BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective To investigate the regulatory role and mechanism of lobetyolin(LBT,a poly-acetylene glycoside isolated from the roots of Codonopsis pilosula)in the proliferation and apop-tosis of brain glioma cells based on the Akt/GSK-3β/Snail signaling pathway.Methods Human brain glioma cell line U-373MG was randomly divided into normal,SC79(Akt activator),LBT,and LBT+SC79 groups.After corresponding interventions,CCK-8 assay,colony formation assay,and flow cytometry were used to detect the proliferation and apoptosis of the cells.Western blot-ting was employed to measure the protein expression levels of the molecules related to prolifera-tion,apoptosis,and Akt/GSK-3β/Snail signaling pathway.After tumor xenograft nude mouse model of U-373MG cells was established,followed by grouping and interventions as above cell experiments,the tumor weight and volume were measured.Immunohistochemical assay and TUNEL assay were performed to detect the proliferation and apoptosis of tumor cells.Western blotting was applied to detect Akt/GSK-3β/Snail signaling pathway related proteins in the nude mouse groups.Results In the LBT+SC79 group,cell viability,number of formed colonies,pro-tein levels of cyclin D1,Bcl-2 and Snail,p-Akt/Akt and p-GSK-3β/GSK-3β,tumor weight and vol-ume,and positive ratios of Ki67,cyclin D1 and Bcl-2 in transplanted tumors were increased(P＜0.05),and cell apoptotic rate[(3.20±1.14)％vs(46.15±1.52)％,P＜0.05],Bax protein level(0.51±0.07 vs 0.89±0.06,P＜0.05),and positive ratios of TUNEL[(51.56±7.13)％vs(74.95±8.61)％,P＜0.05]and Bax[(32.71±5.43)％vs(41.86±4.90),P＜0.05]in transplanted tumors were declined when compared with the LBT group.Conclusion LBT can induce apoptosis and inhibit proliferation of brain glioma cells in vitro and in vivo by blocking activation of the Akt/GSK-3β/Snail signaling pathway.

Objective To compare the efficacy and safety of flexible ureteral lithotripsy(FURL)and non-retrograde percutaneous nephrolithotomy(NR-PCNL)for treating1.5-2.0 cm upper ureteral stones.Methods We retrospectively analyzed clinical data of 130 patients with upper ureteral stones treated between October 2022 and October 2024.Sixty-two patients underwent FURL and 68 underwent NR-PCNL.Comparisons included operative time,pre-and postoperative changes in white blood cells(WBC),hemoglobin(Hb),and creatinine(Cr),postoperative C-reactive protein(CRP)levels,stone-free rate after primary surgery,postoperative hospitalization duration,pain scores,complications,and need for auxiliary treatments.Results Compared to the FURL group,the NR-PCNL group demonstrated advantages in operative time[54.0(44.3,69.3)min vs.82.5(66.0,101.0)min,Z=-5.565,P<0.001],WBC elevation[1.9(0.5,3.5)×109/L vs.4.5(3.0,6.0)×109/L,Z=-4.528,P<0.001],and secondary surgery rate[0%(0/68)vs.14.5%(9/62),P<0.001].The FURL group showed lower Hb reduction[3.0(2.0,6.3)g/L vs.8.0(5.0,11.0)g/L,Z=-4.262,P<0.001],less postoperative Visual Analogue Scale(VAS)pain scores[1.0(1.0,2.0)points vs.2.0(1.0,2.0)points,Z=-2.840,P=0.005],and shorter hospitalization duration[2.0(1.0,2.0)d vs.3.0(2.0,3.0)d,Z=-5.815,P<0.001].No significant differences were observed in Cr elevation,CRP levels,stone-free rate after primary surgery,complications,or analgesic requirements(P≥0.05).Conclusions Both NR-PCNL and FURL are safe and effective for 1.5-2.0 cm upper ureteral stones.FURL offers better patient comfort,while NR-PCNL shows superior overall safety.

