Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents.

There is now compelling evidence that selective stimulation of Aδ nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). Topographical analysis and source modeling revealed in both species, a clear gross somatotopy of the unmyelinated C-fiber input within the S1 contralateral to the stimulated side. In the human EEG, S1 activity could be isolated as an early-latency negative deflection (C-N1 wave peaking at 710-730 ms) after hand stimulation, but not after foot stimulation because of the spatiotemporal overlap with the subsequent large-amplitude supramodal vertex waves (C-N2/P2). In contrast, because of the across-species difference in the representation of the body surface within S1, S1 activity could be isolated in rat ECoG as a C-N1 after both forepaw and hindpaw stimulation. Finally, we observed a functional dissociation between the generators of the somatosensory-specific lateralized waves (C-N1) and those of the supramodal vertex waves (C-N2/P2), indicating that C-fiber unmyelinated input is processed in functionally distinct somatosensory and multimodal cortical areas. These findings demonstrated that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.SIGNIFICANCE STATEMENT Unmyelinated C-fibers are the evolutionarily oldest peripheral afferents responding to noxious environmental stimuli. Whether C-fiber input conveys information about the spatial location of the noxious stimulation to the primary somatosensory cortex (S1) remains an open issue. In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.

[Suprapubic-assisted laparoendoscopic single-site surgery in nephroureterectomy A case series of 4 patients].

Objective: To evaluate the feasibility and clinical value of suprapubic-assisted laparoendoscopic single-site surgery (SA-LESS) in nephroureterectomy using method of transvaginal natural orifice specimen extraction (NOSE) (SA-LESS+TV-NOSE NU). Methods: Four patients (three cases of renal pelvic carcinoma and one case of ureteral carcinoma) undergoing SA-LESS+TV-NOSE NU were enrolled between April 2015 and January 2016. After general anesthesia, the patients were placed in the lithotomy position with the affected side elevated by 60°. Two trocars were inserted at the medial margin of umbilicus, and the third one was inserted into abdominal cavity at the superior margin of pubic symphysis. The operation was performed under a direct vision with a 5.4 mm 0° flexible-tip laparoscope. Firstly, the distal ureter was isolated completely and blocked by a Hem-O-lok clip. Then, the laparoscopic nephrectomy was performed according to the standard method. Finally, the bladder cuff excision was executed and the incision was sutured. The intact specimen was placed inside a homemade bag and removed through the incision at posterior vaginal fornix. Results: All the procedures were successfully performed. The median operative time was 150 (range: 120 to 210) minutes, and the median estimated blood loss was 180 (range: 80 to 350) ml. No major perioperative complications occurred. The mean visual analogue score (VAS) of 24 hours and 48 hours after operation were 3.25 (range: 2 to 5) and 2.25 (range: 2 to 3). All the patients resumed ambulation on postoperative day 1. Pelvic drainage tube was removed on postoperative day 2-4. On postoperative day 7, urethral catheter was removed. The patients were discharged on postoperative day 7-9. During the follow-up of 20-29 months, the patient recovered well with no case of incisional hernia and pelvic, abdominal infections. The vaginal fornix incision healed well, and the umbilical and suprapubic puncture scars were not obvious. All the patients completed the patient-assessed acromegaly symptom questionnaire PASQ. The average PSAQ score of 3 months after surgery was 34.5. Three of them restarted their sex lives, with an average female sexual function index score of 16.0, which was not significantly different with that of preoperation (15.6). There was no tumor recurrence, metastasis and implantation in all cases. Conclusion: SA-LESS+TV-NOSE NU is safe and feasible for upper tract urothelial carcinoma with faster postoperative recovery, less pain, shorter hospitalization time, better cosmetic results, and does not cause negative effect on the female sexual function.

[Application of neuroendoscope combined with minimal-access for elderly patients with idiopathic trigeminal neuralgia in enhanced recovery after surgery of microvascular decompression].

