 causes neurological post-acute sequelae of SARS-CoV-2 (neuro-PASC) remains unclear. Herein, we conducted proteomic and metabolomic analyses of cerebrospinal fluid (CSF) samples from 21 neuro-PASC patients, 45 healthy volunteers, and 26 inflammatory neurological diseases patients. Our data showed 69 differentially expressed metabolites and six differentially expressed proteins between neuro-PASC patients and healthy individuals. Elevated sphinganine and ST1A1, sphingolipid metabolism disorder, and attenuated inflammatory responses may contribute to the occurrence of neuro-PASC, whereas decreased levels of 7,8-dihydropterin and activation of steroid hormone biosynthesis may play a role in the repair process. Additionally, a biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 was preliminarily demonstrated to have high value in diagnosing neuro-PASC. In summary, our study represents the first attempt to integrate the diagnostic benefits of CSF with the methodological advantages of multi-omics, thereby offering valuable insights into the pathogenesis of neuro-PASC and facilitating the work of neuroscientists in disclosing different neurological dimensions associated with COVID-19.

A novel and simple method yields highly dispersed Au/TS-1 catalysts for enhanced propylene hydro-oxidation.

We demonstrate a simple method for preparing highly active Au/TS-1 catalysts for propylene hydro-oxidation, which involves sequentially impregnating HAuCl4 and Cs2CO3 solutions onto TS-1. The Au/TS-1 catalysts synthesized by this method exhibit high Au uptake efficiency (∼100%), high dispersion of Au nanoparticles and superior activity.

Genomic Characterization of Escherichia coli Co-Producing KPC-2 and NDM-5 Carbapenemases Isolated from Intensive Care Unit in a Chinese Hospital.

Background: Around the world, carbapenemase-producing Escherichia coli is becoming more prevalent. The purpose of this research was to analyze the whole plasmid sequences from YL03 isolates of the E. coli strain that produce both KPC-2 and NDM-5 carbapenemases. Materials and Methods: Whole-genome sequencing (WGS) and analysis of E. coli strain YL03, which was isolated from a wound sample, was performed by Illumina Novaseq 6000 and Pacific Biosciences Sequel (PacBio, Menlo Park, CA) sequencers. Following that, the WGS results were used to predict and analyze the YL03 genome composition and function. A complete gene sequence for YL03 with the accession number CP093551 has been uploaded to GenBank. Results: The results showed that YL03 co-carried five resistance genes, which included blaKPC-2, blaNDM-5, blaTEM-1B, blaCTX-M-14, and mdf(A). Furthermore, three resistance plasmids were found in YL03: pYL03-KPC, pYL03-NDM, and pYL03-CTX. Among them, the 53 kb-long pYL03-KPC plasmid belonging to the IncP, carried the replicase gene (repA) and the carbapenemase gene (blaKPC-2). The blaKPC-2 gene was flanked by a composite transposon-like element (Tn3-[Tn3] tnpR-ISKpn27 blaKPC--ISKpn6). Conclusions: The YL03 strain co-carried blaKPC-2 and blaNDM-5 and had a unique multidrug resistance plasmid containing blaKPC-2.

Acrolein-triggered atherosclerosis via AMPK/SIRT1-CLOCK/BMAL1 pathway and a protection from intermittent fasting.

Circadian clock plays a vital role in the pathological progression of cardiovascular disease (CVD). Our previous studies showed that acrolein, an environmental pollutant, promoted atherosclerosis by reducing CLOCK/BMAL1 and disturbing circadian rhythm. Whereas, intermittent fasting (IF), a diet pattern, was able to ameliorate acrolein-induced atherosclerosis. In vivo, mice were fed acrolein 3 mg/kg/day via drinking water and IF for 18h (0:00-18:00). We observed that IF decreased acrolein-accelerated the formation of aortic lesion in ApoE -/- mice. Up-regulation of NF-κB, IL-1ß and TNF-α levels were found in liver and heart tissue upon acrolein exposure, while was down-regulated by IF. Interestingly, IF treatment exhibited higher AMPK, p-AMPK and SIRT1and lower MAPK expression which was caused by acrolein. Besides, circadian genes Clock/ Bmal1 expression were suppressed and disturbed treated with acrolein, while were reversed by IF. Furthermore, consistent with that in vivo, short-term starvation as a fasting cell model in vitro could improve the disorders of CLOCK/BMAL1 and raised SIRT1 via regulating AMPK, as well as ROS-MAPK induced by acrolein. In conclusion, we demonstrated that IF repressed ROS-MAPK while activated AMPK to elevate the expression of circadian clock genes to ameliorate acrolein-induced atherogenesis, which shed a novel light to prevent cardiovascular diseases.

