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.

Objective To explore the clinical efficacy of edaravone dexborneol combined with intravenous thrombolysis with alteplase,in the treatment of patients with acute ischemic stroke(AIS).Methods The patients with AIS undergoing intravenous thrombolysis with alteplase between January 7,2021 and December 31,2022 were enrolled and randomly divided into observation group and control group.The control group was treated with standard treatment according to the AIS guidelines,and the observation group was treated with edaravone dexborneol injection within 48 hours from thrombolysis to the onset of the disease on the basis of the treatment in the control group.7-day post-thrombolysis National Institutes of Health stroke scale(NIHSS),discharged NIHSS,difference between 7-day post-thrombolysis NIHSS and pre-thrombolysis NIHSS,and 3-month all-cause mortality and 3-month poor prognosis ratio were compared between the two groups.Results A total of 232 patients with AIS were randomly allocated to the observation group(n=1 16)and the control group(n=1 16).The differences between the two groups were not statistically significant for 7-day post-thrombolysis NIHSS and difference between 7-day post-thrombolysis NIHSS and pre-thrombolysis NIHSS(P＞0.05),and there were statistical differences in distribution of the discharged NIHSS score between the observation group and control group[2.0(0,3.0)vs.2.0(1.0,5.0),P＜0.05].The 3-month poor prognosis ratio was significantly lower in the observation group than in the control group(12.1％vs.28.4％;OR=0.252,95％CI 0.105 to 0.602,P=0.002).Conclusion Edaravone dexborneol enhances the efficacy of AIS undergoing intravenous thrombolysis with alteplase and improves the 3-month outcome of patients.

Abstract: Objective　To analyze the molecular serotyping and drug resistance of foodborne Listeria monocytogenes (LM)isolates from the food monitoring network of Liaoning Province, and to provide a reference for identifying and tracing the outbreaks of foodborne diseases. Methods　The Listeria monocytogenes isolates were identified, biochemical typing was conducted by VITEK biochemical identification and PCR amplification techniques were applied for molecular serotyping of 67 strains of Listeria monocytogenes detected from 2 797 food samples collected from 15 monitoring sites across the province during 2021-2022. Verification was performed according to the instructions of the serodiagnosis manual. The sensitivity of the strains to ampicillin, penicillin, meropenem, cotrimoxazole, and erythromycin was determined by broth dilution method. Results　In food from Liaoning Province, the molecular serotypes of Listeria monocytogenes carried were identified as 1/2a(3a), 1/2b(3b, 7), 1/2c(3c), and 4b (4d, 4e), with the predominant serotypes being 1/2a accounting for 62.7% (42/67), and 1/2b accounting for 28.4% (19/67). Among them, the 4b strain was isolated in 3 strains, representing 4.5%. The dominant strains of Listeria monocytogenes in 2021 and 2022 in Liaoning Province were 1/2a(3a) and 1/2b(3b, 7), with the most diverse types carried by meat and meat products. Double resistance to cotrimoxazole and erythromycin accounted for 11.9% (8/67), while resistance to only one cotrimoxazole accounted for 9.0% (6/67). Conclusions　The presence of pathogenic serotypes 1/2a(3a), 1/2b(3b, 7), 1/2c(3c), and 4b (4d, 4e) in food in Liaoning Province and the emergence of strains with one or more drug resistances indicate the existence of food safety issues caused by Listeria monocytogenes, posing a potential risk of listeriosis. There is a need to optimize source tracing methods and strengthen the confirmation of Listeria monocytogenes outbreaks.

Objective:To investigate the correlation of relative cross-sectional area of lumbar paravertebral muscle and psoas with lumbar curvature and its clinical significance.Methods:This study was conducted as a retrospective cross-sectional study. Among the patients treated at the Department of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January to April 2023, 107 middle-aged and young patients with changes in lumbar physiological curvature or no apparent abnormalities were included in this study based on MRI findings. The relative cross-sectional area (RCSA) values of the left and right paravertebral muscles and psoas were measured at the lower margin of the L3 vertebral body and at the L3/L4, L4/L5, and L5/S1 intervertebral discs. Furthermore, the correlation between these RCSA values and lumbar curvature was analyzed.Results:The 107 patients were (30.51 ± 4.64) years old, and the proportion of females accounted for 71.96%. There were differences in RCSA between the lower margin of L3, L3/L4, L4/L5, and L5/S1 intervertebral discs (left psoas F = 30.21, P < 0.001; right psoas F = 31.63, P < 0.001; left paravertebral muscle F = 31.04, P < 0.001; right paravertebral muscle F = 26.55, P < 0.001). From L3 to S1, the RCSA of the psoas increased, while the RCSA of the paravertebral muscle decreased. The RCSA values of the total paravertebral muscle/RCSA values of the total psoas major muscle were positively correlated with lumbar curvature at the lower margin of the L3 vertebral body ( r = 0.40, P < 0.001). This correlation could be seen at both L3/L4 ( r = 0.31, P = 0.001) and L4/L5 ( r = 0.24, P = 0.012). However, after considering the influence of left and right muscle groups on lumbar curvature, there was no correlation between the muscle cross-sectional area at the L5/S1 disc position and lumbar curvature ( P > 0.05). Nevertheless, there was still a correlation between the muscle cross-sectional area at other lumbar segments ( P < 0.05). Conclusion:An increase in the RCSA of the psoas relative to the paraspinal muscle may lead to straightening of the lumbar spine curvature, whereas an increase in the RCSA of the paraspinal muscle relative to the psoas may result in an increase in lumbar spine curvature. Improving the quality of the paraspinal muscle may restore the physiological curvature of the lumbar spine, which holds clinical application value.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

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.

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.