[A retrospective analysis of 12 cases of primary thyroid lymphoma].

OBJECTIVE: To discuss the clinical characteristics and diagnostic and therapeutic considerations of primary thyroid lymphoma (PTL) by reviewing PTL cases. METHODS: In the study, 12 cases of PTL diagnosed and treated in Peking University First Hospital between January 1995 and September 2015 were identified. The clinical characteristics, management experiences and prognosis of these cases were reviewed retrospectively. RESULTS: A total of 12 PTL patients (four males and eight females) were collected, with an average age of 63 years (42 to 81 years) at the time of diagnosis. The average time to clarify diagnosis was 5 months (0.5 to 24 months). Eleven patients presented with a rapidly growing neck mass and visited surgical department, except one complained of coughing and suffocated. Seven patients were hypothyroid, and four were euthyroid at the time of diagnosis. In sonography of 11 cases, nine showed bilateral nodules, with an average diameter of 3.87 cm. Pathologic diagnosis of non-Hodgkin's lymphoma was confirmed in all the 12 cases by means of partial thyroidectomy (four) or core needle biopsy (eight). The pathological subtypes were diffuse large B cell lymphoma in nine patients, mucosa-associated lymphoid tissue lymphoma (MALToma) in two, and small B cell lymphoma in the other one patient. Five patients were concomitant with Hashimoto's thyroiditis. Eleven patients received chemotherapy. Only one patient did not have any further treatment after operation due to an inertia type of tumor. The median overall survival time was 24 months (1-117 months), three patients died. Among the patients who survived, seven completed chemotherapy without disease progression, one MALToma case did not receive chemotherapy after thyroidectomy but was still alive with PTL, and one patient just finished his second course of chemotherapy. CONCLUSION: The diagnosis of PTL should be considered when dealing with rapidly growing goiters in elder female Hashimoto's thyroiditis patients whose B ultrasound indicates hypoechogenicity in thyroid nodules or parenchyma, especially with lymphadenopathy and tracheal compressions. Timely use of coreneedle biopsy on suspicious cases can avoid unnecessary surgical trauma, and chemotherapy is the main treatment.

[Clinical analysis of leiomyomatosis peritonealis disseminate after laparoscopic uterine myomectomy in ten cases].

Objective: To investigate the clinicopathological features, treatment and prognosis of leiomyomatosis peritonealis disseminata (LPD). Methods: A total of 10 patients suffered from LPD after laparoscopic uterine myomectomy were collected in the First Affiliated Hospital of Zhengzhou University from September 2012 to September 2016, and all clinical database were retrospectively analyzed. Results: (1)Clinical features: the age of 10 cases was 25-50 years old, and 8 cases of them were in child-bearing age, while 2 cases were in perimenopausal period. Of 10 cases, 2 cases manifested as discontinuous lower abdominal pain, and the other cases were seen the doctor for the examinations found tumors of pelvis or abdomen. All 10 cases had a history of laparoscopic uterine myomectomy under went power morcellation with an average of (4.0±2.2) years (range 1.3 to 8.1 years), 2 cases of them had a history of oral hormone treatment after the first myoma morcellation. (2) Treatment methods and postoperative pathologic diagnosis: during intraoperative exploration, LPD nodules were most distributed in Douglas pouch (10 cases), and next in mesentery (7 cases), abdominal peritoneum (6 cases) and omentum majus (4 cases), etc. Seven of the 8 cases of child-bearing age were performed laparoscopic LPD nodules removal, 1 case gone combined with laparotomy and resecting LPD nodules; 2 cases in perimenopausal period done laparotomy oophorotomy and resected all LPD nodules and omentum. (3) Postoperative relapse and reproductive outcomes: the follow-up time of all cases was 2.8 years, and no recurrence was found during the follow-up period; 2 cases had natural conception and term vaginal birth during the follow-up period. Conclusions: LPD is mainly related to iatrogenic planting and spreading, which is a benign disease and characterized by multiple smooth muscle nodules throughout abdominopelvic cavity, and the nodules of LPD is commonly located in Douglas pouch, mesenteric and omentaum majus, etc. The preferred method of LPD should be individual operative treatment according to different situations, and in which patients may be have better prognosis.

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

OBJECTIVES: Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. MATERIALS AND METHODS: A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. RESULTS: A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. CONCLUSIONS: Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353-361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2.

10-Hydroxycamptothecin induces apoptosis in human neuroblastoma SMS-KCNR cells through p53, cytochrome c and caspase 3 pathways.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, remains one of the most challenging types of cancer to treat. Therefore, the search for novel effective drugs for its treatment is essential. The present study used 10-hydroxycamptothecin (HCPT), which is a naturally occurring alkaloid anticancer agent extracted from the Chinese tree, Camptotheca acuminata, and has a strong anticancer activity in vitro and in vivo. HCPT is able to induce apoptosis in cells of various tumor types. However, few studies have been conducted on its efficacy in NB, and its apoptosis-inducing mechanism has not been elucidated. In the present study, the in vitro effects of HCPT on apoptosis in the human NB cell line, SMS-KCNR, and its underlying molecular mechanisms were investigated. Cell proliferation was measured by an MTT assay and apoptosis was measured using DAPI staining and flow cytometric analysis. In addition, western blot analysis was used to evaluate the apoptosis-associated signaling pathways. HCPT was observed to markedly inhibit cell proliferation and induce apoptosis in SMS-KCNR cells at a relatively low concentration (2.5-20 nM). DAPI staining revealed typical apoptotic feature, namely apoptotic body formation. The flow cytometric analysis revealed that the number of apoptotic cells increased from 20.89% (for 2.5 nM) to 97.66% (for 20 nM) following HCPT treatment for 48 h. Western blot analysis revealed that p53, cytoplasmic cytochrome c, cleaved caspase-3 and poly ADP-ribose polymerase (PARP) proteins were significantly upregulated, while the mitochondrial cytochrome c and pro-caspase-3 proteins were downregulated. However, the B-cell lymphoma 2 and Bcl-2-associated X proteins were unaffected. The results indicated that HCPT may inhibit proliferation and induce apoptosis in the SMS-KCNR cells. The possible mechanism of apoptosis induction is the p53-mediated mitochondrial apoptotic signaling pathway, which promotes cytochrome c release and induces apoptosis by activating caspase-3 and PARP. Our study provides experimental evidence for HCPT as a potent therapeutic drug in NB treatment.

The histological analysis of the anterior cruciate ligament of canine after radiofrequency shrinkage.

OBJECTIVE: Radiofrequency (RF) shrinkage has been widely conducted in clinical practice and the anterior cruciate ligament (ACL) laxity is regarded as one of the indications. However, basic researches regarding the postoperative histological changes were still insufficient. The study aimed to investigate postoperative histological changes of different areas of ACL for further identifying the optimal area for RF shrinkage. MATERIALS AND METHODS: A total of 29 healthy canine (16.5 ± 2.2 kg, 4.1 ± 0.7 years) were recruited, 24 of which were randomly divided into group A and group B. The epiphyseal arrest was confirmed by X-ray examination in all animals. On one canine, an ACL's vascular perfusion model was established by the ink-perfusion method to observe the blood supply of the ACL. The mid-portion of ACL was conducted by RF in group A while the amph-portions of ACL were conducted in group B. Two legs of each canine were sub-divided into fixation group (group A1 and B1) and non-fixation group (group A2 and B2). 8 ACLs were separated from the rest 4 canine. 2 ACLs were sent for the histological examination after RF shrinkage and the rest 6 ACLs were served as blank controls. Masson staining and hematoxylin-eosin (H-E) staining were applied to observe the features of inner fibrous changes of ACL, cell count and vascular density. RESULTS: According to the Masson staining, collagenous tissues were observed in area after RF shrinkage, which was more evident among group B1 than the others. The cellar density in both group A and B was found lower at 12 weeks postoperatively than that at 6 weeks postoperatively (p < 0.05). In addition, the cellar density in B1 group was found higher than that in A1 group at both 6 and 12 weeks postoperatively (p < 0.05). The density of subsynovial vessel in B1 group was found higher than that in A1 group at 6 weeks postoperatively (p < 0.05) and the density of subsynovial vessel in both A1 and B1 groups was found lower at 12 postoperatively weeks than that at 6 weeks postoperatively (p < 0.05). In both A2 and B2 groups, all ACLs were found ruptured at 12 weeks postoperatively. CONCLUSIONS: The postoperative revascularization pattern of RF-treated ACL was permeating from the synovium to the RF-treated areas, and the best area for the RF shrinkage treatment was the amph-portions of the ACL. Moreover, the application of postoperative external fixation to restrict the movement of injured limb was necessary.

A facile preparation of novel multifunctional vectors by non-covalent bonds for co-delivery of doxorubicin and gene.

In this study, novel multifunctional ternary complexes of biotinylated transferrin-avidin-biotin-poly(ethylene glycol)-poly(L-glutamate acid)/poly(2-(2-aminoethylamino) ethyl methacrylate)/doxorubicin-poly(L-aspartic acid)/pDNA (TAB/PIC-D/pDNA complexes) were prepared based on polyion complex micelles (PIC) and the avidin-biotin system, which aimed to target co-delivery of anti-cancer doxorubicin and gene. Cytotoxicity studies revealed that PIC-D could have anti-tumor effect on HeLa cells and HepG2 cells; TAB coating could increase the biocompatibility of PIC-D/pDNA complexes and the targeting delivery efficiency of doxorubicin. TAB/PIC-D/pDNA complexes possessed higher transfection efficiency than the unmodified complexes in serum, and transferrin could enhance luciferase expression in HeLa cells and HepG2 cells. Furthermore, confocal laser scanning microscopy showed that doxorubicin and gene could be delivered into HepG2 cells simultaneously by TAB/PIC-D/pDNA complexes. The formation of the ternary complexes provides a facile approach to constructing a multifunctional delivery system for targeted co-delivery of anticancer drugs and gene.

Non-linear and chaos characteristics of heart sound time series.

Analysis of chaotic time series is common in many fields of science and engineering. It arises primarily from massive interactions between the many different parts of a non-linear system or in non-linear physical phenomena that are intrinsically complex. It is important to analyse the time series of these non-linear dynamic systems based on chaos theory. In recent years, many researchers on heart dynamics have demonstrated that chaos really exists in heart movements. In this study the non-linear and chaos characteristics are investigated and the fractal dimensions (FDs) and largest Lyapunov exponents (LLE) of the heart sound time series are calculated. First, the C-C method is used to estimate the time delay and embedding dimensions which are used to reconstruct the phase spaces. Then, the FDs and LLEs of the different heart sound signals are calculated and analysed, including the healthy heart sound, splitting of the second heart sound, mitral incompetence, and abnormal aortic shrinkage. From the results, the non-linear and chaotic characteristics in heart dynamic movement are found, and the results of LLEs show that the healthy heart has more obvious chaotic movements than abnormal movements.

Stimulatory and entraining effect of melatonin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion.

The aims of the present study were to determine if melatonin exerts an effect on prolactin (PRL) secretion via the tuberoinfundibular dopaminergic (TIDA) neurons and if endogenous or exogenous melatonin has an entraining effect on the rhythmic changes of TIDA neuronal activity and PRL secretion. Melatonin given in the morning (10:00 h), dose- (0.01-1 mg/kg, ip) and time- (at 15 and 60 min, but not at 30 min) dependently stimulated TIDA neuronal activity in ovariectomized (OVX), estrogen-treated rats as determined by 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the median eminence (ME). Serum PRL was concurrently inhibited by the injection. Melatonin administered in the afternoon (15:00 h) was even more effective in stimulating the lowered TIDA neuronal activity and inhibiting the increased PRL level than that given in the morning (10:00 h). S-20098, a melatonin agonist was also effective in stimulating the TIDA neurons. In contrast, S-20928, a putative melatonin antagonist, while it had no effect by itself, blocked the effect of S-20098. Although S-20928 failed to prevent melatonin's effect on ME DOPAC levels, six interspaced injections of S-20928, from 18:00 to 01:30 h, significantly blocked the increase of ME DOPAC levels at 03:00 h, indicating that the endogenous melatonin may play a role. We further used rats that received daily injection of melatonin (1 mg/kg, ip) at 18:00 h for 10 days and found that the injection augmented basal TIDA neuronal activity at 11:00 h and blunted the afternoon PRL surge. In all, melatonin can have an inhibitory effect on PRL secretion by stimulating the TIDA neurons, and it may help to entrain the circadian rhythms of both TIDA neuronal activity and PRL secretion.

Stimulatory effect of central oxytocin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion: neurochemical and electrophysiological studies.

