Trends and Prospects of Genetic and Molecular Research in Plants.

With the exponential advancements in biotechnology research, various studies are being conducted to overcome productivity limitations in crop breeding [...].

The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.

Streamlined measurement of chimeric antigen receptor T-cell concentration, size, viability and two-color phenotyping during manufacturing.

BACKGROUND AIMS: The successful development of CD19-targeted chimeric antigen receptor (CAR) T-cell therapies has led to an exponential increase in the number of patients recieving treatment and the advancement of novel CAR T products. Therefore, there is a strong need to develop streamlined platforms that allow rapid, cost-effective, and accurate measurement of the key characteristics of CAR T cells during manufacturing (i.e., cell number, cell size, viability, and basic phenotype). METHODS: In this study, we compared the novel benchtop cell analyzer Moxi GO II (ORFLO Technologies), which enables simultaneous evaluation of all the aforementioned parameters, with current gold standards in the field: the Multisizer Coulter Counter (cell counter) and the BD LSRFortessa (flow cytometer). RESULTS: Our results demonstrated that the Moxi GO II can accurately measure cell number and cell size (i.e., cell volume) while simultaneously assessing simple two-color flow cytometry parameters, such as CAR T-cell viability and CD4 or CAR expression. CONCLUSIONS: These measurements are comparable with those of gold standard instruments, demonstrating that the Moxi GO II is a promising platform for quickly monitoring CAR T-cell growth and phenotype in research-grade and clinical samples.

Effectiveness of whole-body vibration in patients with cerebral palsy: A systematic review and meta-analysis.

BACKGROUND: This study examined the effects of systemic vibration exercises on cerebral palsy patients. METHODS: Literature published in Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane library, Embase, Physiotherapy Evidence Database (PEDro), and PubMed was reviewed. A total of 2978 studies were initially retrieved. After further reading of the full texts 17 articles were finally included. A quality assessment of the included studies was conducted using the risk of bias (RoB) 2.0, and the Funnel plot and the Egger test were conducted to confirm the publication bias. Subgroup analysis was carried out according to the dependent variables, the international classification of functioning, disability, and health (ICF), frequency, treatment period and age. RESULTS: The overall effect size of homogeneity was 0.474 (CI = 0.148-0.801). The analysis of the dependent variables showed the following order of the effect size: balance, muscle strength, spasticity, bone density, range of motion of the joint, gait function, and motor function. In the ICF classification, the effect size was observed to follow the order of body structure and function, activity, and participation. The effect size in the intervention according to the treatment period showed the following order: 7 to 12 weeks, 1 to 6 weeks, and 14 to 24 weeks. The age-dependent classification showed the following order in the effect size: school age, adolescent and adult, and infant and school age. CONCLUSIONS: Systemic vibration is the most effective intervention to improve the balance and gait in patients with cerebral palsy and improve the body structure and function according to the ICF.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Genetic Analysis Based on CRISPR/Cas9 Technology in Plants.

Genome-editing technology is a type of genetic engineering in which DNA is inserted into, replaced in, or deleted from the genome using artificially engineered nucleases or genetic scissors [...].

Epidemiological and Molecular Approaches for a Fatal Feline Panleukopenia Virus Infection of Captive Siberian Tigers (Panthera tigris altaica) in the Republic of Korea.

Feline panleukopenia virus (FPV), a member of the species Protoparvovirus carnivoran1, is one of the most fatal pathogens of domestic and wild carnivores. The virus endemically infects domestic carnivores worldwide and its cross-species transmission threatens endangered wild carnivores, including Siberian tigers. In this study, a fatal FPV infection in endangered Siberian tigers was investigated to trace the origin of the virus and elucidate the reason behind FPV's infection of the vaccinated tigers. Our genetic characterization and phylogenetic analysis revealed that the virus detected in the infected tigers, designated as the KTPV-2305 strain, was closely related to FPV strains circulating in Korean cats, suggesting that it might have been transmitted from stray cats wandering around the zoo. Compared with the prototype FPV reference strains, the KTPV-2305 strain carried three distinct amino acid (aa) mutations in the VP2 protein sequence (I101T, I232V, and L562V) in this study. These three mutations are commonly found in most global FPV strains, including Korean strains, indicating that these mutations are common evolutionary characteristics of currently circulating global FPVs. The reason why the vaccinated tigers were infected with FPV was most likely the insufficient protective immunity of the affected tigress or vaccine failure triggered by the interference of maternal-derived antibodies in the affected tiger cubs. These findings suggest that improved vaccination guidelines are urgently needed to save the lives of wild carnivores from this fatal virus.

