[Report of six cases with mast cell leukemia and a literature review].

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia (n=4), fatigue (n=3), fever (n=2), abdominal discomfort (n=2), osteolytic lesions (n=2), dizziness (n=1), skin flushing (n=1), and weight loss (n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) µg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Heat shock protein 90 maintains the stability and function of transcription factor Broad Z7 by interacting with its Broad-Complex-Tramtrack-Bric-a-brac domain.

Heat shock protein 90 (Hsp90) is a highly conserved chaperone protein that interacts with various client proteins to mediate their folding and stability. The Broad-Complex-Tramtrack-Bric-a-brac (BTB) domain, also known as poxvirus and zinc finger (POZ) domain, exists widely in different proteins and is highly conserved. However, the stability mechanism of BTB domain-containing proteins has not been fully understood. Co-immunoprecipitation and a protein pull-down assay were performed to investigate the interaction between Hsp90 and the transcription factor Broad isoform Z7 (BrZ7) in vivo and in vitro. The middle domain of Hsp90 directly associated with the BTB domain of BrZ7. The Hsp90 inhibitor 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) interrupted the interaction between Hsp90 and BrZ7 and decreased the protein level of BrZ7 but did not affect the mRNA level of BrZ7. The addition of the proteasome inhibitor peptide aldehyde Cbz-leu-leu leucinal suppressed the 17-AAG-induced degradation of BrZ7. BTB domain deletion and 17-AAG treatment resulted in inhibition of BrZ7 function in gene expression in the 20-hydroxyecdysone and juvenile hormone pathways. These results reveal that the middle domain of Hsp90 associates with the BTB domain of BrZ7 to prevent BrZ7 degradation and maintain BrZ7 function in gene expression in the lepidopteran insect Helicoverpa armigera.

Clinical effects and safety of interventional therapy for parenchyma vascular malformation.

Parenchyma vascular malformation (VM) is a common disease in modern society. Here, we investigated the clinical effects and safety of interventional therapy (IT) on the treatment of parenchyma VM. From January 1998 to December 2010, 31 patients with VM who elected IT were investigated, including 11 cases of venous VM and 20 cases of arteriovenous malformation. There were 19 males and 12 females, ranging from 12 to 51 years in age. VM often occurred in the four limbs and other areas, such as the trunk and reproductive organs. Under the guidance of digital subtraction angiography, vascular hardener was injected into the VM spot via percutaneous puncture. Then, embolotherapy was conducted via the transcatheter feeding artery. We found that, in all cases, the malformed vessels were completely or partially blocked. After treatment, the local swelling of vessels was alleviated and the diabrosis and bleeding ceased. The soft tissue lump shrank, then stiffened and became fixed. There was no occurrence of severe intraoperative or postoperative complications in any patient. In summary, IT is an effective method for treating parenchyma VM, causes only a minor operative wound, and should be viewed as the first choice intervention.

Ultrasonic imaging characteristics of transplanted kidneys with delayed graft function.

We investigated the ultrasonic imaging characteristics of transplanted kidneys with delayed graft function (DGF). Ultrasonography was performed in 44 patients after kidney transplantation, and a time-intensity analysis was performed to compare the differences between patients with normal graft function (NGF) and those with DGF. Compared with the NGF group, the DGF group had earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity (P < 0.05). The variation-of-intensity parameters in different renal cortices increased, whereas the variation-of-time parameter decreased, in those with DGF (P < 0.05). In conclusion, compared with the NGF group, the microcirculation perfusion of transplanted kidneys in the DGF group showed higher perfusion with earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity. In addition, the intensity variations of contrast agent in different renal cortices from patients with DGF were greater, whereas the variations in perfusion time were smaller than those in patients with NGF.

[Surgical plan selection and efficacy analysis in 32 cases of laryngotracheal stenosis].

Objective: To explore the optimization of surgical procedures for laryngotracheal stenosis and its effect analysis. Methods: The data of 32 patients with acquired laryngotracheal stenosis who received surgical treatment from October 2015 to December 2021 were analyzed retrospectively. The age ranged from 19 to 72 years, with an average of (34.0±9.0) years. The medical history ranged from 1 to 32 months (median 3 months). As for etiology, there were 30 cases of iatrogenic laryngotracheal stenosis, including 20 cases of tracheal intubation and 10 cases of tracheotomy (7 cases of percutaneous tracheotomy and 3 cases of traditional tracheotomy). There were 1 case of laryngotracheal trauma and 1 case of airway Penicillium marneffei infection. According to Myer-Cotton grading system, grade Ⅳ stenosis was found in 14 cases, including 12 cases involving trachea and 2 cases involving trachea and subglottic area.There were 18 cases of grade Ⅲ, all of which involved the cervical trachea 5 cases failed in operation in other hospitals. According to stenosis grading, course of disease, primary disease control and the patient's general condition, the surgical plan was determined individually. The operations of end-to-end anastomosis, circumferential tracheal partial resection, T-tube placement and CO2 laser tracheal scar resection were performed respectively. The recovery of airway function and perioperative complications were observed one year after operation. Results: End-to-end anastomosis was performed in 16 cases, and partial circumferential tracheal resection in 2 cases, and tracheal granulation (scar) resection by CO2 laser in 2 cases and T-tube insertion in 12 cases. Eighteen cases which performed end-to-end anastomosis, partial resection of circumferential trachea in and 2 cases which performed laser tracheal scar resection were all recovered airway function at one stage. After 1 year, 19 cases were cured and 1 case was effective. Of 12 patients with T tube implantation, 11 cases were successfully extubated after 6-12 months, 7 cases were cured after 1 year, 2 cases were effective and 3 cases were ineffective. Among the 3 cases of failure, 2 cases were successfully extubated by sleeve resection and end-to-end anastomosis in the second stage, and the other case refused to accept other treatment methods and the T-tube was placed again, and the tube was blocked and the patient survived. During the follow-up period, the total cure rate was 87.5%, the effective rate was 9.4%, and the total extubation rate was 96.9%.The most common complication was subcutaneous emphysema, accounting for 78% (25/32), but no serious mediastinal emphysema or pneumothorax occurred. In the T-tube implantation group, granulation tissue grew in different degrees around the neck wound after operation, and improved or disappeared after 6-9 months. Anterior cervical tracheal fistula occurred in 4 cases of T-tube implantation group after extubation, which were cured by sealing the stoma. There were no complications such as severe bleeding or perioperative death. Conclusion: When there were various factors, the optimization of the surgical plan according to the degree of stenosis, the course of disease, the control of primary disease and the general condition was an important guarantee to improve the curative effect of laryngotracheal stenosis.

