Objective To evaluate the clinical efficacy and safety of the daratumumab-based regimens,including daratumumab,dexamethasone,and lenalidomide(DRd),as well as daratumumab,dexamethasone,and bortezomib(DVd),in the treatment of patients with relapsed or refractory multiple myeloma(RRMM)at our center.Methods Eighty patients with RRMM were assigned to either the DRd group(42 cases)or the DVd group(38 cases)based on their treatment regimens.Both groups received a baseline treatment of daratumumab combined with dexamethasone(Dd regimen).In the DVd group,1.3 mg/m2 of bortezomib was administered subcutaneously on days 1,4,8,and 11 of each cycle,followed by a 10 day drug-free interval(days 12～21),repeated every 3 weeks until disease progression.In the DRd group,25 mg of lenalidomide was orally administered daily from day 1 to day 21 of each cycle,in addition to the Dd regimen,continuing until disease progression.The two groups were compared in terms of laboratory parameters,tumor markers,clinical efficacy,safety profiles,and long-term prognostic outcomes.Results After treatment,the overall response rate(ORR)of the DRd group and the DVd group was 78.57%(33 out of 42 cases)and 52.63%(20 out of 38 cases),respectively.The serum creatinine(SCr)levels were(92.54±14.33)and(102.07±15.41)μmol/L,respectively;the M protein contents were(19.62±2.04)and(21.08±2.23)g/L,respectively;the β2-microglobulin(β2-MG)levels were(3.49±1.12)and(4.16±1.25)mg/L,respectively;and the progression-free survival rates were 42.86%(18 out of 42 cases)and 26.32%(10 out of 38 cases),respectively.All these indicators showed statistically significant differences between the DRd group and the DVd group(all P<0.05).The incidence rates of adverse reactions in the observation group and the control group were 14.29%(6 out of 42 cases)and 13.16%(5 out of 38 cases),respectively,and the difference was not statistically significant(P>0.05).Conclusion The DRd regimen demonstrates superior efficacy compared to the DVd regimen in treating patients with RRMM,leading to improved patient prognosis with a favorable safety profile.

Objective:To investigate the efficacy of posterior cranial fossa in- situ floating bone flap osteotomy in the treatment of syndromic craniosynostosis(SCS). Methods:The clinical data of SCS children who underwent posterior cranial fossa in- situ floating bone flap osteotomy at the Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine from April 2020 to August 2022 were retrospectively analyzed. The surgical procedures were as follows. The occipital bone was cut into several mosaic bone flaps of varying sizes, without peeling it off the dura, which were left as a small free floating bone flap. The anteroposterior cranial diameter, cranial height, intracranial volume, and degree of improvement in tonsillar herniation and hydrocephalus of the children (hydrocephalus quantification was performed using the ratio of the ventricular diameter to the biparietal diameter)were measured preoperatively, 7 days postoperatively, 3 months postoperatively, and at the last follow-up (at least 12 months after the operation) to evaluate the surgical outcomes. The measurement data of normal distribution were expressed as Mean±SD. The paired t-test was used for comparison within the repeated measurement data groups at the two time points. One-way repeated measures analysis of variance (ANOVA) was performed on the repeated measurement data at multiple time points, and pairwise comparisons in post hoc tests were corrected using the Bonferroni method. Results:A total of 17 pediatric patients with SCS were included, comprising 10 males and 7 females, with ages ranging from 4 to 18 months (mean age: 9.5 months). Among them, 12 patients were complicated with Chiari malformation and hydrocephalus (1 severe case, 8 moderate cases, and 3 mild cases). Postoperative follow-up lasted 12 to 35 months, with an average of 17 months. After surgery, the posterior cranial appearance of the children was enlarged, with increased convexity of the occiput and a full contour. At the last follow-up, the middle cranial height [(107.80±10.72) mm vs. (102.82±10.09) mm, P<0.05], the posterior cranial height [(124.91±10.40) mm vs. (107.58±13.46) mm, P<0.01] and anteroposterior diameter [(153.30±11.26) mm vs. (123.64±17.44) mm, P<0.01] as well as the intracranial volume [(1 317.92±225.77) cm 3 vs. (1 014.93±231.81) cm 3,P<0.01] were increased compared with the preoperative period, and the average improvement rate of intracranial volume was 37.0% (18.1%-79.2%). Among the 12 cases of tonsillar herniation, 7 cases had improvement. Moreover, all the 12 cases of hydrocephalus witnessed a mitigation in severity, from (46.33±9.34)% preoperatively to (35.24±9.88)% postoperatively, with a statistically significant difference ( P<0.01). Conclusion:Posterior cranial fossa in- situ floating bone flap osteotomy can effectively improve the appearance of patients with SCS, increase the intracranial volume, relieve the degree of hydrocephalus, and reduce the intracranial pressure.

AIM:To explore the mechanism of ac-tion and clinical significance of NLRC4 in multiple myeloma by analyzing the relative expression and clinical significance of NLRC4 mRNA in bone mar-row fluid of patients with multiple myeloma(MM),so as to guide the formulation of disease treatment and the evaluation of clinical prognosis.METHODS:MMRF database and GTEx database were used to compare the expression and survival correlation of inflammatory bodies between myeloma patients and normal controls.Real-time fluorescent quanti-tative polymerase chain reaction(qPCR)was used to detect the expression of inflammatory bodies in bone marrow fluid of 26 newly diagnosed myeloma patients and 19 post-treatment myeloma patients and peripheral blood of 28 normal volunteers ad-mitted to the First Affiliated Hospital of Anhui Medi-cal University from January to September 2023.The mRNA expression differences of each inflammatory body and the correlation between NLRC4 inflamma-tory body expression and clinicopathologic fea-tures,inflammatory factor/chemokine expression of newly diagnosed patients were analyzed.RE-SULTS:Compared with the control group and the treatment group,the expression of inflammasome mRNA in the newly diagnosed group was increased except for NLRP3,and the expression of NLRC4 mRNA was significantly increased(P<0.01).The he-moglobin count,creatinine level and calcium ion level were linearly correlated with NLRC4 mRNA ex-pression level in newly diagnosed patients(P<0.05).The mRNA expression levels of IL-18,CCL-3 and NL-RC4 in newly diagnosed patients were linearly cor-related(P<0.05).CONCLUSION:NLRC4 inflammato-somes are highly expressed in MM,and promote the occurrence and development of tumor by pro-moting the production and release of inflammatory cytokines/chemokines IL-18 and CCL-3,which is of great significance for the formulation of treatment plan and clinical prognosis evaluation of multiple myeloma.

AIM To analyze the dynamic change patterns of aflatoxin B1,aflatoxin B2,aflatoxin G1,aflatoxin G2,T-2 toxin and deoxynivalenol contents during the fermentation of Massa Medicata Fermentata.METHODS The analysis was performed on a 40 ℃ thermostatic Waters ACQUITY UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.01％formic acid-[acetonitrile-methanol(1∶1)]flowing at 0.3 mL/min,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.RESULTS Six mycotoxins showed good linear relationships within their own ranges(R2＞0.998 0),whose average recoveries were 76.1％-119.3％with the RSDs of 0.49％-9.27％,and except for deoxynivalenol,their contents demonstrated the trends of growing out of nothing and gradually increasing.CONCLUSION The risk of mycotoxin infection exists in the fermentation of Massa Medicata Fermentata.This simple,efficient,rapid and sensitive method can provide a reference for whole-process monitoring the fermentation process for Massa Medicata Fermentata.

AIM:To explore the mechanism of ac-tion and clinical significance of NLRC4 in multiple myeloma by analyzing the relative expression and clinical significance of NLRC4 mRNA in bone mar-row fluid of patients with multiple myeloma(MM),so as to guide the formulation of disease treatment and the evaluation of clinical prognosis.METHODS:MMRF database and GTEx database were used to compare the expression and survival correlation of inflammatory bodies between myeloma patients and normal controls.Real-time fluorescent quanti-tative polymerase chain reaction(qPCR)was used to detect the expression of inflammatory bodies in bone marrow fluid of 26 newly diagnosed myeloma patients and 19 post-treatment myeloma patients and peripheral blood of 28 normal volunteers ad-mitted to the First Affiliated Hospital of Anhui Medi-cal University from January to September 2023.The mRNA expression differences of each inflammatory body and the correlation between NLRC4 inflamma-tory body expression and clinicopathologic fea-tures,inflammatory factor/chemokine expression of newly diagnosed patients were analyzed.RE-SULTS:Compared with the control group and the treatment group,the expression of inflammasome mRNA in the newly diagnosed group was increased except for NLRP3,and the expression of NLRC4 mRNA was significantly increased(P<0.01).The he-moglobin count,creatinine level and calcium ion level were linearly correlated with NLRC4 mRNA ex-pression level in newly diagnosed patients(P<0.05).The mRNA expression levels of IL-18,CCL-3 and NL-RC4 in newly diagnosed patients were linearly cor-related(P<0.05).CONCLUSION:NLRC4 inflammato-somes are highly expressed in MM,and promote the occurrence and development of tumor by pro-moting the production and release of inflammatory cytokines/chemokines IL-18 and CCL-3,which is of great significance for the formulation of treatment plan and clinical prognosis evaluation of multiple myeloma.

Objective To evaluate the clinical efficacy and safety of the daratumumab-based regimens,including daratumumab,dexamethasone,and lenalidomide(DRd),as well as daratumumab,dexamethasone,and bortezomib(DVd),in the treatment of patients with relapsed or refractory multiple myeloma(RRMM)at our center.Methods Eighty patients with RRMM were assigned to either the DRd group(42 cases)or the DVd group(38 cases)based on their treatment regimens.Both groups received a baseline treatment of daratumumab combined with dexamethasone(Dd regimen).In the DVd group,1.3 mg/m2 of bortezomib was administered subcutaneously on days 1,4,8,and 11 of each cycle,followed by a 10 day drug-free interval(days 12～21),repeated every 3 weeks until disease progression.In the DRd group,25 mg of lenalidomide was orally administered daily from day 1 to day 21 of each cycle,in addition to the Dd regimen,continuing until disease progression.The two groups were compared in terms of laboratory parameters,tumor markers,clinical efficacy,safety profiles,and long-term prognostic outcomes.Results After treatment,the overall response rate(ORR)of the DRd group and the DVd group was 78.57%(33 out of 42 cases)and 52.63%(20 out of 38 cases),respectively.The serum creatinine(SCr)levels were(92.54±14.33)and(102.07±15.41)μmol/L,respectively;the M protein contents were(19.62±2.04)and(21.08±2.23)g/L,respectively;the β2-microglobulin(β2-MG)levels were(3.49±1.12)and(4.16±1.25)mg/L,respectively;and the progression-free survival rates were 42.86%(18 out of 42 cases)and 26.32%(10 out of 38 cases),respectively.All these indicators showed statistically significant differences between the DRd group and the DVd group(all P<0.05).The incidence rates of adverse reactions in the observation group and the control group were 14.29%(6 out of 42 cases)and 13.16%(5 out of 38 cases),respectively,and the difference was not statistically significant(P>0.05).Conclusion The DRd regimen demonstrates superior efficacy compared to the DVd regimen in treating patients with RRMM,leading to improved patient prognosis with a favorable safety profile.

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides