Objective: This study aimed to analyse the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and 25-hydroxy-vitamin D (25[OH]D) and early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) and evaluate the potential roles of these two biomarkers in the clinical diagnosis of DKD. Methods: A total of 422 inpatients with T2DM were retrospectively enrolled between January 2018 and March 2022 at the First Affiliated Hospital of Nanjing Medical University. The baseline clinical parameters of each patient were determined, and their demographic characteristics were extracted from the hospital information system. The patients were separated into groups according to serum Lp-PLA2 and 25(OH)D levels and binary logistic regression analysis was used to determine independent predictors of early DKD incidence. Results: Levels of Lp-PLA2 significantly increased and those of 25(OH)D significantly decreased with DKD progression (both P < 0.001). Lp-PLA2 concentrations were positively correlated with albuminuria levels (r = 0.37, P < 0.001), whereas 25(OH)D levels were negatively correlation (r = -0.34, P < 0.001). The incidence of DKD was higher in the Lp-PLA2 elevated and 25(OH)D deficient groups (all P < 0.001). Body mass index, systemic immune-inflammatory index, serum uric acid, C-peptide, and triglyceride-glucose indices were positively associated with Lp-PLA2 levels (all P < 0.001) and negatively associated with 25(OH)D (all P < 0.05). Furthermore, LpPLA2 was an independent risk factor (OR = 1.003, P = 0.015), and 25(OH)D was an independent protective factor (OR = 0.937, P = 0.008) for early DKD occurrence in binary logistic regression analysis. The area under the curve for the combination of Lp-PLA2 and 25(OH)D for diagnosing DKD was 0.867, with a sensitivity of 70.4 % and a specificity of 89.5 %. Conclusions: Increased serum Lp-PLA2 and decreased 25(OH)D levels are risk factors for early DKD in patients with T2DM. The combined detection of Lp-PLA2 and 25(OH)D may enhance the diagnostic efficacy of DKD.

Objectives:This meta-analysis aimed at determining the association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumors of the bone. Methods and Materials:Web of Science, EMBASE, Cochrane Library, and PubMed were comprehensively searched on April 20th, 2022. Data from the included articles were analyzed using meta-analysis. The bias of all included studies was evaluated according to ROBINS-I. Also, subgroup and sensitivity analyses were performed. Results:Eight studies with 1270 cases (195 in the denosumab group and 1075 in the control group) were eventually included. Patients receiving denosumab before curettage had a higher risk of local recurrence than those who underwent curettage alone (odds ratio: 2.29, 95% confidence intervals: 1.44-3.64, P = 0.0005). The denosumab group showed a significantly higher risk of local recurrence in most subgroup analyses, except for those with preoperative denosumab duration ≤six months/doses (P = 0.66) and sample size ranging from 100 to 180 (P = 0.69). Conclusion:Denosumab before curettage may increase the risk of local recurrence in patients with giant cell tumor of the bone. Preoperative denosumab should be used with caution after weighing an increased risk of local recurrence against the clinical benefits and a duration time of less than six months before surgery is recommended.

Abstract Background and aims Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD‐LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD‐LM. Materials and methods The level of CEACAM6 was determined by enzyme‐linked immunosorbent assay (ELISA) in CSF from 40 LUAD‐LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD‐LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21‐1) and neuron‐specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD‐LM. Results CSF CEACAM6 level was higher in LUAD‐LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non‐LM in LUAD patients (0.95 vs. 0.64, p < 0.001). Conclusion CEACAM6 may serve as a potential biomarker in diagnosing LUAD‐LM.

Abstract Leptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RNA sequencing (scRNA‐seq) data from GEO database including five patient‐derived CSF samples of BC‐LM and LC‐LM, and four patient‐derived CSF samples of idiopathic intracranial hypertension (IIH) as controls, we analysed single‐cell transcriptome characteristics of CSF TME in LM patients compared to controls simultaneously and comprehensively. In addition, we performed 10× genomics scRNA‐seq on CSF cells derived from a BC‐LM patient to help generate a solid conclusion. The CSF macrophages in LM patients showing M2‐subtype signature and the emergence of regulatory T cells in LM confirmed the direction of tumour immunity toward immunosuppression. Then, the characteristics of CSF circulating tumour cells (CTCs) of breast cancer LM (BC‐LM) patients were classified into five molecular subtypes by PAM50 model. The communication between macrophages and five subtype‐specific CSF‐CTCs showed largest number of ligand‐receptor interactions. The five subtypes‐specific CSF‐CTCs showed great heterogeneities which were manifested in cell proliferation and cancer‐testis antigens expression. Gene regulatory networks (GRNs) analysis revealed that transcription factor SREBF2 was universally activated in the five subtypes‐specific CSF‐CTCs. Our results will provide inspiration on new directions of the mechanism research, diagnosis and therapy of LM.