Objective: To explore the value of neuroendoscope and minimal-access in enhanced recovery after surgery of microvascular decompression (MVD) for treatment elderly patients with idiopathic trigeminal neuralgia (ITN). Methods: The clinical data of 62 elderly patients with ITN who undergoing neuroendoscope-assisted minimal-access microvascular decompression were analyzed retrospectively, including operative data and follow-up results. Results: In 62 cases, the effective rate was 96.8%, with 88.7% complete cure and 8.1% little residual pain. Sixty successful cases were followed-up for an average of 61 months.Three cases recurred within 3 years after operation.Eight cases had complications after MVD. Conclusions: There was no serious complications that could be ascribed to old age and the operative result was satisfactory compared with younger age cases.Endoscope and minimal-access can help shorten operation time, raise the effectiveness of MVD, reduce postoperative recurrence rate, and enhanced recovery after surgery for elderly patients.

Distribution of killer-cell immunoglobulin-like receptor genes in Eastern mainland Chinese Han and Taiwanese Han populations.

The interaction between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules expressed on target cells is known to modulate the cytolytic activity of natural killer (NK) cells. To date, a wide range of KIR genotypes has been observed, which varies among different ethnic populations. We report here comparison of the KIR gene content and genotypic structure of KIRs in 106 individuals from Eastern mainland Chinese Han and 97 from Taiwanese Han. All 17 KIR genes were observed in the two populations. Framework genes 2DL4, 3DL2, 3DL3 and 3DP1 were present in all individuals. The two populations had very similar frequencies in most loci, however, significant differences were noted in the frequencies of KIR3DS1 and KIR2DS4D (KIR2DS4 deletant variant). A total of 35 and 29 genotypes were identified in the individuals from the Eastern mainland Chinese and the Taiwanese Hans, respectively. Some pairs of KIRs showed significant positive and negative linkage disequilibrium (LD). Our data showed that there were minor distinctions in KIR gene frequencies, genotypes and LD between the two populations, which shed light on a possible geographic genetic demarcation among different Chinese communities.

[Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study].

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions: Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

A potential molecular marker for selection against abdominal fatness in chickens.

The peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was investigated as a candidate gene for growth and fatness traits in chicken because of its prominent role in muscle fiber specialization and adipogenesis. A single nucleotide polymorphism (SNP) from G to A at position 646 of the open reading frame of chicken PGC-1alpha gene causing an Asp216Asn amino acid substitution was identified. The frequencies of alleles and genotypes were significantly different among 6 chicken breeds (P < 0.01). The White Plymouth Rock had the highest frequency (0.67) of allele G, whereas the White Leghorn had the lowest (0.18). The associations of the SNP with the growth and fatness traits were evaluated in 332 F(2) birds from an experimental cross of White Plymouth Rock x Silkies. No association was found between the SNP and growth-related traits. However, abdominal fat weight at 12 wk of age for birds with genotype GG was 34.26 and 28.71% higher than those with genotypes AA and AG, respectively (P < 0.01), indicating that the Asp216Asn polymorphism of the PGC-1alpha gene could be used as a novel potential molecular marker for selection against abdominal fatness without interfering in regular breeding for growth rate of chickens.

A practical procedure for the cryopreservation of marrow cells intended for autotransplantation.

A simple and practical method of unfractionated bone marrow processing and cryopreservation was studied. The date shows that RBCs can be rapidly sedimented by methylcellulose or sodium carboxymethyl starch within 15-45 min. The cells can be cryopreserved in a mixture consisting of 5% DMSO, 6% HES and 4% Albumin prepared in a Lactated Ringer solution which is widely used, and can be simply immersed into a -80 degrees C freezer and stored in liquid nitrogen until infusion. Recovery percentages of nucleated cell, cell viability and CFU-G were similar to those cryopreserved with the conventional method. Clinical toxicity was mild in 12 infused patients. Of them 8 patients had received high dose chemotherapy +/- TBI and their peripheral WBC recovery was rapid. The recovery of WBC or Platelet (PLT) in the study group was similar to that of the control group whose marrow cells were cryopreserved in 10% DMSO. Therefore, cells cryopreserved with this method can also accelerate the hematopoietic recovery in myeloablatively treated patients.

Expression, Purification and Functional Identification of Extracellular Part of Discoidin Domain Receptor 2.