The posterior pituitary hormone, oxytocin (OT), has been shown to have either a stimulatory or an inhibitory effect on PRL secretion depending on the route of administration. Whether its central inhibitory effect involves the tuberoinfundibular dopaminergic (TIDA) neuron was the focus of this study. Adult female Sprague-Dawley rats ovariectomized for 1 week, implanted with sc estrogen-containing capsules and intracerebroventricular cannulas for 6 more days were used. TIDA neuron activity was determined by measuring the concentration of 3,4-dihydroxyphenylacetic acid or 3,4-dihydroxyphenylalanine in the median eminence by HPLC with electrochemical detection. Intracerebroventricular injection of OT induced both dose (0.01-1 microgram/rat)- and time (30-90 min)-dependent increases in 3,4-dihydroxyphenylalanine or 3,4-dihydroxyphenylacetic acid levels in the median eminence. Serum PRL levels were also decreased 30 min after the injection. The use of a specific OT antagonist, [d(CH2)5, Tyr(Me)2, Orn8]vasotocin, not only blocked the effect of OT on TIDA neuron activity, it further lowered it to below control levels, indicating the existence of an endogenous OT activity. When 1 microgram OT was administered at 1200 h, it also reversed the diurnal decrease in TIDA neuron activity at 1500 h. The effects of OT on the electrical activities of dorsomedial arcuate neurons were also tested using single unit recording in brain slices. In 33 neurons tested with OT, 66.7% were stimulated by OT in 0.5- to 50-nmol doses, and no inhibitory effect was observed. The rest were not responsive. In conclusion, both neurochemical and electrophysiological studies demonstrated that central OT may play a stimulatory role in regulating the TIDA neurons and, in turn, inhibition of PRL secretion.

Use of acitretin for the skin complications in renal transplant recipients.

AIM: To review our experience using acitretin for the skin complications in renal transplant recipients. METHODS: Fifteen longterm caucasian renal transplant recipients suffering skin complications were treated with acitretin (10-50 mg daily), a second generation retinoid. Indications for its use were progressive actinic keratoses, widespread warts or recurrent skin malignancies. The therapeutic benefit was assessed by the general condition of of the skin and the number of skin malignancies excised, and the side effects by regular enquiry, skin examination and laboratory tests. RESULTS: All 15 patients reported that the skin became softer and smoother. Actinic keratoses and warts improved or disappeared. Six patients had been on acitretin for over 12 months. The number of malignancies decreased in four of these six patients. Nine patients had cutaneous side effects due to acitretin necessitating a reduction in dose in five patients and discontinuation in the remaining four patients. No patient had any disturbance of their liver or renal function tests or lipid profile. No interaction was found between cyclosporin A and acitretin (seven patients). CONCLUSIONS: Most patients treated with acitretin experienced subjective improvement and actinic keratoses and warts improved or disappeared. Its effect on the skin malignancy rate was variable. Acitretin was reasonably well tolerated. The benefits of this drug remain anecdotal, making a prospective, multicentre, placebo controlled study essential.

Cyclosporin in renal transplantation: a 9 year experience.

AIM: Review our 9 year experience using cyclosporin A (CyA) in a triple immunosuppressive regimen for renal transplantation. PATIENTS: Between 1 October 1984 and 30 June 1993 117 patients had a total of 130 renal transplants. This review was confined to 52 of these patients who had been on CyA for at least 12 months and had remained under regular surveillance in this clinic. RESULTS: Patients were given 10 mg/kg of CyA prior to transplantation then 8 mg/kg/d in two divided doses after the onset of graft function. The maintenance dose was tapered to a mean of 3.5 mg/kg/d (SD 1.4) within 9 months and thereafter ranged from 3.0-3.4 mg/kg/d. Individual patients differed significantly in the trough whole blood CyA concentrations that they produced on a certain dose. Chronic CyA nephrotoxicity occurred in 3 patients and equivocal changes in another patient, while on a CyA dose of 3.0-4.0 mg/kg/d. CONCLUSION: CyA was an effective drug as part of a triple immunosuppressive regimen for renal transplantation. Chronic CyA nephrotoxicity was an unpredictable finding and occurred with doses as low as 3.0-4.0 mg/kg/d and with drug concentrations within the recommended therapeutic range. All patients on CyA should be under regular supervision and early graft biopsy undertaken if there is evidence of graft dysfunction.