Objective:To develop the Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)for assessing psychological crises in adolescents using item response theory(IRT).Methods:A total of 8 679 students,aged 9 to 19 years,were sampled from 14 primary and secondary schools.The item bank was constructed by examining unidimensionality,independence,discrimination,and Differential Item Functioning(DIF).The AMH-CAT algorithm was developed using R software and validated for reliability and validity through real and simulated data.The School Psychological Interview Evaluation Form served as the criterion tool to assess the predictive validi-ty of AMH-CAT in evaluating psychological crises levels.Results:The item bank,consisting of 43 items,demon-strated unidimensionality and independence,with discrimination values＞0.80 and no DIF across genders.Under va-rious stopping rules,AMH-CAT showed ABS values＜0.40,RMSE values＜0.50,and a correlation(r)＞0.87(P＜0.001)between estimated and true psychological crises levels.Real participants answered an average of 10 items under the SE(θ)≤0.4 stopping rule,with a reliability of 0.89,and the scores were positively correlated with the complete item bank scores(r=0.95,P＜0.001).The predictive accuracy for Level 1 and Level 2 concerns was 0.89 and 0.90,respectively.Conclusion:The Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)demonstrates excellent validity,reliability and assessment efficiency for evaluating adolescent psychological crises.

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.

Objective:To develop the Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)for assessing psychological crises in adolescents using item response theory(IRT).Methods:A total of 8 679 students,aged 9 to 19 years,were sampled from 14 primary and secondary schools.The item bank was constructed by examining unidimensionality,independence,discrimination,and Differential Item Functioning(DIF).The AMH-CAT algorithm was developed using R software and validated for reliability and validity through real and simulated data.The School Psychological Interview Evaluation Form served as the criterion tool to assess the predictive validi-ty of AMH-CAT in evaluating psychological crises levels.Results:The item bank,consisting of 43 items,demon-strated unidimensionality and independence,with discrimination values＞0.80 and no DIF across genders.Under va-rious stopping rules,AMH-CAT showed ABS values＜0.40,RMSE values＜0.50,and a correlation(r)＞0.87(P＜0.001)between estimated and true psychological crises levels.Real participants answered an average of 10 items under the SE(θ)≤0.4 stopping rule,with a reliability of 0.89,and the scores were positively correlated with the complete item bank scores(r=0.95,P＜0.001).The predictive accuracy for Level 1 and Level 2 concerns was 0.89 and 0.90,respectively.Conclusion:The Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)demonstrates excellent validity,reliability and assessment efficiency for evaluating adolescent psychological crises.

Objective:To analyze the clinicopathological characteristics of atypical teratoid/rhabdoid tumors (AT/RT) and the causes of pathological misdiagnosis, and summarize diagnostic strategies.Methods:A case series study was conducted.Specifically, the data of 5 misdiagnosed(misdiagnosed group) and 8 confirmed AT/RT cases(confirmed group) in the Department of Pathology of Xi′an Children′s Hospital from January 2010 to December 2018 were retrospectively analyzed.Hematoxylin-eosin and immunohistochemical staining were performed to analyze clinical features, morphology, and immune phenotypes.Rates were compared between the misdiagnosed and confirmed groups by a Fisher′s exact test.Means were compared using an independent sample t-test.Medians were compared by a Mann-Whitney U test. Results:(1)There were 4 males and 1 female in the misdiagnosed group, with a median age of 24 months.In this group, 4/5 tumors were located in the posterior cranial fossa, and 1/5 tumors were located in the spinal cord.Morphologically, rhabdoid cells were detected in 3/5 cases, and the other 2/5 cases consisted of small embryonal cells.Immunohistochemically, INI1 and BRG1 expressions were absent in 4/5 and 1/5 cases, respectively.All of them showed multiple immunephenotypes.There were 7 males and 1 female in the confirmed group, with a median age of 22 months.In the confirmed group, 4/8 tumors were located in the supratentorial region and 4/8 tumors were located in the infratentorial region.Rhabdoid cells, deficient INI1 expression and multiple immunephenotypes were observed in all 8 cases.(2)The percentage of rhabdoid cells in the misdiagnosed group was significantly lower[0.45(0, 0.46)] than that in the confirmed group[0.55(0.40, 0.85)]( Z=-2.064, P=0.039). Conclusions:The causes of misdiagnosis of AT/RT are variable sites of occurrence, diverse histomorphology, multiple phenotypes in immunohistochemistry and rare BRG1 deficiency.For high-grade rhabdoid, epithelioid, and/or embryonic small cell tumors, AT/RT should be differentiated and immunohistochemistry protocols should include INI1 and BRG1.