Global emergence of double and multi-carbapenemase producing organisms: epidemiology, clinical significance, and evolutionary benefits on antimicrobial resistance and virulence.

Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are Klebsiella pneumoniae and Acinetobacter baumannii, which exhibit varying proportions of carbapenemase combinations. Certain species-carbapenemase combinations, such as K. pneumoniae carrying New Delhi metallo-ß-lactamase (NDM) + oxacillinase (OXA) (56.76%) and K. pneumoniae carbapenemase (KPC) + Verona integron-encoded metallo-ß-lactamase (VIM) (50.00%) carbapenemases, are associated with high mortality rates. In patients with RCP strains isolated from the bloodstream and respiratory system, the mortality rates are 58.70% and 69.23%, respectively. Analysis of plasmids from RCP strains suggests that they may acquire additional antibiotic resistance phenotypes and virulence factors. Carbapenem-resistant bacteria carrying redundant carbapenemases pose a significant global health threat. This study provides valuable insights into the epidemiology and genetic mechanisms of these bacteria, supporting the development of effective control and prevention strategies to mitigate their transmission.IMPORTANCEThis study examined the global distribution patterns of 1,780 bacteria with double or multiple carbapenemases from 277 articles and assessed their clinical impact. The presence of multiple carbapenemases increases the chances of co-resistance to other classes of antibiotics and more virulence factors, further complicating the clinical management of infections.

Unhealthy diets increase the likelihood of being overweight or obese among African migrant students in China, but not among African non-migrant students: a cross-sectional study.

Background: The impact of non-communicable diseases (NCDs) is disproportionately felt by immigrants from low- to medium-income countries (LMICs), partly due to their dietary habits. To thrive in their new environment, migrants either omit or consume certain food items, which could lead to nutritional deficits. As a result, most migrants experience more NCDs than their compatriots in their native countries. Therefore, we evaluated the difference in dietary habits, quality, and the influencing factors of overweight or obesity among African migrant students in Nanjing (China) and non-migrant students in Africa using cross-sectional data. Methods: The researchers used the food frequency questionnaire and the global diet quality score metrics to assess food intake and quality, respectively. Then, cross-tabulation was employed to explore the differences between the groups in meal skipping, eating habits, and diet quality. Finally, the factors associated with overweight or obesity were assessed with binary logistic regression stratified by African students in Nanjing and students in their native countries. Results: Approximately 678 responses were received, mainly between 18-25 years (46.7%) and 26-36 years (45.4 %). The majority of them (52.3%) were international students. The non-migrant African students' diets lacked citrus fruits (22.2%), deep orange fruits (15.4%), deep orange vegetables (18%), cruciferous vegetables (24.6%), and dark leafy vegetables (26.5%). While the African migrant students consumed more high-fat dairy (50.7%), processed meats (23.9%), sweets and ice creams (51.3%), sugar-sweetened beverages (40.5%), and juice (61.5%), p < 0.001. Furthermore, consuming late-night meals constantly [Exp (B) = 39.607, p = 0.049], eating twice a day [Exp (B) = 6.527, p = 0.036], consuming red meat [Exp (B) = 29.287, p = 0.001], processed meats [Exp (B) = 719.979, p = 0.0011], refined grains and baked foods [Exp (B) = 15.752, p = 0.013], and sweets and ice cream [Exp (B) = 193.633, p = 0.006] were factors inducing overweight or obesity among only African migrant students. Conclusion: Controlling the what (Western diet and nature of late-night meals) and the when of eating can drastically reduce their influence on obesogenic condition formation in African migrant students in China and elsewhere.

