Efficacy and safety of continuous radiofrequency thermocoagulation plus pulsed radiofrequency for treatment of V1 trigeminal neuralgia: A prospective cohort study.

Patients may develop serious eye complications after continuous radiofrequency thermocoagulation (CRF) for V1 (ophthalmic division) trigeminal neuralgia (TN) at a higher temperature. Therefore, the temperature of clinical CRF for V1 TN has long been disputed, but there have few reports been found about how to achieve satisfactory pain relief, reduce the incidence rates of complications, and shorten the recovery time after CRF for V1 TN.To observe whether pulsed radiofrequency (PRF) can lead to increased rate in pain relief, reduced rate of complications, or shortened recovery time after CRF is used to treat V1 idiopathic trigeminal neuralgia (ITN).The prospective cohort study enrolled 56 patients with V1 ITN from May 2012 to April 2015. The patients were randomized into 2 treatment groups as follows: CRF only (group A, n = 28) and CRF plus PRF (group B, n = 28). The patients were followed 3 years up for pain relief, complications, and health-related quality of life (HRQoL).All the patients in either group achieved satisfactory pain relief at discharge. After treatment, patients completely pain free in group A and group B accounted for 81.6%, 92.0% at 1 year, 68.4%, 92.0% at 2 years, and 68.4%, 83.6% at 3 years, respectively. The pain relief rate was higher in group B patients than in group A, but the difference was not statistically significant. During the follow-up period, 9 (32.1%) patients in group A and 2 (7.1%) patients in group B developed recurrence (P < 0.05). Eleven patients in group A occurred corneal hypoesthesia and with recovery time was 11.9 ±â€Š7.5 (4-18) months versus 3 patients in group B with recovery time was 3.4 ±â€Š2.5 (2-6) months, the differences of incidence rate and recovery times were all significant (P < 0.05) between groups A and B. The mean scores of HRQoL in group B patients were higher than that in group A patients (P < 0.05).PRF after CRF results in decreased recurrence of V1 TN, reduced numbers of corneal hypoesthesia, shortened recovery time, and increased HRQoL scores. Its clinical use is recommended.

Radiofrequency thermocoagulation for V2/V3 idiopathic trigeminal neuralgia: effect of treatment temperatures on long-term clinical outcomes: A Cohort Study.

Radiofrequency thermocoagulation (RFT) is widely used to treat trigeminal neuralgia (TN); however, the optimal temperature at which RFT is most efficacious remains under much debate. Thus, the aim of the present study was to determine the lowest temperature at which morbidity could be minimized and patient outcomes maximized.A multivariate analysis was used to study 1354 patients who underwent computed tomography (CT)-guided RFT for V2/V3 idiopathic trigeminal neuralgia (ITN) during from June 2006 to May 2015. RFT was carried out at 62, 65, and 68°C, while keeping all other RF parameters the same. This was a prospective cohort study, in which we assessed intra- and postoperative complications, pain relief, and long-term health-related quality of life (HRQoL).The intraoperative and in-hospital complications of patients were mainly facial hematoma, mouth and external auditory meatus penetration, nausea, vomiting, dizziness, and headache, which were all treated symptomatically. In long-term follow-up, patients with pain relief (defined as no pain and no required drug intervention) at 62, 65, and 68°C accounted for 94.2%, 98.3%, and 98.8% (at discharge); 83.8%, 90.1%, and 91.4% (at 1 year); 66.7%, 80.5%, and 88.2% (at 3 years); 59.0%, 64.3%, and 77.2% (at 5 years); 48.7%, 57.8%, and 72.3% (at 7 years); 40.6%, 53.7%, and 60.3% (at 9 years), respectively. The number of patients with facial numbness, masticatory atonia, or corneal hypoesthesia was increased with the elevation of temperature, but these complications were all mild. No blindness, deafness, intracranial hemorrhage, or death as a result of the surgical intervention occurred in any patients. SF-36 scores showed highest HRQoL in the group treated at 68°C, followed by the 65 and 62°C groups, respectively.Our results demonstrate that 68°C is a good choice for RFT of V2/V3 ITN. The alternative option is 65 or 62°C for RFT to minimize the occurrence of complications including facial numbness, yet which often yields a higher recurrence rate.

