[Clinicopathological features of colorectal amphicrine carcinoma].

Objective: To investigate the clinicopathological, immunophenotypic and molecular features of colorectal amphicrine carcinoma (AC). Methods: Eight cases of colorectal AC were collected at the Nanjing Drum Tower Hospital and Nanjing First Hospital, Nanjing, China from 2013 to 2020. The histopathological, immunohistochemical and molecular features were analyzed. The relevant literature was reviewed. Results: There were 6 males and 2 females, with an average age of 56 years (range 28-80 years). The tumor sites were as follows: 4 cases in sigmoid colon, 3 cases in rectum, and 1 case in transverse colon. Microscopically, there were three different patterns in the tumors, including nests with collagen hyperplasia, sheets of cells with scant stroma, and glandular or cribriform growth of goblet- or signet ring-like cells. The tumor cells generally had abundant cytoplasm with abundant mucin or eosinophilic granules. The nuclei were oval or irregular with fine chromatin and inconspicuous nucleoli. Mitotic figures were common. Neuroendocrine granules and mucin granules could be identified clearly under electron microscope. All cases showed frequent perineural and lymphovascular invasions, lymphatic metastasis, and advanced stage. Regarding immunohistochemical and specific stains, the tumor cells expressed more than two neuroendocrine markers, particularly CD56 and synaptophysin which were diffusely positive in 7 of the 8 cases. They also showed intracellular mucin in the amphicrine components which was positive for D-PAS. KRAS G12C or NRAS Q61 gene mutations were found in 2 patients. Among the six cases with complete follow-up, four of them died of the disease within three years of the diagnoses, while two were alive without known disease progression. Conclusions: Colorectal AC is a rare, distinct entity with both epithelial and neuroendocrine differentiation. It mainly occurs in the sigmoid colon and rectum. It typically has aggressive clinical courses, dismal prognosis and characteristic histological features and immunophenotype, which highlight the importance of recognizing this entity for clinicians and pathologists.

[Analysis of PKD1 gene mutation in a pedigree affected with autosomal dominant polycystic kidney disease].

Objective: To analyze the clinical phenotype and detect the pathogenic gene in a Chinese pedigree with autosomal dominant polycystic kidney disease(ADPKD). Methods: The proband of this study was hospitalized in Dongguan City People's Hospital on October 10, 2017, due to "left maxillary apical cyst". Clinical phenotypes were noted, imaging examinations and determination of biochemical indicators were carried out for the clinical diagnosis of the proband. Genomic DNA was extracted from peripheral venous blood. Whole-exome genotyping of the proband was performed with the next generation sequencing technology, and the candidate mutation site of the patient and his family members was verified by PCR and Sanger sequencing technology. The mutation site was further screened in 150 unrelated healthy Chinese controls. Mutation frequency within human populations and bioinformatics analysis were predicted with softwares including ExAC, dbSNP, HGMD, 1000 genomes, ClinVar, PKDB, Mutation Taster and PhyloP. Results: The proband, a 46-year-old male, was diagnosed with hypertension, positive urine occult blood and elevated blood creatinine. B-ultrasound and CT examinations showed that he had bilateral polycystic kidney with left kidney stones and polycystic liver. The gene analysis showed that the c.11017-10C>A heterozygous splice mutation in PKD1 gene was identified in the proband, his second younger brother, younger sister, daughter and niece, but absent in 150 healthy controls. Bioinformatics analysis showed it has been reported in the dbSNP, ClinVar, HGMD, PKDB and Mutation Taster databases. Some databases predicted it has a harmful function for probably leading to production of a truncated polycystin1(PC1) protein. Conclusion: c.11017-10C>A underlies the Chinese ADPKD pedigree and expands mutation spectrum of PKD1.

[Analysis of influencing factors of ureteral anastomotic stenosis following urinary diversion after laparoscopic radical cystectomy].

Objective: To investigate the influencing factors of ureteroenteric strictures (UES) in patients undergoing laparoscopic radical cystectomy plus urinary diversion (UD). Method: A total of 412 patients who underwent UD after radical prostatectomy from January 2008 to December 2016 were retrospectively included in this study. Age, gender, body mass index (BMI), diversion type, time to diagnosis of UES, duration of ureteral stent, postoperative complications, including urinary tract infections, ureteroenteric leakage and UES were collected. Kaplan-Meier curves were used to describe time to developing UES. Prognostic factors of UES were analyzed using COX proportional hazard regression model. Result: Median follow-up time was 37 (IQR 17-120) months. A total of 59 patients (70 sides) developed UES, including 34 cases on the left side, 14 cases on the right side and 11 cases on both sides, following UD after radical cystectomy. The median time to diagnosis of UES was 7 (IQR 4-11) months. The total incidence of UES was 14.3%. The incidence of UES was 10.9%, 13.3% and 14.1% at 1, 3 and 5 years after UD, respectively. Cox proportional hazard regression model analysis demonstrated that BMI≥25kg·m(-2) (P=0.008), ureteroenteric leakage (P=0.001) and urinary tract infections (P=0.037) were the independent risk factors associated with UES following UD after radical cystectomy. Conclusion: The incidence rate of UES following UD after radical cystectomy was relatively high, which occurs more common on the left side. Obese patients, combined with ureteroenteric leakage, urinary tract infection after UD, are more likely to develop into UES.

[Impact of diverse shapes of prostatic apex on positive apical margin rate and biochemical recurrence following laparoscopic radical prostatectomy].

Objective: To explore the effects of various forms of prostatic apex on positive apical margin rate (PAM) and biochemical recurrence (BCR) after laparoscopic radical prostatectomy. Methods: A retrospective analysis of 309 patients (aging (65±6) years) who were experienced laparoscopic radical prostatectomy from January 2010 to December 2016 at the Department of Urology, First Affiliated Hospital of Fujian Medical University. According to the relationship between prostate apex and membrane urethra at the mid-sagittal plane of preoperative MRI, all patients were classified into 4 categories. There were 31 patients for type 1, apex covering both anterior and posterior aspects of membranous urethra, 139 patients for type 2, apex covering anterior side of membranous urethra, 63 patients for type 3, apex covering posterior aspect of membranous urethra, 76 patients for type 4, apex not covering membranous urethra. PAM and BCR after operation were compared between this four groups respectively. The χ(2) test was used to compare PAM among the 4 types. Logistic regression analysis were undertaken to analyze the factors affecting PAM. Cox's proportional hazards regression model was undertaken to identify the variables influencing BCR. Results: There was no significant difference in the 4 groups concerning age, body mass index, prostate volume, preoperative prostate-specific antigen (PSA) value, postoperative Gleason score and pathological stage (P>0.05).The median follow-up time was 32 months (ranged from 12 to 60 months).The data showed that the apical type 3 patients has the highest PAM. There was statistical difference among the 4 groups in PAM (χ(2)=15.592, P=0.001). Preoperative level of PSA (OR=20.356, 95% CI: 2.440 to 169.810, P=0.005), postoperative Gleason score (OR=4.113, 95% CI: 1.911 to 8.849, P=0.001), pathological stage (OR=3.422, 95% CI: 1.600 to 7.319, P=0.002) and apical type 3 (OR=6.134, 95% CI: 2.196 to 17.132, P=0.001) were independent relactive factors of PAM. Preoperative level of PSA (HR=1.362, 95% CI: 1.006 to 1.843, P=0.045), postoperative Gleason score (HR=1.920, 95% CI: 1.384 to 2.665, P=0.001), pathological stage (HR=1.476, 95% CI: 1.098 to 1.983, P=0.010), PAM (HR=3.497, 95% CI: 2.407 to 5.081, P=0.001)and apical type 3 (HR=1.828, 95% CI: 1.266 to 2.639, P=0.001) were independent prognosis factors of BCR. Conclusion: Prostate apical type 3 could be a significant independent predictor of PAM, and an independent prognosis factor for BCR.

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs.

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.

Analysis of a clinical sign in traditional Chinese medicine using Doppler ultrasound.

Using Doppler ultrasound, a study was done on the characteristics of the radial pulse at the wrist in pregnant and non-pregnant women in order to test the hypothesis that the traditional Chinese medicine 'smooth pulse' of pregnancy has a physiological basis. Comparison of pulse characteristics in a small series of subjects strongly supports this hypothesis.

[The principle and application technology of plasma sterilization].

Plasma sterilization is a new sterilization technology. The advantages of this method are low temperature, time-saving and non-poison. The good sterilization effectiveness has been confirmed through experiments.

