Purpose To investigate the value of real-time three-dimensional contrast-enhanced ultrasound (RT3D-CEUS) for the evaluation of blunt renal trauma hemorrhage. Materials and Methods Nine healthy New Zealand white rabbits were randomly divided into three groups, and after heparinization, the models of ongoing hemorrhage of blunt renal trauma were developed by self-made minitype striker in the three groups with different force levels:77.2 N (group A), 106.2 N (group B), 135.1 N (group C). All rabbits were performed ultrasonography (US), color Doppler flow imaging (CDFI) and RT3D-CEUS before and after strike (within 20 minutes). The results achieved by US, CDFI, 2D-CEUS (A-plane results in RT3D-CEUS) and RT3D-CEUS were compared with each other, and further compared with the pathological results of the executed animals after blood pressure decreased lower than 40 mmHg. Results All rabbits showed traumatic renal lesions and it proved that the bigger the force the heavier the injury (group A: 1 case of levelⅠ, 2 cases of levelⅡ;group B:3 cases of levelⅢ;group C:1 case of levelⅢ, 2 cases of level Ⅳ ). After strike, US identified the presence of increasing hematoma under the capsule but could not detect active bleeding. In CDFI, only 1 case was detected ongoing hemorrhage. 2D-CEUS clearly presented the bleeding in all cases. RT3D-CEUS presented a vivid real-time and stereoscopical image of active hemorrhage in all cases and also showed that the wider the bleeding area was shorter than the shock duration time. Conclusion RT3D-CEUS can present a real-time dynamic bleeding and locate headstream of blood in renal trauma vividly and stereoscopically, and can be used to preliminarily evaluate the degree of ongoing hemorrhage in traumatic kidney.

The level of minimal residual disease (MRD) is closely associated with prognosis in patients with acute lymphoblastic leukemia (ALL). Currently, 3 kinds of ALL-MRD detection methods commonly used at home and abroad include immunoglobulin heavy chain and T-cell receptor (IGH/TCR) gene rearrangement assessment, flow cytometry (FCM) and leukemia-associated fusion gene detection. IGH/TCR gene rearrangement assessment methods include real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). RT-qPCR mainly detects the variable region of IGH/TCR rearrangement genes; it is about one log more sensitive than FCM, but microclones may be easily ignored leading to false negative results. NGS also detects the variable region of IGH/TCR rearrangement genes. The sensitivity of NGS-based MRD assays is higher than that of FCM and RT-qPCR, and its sensitivity is up to 10 -6, while small subclones causing recurrence can be tracked. The sensitivity of MRD was 10 -4 detected by using FCM, while FCM with ≥8-color can achieve 10 -6. However, such high level of sensitivity requires (2-5)×10 7 nucleated cells, which is rarely obtainable from remission marrows. FCM also requires substantial expertise on inspectors, and results may be easily affected by clonal evolution or phenotype shift. RT-qPCR can be used to detect fusion genes such as BCR-ABL, with a sensitivity of up to about 10 -5, but only few ALL patients carry specific gene fusions change that can be used as the monitoring of MRD. For Philadelphia chromosome-positive ALL patients, RT-qPCR is recommended to detect the level of MRD. For Philadelphia chromosome-negative ALL and T-cell ALL patients, FCM, RT-qPCR and NGS methods are all applicable.

Objective:To explore the values of peripheral blood neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) in the differential diagnosis of cytopenic diseases.Methods:A retrospective case series study was conducted. The clinical data of 105 newly diagnosed patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) or primary immune thrombocytopenia (ITP) who were admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from August 2017 to November 2020 were retrospectively analyzed. There were 42 patients with MDS (13 cases of hypoplastic MDS, 23 cases of non-hypoplastic MDS, 6 cases could not be classified), 42 patients with ITP, and 21 patients with AA. The peripheral blood lymphocyte count, neutrophil count, monocyte count, and platelet count of each untreated patient at the time of initial diagnosis were recorded, the NLR, MLR and PLR were calculated, and the differences of NLR, MLR and PLR among different diseases were compared; the differential diagnostic values of each index for AA, MDS and ITP were evaluated by using the receiver operating characteristic (ROC) curve.Results:The NLR [ M (IQR)] in ITP, AA and MDS groups was 3.08 (2.42), 0.57 (0.66) and 0.83 (1.27) ( χ2 = 56.84, P<0.001), the MLR was 0.26 (0.15), 0.13 (0.14) and 0.20 (0.33) ( χ2 = 18.71, P<0.001), and the PLR was 5.12 (9.97), 8.67 (14.21) and 49.32 (78.66) ( χ2 = 47.07, P<0.001). The best cut-off value of NLR for distinguishing ITP from MDS was 1.757, and the area under the curve (AUC) was 0.833 (95% CI: 0.811-0.955), while the sensitivity and specificity were 78.6% and 83.3%, respectively. The best cut-off value of NLR for distinguishing ITP from AA was 1.350, and the AUC was 0.993 (95% CI: 0.981-1.000), while the sensitivity and specificity were both 95.2%. The best cut-off value of PLR for distinguishing AA from MDS was 23.542, and the AUC was 0.841 (95% CI: 0.739-0.944), while the sensitivity and specificity were 85.7% and 73.8%, respectively. The best cut-off value of NLR for distinguishing AA from MDS was 0.764, and the AUC was 0.687 (95% CI: 0.556-0.891), while the sensitivity and specificity were 71.4% and 64.3%, respectively. The best cut-off value of MLR for distinguishing AA from MDS was 0.148, and the AUC was 0.736 (95% CI: 0.614-0.859), while the sensitivity and specificity were both 71.4%. Conclusions:The peripheral blood NLR, MLR and PLR have certain reference values for differential diagnosis of AA, MDS and ITP.

Objective:To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients.Methods:Coagulant assays: activated partial thromboplastin time(APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients’ DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. After purified, the products of PCR were sequenced directly, the mutations were detected by comparing with wild sequences and analyzed using some bio-informatics softwares. Results:The two patients were diagnosed with coagulation factor Ⅺ deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FⅪ. The results of APTT, FⅪ∶C were 88.1s, 1.1% and 107.1s, 3.8% , and the prolonged APTT could be corrected to normal range 32.9s and 31.5s, respectively. Through genetic analysis, we discovered compound heterozygous mutations g. 1305-1G>A and g. 1325delT in patient 1 and the sequencing results of TA plasmid clones showed that the two mutations were located on different strands of chromosomes. Compound heterozygous mutations g. 1124A>G and g. 1550C>G were detected in patient 2 resulting in Lys357Arg and Cys482Trp. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed.Conclusion:Compound heterozygous mutations g. 1305-1G>A, g. 1325delT and g. 1124A>G, g. 1550C>G had been identified in two coagulation factor Ⅺ deficiency patients which might be responsible for their prolonged APTT and low FⅪ∶C. To the best of our knowledge, g. 1325delT and g. 1550C>G have been reported, while g. 1124A>G and g. 1305-1G>A are reported for the first time in the literature.

Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University’s Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

OBJECTIVE: To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma. METHODS: Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. RESULTS: A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma. CONCLUSION As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.
Adenocarcinoma, Mucinous ; pathology ; radiotherapy ; surgery ; therapy ; Female ; Humans ; Male ; Neoplasm Staging ; Proctectomy ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; pathology ; radiotherapy ; surgery ; therapy ; Retrospective Studies ; SEER Program ; Survival Analysis ; Treatment Outcome