[Clinical features and prognosis of patients with leptomeningeal metastases].

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95%CI:2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival (P<0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

[The predictive value of ultrasonic measurement of the diaphragmatic thickening fraction combined with the maximal inspiratory pressure in mechanical ventilation patients].

Objective: To evaluate the value of the diaphragmatic thickening fraction (DTF) combined with the maximum inspiratory pressure (MIP) for the prediction of weaning success in mechanically ventilated patients. Methods: Patients admitted to the intensive care unit (ICU) of Yijishan Hospital of Wannan Medical College and on mechanical ventilation for 24 hours from June 2018 to April 2019 were selected as the study subjects. A low-level pressure support ventilation (PSV) method was applied to conduct a spontaneous breathing test (SBT) for 30 minutes after the patients met the screening conditions for clinical weaning; and the patients were weaned when they met the clinical weaning criteria. Before weaning, the patient's MIP was measured. The right hemidiaphragmatic excursion (DE) and the thickness of the diaphragm at the end of inspiration and at the end of exhalation were measured by ultrasound, and the DTF was calculated. The statistical relationship between the DTF, DE and MIP was analyzed. The predictive value for the success of weaning was calculated with the DTF, DE and MIP and was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 73 patients were included in this study, including 57 patients who were successfully weaned, and 16 patients who experienced failure. The DTF of the successful weaning group (35%, 8%) was significantly higher than that of the failed weaning group (25%±5%), and the difference was statistically significant (t=6.401, P<0.01). The MIP (34±9 cmH(2)O) in the successful weaning group was significantly higher than that in the failed weaning group (23±3 cmH(2)O), and the difference was statistically significant (t=7.186, P<0.01). The ROCs for the DTF, MIP, and diaphragmatic displacement were 0.907, 0.896, and 0.749, respectively. A DTF ≥ 27.78%, with a sensitivity of 92.98%, a specificity of 81.25%, and an AUC of 0.907 (95% CI: 0.816-0.963), was used as the standard to predict the success of weaning. An MIP>26.5 cmH(2)O, with a sensitivity of 80.7%, a specificity of 93.75%, and an AUC of 0.896 (95% CI: 0.803-0.955), was used as the standard to predict the success of weaning. The AUC of DTF ≥ 27.78% and MIP ≥ 26.5 cmH(2)O was 0.920 (95% CI:0.832-0.971), and the specificity increased to 87.7%, but the sensitivity was slightly reduced to 87.5%. Conclusions: The DTF and MIP play a crucial role in determining the appropriate time and predicting the outcome of weaning of mechanical ventilation patients. Compared with the DTF and MIP alone, the DTF combined with MIP greatly improved the accuracy of predicting successful weaning.

Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine.

The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.

Hsa_circ_0041103 induces proliferation, migration and invasion in bladder cancer via the miR-107/FOXK1 axis.

OBJECTIVE: CircRNAs have been proven to be vital during the process of malignant tumors. Their functions in bladder cancer (BCa) process remain largely unclear. This study aims to elucidate the role of circ0041103 in affecting the malignant phenotypes of BCa, and the possible molecular mechanism. PATIENTS AND METHODS: Circ0041103 expression levels in BCa tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The clinical significance of circ0041103 in influencing tumor size, tumor staging and lymphatic metastasis of BCa was analyzed. Regulatory effects of circ0041103 on proliferative and metastatic capacities of T24 and UM-UC-3 cells were examined through functional experiments. The binding target of circ0041103 and its downstream protein were predicted by online bioinformatic tools, which were further confirmed by Dual-Luciferase reporter assay and Pearson correlation test. The role of circ0041103/miR-107/ FOXK1 axis in regulating BCa process was explored by rescue experiments. RESULTS: Circ0041103 was abnormally upregulated in BCa tissues and cell lines. Its level was higher in BCa tissues with a larger tumor size, or worse tumor staging, or BCa cases with lymphatic metastasis. Knockdown of circ0041103 inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells. MiR-107 was the binding target of circ0041103, and FOXK1 was the downstream gene of miR-107. Overexpression of circ0041103 could reverse the inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells overexpressing miR-107. CONCLUSIONS: Circ0041103 is upregulated in BCa and predicts a poor prognosis in BCa. It stimulates BCa cells to proliferate and migrate via the miR-107/FOXK1 axis.

Effects of silencing PTTG expression by small interference RNA.

