Objective To investigate the expressions of H3.3G34W,p63 and SATB2 in giant cell tumor of bone(GCTB)and the effect and value of their combined application in the diagnosis of GCTB.Methods We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone(14 cases of aneurysmal bone cyst,16 cases of chondroblastoma and 53 cases of non-ossifying fibroma)diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi'an Jiaotong University.The expressions of H3.3G34W,p63 and SATB2 were detected by EliVision immunohistochemical method.X2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W,p63 and SATB2 among all the groups.The combined diagnostic model including H3.3G34W,p63 and SATB2 was established by Logistic regression analysis,and the diagnostic value of the model was evaluated by ROC curve analysis.Results The positive rates of H3.3G34W,p63 and SATB2 in GCTB group were 81.5％,90.7％and 92.6％,respectively;the positive rates in NGCTB group were 2.4％,28.9％and 62.7％.Compared with NGCTB group,the age of GCTB group was significantly older[(41.222±14.849)vs.(16.566±9.439),P＜0.001],and the prevalence was higher in women than in men(51.9％vs.48.1％,P＜0.001).In addition,compared with the NGCTB group,the positive rates of H3.3G34W(81.5％vs.2.4％,P＜0.001),p63(90.7％vs.28.9％,P＜0.001)and SATB2(92.6％vs.62.7％,P＜0.001)were significantly higher in the GCTB group.Univariate regression analysis built a univariate prediction modeland ROC curve analysis showed that age(AUC=92.9％,P＜0.001),sex(AUC=64.5％,P=0.004),H3.3G34W positive rate(AUC=89.5％,P＜0.001),p63 positive rate(AUC=80.9％,P＜0.001)and SATB2 positive rate(AUC=65.0％,P=0.003)were independent predictors of diagnosis of giant cell tumor of bone.Multivariate regression analysis(Logistic)constructed a hybrid prediction model.ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model(AUC=98.4％,P＜0.001).Conclusion H3.3G34W,p63 and SATB2 are effective molecular markers for the diagnosis of GCTB,and their combined application can improve the prediction efficiency of the diagnosis of GCTB.

Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.

Objective To explore the influencing factors of rational perioperative drug use,and to establish a rationality prediction model based on machine learning to assist pharmacists in prescription review.Methods A retrospective analysis was conducted on the perioperative prescription data of neurosurgery patients from a tertiary hospital and a central hospital in Shanxi Province between March 2021 and March 2023.Univariate analysis and multivariate Logistic regression were initially used to identify factors influencing rational drug use,followed by Lasso regression and multicollinearity analysis to select important variables.The data was split into a training set and test set at a ratio of 7∶3,and decision tree(DT),multi-layer perceptron(MLP),extreme gradient boosting(XGBoost),support vector machine(SVM),and random forest(RF)learning models were constructed.Results A total of 1 500 prescriptions were included,of which 668 were classified as rational and 832 as irrational.In both the training and test sets,the AUC values of the DT,XGBoost,and RF models exceeded 0.9.The DT model showed the highest sensitivity(0.81),while the RF model demonstrated the highest specificity(0.90).In the RF model,the number of comorbidities,preoperative waiting time,total hospitalization cost,prescribing physician's title,and adverse reaction occurrence negatively impacted prescription rationality,whereas the number of drugs,age,and administration route positively influenced rationality.Conclusion The machine learning-based rational drug use prediction model demonstrates strong predictive performance,effectively assisting pharmacists in prescription review and helping to reduce the incidence of irrational drug use.

Objective:To explore the automated synthesis of glucagon-like peptide-1 receptor agonist 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys) 39-exendin-4 ( 18F-exendin-4), and verify its diagnostic efficacy on insulinoma with PET/CT. Methods:Using NOTA-Mal-Cys 39-exendin-4 as the labeled precursor, 18F-exendin-4 was obtained by constructing Al 18F one-step reaction sequence and using All in one multifunctional chemical synthesizer for radiolabelling, purification and preparation. After the quality control, 18F-exendin-4 PET/CT imaging was performed on 1 patient (female, 55 years old) with clinical suspicion of insulinoma. Results:Radiolabelling of 18F-exendin-4 took about 40 min, with the non-decay corrected radiochemical yield of (18.03±2.67)% ( n=3), the molar activity>39.74 GBq/μmol, and the radioactivity concentration>390.00 MBq/ml. The injection was a colorless transparent liquid with pH value of 6.5, and the radiochemical purity>96%. Results of bacteria and endotoxins testing met the standards of Pharmacopoeia of the People′ s Republic of China (2020). PET/CT image analysis showed a nodular high uptake of 18F-exendin-4 in the pancreatic body. The pathological and immunohistochemical results were consistent with the characteristics of neuroendocrine neoplasm (G2). Conclusions:The automatic radiolabelling of 18F-exendin-4 is successfully realized by All in one multifunctional chemical synthesizer. 18F-exendin-4 has been proved to be of clinical value in diagnosis of insulinoma, and is suitable for promotion in medical institutions equipped with medical cyclotrons.

