Retrobulbar dexmedetomidine in pediatric vitreoretinal surgery eliminates the need for intraoperative fentanyl and postoperative analgesia: A randomized controlled study

Purpose: This study evaluated the efficacy of retrobulbar ropivacaine plus dexmedetomidine compared with systemic fentanyl in pediatric vitreoretinal (VR) surgery. Methods: This prospective double-blind, randomized controlled study was performed in 60 children undergoing VR surgery, age from 2 to 7 years. After general anesthesia, the following procedure was administrated: (1) retrobulbar block with 0.5% ropivacaine plus dexmedetomidine 1 ?g/kg (group RD, n = 20), (2) retrobulbar block with 0.5% ropivacaine (group RB, n = 20), and (3) control group with general anesthesia only (group F, n = 20). Hemodynamics, postoperative pain scores, anesthetics consumption (remifentanil, propofol, fentanyl), and emergence agitation were recorded. Results: Respiratory depression was observed in 7 of the 20 patients in group F after the laryngeal mask airway was removed in the operating room, compared with none in groups RD and RB. All patients in group F required intraoperative rescue fentanyl (average intraoperative fentanyl consumption, 26.6 ± 12.6 ?g per patient). Some rescue fentanyl was required in group RB (three patients required one dose of rescue fentanyl). Patients in group RD required none. Groups RD and RB reported lower pain scores than group F at 4 h postoperatively (RD group: P < 0.001; RB group: P =0.002); pain scores in group RD were lower than that in group F at 6 h postoperatively (P < 0.001). Conclusion: Retrobulbar dexmedetomidine as an adjuvant to ropivacaine is a safe and effective alternative to systemic fentanyl. This regimen provides better pain management, hemodynamic stability, and stress response suppression in pediatric VR surgery.

Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg-1·day-1; and oral KXS at a dose of 676 mg·kg-1·day-1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg-1·day-1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg-1·day-1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

Toxicity and adverse effects of everolimus in the treatment of advanced nonsmall cell lung cancer pretreated with chemotherapy‑Chinese experiences.

BACKGROUND: There is not more treatment selection for advanced nonsmall‑cell lung cancer (NSCLC) patients who had disease progression after two previous treatments. Everolimus is an oral inhibitor of the mammalian target of rapamycin pathway, which is aberrantly activated in NSCLC. PATIENTS AND METHODS: Stage IV NSCLC patients, with one or multiple prior chemotherapy regimens, received everolimus 5–10 mg/day with or without chemotherapy until progression or unacceptable toxicity. The primary objective were toxicity of everolimus and overall disease control rate (DCR). RESULTS: 22 patients were enrolled. Common ≥grade3 events were stomatitis, dyspnea, vomiting, thrombocytopenia. Overall disease control rate was 54.5% among 22 patients, 1 had a partial response, and 11 had disease stabilization. Common ≥Grade 3 events were stomatitis, dyspnea, vomiting, and thrombocytopenia. CONCLUSION: Everolimus was well tolerated, showing the modest clinical activity in heavily pretreated advanced NSCLC.

Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.

Strain complex of Schistosoma japonicum in the mainland of China.

The present paper deals with studies on the characteristics of Schistosoma japonicum isolated from five localities in the mainland of China. The following items were observed and compared including morphometric data, susceptibility of six mammalian hosts, prepatent period, compatibility between larvae and snail hosts, size of hepatic granuloma produced by eggs, immunoreactions in experimental animals, sensitivity to praziquantel, SDS-PAGE protein pattern and its antigenicity analysis, DNA hybridization and genetic variation and differentiation by analysis with multilocus enzyme electrophoresis. By means of these multidisciplinary methods, from morphological to molecular level, the following conclusions may be drawn from our results. The evidence indicates firstly that S. japonicum in the mainland of China comprises a strain complex with several components of geographically distributed strains. At least four distinct strains exist, ie Yunnan, Guangxi, Sichuan and Anhui-Hubei. Characteristics of each strain are distinct and the results of these studies lead to discussion on the problem of the intraspecific and interstrain differentiation of S. japonicum in the mainland of China.

Sensitivity of different isolates of Schistosoma japonicum from China to praziquantel.