Background. Cell-free DNA (cfDNA) has attracted considerable attention in precision medicine. However, few data are available regarding to the prognostic value of cfDNA variables in CA15-3 normal breast cancer (BC) patients. Here, we aimed at investigating the prognostic value of cfDNA variables including gene mutations in CA15-3 normal BC patients. Methods. A total of 68 BC patients with normal CA15-3 levels were enrolled. cfDNA concentration and integrity were assessed based on qPCR. cfDNA gene mutations were conducted by using next gene sequencing (NGS). The association between cfDNA variables and the prognosis of patients was analyzed. Results. cfDNA concentration was related to tumor stage (P=0.002), metastases (P=0.001), and distant metastases (P < 0.001). The elevated copy number variants (CNV) were found in distant metastasis patients compared with patients without distant metastases (P=0.008). Nineteen mutant genes were validated in enrolled CA15-3 normal BC patients. Thirty-two patients (47.0%) had single nucleotide variants (SNV), and 13 (19.1%) patients had TP53 mutations (TP53(mut)). SNV (P=0.033) was related to tumor stage, and TP53(mut) was related to metastases (P=0.016) and distant metastases (P=0.006). In multivariate logistic analysis, cfDNA concentration was associated with metastases (OR=3.404, 95% CI: 1.074-10.788, P=0.037) and distant metastases (OR=13.750, 95% CI: 1.473-128.358, P=0.021). Cases with high cfDNA levels (> 15.6 ng/ml), SNV, and TP53(mut) showed worse DFS compared with patients with low cfDNA levels (P < 0.001), without SNV (P=0.002) and with TP53 wildtype (P < 0.001), respectively. In the multivariate Cox proportional hazard model, cfDNA concentration was an independent predictor of poor survival (HR=5.786, 95% CI: 1.101-30.407, P=0.038). Conclusions. Assessment of cfDNA concentration, CNV, SNV, and TP53(mut) could be useful in predicting prognosis for CA15-3 normal BC patients. The cfDNA concentration was an independent predictor prognostic factor in CA15-3 normal BC patients.

Purpose: Mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) are aggressive colorectal cancer histological subtypes with dismal prognosis. This study investigated prognostic factors and constructed novel nomograms for MA and SRCC patients who survived for over 5 years to optimize the follow-up regime, especially for early-onset patients. Patients and Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2004 and 2018 were extracted. MA and SRCC patients were divided into two groups with survival time of 5 years as a cut-off point. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were determined by Cox regression models, and survival curves were plotted by the Kaplan-Meier method. Results: We identified 8286 MA patients (45.73%) and 551 SRCC patients (20.32%) who survived for over 5 years. Multivariable Cox analyses identified age, tumor location, N stage, metastasis, CEA level, surgery, and lymph nodes dissection as independent risk factors for MACSS. SRCC was more aggressive and only N2 stage (P = 0.011) and metastasis (P = 0.043) were inversely associated with SRCCSS. Furthermore, we observed that small tumor size, well differentiation, and chemotherapy no longer provided survival benefit to >= 5-year survivors. Therefore, we constructed novel nomograms appropriate for MA patients who survived for over 5 years. The consistency indexes for predicting 10-year OS and CSS were respectively 0.717, 0.712 in the training cohort and 0.727, 0.735 in the validation cohort. Conclusion: Our well-calibrated nomograms represent the first clinical prognostic models developed especially for MA patients with a survival longer than 5 years. For both MA and SRCC patients, TNM stage was a stable prognostic factor, while the prognostic values of tumor size, differentiation grade, and chemotherapy changed over time. We are hopeful that our prognostic models will help define personalized follow-up managements to further prolong patient survival.

Background Lung cancer has a high incidence and a 5-year survival rate of less than 15%. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Chemotherapy and immunotherapy are the most frequently used alternative treatments for patients with advanced-stage NSCLC in whom surgery failed. Previous studies have suggested that miR-27a is involved in cancer development and progression. The purpose of this study was to investigate the clinical value of miR-27a in the prognosis of NSCLC patients after chemotherapy. Methods Flow cytometry was used to detect the apoptosis rate of SPC-A1 cells treated with optical cisplatin at different times. Simultaneously, the expression of miR-27a in supernatants and cells was detected. Fifty-two newly diagnosed NSCLC patients were recruited. All patients received gemcitabine and cisplatin as first-line chemotherapy and docetaxel as second-line chemotherapy. At the end of every chemotherapy cycle, a therapeutic evaluation was performed according to the RECIST criteria. The expression of serum miR-27a was detected in each cycle. Results After treatment with 2.5 µg/mL cisplatin, the apoptosis rates of SPC-A1 cells were significantly greater than those of the paired untreated control groups at 12, 24, 48 and 72 h. The expression of miR-27a in supernatants and cells was also consistent with the apoptosis rate and changed a time-dependent manner. The chi-square test showed that an increase in miR-27a after chemotherapy was more common in patients who achieved partial response (PR) than in those who achieved no response (NR) (61.5% vs. 30.8%, P=0.026). Kaplan-Meier survival analysis indicated that patients with decreased miR-27a levels had poorer outcomes than those with increased miR-27a levels (P<0.05). Furthermore, dynamic changes in serum miR-27a with a gradual increasing trend during chemotherapy predicted a good prognosis. Conclusions Collectively, our results suggest that miR-27a is involved in the apoptosis of lung cancer cells and that serum miR-27a levels are related to the prognosis of NSCLC patients. The expression levels of miR-27a in the serum may be an independent predictor for the prognosis of NSCLC.