Objective:To study the combined use of neoadjuvant chemotherapy and immunotherapy in patients with borderline resectable pancreatic cancer.Methods:The clinical data of patients with pancreatic cancer who were planned to undergo perioperative treatment before surgical treatment at the Fifth Medical Center of PLA General Hospital from January 2019 to June 2021 were retrospectively studied. Of 22 patients with pancreatic cancer, there were 10 males and 12 females, aged (56.0±10.2) years old. Preoperative treatment with chemotherapy (nab-paclitaxel and S-1, AS) and immunotherapy regimen before surgery were given. The baseline characteristics, treatment efficacy, surgical pathology and prognosis were analyzed.Results:Of 22 patients who were treated with neoadjuvant chemotherapy combined with programmed death-1 (PD-1) monoclonal antibody, 11 patients (50%) had tumors in the head, neck and uncinated process of pancreas. On radiographic assessment, one patient achieved CR (4.5%, 1/22), 9 patients PR (40.9%, 9/22), and 11 patients SD (50.0%, 11/22). All patients subsequently underwent R 0 resection. The postoperative pTNM staging showed 91% (20/22) of patients were in stage IA-IIB, 31.8% (7/22) of patients had pT2, 63.6% (14/22) had N0, and 1 patient had pCR. Thirteen patients (54.2%, 13/22) received postoperative adjuvant therapy. The median recurrence-free survival (RFS) was 6.4 months and the median time to progression (TTP) was 12.8 months. The median overall survival of patients was not reached. Postoperative pathology TNM staging IIA to III ( HR=3.63, 95% CI: 1.18-11.20, P=0.025) and postoperative pathology T2-3 stage ( HR=2.02, 95% CI: 1.01-5.05, P=0.049) were significantly associated with RFS. Postoperative pathology TNM stages IIA to III ( HR=2.39, 95% CI: 1.04-5.50, P=0.041) and postoperative pathology T2-3 stage ( HR=2.53, 95% CI: 1.26-5.09, P=0.009) were significantly associated with TTP. Conclusion:AS combined with PD-1 monoclonal antibody showed good efficacy as a neoadjuvant therapy for patients with borderline-resectable pancreatic cancer.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

When this paper was first published, the authors’ affiliation

Objective To investigate the related mechanism of Slug inhibiting the proliferation of cervical cancer cell through CDH3/β-catenin/C-myc. Methods SiHa cells with stable Slug expression were screened. The expression of CDH3 in Slug-overexpressed SiHa cell was detected by RNA-sequence, Real-time PCR, Western blot and immunocytochemistry. The expression of CDH3 in SiHa and HeLa cells were detected by Western blot and immunocytochemistry. The protein level of CDH3 was up-regulated in HeLa cells or rescued in SiHa-Slug cells by transient transfection of CDH3 expression vector. The protein levels of β-catenin and C-myc were detected by Western blot, the cell growth was detected by cell counting and CCK-8 assays. Luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) were performed to detect the effect of Slug on regulating the promoter region of CDH3. Results SiHa cell line with stable Slug expression was successfully constructed. Slug overexpression inhibited CDH3 expression in SiHa cells. CDH3 promoted cell proliferation and up-regulated the protein level of β-catenin and C-myc in HeLa and SiHa-Slug cells. Slug could recognize and bind to the E-boxes in the CDH3 promoter region and inhibited the transcription of CDH3 in SiHa cells. Conclusion Slug could inhibit the expression of β-catenin and C-myc by inhibiting CDH3 transcription in SiHa cells, and then attenuate the growth of SiHa cells.

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) .Methods:The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed.Results:All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively ( P=0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P=0.033; OS: 6.3 months vs not reached, P=0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P=0.004) . Conclusion:Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Objective:To prepare a novel tri-specific T cell engager (19TriTE) targeting CD19 antigen, and to investigate its immunotherapeutic effect on CD19-positive hematological malignancies.Methods:19TriTE was constructed by molecular cloning technology and successfully expressed through the eukaryotic expressing system. The effects of 19TriTE on the proliferation and activation of T cells, as well as the specific cytotoxicity against CD19 positive tumor cell lines were verified.Results:①19TriTE expressing plasmid was constructed and successfully expressed through the eukaryotic expressing system. ②19TriTE can specifically bind to T cells and Nalm6 cells, with equilibrium dissociation constants of 19.21 nmol/L and 11.67 nmol/L, respectively. ③The expression rates of CD69 positive T cells and CD25 positive T cells were 35.4% and 49.8% respectively, when 2 nmol/L 19TriTE were added in the co-culture system, which were significantly higher than those in the control group. ④19TriTE can significantly promote the proliferation of T cells. The absolute count of T cells expanded from the initial one million to 74 million with an 74 fold increase at the concentration of 1 nmol/L on day 12. ⑤19TriTE can significantly mediate T cells killing of CD19 positive target cells in a dose-dependent manner. At the concentration of 10 nmol/L, the target cells lysis reached 50%. ⑥Degranulation experiment verified that 19TriTE can activate T cells in the presence of CD19 positive target cells, and the activation of T cells positively correlated with the dose of 19TriTE. ⑦When 19TriTE fusion protein co-cultured with T cells and target cells overexpression RFP and luciferase genes respectively, 19TriTE can notably mediate T cells killing of CD19 positive target cells through fluorescent microscope or bioluminescence imaging technology.Conclusion:In this study, we successfully constructed and expressed 19TriTE fusion protein and verified that it can effectively activate T cells and promote their proliferation in vitro. At the same time, it can bind to CD19 positive target cells and T cells, as well as enhance T cells anti-leukemia effect in vitro, providing the foundation for further clinical research.