Discoidin domain receptor 2 (DDR2) is a new type of receptor tyrosine kinases, and was thought to be involved in the metastasis of some tumors. Its ligand is fibrillar collagen. The activation of DDR2 induced by collagen mediates the over-expression of matrix metalloproteinase 1 (MMP-1) in cells. A specific inhibitor of DDR2 was necessary for the study of DDR2 function. Theoretically, a soluble receptor could possibly be used as specific inhibitor for the native receptor on cell membrane. In this report, a fragment (DB) of extracellular part of DDR2 was cloned and expressed for the use as potential inhibitor. This DB fragment corresponded to the polypeptide from the 23rd amino acid residue to the 293rd amino acid residue of DDR2. The fragment was amplified by RT-PCR from human lung cancer tissue, and the product was cloned into pMD18-T vector. After identification by sequence analysis, the fragment was sub-cloned into pGEX-4T-1 vector. Fusion protein of GST-DB was expressed in JM109 E.coli cells as expected and the soluble part accounted for about 13% of the total fusion protein. The soluble fusion protein was then purified with glutathione affinity resin, and GST-DB with purity of 86.1% was obtained. Competitive combination inhibitory test showed that the purified GST-DB inhibited the interaction between collagen II and DDR2 on the surface of RA synovial fibroblasts. Zymography analysis showed that the level of MMP-1 of both NIH 3T3 cell and RA synovial fibroblasts with collagen II-stimulation decreased after adding GST-DB fusion protein. The results indicated that the fusion protein GST-DB could inhibit the function of DDR2 on cells, and DDR2 might mediate collagen II-induced over-expression of MMP-1 in these cells.

[Effects of tramadol hydrochloride injection in relief of cancer pain].

In a prospective multi-centre study, the pain-relieving effects of Tramadol Hydrochloride injection were observed in 98 patients with cancer pain. Tramadol was administered 100 mg intramuscularly p.r.n. for 1-3 days, and then the patients were crossed over to AP-237 injection (a common non-narcotic analgesic in China) or Tramal injection (product of Grunenthal) as control. The results showed that the response rates for Tramadol, Tramal and AP-237 were 82.6%, 81.8% and 62.1%, while the side effects were seen in 31%, 21% and 41%, respectively. In conclusion, the pain-relieving effect of Tramadol is as good as that of Tramal, but superior to AP-237.

[High dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) as a first line therapy to treat advanced adult high-grade malignant T-cell non-Hodgkin's lymphoma--a pilot clinical study].

Four patients with advanced adult high-grade malignant T-cell non-Hodgkin's lymphoma (NHL) were treated with high dose chemoradiotherapy and ABMT as a first line therapy. Case 1 was of stage IIIb; case 2, 3 and 4 were of stage IV. Bone marrow was involved (19% blast cells) in case 2, and nervous system was involved in case 4. All of them were given at first an inductive chemotherapy with 3-4 courses of BACOP regimen before ABMT. 40-50 days later, Vp-16, CTX and TBI were given as a conditioning regimen (case 1: TLI). Case 1 and 2 only reached partial remission after inductive treatment (case 2: relapse at primary sites one month after inductive therapy, but complete remission (CR) of bone marrow). All of the four patients reached CR after ABMT. Case 2 had systemic relapse (bone marrow blast cells: 8%) at 110 days after CR and died from relapse 210 days after ABMT. So far, case 1, 3 and 4 have survived free of disease for 24, 19 and 9 months, respectively. There was no fatal marrow transplant regimen-related toxicity during inductive and ABMT treatment. The results of this pilot study suggest that treatment of high-grade malignant NHL may be improved by combined use of high dose chemoradiotherapy and ABMT, and the toxicities can be tolerated.

[Pain-relief effect of tramadol HCL capsule for moderate and severe cancer pain].

Fifty-one patients with moderate (11/51) and severe (40/51) cancer pain were given a new non-narcotic analgesic -Tromadol HCL capsule (THC). In 42 of these patients, partial relief was obtained with an average relief time (ART) of 4.1 hours. The average starting time was 58 minutes. Pain relief rate (PRR) in moderate and severe pain was 82% (P = 0.945), and the ARTs were 7.4 hr. and 3.2 hr., respectively (P = 0.005). In 43 patients who were entered into a randomized study with control drugs of AT-237 (36 cases) or Anfendein (7 cases), the PRR was 60.4% (26/43), ART was 1.3 hours. The PRR and ART of THC and control drugs were statistically significant (P less than 0.001 and P = 0.023). Within adequate dose range, increase of THC dose could improve its analgesic effect (P = 0.011). The main side-effects were: somnolence (37.3%), nausea (35.3%), dizziness (33.3%), palpitation and anorexia (25.5%) and constipation (9.8%) which did not necessitate the suspension of THC administration.

