Objective To examine the distribution of high-affinity neurotrophin receptors, viz. TrkA, TrkB and TrkC receptors, in the four-order central pathway of trigeminal proprioception in the rat. Methods Avidin-biotin-peroxidase complex (ABC) method of immunohistochemistry with diaminobenzidine (DAB) as the chromogen was employed to identify the immunoreactive cells. Results All three receptors were detected in the mesencephalic trigeminal nucleus, the second-and third-order nuclei in the central pathway of trigeminal proprioception. Within each of these nuclei, cells immunostained for the three receptors differed in density. TrkA-and TrkB-immunostaining was observed on the cell bodies and processes; TrkB, however, labelled much longer processes. TrkC staining was mainly restricted to the cell bodies.Conclusion In the central pathway of the trigeminal proprioception, each of the three receptors may play a specific role in maintaining the survival of neurons and in regulating the neurotransmitter release.;

Objective To investigate whether the serotonin(5\|HT)\|like immunoreactive axons synapse upon the second\|order neurons on the central pathway of the trigeminal proprioception in the rat. Methods Electron microscopic double\|labeling of retrograde tract\|tracing technique combined with immunohistochemistry. Results Following the injection of wheat germ agglutinin\|horseradish peroxidase (WGA\|HRP) into the dorsomedial part of the principal sensory trigeminal nucleus(Vpdm) of the rat and the immunostaining for 5\|HT, there were neurons retrogradely labeled by WGA\|HRP and axon terminals with 5\|HT\|like immunoreactivity(5\|HT\|LI) in the dorsomedial part of the subnucleus oralis of the spinal trigeminal nucleus and its adjacent lateral reticular formation(Vodm\|LRF).At the electron microscopic level,the 5\|HT\|immunostained axonal profiles were observed to make synaptic contacts with the WGA\|HRP\|labeled neurons.Both the axon\|somatic and axon\|dendritic synapses were found.These synapses were mainly of symmetric type although the asymmetric ones were also seen.Conclusion\ The present results provided a morphologic basis for the serotoninergic terminals which might be involved in the regulatory effect for the trigeminal proprioceptive information transmission.\;[

Previous studies showed that the Vodm-LRF-including the dorsomedial part of the subnucleus oralis of the spinal trigeminal nucleus and its adjacent lateral reticular formation--contained the second-order neurons on the central pathway of the trigeminal proprioceptive sensation of the rat and the "zone-shaped area"-including the caudolateral part of the supratrigeminal nucleus (Vsup-CL). The dorsomedial part of principal sensory trigeminal nucleus (Vpdm) and two newly found nuclei: the areaventral to the motor trigeminal nucleus (AVM) and the area dorsal to the superior olivary nucleus (ADO)-contained the third order neurons of this pathway. Parvalbumin (PV) is one of the calcium-binding proteins, In this pathway, many PV-like immunoreactive (PV-LI) neurons were observed in Vodm LRF and the "zone-shaped arena", hut there has been no reports so far regarding whether these PV-LI neurons are projection neurons responsible for the transmission of proprioceptive information or the interneurons serving the modulatory function, in the present study, our aim was to solve the problem by a double labeling study by using retrograde tracing method combined with immunofluorescence histochemistry. The results showed that: (1) following the unilateral Fluoro-Gold (FG) injections into the ventral posteromedial nucleus (VPM) of the thalamus and the separated parts of the "zone-shaped area", viz, Vpdm, ADO and AVM, many FG-labeled neurons were always found contralaterally in the "zone-shaped area" and ipsilaterally in the Vodm-LRF, respectively; (2) in either the "zone-shaped area" or the Vodm-LRF, a substantial number of the FG retrogradely labeled neurons showed PV-LI. In the Vsup-CL, Vpdm, AVM and ADO, about 57%, 55%, 11% and 4% of the neurons projecting to the VPM of the thalamus showed pV-LI, respectively. Of the total population of PV-LI neurons in the Vsup-CL, Vpdm. AVM and ADO, about 23%, 79%, 53% and 16% were labeled by FG, respectively. Most of these PV/FG double-labeled neurons were medium- to small-sized, round, piriform or irregular in shape. On the other hand, in the Vodm-LRF, approximately 33%, 34% and 50% of the neurons which projected to the Vpdm, AVM and ADO expressed PV-LI, respectively. The percentage of PV/FG double-labeled neurons to the total number of the PV-LI neurons in Vpdm, AVM or ADO were 26%, 17% or 11%, respectively, The present results indicated that PV might play an important role in the transmission of the trigeminal proprioceptive information of the rat from Vndm-LRF to the contralateral VPM of the thalamus through the "zone-shaped area".