Clinical characteristics and risk factors of in-hospital mortality in patients coinfected with Pneumocystis jirovecii and Aspergillus.

OBJECTIVE: To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus. METHODS: This study included 53 patients with coinfection of P. jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) in our center from January 2011 to December 2021. All cases were divided into survivor (n=27) and non-survivor groups (n=26). Medical records, laboratory and radiology data were collected. Risk factors for in-hospital mortality were identified by multivariable analyses. RESULTS: HIV-positive patients accounted for 3.8%. Fever (77.4%), dyspnea (69.8%) and wet cough (24.5%) were common symptoms. Ground-glass opacity (83.0%), consolidation (71.7%), septal thickening (66.0%), and nodules (54.7%) were the most common radiological signs. CD4+ T cell count and serum albumin (ALB) level were significantly lower in non-survival group than in the survival group. Conversely, serum lactate dehydrogenase (LDH) and procalcitonin (PCT) levels were higher in non-survival group than in survival group. Lactic acidosis [odds ratio (OR): 33.999,95% confidential interval (CI): 3.112-371.409; p=0.004], low CD4+ T cell count (<114 cell/µL) [OR: 19.343, 95% CI: 1.533-259.380; p=0.022] and high level of LDH (> 519 U/L) [OR: 11.422, 95% CI: 1.271-102.669; p=0.030] were independent risk factors for mortality. CONCLUSION: PJP coinfected with IPA incurs high mortality with nonspecific clinical characteristics and is more likely to involve HIV-negative patients. Lactic acidosis, low CD4+ T cell count and high LDH level are independent risk factors for mortality, close monitoring of these parameters is necessary to help distinguish high-risk patients and make appropriate clinical decisions.

Diagnostic accuracy of interleukin-2 receptor in sarcoidosis: a systematic review and meta-analysis.

INTRODUCTION: Soluble interleukin-2 receptor (sIL-2 R), a valuable diagnostic biomarker for sarcoidosis, has been reported with variable results. Based on the literatures currently accessible, a systematic review and meta-analysis of the diagnostic performance of serum sIL-2 R for sarcoidosis were performed. METHODS: Relevant studies investigating sIL-2 R for sarcoidosis diagnosis in several databases were searched and data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled by STATA 16.0 software. Overall test performance was assessed using summary receiver operating characteristic curves and the area under the curve (AUC). Potential publication bias was assessed by Deeks test. RESULTS: We included eleven studies involving 1,424 subjects, with 1,099 cases of sarcoidosis and 325 of non-sarcoidosis. The pooled parameters of sIL-2 R in diagnosing sarcoidosis were summarized as follows: sensitivity, 0.85 (95% CI: 0.72-0.93); specificity, 0.88 (95% CI: 0.72-0.96); PLR, 7.3 (95% CI: 2.7-20.1); NLR, 0.17 (95% CI:0.08-0.36); DOR, 44 (95% CI: 8-231); and the AUC, 0.93 (95% CI: 0.90-0.95). No publication bias was identified (P = 0.64). CONCLUSIONS: Evidence suggests sIL-2 R performs well in diagnosing sarcoidosis. Nevertheless, results of sIL-2 R assay should be interpreted with other diagnostic examinations.

Glucose restriction induces AMPK-SIRT1-mediated circadian clock gene Per expression and delays NSCLC progression.

