Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

Objective To investigate the protective effects of mitochondrial preconditioning in pericytes(PC)against pulmonary vascular leakage in septic rats.Methods ① 128 specific-pathogen-free SD rats(equal gender,200±20 g)were randomized into:Sham group(postoperative tail vein injection of 0.5 mL saline),Sepsis(Sep)group(CLP+saline),PC group(CLP+untreated PC:106 cells/rat),and Mito-PC group(CLP+PC preconditioned with 2 μg mitochondria/104 cells for 12 h).Assessments included:PC lung colonization(flow cytometry),pulmonary barrier function(Evans blue assay),lung histopathology(HE staining),serum organ injury markers[cTnT(cardiac),urea/creatinine(renal)],and inflammatory cytokines(TNF-α,IL-6).② MSC-derived mitochondria were validated by electron microscopy/flow cytometry;primary retinal PCs from weaned SD rats were purity-verified(confocal microscopy).In vitro groups:Control(PC),Mito-PC,PC+H2O2(0.5 μmol/L,4 h),and Mito-PC+H2O2.Antioxidant capacity was assessed via pentose phosphate pathway(PPP)activity,NADPH levels,G6PD activity,and NADP+/NADPH ratio.Results① Compared with Sham,Sep group showed significant increase in pulmonary leakage(Evans blue P<0.05),severe lung injury,elevated serum markers(TNF-α,IL-6,cTnT,urea,creatinine all P<0.05),0％72 h survival.PC group showed partial improvement(P<0.05).Mito-PC group demonstrated significant reduction in vascular leakage(P<0.05 vs PC group),improved histopathology and organ function(P<0.05),attenuated inflammation(P<0.05),higher 72 h survival rate(P<0.05).② Mitochondrial preconditioning significantly enhanced PPP activation and NADPH-mediated antioxidative capacity,Mito-PC+H2O2 vs PC+H2O2 showed improved cell viability(P<0.05),Mito-PC vs PC showed increased G6PD activity(P<0.05),decreased NADP+/NADPH ratio(P<0.05).Conclusion Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.

Multiple myeloma (MM) is a malignant plasma cell disease that currently cannot be cured. Several new drugs have continuously been introduced in the recent years. New drugs targeting B-cell maturation antigen (BCMA) have greatly improved the efficacy and prognosis of MM compared with traditional treatments. This article reports the case of an IgD type relapsed and refractory MM patient with poor efficacy of BCMA×CD3 bispecific antibody. The patient achieved deep remission after receiving BCMA-targeted CAR-T cell therapy after initial seven lines of treatment. Literature review was also conducted to improve the clinical physicians’ understanding of BCMA target therapy for relapsed and refractory MM patients.

Objective:To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors.Methods:Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups.Results:In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type ( P=0.010) , severer anemia ( P=0.014) , a higher proportion of bone marrow plasma cells ( P=0.013) , more extramedullary lesions ( P=0.001) , and increased lactic dehydrogenase (LDH) ( P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM ( P=0.026) . At the initial diagnosis, LDH ( P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions ( P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion:Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Objective To investigate the role of gamma-aminobutyric acid (GABA) A receptor (GABAAR) in lung tissues in lipopolysaccharide (LPS)-induced acute lung injury in rats.Methods Thirty-two male Wistar rats,aged 8 weeks,weighing 200-230 g,were randomly divided into 4 groups (n =8 each) ∶ control group (group C),group LPS,GABA pretreatment + LPS group (group GABA) and GABAAR antagonist bicuculline pretreatment + LPS group (group BIC).Acute lung injury was induced by intravenous LPS 5 mg/kg in groups LPS,GABA and BIC,while the equal volume of normal saline was given in group C.GABA 50 mg/kg and bicuculline 10 μmol/kg were injected intraperitoneally 30 min before LPS injection in GABA and BIC groups,respectively.Arterial blood samples were collected at 6 h after LPS injection for measurement of arterial partial pressure of oxygen (PaO2).The animals were then sacrificed and lungs removed for determination of W/D lung weight ratio,GABAAR expression,contents of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissues and for microscopic examination.Results Compared with group C,PaO2 was significantly decreased in the other three groups,and W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in groups LPS and GABA (P ＜ 0.05).Compared with group LPS,W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in group GABA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group BIC and in PaO2 in groups GABA and BIC (P ＞ 0.05).Conclusion GABAA R in lung tissues is involved in the development of acute lung injury induced by LPS.

Objective To evaluate the role of intercellular gap junction in the propofol and sevoflurane anesthesia in rats. Methods Eighty male Wistar rats weighing 210-260 g were randomly divided into 8 groups (n = 10 each): control group (group C), carbenoxolone group (group CA), propofol group (group P), different doses of carbenoxolone + propofol groups (groups CA1 + P, CA2 + P, CA3 + P), sevoflurane group (group S) and carbenoxolone + sevoflurane group (group CA + S). The animals ware anesthetized with intraperitoneal 10% chloraldurate 4 mg/kg and placed in a stereotactic apparatus to locate the lateral ventricle. In group C, after normal saline (NS) 2 μl was injected into the latersl ventricle, intraperitoneal NS 2 ml was injected. In group CA, after carbenoxolone 200 μg was injected into the lateral ventricle, intraperitoneal NS 2 ml was injected. In groups P,CA1 + P, CA2 + P and CA3 + P, NS 2 μl, and carbenoxolone 200, 300 and 400 μg were injected into the lateral ventricle respectively and then propofol 5 mg/100 g was injected intraperitoneally. Group S inhaled 1% sevoflurane (in increments of 0. 1% ) until the righting reflex was lost. Group CA + S inhaled 1% sevoflurane (in increments of 0.1% ) until the righting reflex was lost after carbenoxolono 200 μg was injected into the lateral ventricle. The time of loss of righting reflex, duration of loss of righting reflex and the sevoflurane concentration when the righting reflex disappeared were recorded. Results The loss of righting reflex did not appear in groups C and CA. Compared with group P, the time of loss of righting reflex was significantly shortened and duration of loss of righting reflex prolonged in groups CA1 + P, CA2 + P, CA3 + P ( P ＜ 0.01 ). The time of loss of righting reflex was significandy shorter in groups CA2 + P, CA3 + P than in group CA1 + P (P ＜ 0.05). The sevoflurane concentration when the righting reflex disappeared was significantly lower in group CA + S than in group S ( P ＜ 0.05 ). There was no significant difference in the time of loss of righting reflex and duration of loss of righting reflex between CA + S and S groups ( P ＞ 0.05). Conclusion Although inhibition of the function of gap junction can strengthen the anesthetic effects of propofol and sevoflurane, it is not the major mechanism.

Objective To investigate the effect of sodium nitroprusside (SNP) , an exogenous NO donor, on expression of hemeoxygenase-1 (HO-1) and inducible NO synthase (iNOS) in the lung tissue in a rat model of lpopolysaccharide (LPS)-induced acute lung injury and the underlying mechanism.Methods Thirty-two Wistar rats of either sex weighing 190-210 g were randomly divided into 4 groups ( n = 8 each) : Ⅰ sham operation (S) ;Ⅱ LPS;Ⅲ hemin + LPS and Ⅳ SNP + LPS. The animals were anesthetized with intraperitoneal (IP) 7% chloralhydrate 5 ml?kg-1. LPS 750 ?g?kg-1 in 300 ?l was instilled into the lungs via trachea in group Ⅱ . In group Ⅲ hemin (a HO-1 inducer) 40 ?mol?kg-1 was injected IP 12 h before LPS. In group Ⅳ SNP 25 ?g?kg-1 + LPS 750 ?g?kg-1 in 300 ?l was instilled into the lungs via trachea. In group S normal saline 300 ?l was instilled via trachea instead of LPS. The animals were killed by (1) exsanguination from carotid artery 8h (2) after LPS instillation and lungs were removed for broncho-alveolar lavage (BAL) and detennination of protein concentration in BALF and the expression of HO-1 and iNOS protein in the lung tissue by immune-histochemical technique and HPIAS-2000 image analysis system and MDA content in lung tissue and (3) light microscopic examination (4) wet/ dry lung weight ratio.Results The 4 groups were comparable with respect to body weight and sex (M/F ratio) . The expression of iNOS and HO-1 in lung tissue was significantly higher in LPS group than in S group ( P