[Dihydroetorphine hydrochloride for moderate and severe cancer pain].

One hundred and three patients with moderate and severe cancer pain were given a sublingual analgesic agent--dihydroetorphine hydrochloride (DHE). Relief of cancer pain was moderate or complete in 89.3% (92/103). The average relief time (ART) was 3.9 hours and the average time before effectiveness was 20 minutes. In patients with acute or chronic cancer pain, moderate and complete pain-relief rates were 91.3% and 82.2% (P = 0.237). Difference of ART between them was insignificant (P = 0.299). The main clinical side-effects were somnolence (60%), dizziness (72%), nausea (30%), vomiting (16.5%), constipation (5%) and shortness of breath (8%). In two of the patients, the administration of DHE had to be stopped due to its side-effects. Age, sex and site of cancer pain were not related to the analgesic effects of DHE, but the pain-relief in patients with bladder cancer was poor (P less than 0.001). Within certain range, increase in dose was able to enhance its analgesic effect (P less than 0.001) and reduce drug resistance (P less than 0.001).

[The central mechanism of the high frequency component in heart rate variability in rat].

Experiments were performed on 15 Sprague-Dawley rats to detect the effect of artificial ventilation of different frequencies on the high frequency component of heart rate variability (HRV) by autoregressive modeling with Burg algorithm. With continuous or intermittent electrical stimulation, different patterns of regulating activity of nucleus ambiguus in medulla on HRV were observed. Fast Fourier transform was used to analyze the coherence between neuronal discharge with respiratory rhythm in rostral ventrolateral medulla (rVLM) and HRV. The results showed that (1) the central frequency of high frequency (HF) component of HRV were moved closely with frequencies of artificial ventilation, (r = 0.83, P < 0.0001); (2) there was a favorable coherence between neuronal discharge with respiratory rhythm in rVLM and HRV in HF on spectrum, (k2 = 0.854 +/- 0.1); (3) the area of HF component in HRV was increased significantly during intermittent electrical stimulation of nucleus ambiguus in medulla. The central frequency of HF component in HRV was influenced mainly by frequencies of respiration. These results indicate a significant correlation between the HF in HRV and neuronal discharge with respiratory rhythm in rVLM, suggesting that rVLM participates in the regulation of HRV. The HF component of HRV may reflect mainly the fluctuating activity of vagal center. Coherence analysis of two signals provides a new method to confirm the type and interaction of neurons in the central cardiovascular system.

[The coherence analysis between neuronal discharge in the rostral ventrolateral medulla and the cardiovascular activity in rats].

To analyze the coherence between neuronal discharges (ND) in the rostral ventrolateral medulla (RVLM) and the cardiovascular activity, we observed the neuronal discharge in RVLM responding to electric stimulation of the defense area of the mid-brain. Fast Fourier transform (FFT) was performed to analyze the coherence between the signals of ND and blood pressure to determine if the ND were cardiac rhythmic. The coherence between ND variability (NDV) and heart rate variability (HRV) was also analyzed. The results showed: (1) majority of the neurons (67%) were excited responding to electric stimulation in the defense area of the mid-brain; (2) the electric activity of about 70% of the neurons were substantially inhibited by administration of phenylephrine; (3) 64% of the neurons were actively synchronous with cardiac cycle; and (4) significant coherence between NDV and HRV in HF component was shown in a half of the neurons (50%). The coherence analysis thus provides a new tool to investigate the regulation of the autonomic nervous system.

[Clinical analysis and percutaneous transhepatic cholangiography drainage treatment of 25 patients with clonorciosis].

The clinical data of 25 patients with clonorchiasis were analyzed. Some features shown by B-mode ultrasonography and percutaneous transhepatic cholangiography (PTC) were discussed. Application of percutaneous transhepatic cholangiography drainage (PTCD) for treatment of complete biliary tract obstruction caused by clonorchiasis was introduced.

L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs.

The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.

The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population.

The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.