OBJECTIVE: We investigated the effects of small interference RNA (siRNA) on the cell proliferation inhibition, sensitivity to radiotherapy effects and cell apoptosis. The siRNA used here was specific to the pituitary tumor transforming gene (PTTG). MATERIALS AND METHODS: Vectors containing the specific functional siRNAs for PTTG were designed and constructed. Cells were divided into four groups: (I) blank control group; (II) radiotherapy group: cells were exposed to X-ray radiation; (III) Group PTTG siRNA: transfected with PTTG siRNA; (IV) PTTG siRNA+ radiotherapy group: transfected with PTTG siRNA and then were exposed to X-ray radiation. HEC-1A cells were transfected by the specific interfering plasmids using Lipofectamine 2000 transfection reagent. The PTTG protein expression levels were analyzed using Western blot Cell proliferation was examined by MTT assay and the HEC-1A cell line apoptosis was evaluated by flow cytometry. RESULTS: Recombinant small interference RNA (siRNA) expression vectors targeting PTTG were successfully constructed. The results of MTT showed that the growth of the HEC-1A cell was negatively influenced after cells were transfected with PTTG siRNA. Furthermore, PTTG siRNA combined with radiotherapy demonstrated more powerful inhibitory effects. Cell apoptosis rates were significantly increased in the radiotherapy group and the PTTG siRNA transfection group when compared to the control group. A more pronounced cell apoptosis rate was observed in the group that was treated with PTTG siRNA combined with radiotherapy. CONCLUSIONS: Recombinant small interference RNA (siRNA) expression vector targeting PTTG successfully inhibited the cell proliferation and induced apoptosis in endometrial carcinoma cells and increased the cancer cells vulnerability to the effects of radiation.

Fine mapping of the rice thermo-sensitive genic male-sterile gene tms5.

AnnongS-1, a thermo-sensitive genic male-sterile (TGMS) rice line, has a new TGMS gene. Genetic analysis indicated that the sterility of AnnongS-1 was controlled by a single resessive gene named tms5. In our previous studies based on an F(2) population from the cross between AnnongS-1 and Nanjing11, tms5 was mapped on chromosome 2. Recently, a RIL (recombinant inbred line) population from the same cross was developed and used for the fine mapping of the tms5 gene. Molecular marker techniques combined with BSA (bulked segregant analysis) were used. As a result, two AFLP markers (AF10, AF8), one RAPD marker (RA4), one STS marker (C365-1), one CAPs marker (G227-1) and four SSR markers (RM279, RM492, RM327, RM324) were found to be closely linked to tms5 gene. The DNA sequences of the RFLP marker of C365 and G227 were found in GenBank, and on the basis of these sequences, many primers were designed to amplify the two parents and their RIL population plants. Finally, the tms5 gene was mapped between STS marker C365-1 and CAPs marker G227-1 at a distance of 1.04 cM from C365-1 and 2.08 cM from G227-1.

Differentiation and classification of parental lines and favorable genic interactions affecting F1 fertility in distant crosses of rice (Oryza sativa L.).

This study was intended to investigate the extent of genetic differentiation in parental lines of rice hybrids and to analyze the genetic basis underlying the fertility phenomenon in distant crosses. Two subsets of rice material (111 entries in total) were used, including 81 doubled-haploid (DH) lines and 30 Indica and Japonica rice varieties or lines (as a control). The DH lines was derived from a heterotic Indica/Japonica cross (Gui630/02428) by anther culture. The materials in the control represent a broad spectrum of the Asian cultivated rice gene pool including landraces, primitive cultivars, historically important cultivars, modern elite cultivars, super rice and parents of superior hybrids. In accordance with the NC II design, 57 out of the DH lines were test-crossed to two important wide compatibility lines: photoperiod-sensitive genetic male sterile (PGMS) line N422s and thermo-sensitive genetic male sterile (TGMS) line Peiai64s. The F1s and their parents, 182 entries in total, were examined for the performance of seven traits in a replicated field trial. All the rice materials was surveyed for polymorphisms using 92 RFLP markers selected from two published molecular marker linkage maps. Genotypes of the F1 hybrids at the molecular-marker loci were deduced from the parental genotypes. The analysis showed that there were two types of genetic differentiation in the two subsets of rice material; that is, qualitative differentiation in the control and quantitative differentiation in the DH lines. In addition, favorable genic interactions (both intra- or inter-locus) contributed to better increase the fertility in hybrids of distant crosses through incorporation of a wide-compatibility line as the female parent. Favorable genic interactions can be applied in hybrid rice breeding programs by selecting parents with an appropriate extent of genetic differentiation.