Assessment of patient acceptance and inhalation technique of a pressurized aerosol inhaler and two breath-actuated devices.

OBJECTIVE: To assess inhalation technique in patients after written instruction alone, written and verbal instruction, and clinical use of two new inhalation devices. DESIGN: Randomized, crossover evaluation of the albuterol Diskhaler and the terbutaline Turbuhaler. SETTING: Canadian tertiary-care hospital. PATIENTS: Twenty hospitalized adults with asthma or chronic obstructive pulmonary disease currently using an albuterol metered-dose inhaler (MDI). Nineteen patients received Diskhaler, 16 received Turbuhaler, 15 received both inhalers, and 10 patients used both inhalers for three days each. INTERVENTIONS: Patients were randomized to receive either Diskhaler or Turbuhaler for three days. Inhaler technique was assessed after written instruction, written plus verbal instruction, at the first scheduled dose after instruction, and after three days of clinical use. Patients remaining in the hospital after three days crossed over to the other study inhaler and the same protocol was followed. MAIN OUTCOME MEASURES: Patient inhalation technique was assessed and compared for the MDI, Diskhaler, and Turbuhaler. RESULTS: Assessment of MDI technique revealed that 35 percent of patients used their MDI correctly on the first puff, and 42 percent used it correctly on the second puff. Following written instruction alone, correct technique was demonstrated by 32 percent of patients with Diskhaler and 6 percent with Turbuhaler. Technique significantly improved following verbal instruction, although 40 percent of the patients required up to three attempts to demonstrate correct technique on at least one of the study inhalers. After three days of clinical use, correct technique was demonstrated in only 54 percent of the Diskhaler and 64 percent of the Turbuhaler assessments. Performance at this assessment was, however, significantly better on the Turbuhaler than on the MDI (p = 0.01). Performance on the Diskhaler was not significantly different from the performance on the other inhalers. CONCLUSIONS: Written instruction alone is inadequate in teaching correct inhalation technique. Verbal instruction and technique assessment are essential for patients to achieve proper technique. Patients may perform better on the Turbuhaler than on other inhalation devices.

Multiple and irreversible binding of cis-diamminedichloroplatinum(II) to human serum albumin and its effect on warfarin binding.

Irreversible bindings of cis-diamminedichloroplatinum(II) (cis-DDP) to human serum albumin (HSA) were investigated in a pH 7.4 buffer containing 0.1 M NaCl at various molar ratios (cis-DDP/HSA) up to 60 over a 14 d period (37 degrees C). The metal binding seemed to reach a plateau when incubated at less than 10 times excess of cis-DDP. As the molar ratio increased, the reaction rate was relatively fast within the first day, followed by a moderate increase in the metal binding. When incubated at 60 times excess of cis-DDP, the metal bound as much as 20 mol per mol of HSA in 14 d. Fluorescence quenching of the metal-bound protein suggested that the tryptophan residue was gradually exposed to a hydrophilic environment as the metal binding increased. Furthermore, cis-DDP cleaved disulfide bonds at the ratio of 1 mol of disulfide bond per 5.3 mol of the metal binding. It was therefore suggested that the metal binding also occurred at several sites other than the disulfide bond. Warfarin binding to the metal-bound protein, examined by fluorescence changes, also decreased with increasing metal binding or cleavage of the disulfide bonds. Thus, cis-DDP bound to multiple sites in addition to the lone sulfhydryl group (Cys-34), suggesting that massive conformational changes of the protein took place.

Characterization of a genetically reconstituted high-affinity system for serotonin transport.

By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identified several clonal cell lines that stably express a high-affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-[3H]HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high-affinity 5-HT uptake; (iii) both Na+ and temperature dependences; (iv) kinetic saturability; and (v) high affinity for 5-HT (Km = 0.39 +/- 0.10 microM; Vmax = 2.14 +/- 0.55 pmol/min per mg of protein). This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, we postulate that the observed 5-HT-uptake system resulted from the expression of human gene(s) coding for the 5-HT transporter. Thus, cell lines such as L-S1 may represent novel means for screening and developing therapeutic agents specific for neurotransmitter-uptake systems as well as substrates for the cloning and elucidation of the genes encoding the various neurotransmitter transporters.