The rhythmic expression of the circadian clock is intimately linked to the health status of the body. Disturbed circadian clock rhythms might lead to a wide range of metabolic diseases and even cancers. Our previous study showed that glucose restriction was able to inhibit non-small cell lung cancer (NSCLC). In the current study, we found that glucose restriction enhanced apoptosis and cell growth delay in NSCLC cells. In addition, we used GEPIA database analysis to derive different effects of each circadian clock gene on lung cancer tissue. Among these circadian clock genes, Per (Period) is lowly expressed in cancer tissues and highly expressed in normal tissues. Moreover, the higher expression of Per in cancer patients has a better prognostic significance. Furthermore, we revealed that glucose restriction induced the expression of the circadian clock gene Per in NSCLC cells by upregulating SIRT1 (Sirtuin1) via activation of the energy response factor AMPK (AMP-activated protein kinase). Changes in Per expression following upregulation or downregulation of AMPK were consistent with AMPK expression. Additionally, a low-carbohydrate ketogenic diet significantly delayed tumor progression in a xenograft tumor model of severe combined immunodeficiency (SCID) mice. Meanwhile, the ketogenic diet increased the expression of AMPK, SIRT1 and Per in vivo. Besides, the ketogenic diet was found to restore the normal rhythmic level of Per by Zeitgeber Time (ZT) experiments. Taken these together, these results indicated a novel mechanism that glucose restriction induces AMPK-SIRT1 mediated circadian clock gene Per expression and delays NSCLC progression, which provided more evidence for glucose restriction as an adjuvant clinical therapeutic strategy in NSCLC.

Healthy eating habits and a prudent dietary pattern improve Nanjing international students' health-related quality of life.

Purpose: Low-quality dietary practices, such as fast food consumption and skipping meals, deteriorate the quality of life. However, the available studies on diet and health-related quality of life (HRQoL) used matrices not specific to nutrition. Moreover, how diet affects the HRQoL of international students in China is unknown. Therefore, using a cross-sectional study, the effect of dietary patterns and habits on the HRQoL of international students in Nanjing, China, was examined. Methods: The researchers collected dietary data using a food frequency questionnaire (FFQ) from February to March 2022. Then, the Food Benefit Assessment (FBA) was used to access HRQoL. Finally, the effect of eating habits and dietary patterns on HRQoL was explored using multilinear regression. Results: Approximately 454 responses were obtained, with the responses mostly from male subjects (56.4%) and those aged 26 years and above (75.6%). The quality of life according to the food consumed was about average for all the constructs except for aesthetics and disease prevention, as 65.8% skipped meals, particularly breakfast (47.8%). Furthermore, three dietary patterns were identified: prudent, Western, and animal protein patterns. Consequently, by skipping breakfast, vitality (ß = -2.362, p = 0.04), wellbeing (ß = -3.592, p = 0.007), digestive comfort (ß = -4.734, p = 0.008), and disease prevention (ß = -5.071, p = 0.031) were all reduced. However, consuming at least three meals daily enhanced vitality (ß = 2.254, p = 0.003) and disease prevention (ß = 4.441, p = 0.019). Furthermore, aesthetics (ß = 4.456, p = 0.05), physical appearance (ß = 5.927, p = 0.003), and vitality (ß = 3.323, p = 0.009) were also significantly increased by healthy dietary patterns. However, a more Westernized diet led to frequent snacking (ß = -4.631, p = 0.032), a decline in wellbeing (ß = -5.370, p < 0.001), and discomfort with digestion (ß = -5.101, p = 0.01). Finally, increased frequency of snacking (ß = -6.036, p = 0.012), a decrease in wellbeing (ß = -4.494, p = 0.004), digestive comfort (ß = -9.940, p < 0.001), physical appearance (ß = -4.926, p = 0.027), and disease prevention (ß = -5.835, p = 0.043) were all associated with an increase in animal protein patterns. Conclusion: This research indicates that healthy eating habits and patterns positively impact international students' HRQoL. Therefore, the appropriate authorities should advise students to consume healthy foods regularly to improve their HRQoL.

Langerhans Cell Histiocytosis Involving the Thymus and Heart With Simultaneous Thymoma: A Case Report.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a+/CD207+ cells in lesions. The most frequent sites involved are bone and, less commonly, lymph nodes, lungs, and skin. The thymus or heart is rarely involved with LCH. In this case, we present a 73-year-old woman with a mediastinal mass. Histopathology after thymectomy identified this mass as type AB thymoma; notably, subsequent immunohistochemical tests showed lesions of LCH scattered in the region of thymoma. 18-Fluorodeoxyglucose PET/CT (18-FDG-PET/CT) was performed to make an overall assessment of the extent of this disease, which demonstrated suspicious cardiac involvement of LCH. This report highlights the importance of differentiating abnormalities of the thymus or mediastinal mass from LCH and the necessity of comprehensive evaluation for patients with LCH.