Objective To evaluate mid-term clinical and radiographic outcomes associated with cementless total hip arthroplasty(THA) in a consecutive series of patients with osteonecrosis of the femoral head. Methods This study examined the mid-term (equal to or more than 5 years) results of THA. From January 1998 to March 2001, a series of 71 patients (80 hips) who had undergone THA with cementless components in our hospital were involved in this study. All patients were evaluated both clinically and radiographically. Clinical outcomes were evaluated according to Harris evaluation score. Components migration, bone changes around the implant, the polyethylene wear rate and direction of the acetabular polyethylene wear were measured radiologically. Kaplan-Meier analysis was performed to evaluate the survival of the femoral and acetabulum components. End point was radiographical loosening or revision of the acetabular component, and revision of the femoral component for any reason. Results 62 hips in 54 patients were followed up at least 5 years. The mean Harris hip score improved from preoperation (44.0?8.4) points to (92.4?5.7) points at the time of final follow-up. No component was seen to be loose radiographically or had been revised because of any reason at the time of final follow-up. Only one focal area of pelvic osteolysis in one patient and twelve small focal areas of femoral osteolysis in another patient were identified. The mean linear wear rate was (0.125?0.074) mm/year. When loosening was used as the end point for failure, the survival rate of the acetabular and femoral components was 1.0 (95% confidence interval, 0.98 to 1.00) in both groups. Conclusion Cementless THA in patients with osteonecrosis of the hip had a satisfactory clinical and radiographic outcome at a minimum of five years follow-up. Because polyethylene wear and osteolysis can not avoided, radiographical follow-up for cementless components is very important.

Objective To observe the relationships among the direct projection neurons from the lumbar spinal cord to the lateral parabrachial nucleus(LPB),calbindin D-28K(CB)-like immunoreactive (-LI) neurons,peripheral noxious information transmission as well as substance P receptor(SPR)-LI neurons. Methods Triple-labeled techniques were used by tetramethyl rhodamine(TMR) retrograde tracing combined with immunofluorescence histochemistry for CB-,SPR- or Fos protein.The stained sections were observed under a confocal laser-scanning microscope. Results 1.After injecting TMR to the unilateral LPB,a number of TMR retrogradely labeled neurons were mainly distributed in the lamina Ⅰ,lateral spinal nucleus(LSN),and regions around the central canal of the spinal cord(lamina X) of the ipsilateral spinal cord;2.CB-LI neurons were mainly found in the laminae Ⅰ and Ⅱ of the lumbar spinal cord,especially in the lamina Ⅱ in the dense distribution; 3.SPR-LI neurons were also mainly seen in the lamina Ⅰ,LSN and lamina X of the spinal cord.A few of the SPR-LI neurons were also distributed in the lamina Ⅱ;4.Fos-positive neurons were detected in the laminae Ⅰ and Ⅱ,lateral aspect of the lamina Ⅴ to Ⅶ of the lumbar spinal cord by injecting 5% formalin into the ipsilateral hindpaw;5.Triple-labeled neurons for TMR/CB/SPR or TMR/CB/Fos were mainly found in lamina Ⅰ,while a few of the triple-labeled neurons were also found in lamina Ⅱ of the dorsal horn.TMR/CB/SPR triple-labeled neurons accounted for 103%,98% and 146% of total population of TMR-,CB- or SPR-LI neurons in laminae Ⅰ and Ⅱ,respectively.On the other hand,TMR/CB/Fos triple-labeled neurons formed 118%,106% and 158% of the total population of TMR-,CB-LI or Fos-positive neurons in the laminae Ⅰ and Ⅱ,respectively.Conclusion\ The results indicated that in the laminae Ⅰ and Ⅱ of the lumbar spinal cord some neurons with CB-Like immunoreactivity transmitting the peripheral noxious information and projecting directly to the LPB might receive SPergic primary afferents.

Objective To explore the value of computed tomography (CT)and magnetic resonance imaging (MRI)in the diagno-sis and delineation of the extent of malignant external otitis (MEO).Methods Clinical manifestations and imaging features of 10 pa-tients with definite diagnosis of MEO were collected and analyzed.Plain and contrast-enhanced CT of the ear were performed on all 10 patients,of which 6 patients also received MRI scans.Results Abnormal soft tissue opacity within the external auditory canal and involvement of surrounding structures were found in all 10 patients.Bone erosion of the external auditory canal was showed in 7 pa-tients.Other CT findings included bone erosion of skull base and intracranial involvement.Abnormal soft tissue of the external audi-tory canal,effusion in the mastoid cavity and medullary abnormalities were showed very well on MR images in 6 patients while the cortical bone erosion was not well showed.Conclusion Imaging features of the lesions in the external auditory canal,bone erosion of skull base and intracranial involvement play crucial roles in the diagnosis and delineation of the extent of the lesion in patients with MEO.

Objective To observe the relationship between 5-Hydroxytryptamine(5-HT)-like immunoreactive terminals and the vestibulo-parabrachial nucleus projection neurons which may express 5-HT1A receptor in the vestibular nuclear complex(VNC). Methods Retrograded-tract tracing technique combined with double labeling of immunofluorescence histochemical was used,and the stained sections were observed under a confocal laser-scanning microscope. Results Following injection of tetramethylrhodamine(TMR) into the parabrachial nucleus, many retrogradely labeled neurons were observed bilaterally within VNC,but with an ipsilateral predominance.Immunofluorescence histochemical staining showed that many neurons expressed(5-HT1A) receptor-like immunoreactivity and a large number of 5-HT immunostained fibers or terminals were found in the medial,spinal,superior,lateral vestibular nucleus(MVe,SpVe,SuVe,LVe),X nucleus and Y nucleus.Confocal laser-scanning microscopy revealed that some TMR-labeled neurons were 5-HT_1AR immunopositive,and some of the cell bodies or dendrites of TMR/5-HT1AR double-labeled neurons were closely apposed by 5-HT-like immunoreactive terminals.Conclusion The present study suggests that 5-HT may modulate vestibular signals along the VNC-parabrachial nucleus pathway via 5-HT1A receptor.

