Objective To investigate the predictive value of serum Nesfatin-1 and 25-hydroxyvitamin D3[25(OH)D3]levels for the short-term prognosis of status epilepticus(SE)in children.Methods A total of 104 children with SE admitted to the hospital from March 2020 to March 2023 were enrolled in the study,and the clinical data of the children were collected.According to the Glasgow outcome Scale(GOS)score at dis-charge,the children were divided into a good prognosis group(equal to 5 points)and a poor prognosis group(＜5 points).Univariate analysis and multivariate Logistic regression were used to analyze whether serum Nesfatin-1 and 25(OH)D3 levels were risk factors for poor short-term prognosis in children with SE.The re-ceiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum Nesfatin-1 and 25(OH)D3 levels for the short-term poor prognosis in children with SE.Results At discharge,85 children[81.73％(85/104)]with a GOS score of 5 were included in the good prognosis group,and 19 children[8.27％(19/104)]with a GOS score of＜5 were included in the poor prognosis group.There was no significant differ-ence in gender,age,previous history of epilepsy,and seizure types between the two groups(P＞0.05).There were significant differences in the duration of SE,the time from medication to seizure cessation,electroenceph-alogram(EEG)results,head CT results,and serum Nesfatin-1 and 25(OH)D3 levels between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that SE duration＞60 min,abnormal head CT results,serum Nesfatin-1 and 25(OH)D3 levels were independent risk factors for the short-term poor progno-sis of children with SE(OR=1.945,2.343,1.731,1.505;P＜0.05).The area under the ROC curve of serum Nesfatin-1 and 25(OH)D3 levels combined to predict poor short-term prognosis of children with SE was 0.840(95％CI:0.732-0.949),which was better than that of serum Nesfatin-1 and 25(OH)D3 levels alone[0.607(95％CI:0.453-0.761),0.742(95％CI:0.604-0.880)],respectively.Conclusion Serum Nesfatin-1 and 25(OH)D3 levels are risk factors for poor prognosis in children with SE,and the combination of them has high predictive value for poor prognosis in children with SE.

Objective:To analyze the risk factors related to the prognosis of patients with sepsis in intensive care unit (ICU), construct a nomogram model, and verify its predictive efficacy.Methods:A retrospective cohort study was conducted using data from Medical Information Mart for Intensive Care-Ⅳ 0.4 [MIMIC-Ⅳ (version 2.0)]. The information of 6 500 patients with sepsis who meet the diagnostic criteria of Sepsis-3 were collected, including demography characteristics, complications, laboratory indicators within 24 hours after ICU admission, and final outcome. Using a simple random sampling method, the patients were divided into a training set and a validation set at a ratio of 7∶3. The restricted cubic spline (RCS) was used to explore whether there was a linear relationship between each variable and the prognosis, and the nonlinear variables were truncated into categorical variables. All variables were screened by LASSO regression and included in multivariate Cox regression analysis to analyze the death risk factors in ICU patients with sepsis, and construct a nomograph. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the prediction efficiency of nomogram model. The decision curve analysis (DCA) was used to validate the clinical value of the model and its impact on actual decision-making.Results:Among 6 500 patients with sepsis, 4 551 were in the training set and 1 949 were in the validation set. The 28-day, 90-day and 1-year mortality in the training set were 27.73% (1?262/4?551), 34.76% (1?582/4?551), and 42.98% (1?956/4?551), respectively, those in the validation set were 27.24% (531/1?949), 33.91% (661/1?949), and 42.23% (823/1?949), respectively. Both in training set and the validation set, compared with the final survival patients, the death patients were older, and had higher sequential organ failure assessment (SOFA) score and simplified acute physiology scoreⅡ (SAPSⅡ), more comorbidities, less urine output, and more use of vasoactive drugs, kidney replacement therapy, and mechanical ventilation. By RCS analysis, the variables with potential nonlinear correlation with the prognosis risk of septic patients were transformed into categorical variable. The variables screened by LASSO regression were enrolled in the multivariate Cox regression model. The results showed that age [hazard ratio ( HR) = 1.021, 95% confidence interval (95% CI) was 1.018-1.024], SOFA score ( HR = 1.020, 95% CI was 1.000-1.040), SAPSⅡ score > 44 ( HR = 1.480, 95% CI was 1.340-1.634), mean arterial pressure (MAP) ≤ 75 mmHg (1 mmHg ≈ 0.133 kPa; HR = 1.120, 95% CI was 1.026-1.222), respiratory rate (RR; HR = 1.044, 95% CI was 1.034-1.055), cerebrovascular disease ( HR = 1.620, 95% CI was 1.443-1.818), malignant tumor ( HR = 1.604, 95% CI was 1.447-1.778), severe liver disease ( HR = 1.330, 95% CI was 1.157-1.530), use of vasoactive drugs within 24 hours ( HR = 1.213, 95% CI was 1.101-1.336), arterial partial pressure of oxygen (PaO 2; HR = 0.999, 95% CI was 0.998-1.000), blood lactic acid (Lac; HR = 1.066, 95% CI was 1.053-1.079), blood urea nitrogen (BUN) > 8.9 mmol/L ( HR = 1.257, 95% CI was 1.144-1.381), total bilirubin (TBil; HR = 1.023, 95% CI was 1.015-1.031), and prothrombin time (PT) > 14.5 s ( HR = 1.232, 95% CI was 1.127-1.347) were associated with the death of ICU patients with sepsis (all P < 0.05). Based on the above factors, a nomogram model was constructed, and the model validation results showed that the consistency index was 0.730. The calibration curve showed a good consistency between the predicted results of the nomogram model and observed results in the training and validation sets. ROC curve analysis showed that the area under the ROC curve (AUC) predicted by the nomogram model in the training set and the validation set for 28-day, 90-day and 1-year death risk was 0.771 (95% CI was 0.756-0.786) and 0.761 (95% CI was 0.738-0.784), 0.777 (95% CI was 0.763-0.791) and 0.765 (95% CI was 0.744-0.787), 0.677 (95% CI was 0.648-0.707) and 0.685 (95% CI was 0.641-0.728), respectively. DCA analysis showed that the nomogram model had significant net benefits in predicting 28-day, 90-day, and 1-year death risk, verifying the clinical value of the model and its good impact on actual decision-making. Conclusions:The death risk factors related to ICU patients with sepsis include age, SOFA score, SAPSⅡ score > 44, MAP ≤ 75 mmHg, RR, cerebrovascular disease, malignant tumors, severe liver disease, use of vasoactive drugs within 24 hours, PaO 2, Lac, BUN, TBil, PT > 14.5 s. The nomogram model constructed based on this can predict the death risk of ICU patients with sepsis.