Case Report: A Novel Point Mutation of SOX3 in a Subject With Growth Hormone Deficiency, Hypogonadotrophic Hypogonadism, and Borderline Intellectual Disability.

SOX3 is critical for the development of the pituitary, brain, and face, and SOX3 mutations may lead to hypopituitarism, intellectual disability, and craniofacial abnormalities. Common SOX3 mutations are duplications and deletions of the whole or part of SOX3, yet only a few cases with point mutations were reported by far. We present a case with growth retardation, small penis, and learning difficulty. Further assessment confirmed growth hormone deficiency, hypogonadotropic hypogonadism (HH), and borderline intellectual disability. He also responded well to gonadotropin-releasing hormone stimulation test, which suggests defects in the hypothalamus, contrary to previous studies that reported defects in the pituitary. A pathogenic frame-shift mutation of SOX3 was found. A heterogeneous missense mutation in SEMA3A was identified in this patient as well, which may also contribute to the development of HH. As far as we know, this is the first report that a frame-shift mutation of SOX3 constitutes rare genetic causes of HH and growth hormone deficiency. Whether mutations in these two genes act synergistically in the pathogenesis of the patient's phenotype remains to be further investigated. We believe that our case extends the phenotypic spectrum and genetic variability of SOX3 mutation.

Occurrence of Serratia marcescens Carrying blaIMP-26 and mcr-9 in Southern China: New Insights in the Evolution of Megaplasmid IMP-26.

The spread of multidrug-resistant enterobacteria strains has posed a significant concern in public health, especially when the strain harbors metallo-beta-lactamase (MBL)-encoding and mobilized colistin resistance (mcr) genes as such genetic components potentially mediate multidrug resistance. Here we report an IncHI2/2A plasmid carrying blaIMP-26 and mcr-9 in multidrug-resistant Serratia marcescens human isolates YL4. Antimicrobial susceptibility testing was performed by the broth microdilution method. According to the results, S. marcescens YL4 was resistant to several antimicrobials, including ß-lactams, fluorquinolones, sulfanilamide, glycylcycline, and aminoglycosides, except for amikacin. To investigate the plasmid further, we conducted whole-genome sequencing and sequence analysis. As shown, S. marcescens YL4 possessed a circular chromosome with 5,171,477 bp length and two plasmids, pYL4.1 (321,744 bp) and pYL4.2 (46,771 bp). Importantly, sharing high similarity with plasmids pZHZJ1 and pIMP-26, pYL4.1 has an IncHI2/2A backbone holding a variable region containing blaIMP-26, mcr-9, and two copies of blaTEM-1B. After comprehensively comparing relevant plasmids, we proposed an evolutionary pathway originating from ancestor pZHZJ1. Then, via an acquisition of the mcr-9 element and a few recombination events, this plasmid eventually evolved into pYL4.1 and pIMP-26 through two different pathways. In addition, the phage-like plasmid pYL4.2 also carried a blaTEM-1B gene. Remarkably, this study first identified a multidrug-resistant S. marcescens strain co-harboring blaIMP-26 and mcr-9 on a megaplasmid pYL4.1 and also included a proposed evolutionary pathway of epidemic megaplasmids carrying blaIMP-26.

Blockage of CD72 reduces B cell proliferation in immune thrombocytopenic purpura, involving interleukin 1 and macrophage migration inhibitory factor secretion.

AIM: This study aims to explore the expression and role of CD72 in B lymphocytes in immune thrombocytopenic purpura (ITP). METHODS: The expression level of CD72 in B lymphocytes was detected by flow cytometry in 18 ITP patients and 19 controls of healthy donor or iron-deficiency anemia patients. B cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation (BrdU) in the culture of 17 ITP patients' and 11 controls' peripheral mononuclear cells (PMNCs). The secretion levels of antibodies against human platelet antigens (HPA), as well as B cell proliferation-related cytokine interleukin 1(IL-1) and macrophage migration inhibitory factor (MIF) in culture supernatants were measured by ELISA. RESULTS: CD72 was significantly increased in B cells of newly diagnosed or persistent ITP compared with ITP in remission. B cell proliferation in culture with CD72 antibody addition was significantly decreased both in ITP patients and in controls compared with isotype antibody addition. CD72 antibody did not significantly alter HPA antibody level in ITP patients. CD72 antibody increased IL-1 and MIF levels in ITP patients' cell culture supernatant but not in controls. CONCLUSION: CD72 expression elevation accompanies the active status of ITP. In vitro addition of CD72 antibody has a negative impact on B cell proliferation. The function of CD72 in B cell proliferation in ITP may be related to IL-1 and MIF secretion.

