Objective: To explore the clinical characteristics and diagnosis and treatment plans of neurofibromatosis type 1 (NF1), and to provide references for clinical diagnosis and treatment. Methods : The clinical manifestations and treatment of an 8-year-old female patient with NF1 was reported. A literature review was conducted to summarize the clinical characteristics and therapeutic strategies of NF1. Multiple NF1s occurred on the right cheek, orbit, and eyelid, and recurred after surgical resection. The tumor caused ptosis, incomplete closure, and vision loss in the upper eyelid of the right eye. After a multidisciplinary assessment determined that radical resection was not feasible, selumetinib sulfate targeted therapy was adopted (25 mg, Po, bid), 28 days constitute one treatment course, and 14 courses have been completed, combined with symptomatic ocular treatments, such as Befusu. Result: The follow-up showed that the tumor volume did not continue to increase (stable disease), the uncorrected vision of the right eye improved (0.05 vs 0.1), and no drug-related adverse reactions occurred during the treatment period. The literature review summarizes the diverse clinical manifestations of NF1, with café-au-lait macules, multiple neurofibromas, and Lisch nodules being hallmark features. Currently, surgical intervention remains the most commonly employed and primary therapeutic approach for NF1; however, for patients who do not meet the criteria for surgery, alternative treatment strategies should be considered. MEK inhibitors, such as selumetinib, demonstrate significant efficacy in inhibiting the growth of NF1-associated plexiform neurofibromas, with tumor volume reductions of at least 20% observed in 70% of pediatric patients in the SPRINT clinical trial. Furthermore, these inhibitors exhibit favorable long-term safety profiles. Conclusion Café-au-lait macules, multiple neurofibromas, and Lisch nodules are hallmark features of NF1. Selumetinib is safe and effective for NF1 in the head and neck of children, and it is the preferred treatment option for patients who are not suitable for surgery. Long-term follow-up monitoring of tumor changes and drug safety is required.

OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

Objective: To investigate the feasibility of using a carbon dioxide(CO2) laser in the treatment of facial papilloma in children and to evaluate its curative effect and prognosis. Methods : A case of pediatric facial papilloma treated with a CO2 laser was reported, and the effects of this disease and CO2 laser treatment were reviewed and analyzed in combination with the literature. Results: Under general anesthesia, the lesion tissue of the left lip was excised for pathological biopsy, and the diagnosis was maxillofacial papilloma. The lesions were surgically ablated in stages with a CO2 laser, and erythromycin ointment was applied to the surgical incision after surgery. A total of three rounds of CO2 laser treatment were performed for 3 treatment courses. The child had no complications during or after the operation, the facial appearance was significantly improved, and there was no sign of recurrence during the 6-month follow-up. A literature review showed that CO2 lasers have been widely used in the excision of various surface lesions. In clinical practice, continuous CO2 laser with power of 10-50 W and wavelength of 10.6 μm is used to treat superficial tissue lesions, which can achieve accurate vaporization resection of diseased tissue, less bleeding and a good prognosis. Conclusion CO2 laser was accurate and minimally invasive for the removal of facial papilloma in children.

Objective To explore the related genes that play a key regulatory role in cisplatin resistance in lung adenocarcinoma. Methods Bioinformatics methods were used to download the differentially-expressed genes between cisplatin sensitive group and drug resistant group in patients with lung adenocarcinoma in TCGA database and GDSC database. GO function analysis and KEGG pathway enrichment analysis were carried out to analyze the differentially-expressed genes. The protein-protein interaction network was constructed and hierarchical cluster analysis was carried out to screen the key genes. The key genes were verified at the cell level by real-time fluorescence quantitative PCR and ELISA. Then the expression of the selected key gene in A549/DDP cells was silenced by siRNA and its sensitivity to cisplatin was detected. Results We screened out 178 differentially-expressed genes. After cluster analysis, CXCL9, CXCL10, NKX2-1 and SFTPA1 were regarded as the key genes of cisplatin resistance in lung adenocarcinoma. CXCL10 was temporarily selected for subsequent verification and function experiment. The mRNA expression of CXCL10 in A549/DDP cells was significantly higher than that in A549 cells (P < 0.001), and the expression of CXCL10 protein in the supernatant of A549/DDP cells was higher than that in A549 cells, which were consistent with the prediction of bioinformatics. The sensitivity of A549/DDP cells to DDP increased after silencing CXCL10 expression. Conclusions CXCL10 is a key gene to regulate cisplatin resistance in lung adenocarcinoma. Downregulating the expression of CXCL10 can become a potential target for reversing cisplatin resistance in lung adenocarcinoma.