A novel approach to measure carbonate alkalinity in aqueous solutions using a total organic carbon analyzer.

Carbonate alkalinity is crucial in regulating the pH and buffering capacity of natural water systems. Thus, its accurate measurement is essential to understand various water environments that affect water quality and ecosystem health. However, conventional potentiometric titration has some limitations. It results in inaccurate measurements of carbonate alkalinity when the alkalinity levels are low or when high dissolved organic matter or inorganic ion levels exist. Herein, we propose a novel approach to accurately measure carbonate alkalinity using a total organic carbon (TOC) analyzer. An extensive study comparing the accuracy and reliability of the conventional potentiometric titration method with those of the newly developed TOC method was conducted to develop and verify highly accurate measurements of carbonate alkalinity. The TOC method has several advantages over the conventional potentiometric titration methods, such as its ability to accurately measure carbonate alkalinity in the presence of high dissolved organic matter or inorganic ion levels and its ability to provide rapid and automated measurements with high reproducibility. Because, the limit of detection, limit of quantification, and the variation coefficient of the measurements was 0.016 mM (0.2 mgC/L), 0.050 mM (0.6 mgC/L), and 3.68 % respectively. Thus, the development of a novel TOC method has significant environmental implications as it provides a reliable and accurate means to measure carbonate alkalinity in solutions containing various organic matter types.

Mitigation of benzoic acid-driven autotoxicity in waste nutrient solution using O3 and O3/H2O2 treatments: Seed germination and root growth of Lactuca sativa L.

Benzoic acid (BA), a secondary metabolite released through root exudates, is considered to be the most common inhibitor that leads to plant autotoxicity, even at low concentrations in closed hydroponic systems. In this study, to mitigate BA-driven autotoxicity, the effects of O3 and O3/H2O2 oxidation treatment (O3 concentration: 1, 2, 4, 8 mg L-1, H2O2 concentration: 4, 8 mg L-1) on waste nutrient solution (WNS) were investigated in terms of BA degradation, the rate of germination inhibition (GI), and the rate of root growth inhibition (RI). In the case of O3 treatment, the BA degradation rate improved up to 14.1% as the O3 concentration increased, while alleviation of GI was insignificant (94.6-100%), confirming that a single O3 treatment was unsuitable for mitigating autotoxicity. On the other hand, O3/H2O2 treatment increased BA degradation by up to 24.8%, thereby significantly reducing GI (up to 7.69%) and RI (up to 0.88%). Both the highest BA mineralization rate and phytotoxicity mitigation was observed at BA125 (4-4) (BA mineralization: 16.7%, GI: 12.82%, RI: 11.69%) and BA125 (1-8) (BA mineralization: 17.7%, GI: 7.69%, RI: 0.88%) at each H2O2 concentration. In addition, the operating costs were evaluated by a chemical and electricity cost analysis at the different treatments. As a result, the operating costs of BA125 (4-4) and BA125 (1-8) were calculated to be 0.40 and 0.42 $ L-1 mg-1 of mineralized BA, respectively. After consideration of the mineralization rate, autotoxicity mitigation, and operating cost, BA125 (1-8) was suggested for the optimal treatment condition and our findings would contribute to the alleviation of BA-driven autotoxicity.

Enhanced selectivity and recovery of phosphate and nitrate ions onto coffee ground waste biochars via co-precipitation of Mg/Al layered double hydroxides: A potential slow-release fertilizer.

In this study, the feasibility of Mg/Al layered double hydroxides (LDH) functionalized coffee ground waste biochars (LDHMgAl@CWGB) as a potential adsorbent to selectively recover phosphate (PO43-) and nitrate (NO3-) ions in aqueous phases and their consecutive uses as a slow-release fertilizer for stimulating the plant growth were identified. The higher adsorption capacity of PO43- and NO3- ions by LDHMgAl@CWGB (PO43- = 6.98 mgP/g, NO3- = 2.82 mgN/g) compared with pristine coffee ground waste biochars (CWGB; PO43- = 0.19 mgP/g, NO3- = 0.32 mgN/g) was mainly due to the incorporation of Mg/Al mixed oxides and Cl contents. Chemisorption and intra-particle mainly controlled the adsorptive recovery of PO43- and NO3- ions by CWGB and LDHMgAl@CWGB in aqueous phases and their adsorption toward CWGB and LDHMgAl@CWGB proceeded endothermically and spontaneously. The changes in the major adsorption mechanisms of PO43- and NO3- ions from ligand exchange (CWGB) to electrostatic surface complexation and anion-exchange (LDHMgAl@CWGB) supported the conclusion that the alternation of the surface features through Mg/Al LDH functionalization might improve selectivity and adsorption capacity of PO43- and NO3- ions onto CWGB under the co-existence of Cl-, SO42-, and HCO3- ions. Since PO43-- and NO3--loaded LDHMgAl@CWGB exhibited much higher seed germination, root and shoot growth rates of garden cress seeds (Lepidium sativum L) than other liquid and solid matrices, including 5 mgP/L PO43- and 5 mgN/L NO3-, 10 mgP/L PO43- and 10 mgN/L NO3-, and LDHMgAl@CWGB, it can be postulated that PO43-- and NO3--loaded LDHMgAl@CWGB could be practically applicable to the agricultural field as a slow-release fertilizer to facilitate the seed germination, root and shoot growth of the plants.

Prevalence of asymptomatic infections of Chlamydia psittaci in psittacine birds in Korea.

Avian chlamydiosis is an acute or chronic bacterial disease of birds. Chlamydia psittaci is the primary agent of the disease. It is also an important zoonotic pathogen. Chlamydia avium and Chlamydia gallinacea have also been recognized as potential causative agents of the disease. Clinical signs of this disease can vary in severity. Asymptomatic infections of Chlamydia have commonly been reported in various birds worldwide. In this study, we investigated the distribution of Chlamydia species in healthy psittacine birds in Korea. A total of 263 samples (pharyngeal/cloacal swabs and faeces) were collected from psittacine birds of 26 species in five zoos, five parrot farms and seven parrot cafes between 2020 and 2021. Ages of these birds had a wide range (1 month to 30 years). During sample collection, no bird showed any clinical signs indicating diseases such as chlamydiosis. Samples were tested for the presence of Chlamydia spp. using real-time PCR assays. Chlamydia spp. were detected in 168 (63.9%) samples and C. psittaci was detected in 96 (36.5%) samples. However, C. avium and C. gallinacea were not detected. There were no significant differences in the prevalence of asymptomatic infections in birds among three types of housing environments. Regarding ompA genotypes, 87 C. psittaci-positive samples had genotype A based on sequence analysis (n = 28) and genotype-specific real-time PCR (n = 59). Other positive samples were untyped (n = 9). Overall findings showed high prevalence of asymptomatic infections of C. psittaci in psittacine birds in Korea, posing a significant hazard to public health.

Apoptosis: a Janus bifrons in T-cell immunotherapy.

Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded unprecedented clinical results in hematological malignancies and solid cancers. While T cell-based immunotherapies have multiple mechanisms of action, their ultimate goal is achieving apoptosis of cancer cells. Unsurprisingly, apoptosis evasion is a key feature of cancer biology. Therefore, enhancing cancer cells' sensitivity to apoptosis represents a key strategy to improve clinical outcomes in cancer immunotherapy. Indeed, cancer cells are characterized by several intrinsic mechanisms to resist apoptosis, in addition to features to promote apoptosis in T cells and evade therapy. However, apoptosis is double-faced: when it occurs in T cells, it represents a critical mechanism of failure for immunotherapies. This review will summarize the recent efforts to enhance T cell-based immunotherapies by increasing apoptosis susceptibility in cancer cells and discuss the role of apoptosis in modulating the survival of cytotoxic T lymphocytes in the tumor microenvironment and potential strategies to overcome this issue.

Heterogeneity of circulating CXCR5-PD-1hiTph cells in patients of type 2 and type 1 diabetes in Chinese population.

AIMS: Circulating peripheral helper T (Tph) cells are shown to promote the progression of autoimmune diseases. However, the role of Tph cells in inflammatory diseases such as type 2 diabetes mellitus (T2DM) and the differences between T2DM and autoimmune diabetes remain unclear. METHODS: We recruited 92 T2DM patients, 106 type 1 diabetes mellitus (T1DM) patients and 84 healthy control individuals. Peripheral blood mononucleated cells were isolated and examined by multicolor flow cytometry. We further evaluated the correlations between circulating Tph cells and clinical biochemical parameters, islet function, disease progression and islet autoantibodies. RESULTS: Circulating Tph cells were significantly higher in both T2DM and T1DM patients than in healthy control individuals. A significant positive correlation was observed between Tph cells and B cells in T1DM patients and overweight T2DM patients. Furthermore, Tph cells were negatively correlated with the area under the C-peptide curve (C-PAUC), and Tph cells were significantly positively correlated with fasting glucose and glycated hemoglobin levels in T2DM patients. However, no correlation was found between Tph cells and the above clinical indicators in T1DM patients. The frequency of Tph cells positively correlated with the titer of GAD autoantibodies and duration of disease in T1DM patients. In addition, we demonstrated that the frequency of Tph cells was decreased after rituximab therapy in T1DM patients. CONCLUSIONS: Circulating Tph cells are associated with blood glucose levels and islet function in T2DM patients. In T1DM patients, circulating Tph cells are associated with B cells and islet autoantibodies. This may suggest that Tph cells have different pathogenic mechanisms in the two types of diabetes. CLINICAL TRIAL INFORMATION: http://ClinicalTrials.gov NCT01280682 (registered July, 2010).

Knockout Mutants of OsPUB7 Generated Using CRISPR/Cas9 Revealed Abiotic Stress Tolerance in Rice.

Plants produce and accumulate stress-resistant substances when exposed to abiotic stress, which involves a protein conversion mechanism that breaks down stress-damaged proteins and supplies usable amino acids. Eukaryotic protein turnover is mostly driven by the ubiquitination pathway. Among the three enzymes required for protein degradation, E3 ubiquitin ligase plays a pivotal role in most cells, as it determines the specificity of ubiquitination and selects target proteins for degradation. In this study, to investigate the function of OsPUB7 (Plant U-box gene in Oryza sativa), we constructed a CRISPR/Cas9 vector, generated OsPUB7 gene-edited individuals, and evaluated resistance to abiotic stress using gene-edited lines. A stress-tolerant phenotype was observed as a result of drought and salinity stress treatment in the T2OsPUB7 gene-edited null lines (PUB7-GE) lacking the T-DNA. In addition, although PUB7-GE did not show any significant change in mRNA expression analysis, it showed lower ion leakage and higher proline content than the wild type (WT). Protein-protein interaction analysis revealed that the expression of the genes (OsPUB23, OsPUB24, OsPUB66, and OsPUB67) known to be involved in stress increased in PUB7-GE and this, by forming a 1-node network with OsPUB66 and OsPUB7, acted as a negative regulator of drought and salinity stress. This result provides evidence that OsPUB7 will be a useful target for both breeding and future research on drought tolerance/abiotic stress in rice.

Functionalization of pine sawdust biochars with Mg/Al layered double hydroxides to enhance adsorption capacity of synthetic azo dyes: Adsorption mechanisms and reusability.

This study determined that the adsorption of azo dyes, Methyl Orange (MO) and Sunset Yellow FCF (SYF), using the pristine pine sawdust biochar (PSB) and post-modified PSB with Mg/Al layered double hydroxides (PSB-LDHMgAl) was examined to offer valuable information into the differences in their adsorption mechanisms. Although a lower specific surface area of PSB-LDHMgAl (147.2 m2 g-1) than PSB (495.7 m2 g-1), LDHMgAl were successfully functionalized on the PSB surface through co-precipitation, which was highly related to the improvements of adsorption capacity of PSB-LDHMgAl toward MO and SYF. The MO and SYF adsorption kinetics by PSB and PSB-LDHMgAl were confirmed to the pseudo-second-order and considered chemisorption. The adsorption capacity of MO and SYF adsorbed onto PSB-LDHMgAl (MO = 21.8 mg g-1, SYF = 23.6 mg g-1) were significantly higher than that of PSB (MO = 2.2 mg g-1, SYF = 1.6 mg g-1). The adsorption isotherms of MO and SYF by PSB were well fitted by Freundlich isotherm, whereas the MO and SYF via PSB-LDHMgAl were by Langmuir isotherm. Even after 3 adsorption-desorption cycles using desorbents, the PSB-LDHMgAl remained excellent reusability (reuse efficiency: >81.2%). These findings suggest that post-modification with LDHMgAl might accelerate the adsorption performance (i.e., electrostatic interaction) of azo dyes to PSB in water.

Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.

Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, hematopoietic CD19+-A20 lymphoma and CD19+-B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor-associated antigens (TAAs) cross-presentation compared with CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naive gut microbiota mice. Last, B cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared with unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.

An autopsy study of hollow fiber and multibore ultrafiltration membranes from a pilot-scale ultra high-recovery filtration system for surface water treatment.