mTOR participates in the formation, maintenance, and function of memory CD8+T cells regulated by glycometabolism.

Memory CD8+T cells participate in the fight against infection and tumorigenesis as well as in autoimmune disease progression because of their efficient and rapid immune response, long-term survival, and continuous differentiation. At each stage of their formation, maintenance, and function, the cell metabolism must be adjusted to match the functional requirements of the specific stage. Notably, enhanced glycolytic metabolism can generate sufficient levels of adenosine triphosphate (ATP) to form memory CD8+T cells, countering the view that glycolysis prevents the formation of memory CD8+T cells. This review focuses on how glycometabolism regulates memory CD8+T cells and highlights the key mechanisms through which the mammalian target of rapamycin (mTOR) signaling pathway affects memory CD8+T cell formation, maintenance, and function by regulating glycometabolism. In addition, different subpopulations of memory CD8+T cells exhibit different metabolic flexibility during their formation, survival, and functional stages, during which the energy metabolism may be critical. These findings which may explain why enhanced glycolytic metabolism can give rise to memory CD8+T cells. Modulating the metabolism of memory CD8+T cells to influence specific cell fates may be useful for disease treatment.

Proteomics profiling of ertapenem challenged major porin deficient carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent threat to human health. Major outer membrane proteins (OMPs) porin mutation is one important resistance mechanism of CRKP, and may also affect the inhibition activity of ß-lactam and ß-lactamase inhibitor combinations. The ertapenem-resistant K. pneumoniae strain 2018B120 with major porin mutations was isolated from a clinical patient. Genomic and time-series proteomic analyses were conducted to retrieve the ertapenem-challenged response of 2018B120. The abundance changing of proteins from PTS systems,  ABC transporters, the autoinducer 2 (AI-2) quorum sensing system, and antioxidant systems can be observed. Overexpression of alternative porins was also noticed to balance major porins' defection. These findings added a detailed regulation network in bacterial resistance mechanisms and gave new insights into bypass adaptation mechanisms the porin deficient bacteria adopted under carbapenem antibiotics pressure. SIGNIFICANCE: Outer membrane porins deficiency is an important mechanism of carbapenem resistance in K. pneumoniae. Comprehensive genomic and proteomic profiling of an ertapenem-resistant K. pneumoniae strain 2018B120 gives a detailed systematic regulation network in bacterial resistance mechanisms. Overexpression of alternative porins to balance major porins' defection was noticed, giving new insights into bypass adaptation mechanisms of porin deficient bacteria.

Pan-Genome Analysis of Laribacter hongkongensis: Virulence Gene Profiles, Carbohydrate-Active Enzyme Prediction, and Antimicrobial Resistance Characterization.

Laribacter hongkongensis is a new emerging foodborne pathogen that causes community-acquired gastroenteritis and traveler's diarrhea. However, the genetic features of L. hongkongensis have not yet been properly understood. A total of 45 aquatic animal-associated L. hongkongensis strains isolated from intestinal specimens of frogs and grass carps were subjected to whole-genome sequencing (WGS), along with the genome data of 4 reported human clinical strains, the analysis of virulence genes, carbohydrate-active enzymes, and antimicrobial resistance (AMR) determinants were carried out for comprehensively understanding of this new foodborne pathogen. Human clinical strains were genetically more related to some strains from frogs inferred from phylogenetic trees. The distribution of virulence genes and carbohydrate-active enzymes exhibited different patterns among strains of different sources, reflecting their adaption to different host environments and indicating different potentials to infect humans. Thirty-two AMR genes were detected, susceptibility to 18 clinical used antibiotics including aminoglycoside, chloramphenicol, trimethoprim, and sulfa was checked to evaluate the availability of clinical medicines. Resistance to Rifampicin, Cefazolin, ceftazidime, Ampicillin, and ceftriaxone is prevalent in most strains, resistance to tetracycline, trimethoprim-sulfamethoxazole, ciprofloxacin, and levofloxacin are aggregated in nearly half of frog-derived strains, suggesting that drug resistance of frog-derived strains is more serious, and clinical treatment for L. hongkongensis infection should be more cautious.