Treatment of bilateral idiopathic trigeminal neuralgia by radiofrequency thermocoagulation at different temperatures.

Radiofrequency thermocoagulation (RFT) is an effective treatment for trigeminal neuralgia, but consensus regarding an optimal treatment temperature is lacking. While treatment temperatures ranging from 60°C to 95°C have been reported, RFT at too high a temperature is often followed by serious complications, and comparative evaluations of RFT at different temperatures in a single study are rare.This current prospective cohort study was to compare immediate and long-term outcomes of RFT at varying temperatures in patients with bilateral idiopathic trigeminal neuralgia (ITN) of maxillary division of trigeminal nerve (V2), mandibular division of trigeminal nerve (V3), and V2+V3, including pain relief, complications, recurrence rate, and patient satisfaction. From May 2011 to April 2016, 62 consecutive patients with bilateral ITN of V2, V3, and V2+V3 were enrolled in the study. These patients underwent bilateral RFT at 68°C and 75°C, respectively, using the same RF parameters. Side-to-side results, including pain relief, complications, and patient satisfaction, were compared during a 5-year follow-up period.Overall pain relief was satisfactory after RFT. The rate of pain relief after treatment at 75°C was slightly higher than at 68°C (P > 0.05). The pain-free rate was 95.1% at 75°C and 93.5% at 68°C at 1 year, 84.3% and 78.1% at 3 years, and 80.7% and 74.4% at 5 years. There were 10 and 13 cases of recurrence, respectively, and 6 cases of bilateral recurrence. The incidence and severity of complications were greater at 75°C (P < 0.05) than at 68°C, and therefore the patient satisfaction at the higher temperature was lower (P < 0.05).Patients with bilateral ITN who underwent RFT at different temperatures had consistent pain relief after RFT at both 75°C and 68°C, but there were fewer and less severe complications at 68°C, which was accompanied by greater patient satisfaction. This suggests that RFT at lower temperatures may be preferable, and that a temperature of 68°C can be recommended.

Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain sensitivity in patients with cancer.

OBJECTIVES: To evaluate the effect of COMT and OPRM1 gene polymorphisms on the preoperative pain sensitivity in tumor patients. METHODS: 300 cases of cancer patients undergoing elective surgery were included, and the Val158 Met loci of COMT gene and OPRM1 loci of A118 G gene were genotyped by PCR-RFLP. Pain threshold and pain tolerance threshold were measured using electrical stimulation to investigate the preoperative pain sensitivity in patients with different genotypes. RESULTS: For the COMT gene, the pain threshold and pain tolerance threshold of patients with M allele both decreased (both P < 0.001); for PPRM1 gene, pain threshold and pain tolerance threshold of patients with G allele decreased (both P < 0.001). We also found that there was an interaction between the two genes. CONCLUSION: Gene polymorphisms of COMT and OPRM1 were correlated with the preoperative pain sensitivity of cancer patients. The patients with M allele of COMT and G allele of OPRM1 had higher preoperative pain sensitivity.

Regulatory network of differentially expressed genes in metastatic osteosarcoma.

