OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective To explore the pneumoperitoneum signs of neonates on the bedside abdominal lying film.Methods The pneumoperitoneum signs of 52 neonates on the bedside abdominal lying films were analyzed retrospectively.Results Among 52 neonates with pneumoperitoneum,2 cases had no perforation,and there were 50 cases of digestive tract perforation,with 22 cases of gastric perforation,17 cases of small intestinal perforation and 11 cases of large intestinal perforation.Congenital muscular defect of gastric wall and necrotizing enterocolitis(NEC)were the most common causes of perforation.Forty-three cases with anteroposterior films all had pneumoperitoneum signs;and in 9 cases with anteroposterior and lateral films,6 cases with anteroposterior and lateral films all showed pneumoperitoneum signs,while 3 cases showed pneumoperitoneum signs only on lateral films.Pneumoperitoneum signs included 38 episodes of liver falciform ligament signs,37 episodes of football signs,22 episodes of Rigler signs,21 episodes of round liver ligament signs,10 episodes of liver area bright shadows,9 episodes of inverted"V"signs,6 episodes of scrotal gas,5 episodes of triangular signs,4 episodes of Cupola signs and 1 episodes of dolphin sign.Two or more signs were seen in 46 cases and three or more signs were seen in 31 cases.There was no statistically significant difference in the pneumoperitoneum signs except for scrotal gas among the three groups of gastric,small intestinal and large intestinal perforations(P>0.05).Conclusion Various signs such as liver falciform ligament signs,football signs,Rigler signs and round liver ligament signs can be seen on the bedside abdominal lying film for neonates pneumoperitoneum,and understanding the above signs is conducive to rapid and accurate diagnosis.

A novel technology is proposed for non-contact and real-time detection of atrial fibrillation using millimeter-wave radar.A 60 GHz PCR millimeter wave radar is used to continuously detect the chest echo signal of the subject.After signal acquisition,I-Q signal is generated through I-Q demodulation,and the signal phase information is extracted using effective points phase trend evaluation for obtaining the signals from oscillations in the chest wall,from which the respiratory signals and cardiac signals are extracted through digital filtering for the analysis of cardiac movement.Whether the atrial fibrillation occurs or not is determined by the characteristics of atrial fibrillation wave in the time domain.The effective points phase trend evaluation for extracting more accurate signal phase information and the time-domain method for real-time atrial fibrillation detection are the innovations of the study.The experimental results show that the proposed method achieves a detection accuracy of 99.2%in clinic.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.

OBJECTIVE: To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5. METHODS: Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay. RESULTS: A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype. CONCLUSION A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.
Child, Preschool ; Genetic Testing ; Homozygote ; Humans ; Male ; Mutation ; Thiamine ; Whole Exome Sequencing