Analysis and Study on Epidemiological Features and Prognosis of Nephrotic Syndrome in Xinjiang and Heilongjiang.

BACKGROUNDS: The pathogenesis of nephrotic syndrome (NS) is complex, and there are differences between regions. This study attempted to collect clinicopathological data of patients diagnosed with NS in Xinjiang and Heilongjiang in the past 2 years, so as to explore the onset features of NS and treatment and prognosis of patients in the two regions. METHODS: Clinical data of 375 patients diagnosed with NS using renal biopsy in Xinjiang and Heilongjiang from March 2019 to March 2021 were collected. Clinical data of patients before treatment were collected, and the chi-square test was utilized to compare the differences in the sex distribution of two groups. The U test was utilized to compare abnormal distribution continuous data between two groups, such as age, hemoglobin, plasma albumin, proteinuria, and triglycerides. Independent sample t-test was utilized to compare normal distribution continuous data between two groups, such as serum total protein, serum creatinine, blood urea nitrogen, glomerular filtration rate, and total cholesterol. The independent sample t-test was also used to compare the immunoglobulin levels and complement levels between the two groups after treatment, including IgA, IgG, IgM, C3, and C4. Kaplan-Meier method was used to analyze and plot the cumulative curves of complete remission rate and partial remission rate. RESULTS: For 275 NS patients from Xinjiang, the male-to-female ratio was 0.81 : 1. For 84 patients from Heilongjiang, the male-to-female ratio was 1.05 : 1. The onset ages of patients in Xinjiang and Heilongjiang were 22-45 years old and 22-47 years old, respectively. Respectively, there were 221 cases (80.36%) and 66 cases (78.57%) of primary NS in Xinjiang and Heilongjiang. There were 54 cases (19.64%) and 18 cases (21.43%) of secondary NS in Xinjiang and Heilongjiang, respectively. There was no statistically significant difference in cause distribution between the two regions (p = 0.756). After treatment, immunoglobulin levels (IgA (p = 0.009), IgG (p = 0.002), IgM (p < 0.001)) and complement C3 (p < 0.001) and C4 (p < 0.001) levels in Xinjiang and Heilongjiang were statistically significant. 129 cases in Xinjiang (46.91%) and 55 cases in Heilongjiang (65.48%) were treated with glucocorticoid (GC) combined with immunosuppressive therapy, respectively. After receiving treatment, 67 (24.36%) of 275 patients in Xinjiang achieved complete remission, 166 (60.36%) achieved partial remission, 22 (26.19%) of 84 patients in Heilongjiang achieved complete remission, and 56 (66.67%) achieved partial remission, and there was no statistically significant difference in remission rate between the two regions (p = 0.159). Patients in Xinjiang and Heilongjiang achieved complete remission at an average of 10.34 weeks (9.98-10.70) and 9.95 weeks (9.26-10.65), respectively. There was no significant difference in complete remission rates between the two regions (p = 0.663). Patients in Xinjiang and Heilongjiang achieved partial remission at an average of 8.76 weeks (8.38-9.14) and 7.99 weeks (7.33-8.65), respectively. There was no significant difference in the partial remission rate between the two regions (p = 0.065). CONCLUSION: The causes of NS in Xinjiang and Heilongjiang were similar. After treatment, there were differences in immunoglobulin levels (IgA, IgG, IgM) and complement levels (C3, C4) in the two regions. The main treatment methods used in the two regions were GC combined with immunosuppressive therapy. The prognosis of patients in the two regions was similar. The complete remission rate and partial remission rate after treatment in the two regions were similar, and the average time required to achieve complete remission and partial remission was also similar.