Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of children with refractory nephrotic syndrome （RNS） based on the real world by meta-analysis. METHODS A systematic search was conducted on CNKI， Wanfang， VIP， PubMed， Embase， Web of Science， the Cochrane Library， and CINAHL databases to strictly screen the literature and evaluate their quality. A meta-analysis was performed on the extracted literature data using R 4.2.2 and RStudio software. RESULTS A total of 26 real-world studies were included in this study， involving 996 children with steroid-dependent nephrotic syndrome/frequente-relapse nephrotic syndrome （SDNS/FRNS） and 205 children with steroid-resistant nephrotic syndrome （SRNS）. The results of the meta-analysis showed that the complete remission （CR） rate of RTX treatment for RNS was 46% （95%CI： 37%-56%）， the partial remission （PR） rate was 22% （95%CI： 14%-31%）， and the discontinuation rate was 35% （95%CI： 25%-44%）. The results of subgroup analysis showed that the CR rate of RTX treatment in SDNS/FRNS children was 49% （95%CI： 37%-62%）， PR rate was 25% （95%CI： 0-50%）， discontinuation rate was 41% （95%CI： 29%-52%）； the CR rate in SRNS children was 42% （95%CI： 27%-56%）， PR rate was 22%（95%CI： 12%-32%）， discontinuation rate was 21% （95%CI： 4%-38%）. The recurrence rate in children with SDNS/FRNS was 39% （95%CI： 21%-57%） within 1 year or less， 18% （95%CI： 18%-98%） in 2 years and more. As for safety， the majority of adverse reactions were mild infusion reactions， with an incidence of 13% （95%CI： 8%-22%）. Sensitivity analysis suggested that the results were robust. There was publication bias in mild infusion 20210908-BZ-CACM） reaction rate. CONCLUSIONS RTX is effective and safe in the treatment of RNS in children.

BackgroundVestibular neuritis is a common clinical acute peripheral vertigo disorder. Some patients may experience negative emotions states， leading to chronic exacerbation of vestibular neuritis and a poorer prognosis. Further research is needed to understand the psychological state of patients with vestibular neuritis and its influencing factors. ObjectiveTo explore the relationship between depressive symptoms and vestibular symptoms in patients with vestibular neuritis and its influencing factors， so as to provide references for clinical intervention. MethodsA total of 86 patients with vestibular neuritis， hospitalized in the Department of Neurology of the Third Hospital of Mianyang from June 2021 to June 2023， were included in the study. Assessments were conducted using the Hamilton Depression Scale-17 item （HAMD-17）， Dizziness Assessment Rating Scale （DARS） and Dizziness Handicap Inventory （DHI）. Patients were divided into depression group（n=46） and non-depression group（n=40） based on HAMD-17 score. Pearson correlation analysis was used to examine the correlation among each scale score. Binary Logistic regression was used to identify influencing factors for depressive symptoms. ResultsAmong the 86 patients， 46 （53.49%） exhibited depressive symptoms. Statistically significant differences were observed between depression group and non-depression group in terms of age， disease duration， years of education， DARS score and DHI score （t=4.512， 4.921， 2.712， 3.529， 5.471， P<0.01 ）. In depression group， HAMD-17 score was positively correlated with DARS score and DHI score （r=0.345， 0.335， P<0.01）. Binary Logistic regression analysis showed that age （OR=4.352， 95% CI： 1.520~12.462）， disease duration（OR=3.772， 95% CI： 1.339~10.630）， years of education （OR=0.074， 95% CI： 0.235~0.923）， DARS score （OR=1.213， 95% CI： 0.405~3.628） and DHI score （OR=3.619， 95% CI： 1.246~10.514） were the influencing factors of depressive symptoms among patients with vestibular neuritis. ConclusionDepressive symptoms in patients with vestibular neuritis are positively correlated with vestibular symptoms. Risk factors for depressive symptoms in patients with vestibular neuritis include age， disease duration， DARS score and DHI score， while years of education serve as a protective factor.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

【Objective】 To determine the volume range of suspended erythrocyte and establish its internal control standard. 【Methods】 The theoretical value of suspended erythrocyte volume was calculated according to the screening criteria of healthy blood donors and Quality Requirements for Whole Blood and Blood Components. A total of 2 410 bags of 1 U and 2 U suspended erythrocyte were randomly selected and weighed, and the volume range were formulated by ±2S and ±10% respectively and then compared to determine the volume range in line with the actual situation of our center. 【Results】 The theoretical volume range of 1 U and 2 U suspended erythrocyte were 117-160 mL vs 234-320 mL, and the actual volume range were 142-180 mL vs 276-393 mL. The volume range of 1 U and 2 U suspended erythrocyte formulated by ±2S were 145-181 mL vs 298-358 mL, and by ±10% were 147-179 mL vs 295-361 mL. The hematocrit and hemoglobin content of suspended erythrocyte within the actual volume range met the quality requirements. There were fluctuations in the volume of suspended erythrocyte from different regions. 【Conclusion】 Based on the actual situation of our center and the sampling results of suspended erythrocytes in recent two years, 163 mL±10% and 328 mL±10% were determined as the internal control standards of 1 U and 2 U suspended erythrocyte, respectively. Blood centers should establish accurate and feasible standard of suspended erythrocyte according to the actual situation.

【Objective】 To effectively differentiate adrenal adenoma (AA) and small diameter pheochromocytoma (PCC) by establishing a clinical-radiomic nomogram model before surgery. 【Methods】 A total of 132 pathologically confirmed patients (45 PCC cases, 87 AA cases) were enrolled. After the features of enhanced CT were assessed, the radiomic features and related clinical indicators were extracted. Based on multiple Logistic regression, a clinical-radiomic nomogram with radiomic features and independent clinical predictors was developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used for internal evaluation to compare the diagnostic effectiveness of the three models. The clinical effectiveness of the nomogram was verified with decision curve analysis (DCA). 【Results】 One of the 108 candidate features was used to construct the radiological feature score. Individualized clinical-radiomic nomogram included independent clinical factors (24 h urinary vanmandelic acid/renin/angiotensin I) and original first-order median radiological feature scores. Internal evaluation of the prediction model showed that the AUC was 0.945 (95%CI:0.906-0.984), superior to the single clinical model or radiological model in precise differentiation. DCA showed that the nomogram had the best clinical use. 【Conclusion】 The clinical-radiomic nomogram model can effectively differentiate adrenal adenoma from small diameter pheochromocytoma, which can improve the preoperative differential diagnosis and preparation.

ObjectiveTo investigate the effect and mechanism of Yiyi Fuzi Baijiangsan （YYFZBJ） on the apoptosis of colon cancer cell line HCT116. MethodYYFZBJ at different concentrations （0.5， 1， 2， 4， 6， 8， 10， 12， 14， 16 g·L^-1） was used to intervene in HCT116 cells for 24， 48， 72 h. The cell counting kit-8 （CCK-8） method was used to determine the effect of YYFZBJ on cell proliferation in vitro. The cells were divided into a blank group， a capecitabine group（1.8 g·L^-1）， and low-， medium-， and high-dose YYFZBJ groups （6， 10， and 14 g·L^-1） and treated for 48 hours. Flow cytometry was used to detect the apoptosis. Hoechst 33342 staining was used to observe the apoptotic morphology of cells. Mitochondrial membrane potential （MMP） was analyzed by a mitochondrial-targeted deep-red fluorescent probe （Mito-Tracker Red CMXRos）. The expression of proteins related to the mitochondrial apoptosis pathway， such as B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cysteinyl aspartate-specific protease （Caspase）-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 was detected by Western blot. The mRNA levels of Bcl-2， Bax， Cyt C， Caspase-9， and Caspase-3 were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， YYFZBJ （8， 10， 12， 14， 16 g·L^-1） significantly inhibited the proliferation of HCT116 cells in vitro （P<0.05） in a dose-dependent manner. Compared with the blank group， the medium- and high-dose YYFZBJ groups and the capecitabine group showed increased apoptosis rates of colon cancer cells （P<0.05）. The YYFZBJ groups and the capecitabine group showed reduced number of colon cancer cells with significantly changed cellular morphology and cell apoptosis manifestations， such as strong dark blue fluorescence， nucleus concentration， shrinkage， and fragmentation. With the increase in the mass concentration of YYFZBJ， the blue fluorescence intensity was significantly enhanced. Compared with the blank group， the YYFZBJ groups and the capecitabine group showed reduced MMP in a dose-dependent manner， decreased protein and mRNA levels of Bcl-2， and increased protein expression of Bax， Cyt C， Caspase-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 and mRNA expression of Bax， Cyt C， Caspase-9， and Caspase-3 （P<0.05）. ConclusionYYFZBJ can induce the apoptosis of colon cancer HCT116 cells through the mitochondrial apoptosis pathway.

OBJECTIVES: The aim of this study was to compare the anterior and posterior occlusal plane characteristics of patients with different temporomandibular joint osseous statuses. METHODS: A total of 306 patients with initial cone beam CT (CBCT) and cephalograms were included. They were divided into three groups on the basis of their temporomandibular joint osseous status: bilateral normal (BN) group, indeterminate for osteoarthrosis (I) group, and osteoarthrosis (OA) group. The anterior and posterior occlusal planes (AOP and POP) of the different groups were compared. Then, the regression equation was established after adjusting for confounding factors, and a correlation analysis between the occlusion planes and other parameters was performed. RESULTS: SNA, SNB, FMA, SN-MP, Ar-Go, and S-Go were correlated with the occlusal planes. Relative to the BN and I groups, the FH-OP of the OA group increased by 1.67° on the average, FH-POP increased by 1.42° on the average, and FH-AOP increased by 2.05° on the average. CONCLUSIONS The occlusal planes were steeper in the patients with temporomandibular osteoarthrosis than in the patients without it, and the mandible rotated downward and backward. The height of the mandibular ramus, the mandibular body length, and the posterior face height were small. In clinical practice, attention should be given to the potential risk of temporomandibular joint osteoarthrosis in such patients. In addition, SNB, FMA, SN-MP, Ar-Go, S-Go, and occlusal planes had moderate correlations.
Humans ; Dental Occlusion ; Cephalometry ; Mandible ; Temporomandibular Joint Disorders/diagnostic imaging* ; Temporomandibular Joint/diagnostic imaging* ; Osteoarthritis/diagnostic imaging* ; Mandibular Condyle