The present study aimed to investigate the possible molecular mechanisms underlying the pathogenesis of metastatic osteosarcoma (OS), by examining the microarray expression profiles of normal samples, and metastatic and non­metastatic OS samples. The GSE9508 gene expression profile was downloaded from the Gene Expression Omnibus database, which included 11 human metastatic OS samples, seven non­metastatic OS samples and five normal samples. Pretreatment of the data was performed using the BioConductor package in R language, and the differentially expressed genes (DEGs) were identified by a t­test. Furthermore, function and pathway enrichment analyses of the DEGs were conducted using a molecule annotation system. A differential co­expression network was also constructed, and the submodules were screened using MCODE in Cytoscape. A total of 965 genes were identified as DEGs in metastatic OS. The DEGs were shown to participate in the regulation of DNA­dependent transcription, the composition of the nucleus, cytoplasm and membrane, and protein and nucleotide binding. Furthermore, the screened DEGs were significantly associated with the ribosome, axon guidance and the cytokine­cytokine receptor interaction pathway. Certain hub genes were identified in the constructed differential co­expression network, including matrix metalloproteinase 1 (MMP1), smoothened (SMO), ewing sarcoma breakpoint region 1 (EWSR1) and fasciculation and elongation protein ζ­1 (FEZ1). Brain selective kinase 2 (BRSK2) and aldo­keto reductase family 1 member B10 (AKRIB10) were present in the screened submodules. The results of the present study suggest that genes, including MMP1, SMO, EWSR1, FEZ1, BRSK2 and AKRIB10, may be potential targets for the diagnosis and treatment of metastatic OS.

Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation.

OBJECTIVE: To evaluate the efficacy and safety of sustained-release (SR) oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy (DPN). Design. This was a multicenter, randomized, open-labeled study. SETTING: This study was completed in 12 hospitals in China. PATIENTS: A total of 80 Chinese patients undergoing moderate to severe painful DPN. INTERVENTIONS: An initial dose of 10mg is recommended to be taken orally every 12 hours. Dose titration was done appropriately according to pain intensity and adverse reactions. OUTCOME MEASURES: Data record included days, dosage, analgesic efficacy, quality of sleep, adverse events, and combination therapy when patients were treated with SR oxycodone tablets. The continuous observation period was 6 weeks. RESULTS: After medication for 1 week, pain was significantly (P<0.01) relieved from 6.8±1.4 to 2.8±1.6. Onset time was within 45 minutes in nearly 60% of the patients, and within 1 hour in nearly 95% of that ones. More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P<0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63±7.79mg. The average daily dose of most patients was about 20mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place. CONCLUSION: The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China.

All-optical and polarization-independent spatial filter based on a vertically-aligned polymer-stabilized liquid crystal film with a photoconductive layer.

An all-optical and polarization-independent spatial filter was developed in a vertically-aligned (VA) polymer-stabilized liquid crystal (PSLC) film with a photoconductive (PC) layer. This spatial filter is based on the effect of light on the conductivity of PC layer: high (low)-intensity light makes the conductivity of the PC layer high (low), resulting in a low (high) threshold voltage of the PC-coated VA PSLC cell. Experimental results indicate that this spatial filter is a high-pass filter with low optical-power consumption (about 1.11 mW/cm(2)) in an optical Fourier transform system. The high-pass characteristic was confirmed by simulation. Accordingly, the all-optical and polarization-independent spatial filter can be used to enhance the edges of images.

[HLA-DQA1 genotyping by using oligonucleotide microarrays].

In order to fabricate the HLA-DQA1 genotyping chip and develop an integrated, parallel technical platform to type HLA system, a pair of primers and a set of probes were designed according to the sequences of HLA-DQA1 exon 2, where the polymorphism is concentrated. The oligonucleotide chip was made with the methods developed in our laboratory. The target DNA was asymmetrically amplified with the labeled sense primer. The signals were scanned and analyzed after the hybridization between microarray and PCR product. The allele types of the samples were identified. The result was verified by the standard DNA and DNA sequencing. The results showed that the genotyping was successfully carried out in 50 standard DNA samples and 50 clinical samples. Among them, results of the 50 standard DNA samples matched their templates. In the other 50 samples, results of the randomly selected 10 matched their sequencing results except that two of them got the incompletely result. In reproducible tests, the signal reappear rate was 95%. It is concluded that HLA-DQA1 genotyping by using our array system is simple and convenient with satisfied accuracy and reproducibility.

Mutations of mitochondrial 12S rRNA in gastric carcinoma and their significance.

AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric carcinoma. METHODS: PCR amplified mitochondrial 12S rRNA of 44 samples including 22 from gastric carcinoma tissues and 22 from adjacent normal tissues, was detected by direct DNA sequencing. Then laser capture microdissection technique (LCM) was used to separate the cancerous cells and dysplasia cells with specific mutations. Denaturing high performance liquid chromatography (DHPLC) plus allele-specific PCR (AS-PCR), nest-PCR and polyacrylamide gel electrophoresis (PAGE) were used to further evaluate this mutant property and quantitative difference of mutant type between cancerous and dysplasia cells. Finally, RNAdraw biosoft was used to analyze the RNA secondary structure of mutant-type 12S rRNA. RESULTS: Compared with Mitomap database, some new variations were found, among which np652 G insertion and np716 T-G transversion were found only in cancerous tissues. There was a statistic difference in the frequency of 12S rRNA variation between intestinal type (12/17, 70.59%) and diffusive type (5/17, 29.41%) of gastric carcinoma (P<0.05). DHPLC analysis showed that 12S rRNA np652 G insertion and np716 T-G transversion were heteroplasmic mutations. The frequency of 12S rRNA variation in cancerous cells was higher than that in dysplasia cells (P<0.01). 12S rRNA np652 G insertion showed obviously negative effects on the stability of 12S rRNA secondary structure, while others such as T-G transversion did not. CONCLUSION: The mutations of mitochondrial 12S rRNA may be associated with the occurrence of intestinal-type gastric carcinoma. Most variations exist both in gastric carcinomas and in normal tissues, and they might not be the characteristics of tumors. However, np652 G insertion and np716 T-G transversion may possess some molecular significance in gastric carcinogenesis. During the process from normality to dysplasia, then to carcinoma, 12S rRNA tends to convert from homoplasmy (wild type) to heteroplasmy, then to homoplasmy (mutant type, np717 T-G).

Quantitative analysis of tumor mitochondrial RNA using microarray.

AIM: To design a novel method to rapidly detect the quantitative alteration of mtRNA in patients with tumors. METHODS: Oligo 6.22 and Primer Premier 5.0 bio-soft were used to design 15 pairs of primers of mtRNA cDNA probes in light of the functional and structural property of mtDNA, and then RT-PCR amplification was used to produce 15 probes of mtRNA from one normal gastric mucosal tissue. Total RNA extracted from 9 gastric cancers and corresponding normal gastric mucosal tissues was reverse transcribed into cDNA labeled with fluorescein. The spotted mtDNA microarrays were made and hybridized. Finally, the microarrays were scanned with a GeneTAC laser scanner to get the hybridized results. Northern blot was used to confirm the microarray results. RESULTS: The hybridized spots were distinct with clear and consistent backgrounds. After data was standardized according to the housekeeping genes, the results showed that the expression levels of some mitochondrial genes in gastric carcinoma were different from those in the corresponding non-cancerous regions. CONCLUSION: The mtDNA expression microarray can rapidly, massively and exactly detect the quantity of mtRNA in tissues and cells. In addition, the whole expressive information of mtRNA from a tumor patient on just one slide can be obtained using this method, providing an effective method to investigate the relationship between mtDNA expression and tumorigenesis.

[Quantitation and detection of deletion in tumor mitochondrial DNA by microarray technique].

OBJECTIVE: To develop a method to rapidly quantitate and detect deletion of mitochondrial DNA (mtDNA) by microarray technique as a tool to study its relationship to tumorigenesis. METHODS: A modified PCR was used to amplify full length mtDNA sequence in two samples of normal human blood leukocytes and five samples of gastric cancerous tissues, which were simultaneously labeled with fluorescin. The amplified products were verified by polyacrylamide gel electrophoresis (PAGE) and silver staining. Then, 17 pairs of overlapping primers of mtDNA were designed and their PCR products were used as mitochondrial probes. They were spotted onto amino-slides as microarray and hybridized. Hybridization image was scanned with GeneTAC laser, mtDNA copy number was counted by ScanAnalyzer software. RESULTS: PAGE analysis showed that the designed probes were quite reasonable and strongly specific. The modified PCR method was efficient to amplify the whole mitochondrial genome with high-yield specific bands. The hybridizing spots were distinct, and background was clear. The signals of negative probes were close to those of background, and there was no significant difference between them (P > 0.05). The results were identical to those in the designed experiment. There were no significant differences between the results when the same sample of blood leucocytes or cancer tissues repeatedly examined with the same positive probes (P > 0.05), while there were significant differences when different types of samples were examined (P < 0.01). The hybridizing signals were stable and most of the data distributed in the range of mean +/- 2xSD. CONCLUSION: The method here reported can rapidly, correctly and massively determine whether there exist special deletion and/or quantitative changes of mtDNA in patients with tumors. It will be helpful for the study of the relationship between mtDNA alteration and tumor development.

Variations of mitochondrial D-loop region plus downstream gene 1 2S rRNA-tRNA(phe) and gastric carcinomas.

AIM: To explore the instabilities, polymorphisms and other variations of mitochondrial D-loop region and downstream gene 12S rRNA-tRNA(phe) in gastric cancers, and to study their relationship with gastric cancer. METHODS: Three adjacent regions (D-loop, tRNA(phe) and 12S rRNA) were detected for instabilities, polymorphisms and other variations via PCR amplification followed by direct DNA sequencing in 22 matched gastric cancerous tissues and para-cancerous normal tissues. RESULTS: PolyC or (CA) (n) instabilities were detected in 13/22(59.1 %) gastric cancers and 9/22(40.9 %) in the control (P>0.05). There existed 2/12(16.7 %) and 6/10(60 %) alterations of 12S rRNA-tRNA(phe) in well differentiated gastric cancers and poorly differentiated ones, respectively (P<0.05). Some new variations were found, among which np 318 and np 321 C-T transitions in D-loop region were two of the five bases for H-strand replication primer. np 523 AC-deletion and np 527 C-T transition occurred at mtTF1 binding site (mtTFBS), which were associated with the transcription of downstream mitochondrial genome. Seven samples showed the np 16 182 polyC instabilities, five of which simultaneously showed np 16 189 T-C transitions. CONCLUSION: There is no statistic significance of instabilities and polymorphisms in mitochondrial D-loop region between gastric cancerous and para-cancerous normal tissues, which suggests that the instability might relate to heredity or be dependent on aging. There is a significant correlation between differentiation degree of gastric cancer and variant frequencies of 12S rRNA-tRNA(phe). The poorly differentiated gastric cancers are more prone to 12S rRNA-tRNA(phe) variations, or gastric cancers with 12S rRNA-tRNA(phe) variations are more likely to be poorly differentiated. np 16 189 T-C transition may be one of the important reasons for polyC instability in gastric cancer.

[Optimization of cDNA microarray fabrication].

To optimize and screen the most suitable target gene length,concentration and printing solution in cDNA microarray, housekeeping genes, such as beta actin and GAPDH, were selected as targets and hepatitis B virus gene as negative control. The RT-PCR primers that spanned at least one intron and whose products were at between 189 bp and 1078 bp were designed with primer premier 5.0, so did the hepatitis B virus gene PCR primer. After polymerase chain reaction, the products were purified with ethanol and dissolved in 3xSSC, 50% DMSO and 0.5 mol/L carbonate buffer(pH=9.0)respectively. The concentrations of target genes were adjusted at 0.5 microg/microL, 1.0 microg/microL and 1.5 microg/microL. The hybridization signals had a good specificity. No signal showed in either negative control (HBV) or blank control (printing solution only). There was no significant difference in target gene lengths. The P value of beta actin (189 bp,491 bp,974 bp) and GAPDH (227 bp,552 bp,1078 bp) was 0.378 and 0.866 respectively. There was no significant difference among concentrations(P=0.648),too. However, the higher the concentration was, the stronger the signals would be. Among the three kinds of printing solution, 50% DMSO was the best (P=0.0001), while the other two had no difference by multi-comparison (P=0.142). The target gene at length between 200 bp and 1000 bp has got the same hybridization signals.50% DMSO printing solution and the target gene concentration of 0.5 microg/microl are suitable for good hybridization.