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 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.

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.

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.

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 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.

Objective:To review the literature and summarize the clinical characteristics and treatment methods of rectal buttonhole tears associated with vaginal delivery.Methods:Using the keywords "rectal tear and delivery" "rectal laceration and delivery" "rectal lesion and delivery", and "rectal buttonhole tear", we conducted a search for Chinese-language papers published on the Yiigle, CNKI (China National Knowledge Infrastructure), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Service Platform. Additionally, using the same keywords in English, we searched for papers published on PubMed and Embase. The search period covers from the establishment of the databases up to November 15, 2023. Cases with a clear diagnosis of rectal buttonhole tears associated with vaginal delivery were included. Data on maternal age, parity, gestational weeks, neonatal birth weight, time of rectal tear discovery, whether episiotomy was performed, whether instrumental delivery was used, details of the rectal tear, management after discovering the tear, and prognosis were analyzed. Descriptive statistical analysis was used.Results:A total of 30 papers were included, published from 1952 to 2023, encompassing 48 cases of vaginal delivery with rectal buttonhole tears. (1) Age and parity: The median age of patients was 28.0 years (range 21-44 years), with primiparas and multiparas accounting for 72.5% (29/40) and 27.5% (11/40), respectively. (2) Gestational weeks: The median gestational age at delivery was 39.0 weeks (range 36.0-41.0 weeks). (3) Neonatal birth weight: The median birth weight of the neonates was 3 595 g (range 2 320-4 250 g), with four cases of macrosomia (birth weight≥4 000 g), accounting for 9.5% (4/42) of singleton births. (4) Time at identification of rectal buttonhole tear: Rectal tears were discovered before fetal delivery in 26.7% (12/45) of cases and after delivery in 73.3% (33/45) of cases. (5) Location: Rectal buttonhole tears most commonly occurred at the midline of the posterior vaginal wall (65.6%, 21/32), followed by the right side of the episiotomy wound (12.5%, 4/32). (6) Relationship between rectal buttonhole tears and delivery mode: Rectal buttonhole tears can occur in spontaneous vaginal delivery, episiotomy, and instrumental vaginal delivery. They may occur during the first or second stage of labor. (7) Timing of rectal tear suturing and prognosis: 93.4% (45/48) of patients underwent primary rectal suturing, among whom, 93.3% (42/45) had good healing, while 6.7% (3/45) developed rectovaginal fistula postoperatively.Conclusions:Rectal buttonhole tear is a rare complication of vaginal delivery and should be recognized. If identified promptly and repaired with primary suturing, the prognosis is generally favorable.