Groups of C57BL inbred mice infected with each of the 4 different isolates, (Anhui, Hubei, Sichuan and Yunnan) of Schistosoma japonicum from the mainland of China were treated with praziquantel (PZQ) and the parasiticidal effects were compared. Worm reduction rate was recorded to assess systematically the sensitivity of 4 different isolates to PZQ in the mouse. Three dosage-levels of PZQ, ie 150, 230 and 310 mg/kg body weight in single doses were used. The worm development rates of control groups infected with schistosomes from Anhui, Hubei, Sichuan and Yunnan were 75.5, 81.8, 81.5, and 83.0%, respectively. At the dosage-level of 150 mg/kg, the worm reduction rates for the 4 different isolates were 36.0, 33.9, 25.5 and 35.6%, respectively. At the dosage-level of 230 mg/kg, the rates were 47.1, 46.0, 38.1 and 47.7%, while at the dosage-level of 310 mg/kg, they were 59.3, 58.6, 50.8 and 61.7%, respectively. The results indicated that the worm reduction rate of the Sichuan isolate was lower than that of the other three isolates, however, the differences were not statistically significant, suggesting that schistosomes of Anhui, Hubei, Sichuan and Yunnan isolates bear resemblance in drug response.

Parasitological and histopathological studies on rhesus monkeys infected with Chinese mainland strain of Schistosoma japonicum.

Fifteen rhesus monkeys were infected by cutaneous exposure each with 200 or 300 cercariae of Schistosoma japonicum. The dynamic distribution of schistosomula in the skin showed that 77-90% of them were found in the connective tissue, while 10-23% migrated in the hair follicles and sebaceous glands at different time intervals after cercarial penetration. Dead schistosomula recovered from the skin varied from 8.7% to 28.7%. The average rate of adult worm recovery was 74.4% and 61.3% in the 6th and 15th weeks of infection, thereafter the rate decreased to 32.3% and 9.0% in the 19th and 42nd weeks, respectively. The mean length of mature pair-worms was 13.2 +/- 2.3 mm in male and 18.0 +/- 1.9 mm in female 6 weeks of worm age. Afterwards the body length of females and their sexual gland diminished markedly. The mean prepatent period was 35.0 +/- 0.6 days. The average size of mature eggs in the feces was 86.6 +/- 5.4 x 64.3 +/- 3.6 microns, and the peak of eggs passage in the feces occurred between 7th and 15th weeks after infection, later on the number of eggs markedly decreased. Skin reaction to the primary infection was slight. The pathological changes observed in liver were chiefly cellular infiltration of portal spaces and the lesions produced by egg granulomas. The mean volume of single-egg granulomas of the productive stage in liver was 22.7 +/- 10.5 mm3 x 10(-3). The most intensive damages in the gastro-intestinal tract were observed in the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Compatibility between Oncomelania hupensis and different isolates of Schistosoma japonicum in China.

Oncomelania hupensis from six localities were used for infection with different isolates of Schistosoma japonicum in the mainland of China, ie Anhui in the east, Hubei in the center, Guangxi in the south, Sichuan in the West, Yunnan in the southwest and Fujian in the southeast. Snails from Anhui and Hubei were readily infected with the local isolate of S. japonicum and cross infection also took place readily between the snails and the schistosomes from these two places. Snails from Sichuan and Yunnan were refractory to infection with schistosome isolates from Hubei and Anhui, but the isolates from Sichuan and Yunnan were able to develop in snails from Hubei and Anhui. Though the Guangxi isolate developed readily in both Anhui and Guangxi snails, the average precercarial period in the former was significantly longer than in the latter. None of the other snails from Sichuan, Yunnan and Fujian became infected. On the other hand, snails from Guangxi infected with Anhui parasites also had a longer precercarial period than that in Anhui snails. Snails from Fujian were readily infected with the isolates from Anhui and Yunnan. The present results suggest that there might be different geographic strains of S. japonicum and their Oncomelania snail hosts in the mainland of China.

Characteristics of different isolates of Schistosoma japonicum from China in the final hosts.

The present paper deals with the susceptibility of common laboratory animals, such as mouse, rat, hamster, jird, rabbit and rhesus monkey, to infection with different isolates of Schistosoma japonicum in the mainland of China under laboratory conditions. With the exception of the rat, all the animals under study were permissive hosts for different isolates though their worm recovery rates varied. The mean body length of pair-worms of the Yunnan isolate was considerably smaller than that of the Anhui, Hubei, Guangxi and Sichuan isolates, and the percentage of male specimens with 7 testes in the Yunnan isolate was also significantly less than that in the other 4 isolates. Judging from the egg index (width/length x 100), the eggs of the Sichuan isolate were broad and short in shape, giving a high index; those of Guangxi and Hubei isolates were oblong, giving the lowest index; the other two isolates from Yunnan and Anhui, lay between these two extremes. The mean prepatent periods were longer in mice, hamsters and rhesus monkeys infected with Yunnan and Guangxi isolates, than those with Sichuan isolate. A dendrogram of the 5 isolates of S. japonicum was constructed on the basis of similarity coefficients by means of fuzzy cluster analysis on the biological characters mentioned above. Our results provide evidence of the existence of different strains of S. japonicum in the mainland of China as shown by comparative studies of their characteristics in the final hosts.