Objective To analyze the risk factors of permanent hypoparathyroidism(pHPP)after total thyroidectomy in patients with thyroid cancer and establish a nomogram prediction model.Methods A total of 245 patients with thyroid cancer who received total thyroidectomy in our hospital were enrolled between January 2020 and January 2024.According to presence or absence of postoperative pHPP,patients were divided into the pHPP group and the non-pHPP group.The influencing factors of postoperative pHPP in patients with thyroid cancer were analyzed by univariate and multivariate Logistic regression analysis.The nomogram prediction model for postoperative pHPP in patients with thyroid cancer was constructed and varified,and efficiency of the model was evaluated.Results In 245 patients with thyroid cancer,the incidence of pHPP within 6 months after surgery was 10.20%(25/245).Univariate analysis showed that there were significant differences in tumor size,surgical method,central lymph node dissection,use of nano carbon tracer,envelope invasion,parathyroid excision by mistake,Hashimoto thyroiditis,serum calcium and parathyroid hormone at 1 d after surgery between the two groups(P＜0.05),but there were no significant differences in gender,age,smoking,drinking,extraglandular invasion,parathyroid autologous transplantation,preoperative vitamin D or serum phosphorus at 1 d after surgery between the two groups(P＞0.05).Multivariate analysis showed that maximum tumor diameter≥4 cm,routine and open total thyroidectomy,central lymph node dissection,no use of nano carbon tracer and parathyroid excision by mistake were all independent risk factors for postoperative pHPP in patients with thyroid cancer(P＜0.05).Results of nomogram prediction model showed that C-index was 0.921,the corrected curve was close to ideal curve,and AUC of nomogram model for predicting postoperative pHPP was 0.926(95%CI:0.871-0.981).Conclusion The nomogram prediction model constructed based on independent risk factors of postoperative pHPP has good predictive efficiency in patients with thyroid cancer.

Objective To observe the value of changes of neutrophil-to-lymphocyte ratio(NLR)before and after the first interventional treatment of hepatocellular carcinoma(HCC)for predicting patient's overall survival(OS).Methods Totally 92 HCC patients who underwent the first time TACE or TACE+hepatic artery infusion chemotherapy(HAIC)were retrospectively enrolled.The patients were divided into NLR ratio(NLRR)＜1.29 group(n=54)and≥1.29 group(n=38)based on the ratio of NLR after to before treatment,also ΔNLR＜0.87 group(n=60)and≥0.87 group(n=32)based on the difference of NLR after and before treatment.Clinical data were compared between groups,survival analysis was performed,and the value of NLRR and ΔNLR for predicting OS were analyzed.Results No significant difference of clinical data was found between NLRR＜1.29 and≥1.29 groups,nor between ΔNLR＜0.87 and≥0.87 groups(all P＞0.05).The median OS of 92 patients was 30.90 months,which in NLRR＜1.29 group(55.10 months)was longer than that in NLRR≥1.29 group(22.30 months,P=0.005),while in ΔNLR＜0.87 group(55.10 months)was longer than that in ΔNLR≥0.87 group(14.20 months,P=0.003).Cox regression analysis showed that the maximum diameter of tumor≥5 cm,distant metastasis,ascites,NLRR≥1.29 and ΔNLR≥0.87 were all independent risk factors of OS(all P＜0.05).Taken 1.29 and 0.87 as the best cut-off value,respectively,the area under the curve of NLRR and ΔNLR for predicting OS was 0.620 and 0.610,respectively.Conclusion NLRR and ΔNLR were helpful for predicting OS of HCC patient after the first interventional treatment.

Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.