ObjectiveTo investigate the expression patterns of key steroidogenic enzymes （CYP11A1， HSD3B1， and CYP19A1） in placental tissues from preeclampsia （PE） patients and evaluate​ their potential as biomarkers for PE. MethodsA case-control study was conducted using placental tissues from PE patients （PE group， n=3） and normotensive pregnant women （control group， n=3）. RNA sequencing was performed to identify differentially expressed genes （DEGs）， followed by validation of target gene expression using Western blot， qRT-PCR， and immunohistochemistry. Steroid hormone levels in placental tissues and serum were measured by ELISA. Spearman correlation analysis was used to assess associations between protein expression and clinical parameters， and receiver operating characteristic （ROC） curve analysis was performed to evaluate the predictive value of target genes for PE. ResultsThe results showed that 501 DEGs （P<0.05 and |Log₂Fold Change| >1） were identified in PE placental tissues， with KEGG enrichment analysis revealing significant involvement in steroid hormone biosynthesis pathways. Compared with the control group， PE placental tissues exhibited significantly decreased protein and mRNA expression of HSD3B1 and CYP19A1 （P<0.01）， while CYP11A1 expression was upregulated （P<0.05）. Serum estradiol （E2） and progesterone （P4） levels were significantly reduced in the PE group （P<0.01）， whereas testosterone （T） levels were elevated （P<0.05）. Correlation analysis demonstrated that CYP11A1 expression was positively associated with systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and soluble fms-like tyrosine kinase-1 （sFlt-1） （P<0.01）， but negatively correlated with placental growth factor （PLGF） （P<0.01）. Conversely， HSD3B1 and CYP19A1 expression showed inverse correlations with these clinical parameters （P<0.01）. ROC analysis revealed that CYP11A1， HSD3B1， and CYP19A1 each had an area under the curve （AUC） of 0.778 for predicting PE， with 95%CI ranging from 0.614 to 0.942 （P=0.004）. The sensitivity was 94.4%， and the specificity was 66.7%. ConclusionThese findings suggest that dysregulated expression of steroidogenic enzymes in PE placental tissues contributes to hormonal imbalance， thereby playing a role in PE pathogenesis. Furthermore， CYP11A1， HSD3B1， and CYP19A1 may serve as potential diagnostic biomarkers for PE.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

Diabetic macular edema(DME), a serious complication of diabetic retinopathy(DR), is a chronic condition caused by multiple factors. Throughout its progression, inflammatory factors and vascular endothelial growth factor(VEGF)play a critical role. Anti-VEGF drugs have shown significant effectiveness in the treatment of DME; however, some patients may experience persistent DME after injection or require frequent injections. Dexamethasone intravitreal implants(DEX implants)serve as a sustained-release implant characterized by a reasonable release profile and high bioavailability. They offer safe, effective, and prolonged anti-inflammatory effects, aiding in the repair of retinal barrier and reduction of exudation. To further enhance patients' visual quality, exploring the efficacy of DEX implants in combination with existing treatment regimens has great clinical significance. This review primarily discusses the research advancements in DEX implants, focusing on their pharmacological properties, indications for use, and their combination with existing drugs and treatment methods. It also evaluates the advantages and disadvantages of combination therapy or switching to DEX implants compared to current standard treatments, aiming to provide guidance for personalized treatment options for patients with DME.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Alterations in the gut microbiota can lead to the occurrence of autoimmune diseases and affect the immune system through various metabolic pathways，ultimately causing damage to target organs. Short-chain fatty acids（SCFAs），the common metabolic product of the gut microbiota，are closely related to the functions of multiple organs and diseases. An increasing number of studies have shown that SCFAs can regulate the immune response of the body and influence the immune process of various autoimmune diseases. However，there are relatively few domestic studies on the relationship between SCFAs and autoimmune diseases in childhood. This article aims to explore the role of SCFAs in various common autoimmune diseases in childhood and summarize the alleviation of clinical manifestations in children with various autoimmune diseases by SCFAs，providing research ideas for exploring the pathogenesis of various autoimmune diseases，and enrich the theoretical basis for conducting fecal microbiota transplantation therapy.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People