Objective To analyze the expression of N-MYC and N-MYC downstream regulated gene-1(NDRG1)in gastric cancer tissues,and to assess their effects on biological characteristics of gastric cancer cells.Methods Paired of gastric cancer tissues and adjacent normal tissues resected from 82 cases of patholog-ically confirmed gastric cancer who underwent surgical treatment in the hospital from January 2021 to May 2023 were collected.Gastric cancer tissues and adjacent normal tissues of 82 patients who were surgically re-sected and pathologically diagnosed with gastric cancer in the hospital from January 2021 to May 2023 were collected.Real-time quantitative PCR(qPCR)was used to detect the relative mRNA expression levels of N-MYC and NDRG1,and clinical data of the patients were collected.The correlation between the mRNA expres-sion of N-MYC and NDRG1 and clinicopathological features of the patients was discussed.NCI-N87 cells in logarithmic growth phase were selected and cultured in vitro.N-MYC interference plasmid(si-N-MYC)and its negative control(si-NC)was transfected into NCI-N87 cells,respectively,which were recorded as si-NC group and si-N-MYC group.Moreover,si-N-MYC was co-transfected into NCI-N87 cells with anti-NC and an-ti-NDRG1,respectively,and denoted as si-N-MYC+anti-NC group and si-N-MYC+anti-NDRG1 group.CCK-8 assay was used to detect cell proliferation activity,Transwell assay was used to detect cell invasion ability,and Western blotting assay was used to detect N-MYC and NDRG1 protein expression in cells.Results The relative expression of N-MYC mRNA in gastric cancer tissues was higher than that in paracancer tissues(P＜0.05),and the relative expression of NDRG1 mRNA was lower than that in paracancer tissues(P＜0.05).There were significant differences in the expression of N-MYC and NDRG1 mRNA in patients with different TNM stages,lymph node metastasis and distant metastasis(P＜0.05).Compared with the si-NC group,the cell proliferation and invasion ability of the si-N-MYC group were decreased(P＜0.05),and the expression of NDRG1 protein was down-regulated(P＜0.05).Compared with si-N-MYC+anti-NC group,cell proliferation and invasion ability of si-N-MYC+anti-NDRG1 group were increased(P＜0.05).N-MYC could target and regulate NDRG1,and knocking down NDRG1 could reverse the biological effects of N-MYC on gastric cells.Conclusion In gastric cancer tissue,N-MYC mRNA expression is upregulated and NDRG1 mRNA expression is downregulated,both of which play important roles in the regulation of malignant biological behaviors such as proliferation and invasion of gastric cancer cells.

BACKGROUNDThe time until weight-bearing after arthroscopic microfracture when treating osteochondral lesions of the talus (OLT) is very important to the clinical outcomes of the operation. However, there have been no consistent opinions regarding the optimal time to start weight-bearing postoperatively. Many opinions advocate that weight-bearing should begin not earlier than the sixth or eighth week postoperatively, whereas others point out that earlier weight-bearing could also obtain satisfactory outcomes. The purpose of our study was to evaluate the clinical outcomes of early weight-bearing after arthroscopic microfracture during the treatment of OLT.

METHODSFifty-eight ankles in 58 patients with a single OLT <2 cm(2) were retrospectively studied. All lesions were treated with arthroscopic debridement and microfracture under local anesthesia. After the operation, the patients were allowed to bear full weight under the protection of figure-8-shaped splints. The visual analog scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle--hindfoot scale were evaluated preoperatively and at six postoperative timepoints (1st day, 1st month, 3rd month, 6th month, 12th month, and 24th month). Patients were followed up for 24-52 months (mean (34.97 ± 7.33) months).

RESULTSAll 58 patients achieved excellent recovery with significant relief of their symptoms. The VAS score decreased from 7.31 ± 1.0 preoperatively to 0.95 ± 0.76 at the 24th month follow-up (P = 0.000), whereas the AOFAS score improved from 53.53 ± 8.57 preoperatively to 87.62 ± 5.42 at the 24th month follow-up (P = 0.000).

CONCLUSIONThe successful clinical outcomes of this study demonstrated that early weight-bearing after the treatment of OLT with arthroscopic microfracture can be allowed.

Adolescent ; Adult ; Arthroscopy ; Female ; Fractures, Bone ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Talus ; injuries ; surgery ; Weight-Bearing ; physiology ; Young Adult

OBJECTIVETo analyze the 3 dimensional-fat suppression-spoiled gradient-recalled acquisition (3D-FS-SPGR) sequence in the diagnosis of knee articular cartilage injury.

METHODSA total of 56 knee osteoarthritis patients (26 males, 30 females, ages 52-73 years, mean 61.8 years) treated in Department of Orthopedics, Chinese People's Liberation Army General Hospital between June 2013 and May 2014 were involved in this study. All patients underwent knee MRI, plus 3D-FS-SPGR sequence, arthroscopic exploration, and in contrast to the results of MRI results analysis, evaluation 3D-FS-SPGR and conventional sequence of cartilage damage consistent with the arthroscopic accuracy.

RESULTSDivided 56 knee joints into 336 cartilage articular surface, included 55.1% normal articular surface, 21.4% early osteoarthritis and 23.5% advanced osteoarthritis. The accordance of 3D-FS-SPGR sequence grading and arthroscopic was 90.2%. The sensitivity of 3D-FS-SPGR sequence was 93.1%, specificity was 98.3%, and Kappa value was 0.849. The sensitivity of T2WI sequence was 84.4%, specificity was 96.9%, and the Kappa value was 0.671.

CONCLUSIONFor unicompartment osteoarthritis , MRI 3D-FS-SPGR sequence is effective in sensitivity and specificity of cartilage damage.

Aged ; Arthroplasty ; Arthroscopy ; Cartilage, Articular ; Female ; Humans ; Knee Injuries ; diagnosis ; Knee Joint ; physiopathology ; surgery ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Orthopedic Procedures ; Osteoarthritis, Knee ; surgery ; Preoperative Care ; Sensitivity and Specificity

OBJECTIVETo investigate the proliferation inhibitory role and mechanism of PI3Kδ inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment.

METHODSMM cell lines U266 and RPMI8226 cells were treated with various concentrations of CAL-101. MTT assay and CalcuSyn software were performed to determine the inhibitory effect of CAL-101 and the synergistic effect with PCI- 32765, SAHA (suberoylanilide hydroxamic acid), BTZ (Bortezomib) on MM cells. The protein expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ processed by CAL-101 were analyzed by Western blot.

RESULTSCAL-101 at concentration of 15, 20, 25, 30 and 40 μmol/L could induce significant dose-dependent proliferation inhibition on U266 cells after treatment for 48 hours. The cell proliferation inhibition rates were (33.54 ± 1.23)%, (41.72 ± 1.78)%, (53.67 ± 2.01)%, (68.97 ± 2.11)% and (79.25 ± 1.92)%, respectively. Similar results were found in RPMI8226 cell line. Western blots showed high expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ in cell lines and MM primary cells. p-AKT and p-ERK protein expression levels were down-regulated significantly by CAL-101 treatment. Synergistic effect has been verified between CAL-101 and PCI-32765, SAHA and Bortezomib in U266 cell line, and PCI-32765, Bortezomib in RPMI8226 cell line with CI values less than 1.

CONCLUSIONCAL-101 could inhibit proliferation of MM cell lines. High levels of p-AKT, p-ERK, AKT, ERK and PI3Kδ protein expression were observed in both cell lines and primary cells. Down-regulation of p-AKT and p-ERK probably related with the mechanism of CAL-101 in MM cell proliferation inhibition. CAL-101 has significant synergistic effect with PCI-32765, SAHA and BTZ.

Boronic Acids ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Humans ; Multiple Myeloma ; pathology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Pyrazines ; Pyrazoles ; Pyrimidines ; Quinazolinones ; pharmacology

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone