ObjectiveTo explore whether fluoroethylnormemantine （FENM）， an NMDA receptor antagonist， could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder （OCD） mouse model. MethodsThirty-two mice were randomly assigned to four groups： Saline （n=8）， RU24969 （n=8）， RU+FENM （n=8）， and FENM （n=8）. Mice received FENM or an equivalent volume of saline for pre-treatment， followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling， and serum samples were collected to measure the level of brain-derived neurotrophic factor （BDNF）. Evans Blue dye was intravenously injected to assess dye content in brain tissue， thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior （F=39.850， P＜0.001） and alleviated persistent motor activity （F=50.200， P＜0.001） in RU24969 model mice. Additionally， FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice （F=18.930， P＜0.001）. ConclusionsFENM ， an NMDA receptor antagonist， may alleviate compulsive behaviors in OCD mice by modulating BDNF levels ， thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Background ¹³⁷Cs in atmospheric aerosol is the product of past nuclear weapon tests and nuclear accidents. When ¹³⁷Cs is released into the atmosphere, it will deposit in dry land and marine environment, causing pollution of soil surface, water, agricultural products, and animal byproducts, and affecting public health. Objective To identify the variation pattern of ¹³⁷Cs activity concentration in aerosol and its correlation with dust concentration in Beijing area from 2017 to 2020. Methods A total of 958 aerosol samples were collected from November 1, 2017 to June 30, 2020 in Beijing with a high volume air sampler at a sampling flow rate about 600 m³·h⁻¹ and a collection time for each sample about 24 h. The activity concentration of ¹³⁷Cs in the aerosol samples was determined with a low-background high-purity germanium γ spectrometer. The dust concentration was calculated using the difference in the mass of the aerosol filter before and after sampling. The detection rate of ¹³⁷Cs and dust concentration in different seasons were compared. Spearman rank correlation test was used to analyze the correlation between ¹³⁷Cs activity concentration and dust concentration. Results From 2017 to 2020, the ¹³⁷Cs activity concentrations of 33 from 958 aerosol samples in Beijing were above the minimum detectable activityconcentration, the overall detection rate of ¹³⁷Cs was 3.4%, and the activity concentration ranged from 1.86 to 45.53 μBq·m⁻³, with a median value of 4.85 μBq·m⁻³. The detection rate of ¹³⁷Cs was highest in spring, followed by autumn, and lowest in winter and summer (8.4%, 3.0%, 1.1%, and 0.5%, respectively). The dust concentration ranged from 0.03 to 1.55 mg·m⁻³, with an average value of 0.18 mg·m⁻³. There was a statistically significant difference in the dust concentrations in spring, summer, autumn, and winter (F=45.51, P<0.05), and the highest value was 0.24 mg·m⁻³ in spring (P<0.05). The ¹³⁷Cs activity concentration was positively correlated with the dust concentration (P<0.05). Conclusion The ¹³⁷Cs activity concentration in aerosol in Beijing from 2017 to 2020 fluctuates within the range of background level, and its activity concentration is highest in spring, followed autumn, and lowest in summer and winter.

In recent years,the infection of nontuberculous mycobacterium(NTM)has been increasing rapidly,which captivates widespread attention.The infection rate of NTM in kidney transplant recipients is more significantly elevated due to the impact of immunosuppressive drugs and other factors.However,due to the lack of sufficient research evidence,relevant guidelines for the diagnosis and treatment of NTM after kidney transplantation are still lacking.To further standardize the diagnosis and treatment of NTM disease in kidney transplant recipients,and deepen medical practitioners'understanding and diagnosis and treatment of NTM disease in organ transplantation in China,Branch of Organ Transplantation of Chinese Medical Association organized relevant experts to formulate this guideline by referring to the latest edition of"An official ATS/IDSA statement:diagnosis,treatment,and prevention of nontuberculous mycobacterial diseases","Expert Consensus on the Diagnosis and Treatment of Nontuberculous Mycobacterial Disease",and"Technical Specification for Clinical Diagnosis and Treatment of Nontuberculous Mycobacteria in Organ Transplant Recipients(2019 Edition)",and considering the characteristics of kidney transplant recipients.

Objective　To investigate the contamination status of Bacillus cereus in food, the profile of virulence factors carried, and drug sensitivity characteristics in Liaoning Province. Methods　A total of 620 samples were isolated from 15 monitoring sites, covering four major sample types of food products in Liaoning Province between 2021 and 2022. Bacillus cereus was isolated and identified by GB4789.14—2014, and its virulence was assessed using PCR detection of the groEL and gyrB genes specific to the bacterial group, as well as 11 other virulence genes. Broth microdilution method was used to detect the antibiotic sensitivity of the strain. Results　All 79 Bacillus cereus strains were found to carry virulence genes. The detection rates of non-hemolytic enterotoxin genes nheC, nheA, and nheB were 100% (79/79), 93.3% (74/79), and 83.5% (66/79), respectively. The detection rate of enterotoxin entFM gene was 98.7% (78/79). The 79 strains of Bacillus cereus carried 19 types of virulence gene patterns, with IX and XVII gene patterns being the most prevalent, each accounted for 16.5% (13/79). The resistance rates of 79 strains of Bacillus cereus to 10 antibacterial drugs were 100% for both ampicillin and penicillin. The resistance rates to cotrimoxazole, imipenem, erythromycin, clindamycin, ciprofloxacin, and tetracycline 65.8% (52/79), 10.1% (8/79), 73.4% (58/79), 60.8% (48/79), 75.9% (60/79), and 70.9% (56/79) respectively. The resistance rates to chloramphenicol and gentamicin were both 0%. Conclusion　Food from catering services in Liaoning Province shows contamination by Bacillus cereus, with isolated strains carrying at least four kinds of virulence genes. About 100% of the isolates were resistant to ampicillin and penicillin, whereas high sensitivity was observed to chloramphenicol and gentamicin. Active monitoring, timely targeted prevention and control interventions should be strengthened to provide a theoretical basis for future traceability studies.

Objective : To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway． Methods : Fifty female Wistar rats were randomly divided into Control group ，FA group，FA + MT 5 mg / kg group，FA + MT 10 mg / kg group and FA + MT 20 mg / kg group，with 10 rats in each group．Except for the Control group，all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model，and then treated with different MT doses for 14 d．The tainting was continued during the MT treatment．Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue，lung water content and lung coefficient were weighed and measured，glutathione ( GSH) ，superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ，and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ，in- terleukin (IL) -6，and IL-1 β concentrations，Western blot to detect the protein expression levels of Nrf2，heme ox- ygenase-1 (HO-1) ，nuclear factor-κB ( NF-κB) ，and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues，and quantitative polymerase chain reaction(qPCR) to detect the Nrf2，HO-1，and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels. Results : Compared with the control group，lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ，and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6，and IL-1 β levels were elevated (P＜0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P＜0. 05) ，and p-NF-κB protein expression levels were was ele- vated (P＜0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased，and the relative mRNA expression of Keap1 was elevated (P＜0. 05) ．Compared with the FA group，the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P＜0. 05) ，and the level of 8-OHdG was decreased (P＜0. 05) ; the levels of TNF-α , IL-6，and IL-1 β in the alveolar lavage fluid were de- creased (P＜0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P ＜0. 05) ．p-NF-κB protein expression level was decreased (P ＜0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P＜0. 05) ，and the relative mRNA expression level of Keap1 was decreased (P＜0. 05) in lung tissues，and all of them were in a dose-dependent manner． Conclusion MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.

Hepatocellular carcinoma is the most common malignant tumor of the liver, and more than half of the patients are in the middle and late stage, seriously threatening the life and health of the Chinese people. Although surgical resection remains the only treatment option for liver cancer patients to achieve a cure, the low surgical resection rate and high postoperative recurrence rate greatly limit the survival benefits of patients. Recently, with the continuous successful development and clinical application of systemic new drugs, multi-mode therapy such as TKIs combined ICIs has sprung up, breaking the limitations of a single treatment model, and has become an important corner of "surgery-based comprehensive treatment" for liver cancer. Neoadjuvant therapy, adjuvant therapy and conversion therapy have gradually become the focus of new research, and their success is expected to further improve the survival prognosis of patients with liver cancer, but there are still many challenges. The author reviews the current first-line systematic treatment of liver cancer, and elaborates on the characteristics and advantages of its clinical application.

Objective To evaluate the clinical application value of the 5 estimated glomerular filtration rate(eGFR)formulas,inclu-ding MDRD,MDRD Chinese formula[MDRDCHN],CKD-EPICr,CKD-EPICysC and CKD-EPICr-CysC,in assessing glomerular filtration function and diagnosing chronic kidney disease(CKD),and determine the most suitable formula for the local region.Methods A to-tal of 2 610 outpatients and inpatients from The First Affiliated Hospital of Ningbo University were enrolled as the study subjects.Serum creatinine(Cr)and CysC levels were measured,and eGFR was estimated using the 5 formulas.The differences of eGFR values calcu-lated by different formulas were compared.In 412 inpatients,the correlations between endogenous creatinine clearance rate(cCr)and the 5 eGFR results were analyzed,and ROC curves were plotted to compare the diagnostic efficacy of the five eGFR values for CKD.The reference interval for eGFR was established using data from 239 healthy individuals.Results All the eGFR values calculated by the 5 formulas showed skewed distributions and differences of most pairwise comparisons were statistically significant.All the 5 eGFR values were significantly positively correlated with cCr.The CKD-EPICrCysC showed the highest correlation coefficient(r=0.903).The areas under the ROC curves for diagnosing CKD using the 5 eGFR formulas were 0.968,0.969,0.970,0.967 and 0.976,respectively.CKD-EPICr-CysC showed the best diagnostic performance(sensitivity of 97.3％,specificity of 89.8％).The lower limits of the 95％confi-dence interval for healthy individuals were 76,87,82,99,and 93 mL/min/1.73m2 for the different formulas respectively.Conclusion Among the five eGFR formulas,CKD-EPICr-CysC with a reference interval lower limit of 93 mL/min/1.73m2 was demonstrates as the best diagnostic efficiency for assessing glomerular filtration function and diagnosing CKD,and is worth promoting and applying in Ning-bo region.