The organic fouling characteristics of hollow fiber ultrafiltration (HFUF) and multibore ultrafiltration (MBUF) membranes from long-term ultrafiltration (UF) membrane systems were systemically investigated in this study. The objective was to obtain insights into the fouling behavior of dissolved organic matter (DOM) in a pilot-scale ultra-high-recovery membrane filtration system (p-UHMS) used for surface water treatment. The pilot system consisted of a series of two different UF membranes (1st stage: polyvinylidene fluoride (PVDF) HFUF and 2nd stage: polyethersulfone (PES) MBUF). It was designed to feed the HFUF concentrate to the MBUF membranes to achieve ≥99.5 % total water recovery for surface water treatment, as these advances might enhance the production efficiencies of drinking water. The experimental results confirmed that hydrophobic DOM controlled the formation of HFUF membrane organic fouling, whereas hydrophilic DOM, including polysaccharide-like and protein-like matter, promoted MBUF membrane fouling. These opposing trends were attributed to the hydrophilic characteristics of the MBUF membrane surfaces (contact angle: PVDF = 90-130° and PES ≤ 80°), which reduced the hydrophobic interactions between the UF membrane surfaces and foulants. The performance declines of the MBUF membrane due to fouling layer formation was considerably severer than those of the HFUF membrane, decreasing total permeate water in the p-UHMS. Moreover, the quantity of the desorbed MBUF membrane foulants via 0.1 N NaOH was roughly 7.2 times larger than that of the desorbed HFUF membrane foulants through 0.1 N NaOH, indicating that alkaline-based cleaning agent could much more efficiently recover the performance of the fouled MBUF membranes. Hence, adequate cleaning strategies using alkaline-based agent for the MBUF membrane appeared to be essential for preventing the performance deterioration of the p-UHMS.

Antimicrobial resistance of commensal Escherichia coli and Enterococcus faecalis isolated from clinically healthy captive wild animals in Seoul zoo.

Despite the importance of antimicrobial resistance, only a few studies on the antimicrobial susceptibility on wild animals have been conducted owing to their population, accessibility, and characteristics. The objective of this study was to investigate the prevalence and characteristics of antimicrobial resistance pattern in Escherichia coli and Enterococcus faecalis isolated from the feces of captive wild animals in a zoo. A total of 61 captive wild animals were included in this study. E. coli was isolated from 58 of the 61 animals and E. faecalis was isolated from 29 animals. Among the isolated E. coli strains, ampicillin exhibited the highest resistance rate (27/29, 93.1%). Of these, 18 strains (18/29, 62%) showed multidrug resistance. The multilocus sequence typing (MLST) test showed that only ST155 was detected twice, while the other 16 strains showed different ST types. Among the E. faecalis strains, two were susceptible to all tested antimicrobials, whereas the remaining 27 strains showed resistance to one or more antimicrobials. Nine strains (9/27, 31%) showed multidrug resistance. Among the E. faecalis strains, resistance to quinupristin/dalfopristin was the highest at 96.3% (26/27), while the MLST of the nine MDR strains showed no predominant ST. Genetic association with human isolates or livestock products was observed in the isolated ST types. This indicates that antibiotic resistance in the zoo is responsible for the use of antibiotics and the partial horizontal transmission between humans and animals through feeding or contact.

Analysis of high risk factors for chromosomal aberrations in peripheral blood lymphocytes of 200 radiation workers in Hainan Province / 上海预防医学

ObjectiveTo investigate the current status and high-risk factors of chromosomal aberrations in peripheral blood lymphocytes （PBL） of radiation workers in Hainan Province. MethodsA total of 200 radiological workers who underwent occupational health examination in Hainan Provincial Hospital of Traditional Chinese Medicine from January 2021 to December 2021 were selected to collect the occupational health examination data and the rate of PBL chromosomal aberrations. The influencing factors of PBL chromosomal aberrations were analyzed by logistic regression model. The predictive value of logistic regression prediction model on PBL chromosomal aberrations were determined by using the reciver operator characteristic （ROC） curve. ResultsA total of 20 000 cells （100 cells/person） were tested. The chromosomal aberration rate was 0.37% （74/20 000） and the PBL chromosomal aberration rate in the subjects was 6.00% （12/200）. Univariate analysis showed that PBL chromosomal aberrations in radiological workers were related to age， length of service， type of work and education （all P<0.05）， but not to gender （P>0.05）. The logistic regression prediction model was constructed based on the influencing factors， with χ2=9.413， df=9， P=0.852， suggesting a good model fit. The logistic regression prediction model predicted the area under the curve （AUC） for the occurrence of PBL chromosomal aberrations in radiation workers was 0.914 （95%CI： 0.866‒0.949）， with a cut-off value of 3.05， corresponding to a prediction sensitivity and specificity of 100.00% and 75.98%， respectively. ConclusionThe incidence of PBL chromosomal aberrations in radiological workers in Hainan Province was 6.00%， with age， working age and job type as high-risk factors and education level as a protective factor. The prediction model constructed by the above factors can provide a reliable basis for clinical prediction of PBL chromosomal aberrations in radiological workers.

Clinicopathological analysis of primary gastric (gastrointestinal)-type mucoglandular lesion of endometrium / 中华病理学杂志

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.