Clinical significance of overexpressed cyclin-dependent kinase subunits 1 and 2 in esophageal carcinoma.

The mammalian cyclin-dependent kinase subunit (Cks) family has two members, Cks1 and Cks2. Overexpression of Cks1 and Cks2 has been reported to be associated with high aggressiveness and poor prognosis in several malignancies, including prostate and hepatocellular carcinomas. However, whether Cks1 and Cks2 are overexpressed in esophageal carcinoma remains uncharacterized. To investigate whether overexpression of the Cks family is clinically relevant in esophageal carcinoma, and whether expression patterns of Cks1 and Cks2 can serve as biomarkers for esophageal carcinoma. Real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot analyses were applied to detect the expression of Cks1 and Cks2 at the mRNA and protein levels, respectively. The associations between Cks1 or Cks2 expressions and clinical features and p27(kip1) expressions in esophageal carcinoma were analyzed. Comparing with the adjacent noncancerous tissues, esophageal carcinoma exhibited elevated expression of Cks1 in 58% cases at the mRNA level and 54% cases at the protein level, and elevated expression of Cks2 in 65% cases at the mRNA level and 61% cases at the protein level, respectively. The expressions of both Cks1 and Cks2 were negatively associated with the p27(kip1) protein level in the tumor tissues. Furthermore, overexpression of Cks1 and Cks2 in esophageal carcinoma was closely associated with poor pathological features of esophageal carcinoma, including higher histologic grade of tumor, regional lymph nodes invasion, and neoplastic embolus. Overexpression of Cks1 and Cks2 is associated with the aggressive tumor behaviors of esophageal carcinoma. Further efforts are needed to determine whether overexpression of Cks1 and Cks2 can serve as novel biomarkers for esophageal carcinoma.

Clinical characteristics and microbiology of nosocomial enterococcal bloodstream infections in a tertiary-level hospital: a retrospective study, 2007-2019.

BACKGROUND: Enterococci are important pathogens causing nosocomial bloodstream infections (BSIs) and cannot be treated with appropriate timely empirical antibiotics due to their natural resistance to many kinds of antibiotics. AIM: To analyse the clinical characteristics and microbiological features of nosocomial bloodstream infections caused by enterococci. METHODS: The clinical characteristics and microbiological features of nosocomial enterococcal BSI patients in Xiamen University Zhongshan Hospital were examined in a case-controlled retrospective study. All patient information was collected through an electronic surveillance system. FINDINGS: A total of 199 cases were identified as nosocomial enterococcal BSIs over a period of 13 years. The incidence of BSIs fluctuated from 0.21% to 0.81%. In the distribution of wards, enterococcal BSIs in hepatobiliary surgery ranked first. Intra-abdominal diseases (odds ratio: 3.36; 95% confidence interval: 2.15-5.27; P < 0.001), chemotherapy history (4.37; 2.06-9.25; P < 0.001), and urinary catheterization (2.34; 1.52-3.61; P < 0.001) were risk factors for nosocomial enterococcal BSI acquisition. Vancomycin-resistant enterococci and linezolid-insensitive enterococci strains were not found. CONCLUSION: Patients with a history of intra-abdominal disease, chemotherapy and urinary catheterization are at higher risk of nosocomial enterococcal bloodstream infections. The enterococcus strains were still sensitive to commonly used antibiotics.

Purification of a yeast centromere-binding protein that is able to distinguish single base-pair mutations in its recognition site.

A centromere-specific DNA-binding protein has been purified to homogeneity by a combination of conventional and sequence-affinity chromatography from the yeast Saccharomyces cerevisiae. This protein (designated CBP-I) has an apparent molecular weight of 16,000. It binds specifically to the CDEI (centromere DNA element I) region of yeast centromere DNA, as shown by the electrophoretic mobility retardation assay and DNase I protection analysis, but does not bind specifically to other regions of yeast centromere DNA such as CDEII and CDEIII. The relative binding affinity of purified CBP-I to five different point mutations of CDEI correlates directly with the previously determined ability of each point mutation to convey centromere function in a mitotic chromosome segregation assay (J. H. Hegemann, J. H. Shero, G. Cottarel, P. Philippsen, and P. Hieter, Mol. Cell. Biol. 8:2523-2535, 1988). This supports the authenticity of CBP-I as a functional component of the yeast kinetochore.