Objective To investigate the early changes of CD4 + T cells and the relevant cytokines in blood of patients with severe trauma.Methods Sixty-one consecutive patients with trauma admitted into the 97th Hospital of PLA from September 2009 to November 2011 were enrolled in this study.The exclusion criteria included:① Patients were younger than 18 or older than 75 years.②Patients received blood transfusion.③Those suffered from immune system disorders,tumors or diabetes,or recent history of virus,bacteria or parasites infections.④ Those had current or recent treatment with corticosteroids or immunosuppressive drugs.According to ISS score ≥ 16,there were 61 traumatic patients divided into mild trauma group and severe trauma group.Seventeen healthy volunteers were taken as control subjects.At admission,the peripheral venous blood samples of patients were taken to count the number of CD3+,CD4 +,CD8 + T cells by flow cytometry and to detect TNF-α,INF-γ,IL-1,IL4,IL-6 and IL-12 levels in plasma by enzyme linked immunosorbent assay,meanwhile the ratio of Th1 / Th2 type cytokine were calculated.Data were analyzed with t test and ANOVA or Kruskal-Wallis test by using SPSS version 16.0package.P value ＜ 0.05 was considered to be statistical significance.Results Compared with control group,mild trauma and severe trauma groups showed a similar decrease in number of CD3 + T cells,and severe trauma group showed a most significant decrease in number of CD4 + T cells.Severe trauma group had a lower INF-γ level compared with control group; IL-1 level in both mild trauma and severe trauma groups were lower than that in the control group; INF-γ/ IL-6 in severe group was significantly lower than that in the mild group.However,INF-γ IL-6 in mild group was higher than that in the control group.Conclusions The early stage of severe trauma exhibits a significant decrease in number of both CD3 + and CD4 +T cells,accompanied by a significant reduction in most of cytokines,and has a tendency of shift to Th2 type cytokine.Therefore,the changes of immune cells should be promptly and successively monitored after severe trauma.

Objective To retrospectively observe and compare the efficacy and safty of irinotecan or oxaliplatin combined with fluoropyrimidine in the first line treatment of advanced gastric cancer. Methods 71 patients were divided into two groups. The irinotecan group consisted of 37 patients. Irinotecan 180 mg/m2 was injected in 90 minutes on d1. And the oxaliplatin group consisted of 34 patients. Oxaliplatin 85 mg/m2 was injected on d1. All the groups combined fluoropyrimidine. 5-Fluorouracil (5-Fu) 400 mg/m2 and leucovorin 200 mg/m2 were injected on d1,2 and 5-Fu 600 mg/m2 was 22 h continuous injected on d1,2, every 2 weeks was a cycle. It could also take capecitabine 1.0 g/m2 or tegafur-gimeracil-oteracil potassium 25 mg/m2 Bid for d1~14 orally, every 3 weeks was a treatment. Results 65 patients were evaluated. The response rates were 32.35% and 22.58%, the disease con-trol rates were 76.47% and 70.97%, and the median progression free survival (PFS) were 5 (3.962~6.038) months and 4 (2.730~5.270) months in irinotecan group and oxaliplatingroup, respectively, with no significant difference (P>0.05). Toxicity was tolerable, major adverse events were neutropenia, nausea and vomiting in two group. The incidence rate of diarrhea (45.95%) was higher in irinotecan group, and the peripheral nerve toxicity was 29. 41% in oxaliplatin group. Conclusion The effects of irinotecan or oxaliplatin combined with fluoropyrimi-dine in the treatment of advanced gastric cancer are comparable, and their toxicities are tolerable.

Development of small molecule drugs is important for targeted and personalized therapy for cancers.However,it is staggering to take new compounds from the research bench to clinical trial pipelines and eventually to the clinical practice,due to the time,effort and costs.Most drugs need five years of development after discovery in the laboratory before they are ready to be tested for efficacy and safety.Compared to development of new drugs from scratch, increasing research efforts have been made to turn existing drugs to new uses to treat cancers, which may bypass years of costly work.Metformin used in cancer care is a good example of giving old drugs a new life.The activity of metformin on anti-cancer has recently drawn significant attention.Epidemiological and experimental studies have shown that metformin can cut down the incidence of cancer in diabetic patients and reduce metabolism-related cancers.Meanwhile, recent study has found metformin can induce autophagy of esophageal cancer cells by inhibiting inflammatory signaling pathway.In recent years, increasing studies have shown that metformin plays a major role in suppressing cancers via multiple mechanisms.In this mini-review,we summarize the updates of the research on metformin in cancer prevention and treatment.