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

Objective:To summarize the clinical experience of transurethral columnar balloon dilation of prostate (TUCBDP) in the treatment of patients with benign prostatic hyperplasia(BPH).Methods:A retrospective analysis of 379 BPH clinical data from the Hubei Provincial Hospital of Traditional Chinese Medicine using TUCBDP was performed between June 2015 and June 2018.Their age was (71.3±14.5)years old. The history of disease ranged from 1 month to 36 years. The prostate volume was(47.4±2.1) ml. Preoperative maximum urinary flow rate was (Q max)(9±4) ml/s, postvoid residual urine(PVR) was (123.1±72.4) ml. Their international prostate symptom score (IPSS) was (21±6) points. The quality of life score (QOL)was (5±1) points. The international index erectile function questionnaire (IIEF-5)in 32 patients, who had sex before surgery, was 15±4. We set the time of catheter structure improvement in June 2016 as the boundary, including the early stage (June 2015 to May 2016, 121 cases) and the recent stage (June 2016 to June 2018, 258 patients). In the early stage, the principle of operation is the inner balloon of the catheter to dilate the membrane urethra, and the outer balloon to dilate the urethra of the prostate and the bladder neck. The main surgical steps include the insertion of a dilatation catheter, localization by touching the skin of the scrotum bottom, the inner and outer balloon are filled with water, the first time of drainage and decompression in the inner and outer balloon, the catheter continuous irrigation, drainage and decompression of the inner and outer balloon again, removing the dilatation catheter, and the ordinary urinary catheter was replaced and continuous irrigation. In the recent stage, the principle of surgery is that the inner balloon only served for positioning and fixation. The outer balloon is used to dilate the membrane urethra, prostate urethra, and bladder neck. The inner and outer balloon are drained and decompressed at one time after surgery. The main surgical steps are that the resectoscope was used to examine the bladder and urethra and to guide the dilatation catheter into the bladder. The apex of the prostate touching was used to conform the location. The inner balloon water filling was used for fix the positioning. The inner and outer balloon are filled with water, decompressed and pulled out for urination test, the gland expansion is observed under the resectoscope, and ordinary urinary catheter is replaced for continuous flushing. We observed the changes in Q max, PVR, IPSS, and QOL at 1, 3, 6, 12, and 24 months after the operation. the complications differences in two-stage patien, including the International Incontinence Advisory Committee Urinary Incontinence Questionnaire (ICI-Q-SF) score; those who had sex before surgery were recorded changes in the IIEF-5 score, was compared. Results:There were no deaths during and after operation in this study. The operation time was (18.5±6.7) min. The number of follow-up cases at 1, 3, 6, 12, and 24 months after operation were 326, 253, 201, 194, and 181, respectively. The Q max at 1, 3, 6, 12, and 24 months after operation were (17±9)ml/s, (15±2)ml/s, (12±4)ml/s, (13±6)ml/s and (13±4)ml/s, respectively. The PVR were (17.4± 11.6) ml, (20.6±9.8)ml, (25.4±13.1)ml, (31.5±11.5)ml, and (29.1±12.4)ml, respectively. The IPSS were(7±5) points, (4±4) points, (4±4) points, (6±5) points, (4±4) points, respectively. The QOL were (2±1) points, (2±1) points, (2±1) points, (2±1) points, and (2±1), respectively. All those results that were significantly different from those before surgery ( P<0.05). There were 32 patients who had sex before the operation. The postoperative IIEF-5 score was (17± 6), which was not significantly different from that before the operation ( P>0.05). Two patients had transient retrograde ejaculation, which relieved spontaneously within the 6 month. 4 cases with pseudourinary incontinence in the recent stage (1.5%) were not statistically different from 6 cases (4.9%) in the early stage ( P>0.05). one case(0.4%) of major bleeding in the recent stage was statistically different from 6 cases (4.9%) in the early stage ( P<0.05). 2 cases (0.7%) of patients with acute urinary retention in the recent stage were significantly different from 15 cases (12.4%) in the early stage ( P<0.05). Conclusions:TUCBDP has a positive overall effect and high safety. The major complications of surgery in the recent stage, except for pseudo-urinary incontinence, are significantly lower than that in the early stage, which may be related to the improvement of the catheter structure and the accumulation of clinical experience.

Objective:To investigate the CT imaging features of epidural hematoma (EDH) surrounding subdural effusion (satellite effusion sign) and its application value in diagnosis of EDH.Methods:A retrospective analysis of clinical and imaging data of 30 patients with EDH and 122 patients with acute subdural hematoma (SDH), admitted to our hospitals from December 2017 to February 2020, was performed. The frequencies of satellite effusion sign were compared in the two groups, and the differences between the correct diagnosis rate of traditional CT performance and the correct diagnosis rate of traditional CT performance+satellite effusion sign were compared in the two groups; the specific characteristics of satellite effusion sign was clarified and its relations with morphological characteristics and distribution of hematoma were analyzed.Results:Among 30 patients with acute EDH, the occurrence rate of satellite effusion sign was 63.3% (19/30); among 122 patients with acute SDH, the occurrence rate of satellite effusion sign was 2.5% (3/122); the difference was statistically significant ( χ2=67.248, P=0.000). Among the 30 patients with acute EDH, the correct diagnosis rate of traditional CT manifestation was 86.7% (26/30), and the correct diagnosis rate of traditional CT manifestation+satellite effusion sign was 93.3% (28/30), without statistically significance ( χ2=0.185, P=0.667). The length of the satellite effusion sign was (1.1±0.9) cm, ranged from 0.2 cm-3.1 cm; the width was (3.6±2.0) mm, ranged from 1.4 mm-7.5 mm. The incidence of satellite effusion sign in the frontotemporal EDH patients (73.9%) was significantly increased as compared with that in the occipitoparietal EDH patients (28.6%, P<0.05); that of patients with clinically diagnosed cerebral contusion, laceration, cerebral hernia or other severe to extremely severe craniocerebral injuries (22.2%) was significantly reduced as compared with that of patients with mild to moderate craniocerebral injuries (81.0%, P<0.05). Conclusion:Satellite effusion sign is an important new CT sign in the diagnosis of EDH, which is closely related to the locations of hematoma and severities of craniocerebral injury.