Oropharyngeal carcinoma is a highly heterogeneous disease that is mainly caused by tobacco and alcohol abuse or high-risk human papillomavirus (HPV) infection. HPV-positive oropharyngeal carcinoma and HPV-negative oropharyngeal carcinoma have obvious differences in etiology, epidemiology and prognosis; therefore, different methods should be adopted for treatment. It is known that the TP53 gene is not mutated in HPV-positive oropharyngeal carcinoma, and radiation therapy can activate it and induce cell apoptosis via DNA damage. There are common repair pathways to DNA damage, such as nonhomologous end joining, and this pathway is more sensitive to radiotherapy under the inhibition of HPV oncoprotein. In addition, the further activation of the immune response under the effect of radiation also participates in the elimination of tumors. In this paper, we reviewed the research on the sensitivity of HPV-positive oropharyngeal cancer to radiotherapy to provide a scientific basis for targeted treatment for various pathogenic factors and clinical stages of oropharyngeal cancer in the future.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Objective:To establish a classification model for rapid identification of hypervirulent subtype ST17 clones of Group B Streptococcus (GBS) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS).Methods:In a retrospective study, 235 strains of GBS strains were selected from multiple centers in China during 2015-2018. For model generation,45 strains of ST17 and 50 strains of non-ST17 (20 ST19, 15 ST12 and 15 ST10 strains) were enrolled as the modeling group. The remaining 90 main ST strains (40 ST17, 16 ST10, 17 ST12 and 17 ST19) were served as validation group. 50 GBS strains classified as other minor ST subtypes were regarded as taxonomic groups. MS spectra were collected by Bruker mass spectrometry, and then loaded for model generation and verification, and screening of differential peptide peaks by genetic algorithm (GA) and model verification on ClinProTools 3.0 software.Results:The recognition rate for ST17-GA model were 99.4% with cross validation value of 96.9%. Among the ten differential peptide peaks for the classification model, the weights of both two main peptide peaks m/z 2 956 and m/z 5 912 were greater than 1, while the weights of the all other eight peptide peaks were less than 0.5. Model validation showed only one of the ST17 was misjudged as non-ST17 strain, resulting in diagnostic accuracy of 98.9%, sensitivity of 97.5% and specificity of 100%, positive predictive value of 100% and negative predictive value of 98.0%, respectively. For other sporadic STs, 42.0% (21/50) of them were misdiagnosed as ST17 subtype.Conclusion:A MALDI-TOF MS classification model for hypervirulent subtype of ST17 GBS strains has been successfully established with good diagnostic efficacy.

Objective: To evaluate the outcomes and prognostic factors of myelodysplasia syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 165 cases of MDS who underwent allo-HSCT from Jan. 2010 to Mar. 2018 were analyzed retrospectively, focusing on the overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) and their related risk factors. Results: Of all the 165 cases, 105 were male and 60 were female. The 3-year OS and DFS rate were 72.5% (95%CI 64.9%-80.1%) and 67.4% (95%CI 59.17%-75.63%) , respectively. The 3-year cumulative incidence of relapse and NRM were 12.11% (95%CI 7.03%-18.65%) and 20.44% (95%CI 14.15%-27.56%) , respectively. HCT-comorbidity index (P=0.042, HR=2.094, 95%CI 1.026-4.274) was identified as independent risk factor for OS by the multivariate analysis. Intensive chemotherapy before HSCT or hypomethylation agents treatment had no effects on OS[ (67.0±7.5) %vs (57.7±10.9) %, χ²=0.025, P=0.874]. Conclusions allo-HSCT is a promising means for MDS, and NRM is the major cause of treatment failure. MDS with refractory anemia with excess blasts and secondary acute myeloid leukemia patients may not benefit from intensive chemotherapy or hypomethylation agents treatment before HSCT.

Objective To estimate the value of transrectal ultrasound/magnetic resonance imaging (TRUS/MR) fusion targeted prostate biopsy(targeted biopsy,TB) in the biopsy naive patients.Methods Between September 2015 and September 2016,91 patients with PI-RADS ≥ 3 suspicious regions on the multiparametric magnetic resonance imaging (mpMRI) were retrospectively evaluated.The age of patients was 46-83 years (median 68).Serum PSA level before biopsy was 1.2-85 ng/ml (median 11.2 ng/ ml),in which 36 cases with PSA ＜ 10 ng/ml,30 cases 10-20 ng/ml,and 25 cases ＞ 20 ng/ml.Two-core TB using real-time virtual sonography (RVS) platform for mpMRI-suspicious lesions was followed by 12-core systematic biopsy (SB).The detection rates for any cancer (PCa) and clinically significant prostate cancer (CsPCa) were compared between TB and SB.Results The total detection rate for PCa was 57.1％,with a comparable positive rate between TB (44.0％) and SB (51.7％) groups which did not significantly differ (P =0.14).The proportion of CsPCa in TB group was higher than that in SB group (80.0％ vs.68.1％,P =0.21).In TB group,detection of PCa for grade 5 lesions was significantly higher than that for grade 3 lesions (77.1％ vs.10.3％,P ＜0.001).Detection of PCa was comparable between TB and SB groups in different regions of PSA ＜ 10 ng/ml,10 ～ 20ng/ml and ＞ 20ng/ml (27.8％ vs.36.1％,50％ vs.56.7％,60％ vs.68％,respectively).Conclusions This study revealed a similar rate of prostate cancer detection between 2-core targeted biopsy guided by TRUS/MR fusion and 12-core random biopsy in different PSA regions for no prior biopsy men.TB maybe tend to detect high proportion of CsPCa.PI-RADS is instructive to select appropriate patients for TB.

BACKGROUND/AIMS: Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. METHODS: The effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. RESULTS: Low concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. CONCLUSIONS: Neurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.
Absorption ; Animals ; Baths ; Colon* ; In Vitro Techniques ; Interstitial Cells of Cajal ; Lidocaine ; Myenteric Plexus ; Neural Conduction ; Neurotensin* ; Peristalsis ; Rats* ; Receptors, Neurotensin ; Video Recording