Aquaporins and Neuropathic Pain.

Neuropathic pain is a chronic secondary pain condition resulting from lesions or diseases of the peripheral or central nervous system (CNS). Neuropathic pain is closely related to edema, inflammation, increased neuronal excitability, and central sensitization caused by glutamate accumulation. Aquaporins (AQPs), mainly responsible for the transport and clearance of water and solute, play important roles in developing CNS diseases, especially neuropathic pain. This review focuses on the interaction of AQPs with neuropathic pain, and the potential of AQPs, especially aquaporins 4, as therapeutic targets.

Pelvic Injury Discriminative Model Based on Data Mining Algorithm.

OBJECTIVES: To reduce the dimension of characteristic information extracted from pelvic CT images by using principal component analysis (PCA) and partial least squares (PLS) methods. To establish a support vector machine (SVM) classification and identification model to identify if there is pelvic injury by the reduced dimension data and evaluate the feasibility of its application. METHODS: Eighty percent of 146 normal and injured pelvic CT images were randomly selected as training set for model fitting, and the remaining 20% was used as testing set to verify the accuracy of the test, respectively. Through CT image input, preprocessing, feature extraction, feature information dimension reduction, feature selection, parameter selection, model establishment and model comparison, a discriminative model of pelvic injury was established. RESULTS: The PLS dimension reduction method was better than the PCA method and the SVM model was better than the naive Bayesian classifier (NBC) model. The accuracy of the modeling set, leave-one-out cross validation and testing set of the SVM classification model based on 12 PLS factors was 100%, 100% and 93.33%, respectively. CONCLUSIONS: In the evaluation of pelvic injury, the pelvic injury data mining model based on CT images reaches high accuracy, which lays a foundation for automatic and rapid identification of pelvic injuries.

ß-Hydroxybutyrate Attenuates Painful Diabetic Neuropathy via Restoration of the Aquaporin-4 Polarity in the Spinal Glymphatic System.

Waste removal is essential for maintaining homeostasis and the normal function of the central nervous system (CNS). The glymphatic system based on aquaporin-4 (AQP4) water channels on the endfeet of astrocytes is recently discovered as the excretion pathway for metabolic waste products of CNS. In the CNS, α-syntrophin (SNTA1) directly or indirectly anchors AQP4 in astrocyte membranes facing blood vessels. Studies have indicated that ß-hydroxybutyrate (BHB) can raise the expression of SNTA1 and thus restoring AQP4 polarity in mice models with Alzheimer's disease. The study aims to evaluate the neuroprotective mechanism of BHB in rats with painful diabetic neuropathy (PDN). PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. Magnetic resonance imaging (MRI) was applied to observe the clearance of contrast to indicate the functional variability of the spinal glymphatic system. Mechanical allodynia was assessed by paw withdrawal threshold. The expressions of SNTA1 and AQP4 were tested, and the polarity reversal of AQP4 protein was measured. As demonstrated, PDN rats were manifested with deceased contrast clearance of the spinal glymphatic system, enhanced mechanical allodynia, lower expression of SNTA1, higher expression of AQP4, and reversed polarity of AQP4 protein. An opposite change in the above characteristics was observed in rats being treated with BHB. This is the first study that demonstrated the neuroprotective mechanism of BHB to attenuate PDN via restoration of the AQP4 polarity in the spinal glymphatic system and provides a promising therapeutic strategy for PDN.

Plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy induced by type 2 diabetes mellitus.

The glymphatic system is a recently discovered glial-dependent macroscopic interstitial waste clearance system that promotes the efficient elimination of soluble proteins and metabolites from the central nervous system. Its anatomic foundation is the astrocytes and aquaporin-4 (AQP4) water channels on the endfeet of astrocytes. The aim of this study is to evaluate the plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy (PDN) induced by type 2 diabetes mellitus. PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. MRI was applied to observe the infiltration and clearance of contrast to indicate the functional variability of the glymphatic system at the spinal cord level. The paw withdrawal threshold was used to represent mechanical allodynia. The numerical change of glial fibrillary acidic protein (GFAP) positive astrocytes was assessed and the polarity reversal of AQP4 protein was measured by immunofluorescence. As a result, deceased contrast infiltration and clearance, enhanced mechanical allodynia, increased number of GFAP positive astrocytes, and reversed polarity of AQP4 protein were found in the PDN rats. The above molecular level changes may contribute to the impairment of the spinal glymphatic system in PDN rats. This study revealed the molecular and functional variations of the spinal glymphatic system in PDN rats and for the first time indicated that there might be a correlation between the impaired spinal glymphatic system and PDN rats.

Effects of dynamic individualized PEEP guided by driving pressure in laparoscopic surgery on postoperative atelectasis in elderly patients: a prospective randomized controlled trial.

BACKGROUND: Driving pressure (ΔP = Plateau pressure-PEEP) is highly correlated with postoperative pulmonary complications (PPCs) and appears to be a promising indicator for optimizing ventilator settings. We hypothesized that dynamic, individualized positive end-expiratory pressure (PEEP) guided by ΔP could reduce postoperative atelectasis and improve intraoperative oxygenation, respiratory mechanics, and reduce the incidence of PPCs on elderly patients undergoing laparoscopic surgery. METHODS: Fifty-one elderly patients who were subject to laparoscopic surgery participated in this randomized trial. In the PEEP titration group (DV group), the PEEP titration was decremented to the lowest ΔP and repeated every 1 h. Additional procedures were also performed when performing predefined events that may be associated with lung collapse. In the constant PEEP group (PV group), a PEEP of 6 cmH2O was used throughout the surgery. Moreover, zero PEEP was applied during the entire procedure in the conventional ventilation group (CV group). The primary objective of this study was lung ultrasound score noted at the end of surgery and 15 min after admission to the post-anesthesia care unit (PACU) at 12 lung areas bilaterally. The secondary endpoints were perioperative oxygenation function, expiratory mechanics, and the incidence of the PPCs. RESULTS: The lung ultrasound scores of the DV group were significantly lower than those in the PV group and CV group (P < 0.05), whereas there was no significant difference between the PV group and CV group (P > 0.05). The lung static compliance (Cstat) and ΔP at all the intraoperative time points in the DV group were significantly better compared to the PV group and the CV group (p < 0.05). CONCLUSIONS: Intraoperative titrated PEEP reduced postoperative lung atelectasis and improved respiratory mechanics in elderly patients undergoing laparoscopic surgery. Meanwhile, standard PEEP strategy is not superior to conventional ventilation in reducing postoperative pulmonary atelectasis in laparoscopic surgery.

Adding a vacuum erection device to regular use of Tadalafil improves penile rehabilitation after posterior urethroplasty.

This study aimed to evaluate whether adding a vacuum erection device (VED) to regular use of Tadalafil could achieve better penile rehabilitation following posterior urethroplasty for pelvic fracture-related urethral injury (PFUI). Altogether, 78 PFUI patients with erectile dysfunction (ED) after primary posterior urethroplasty were enrolled and divided into two treatment groups: VED combined with Tadalafil (Group 1, n = 36) and Tadalafil only (Group 2, n = 42). Changes in penile length, testosterone level, International Index of Erectile Function-5 (IIEF-5) questionnaire, Quality of Erection Questionnaire (QEQ), and nocturnal penile tumescence (NPT) testing were used to assess erectile function before and after 6 months of ED treatment. Results showed that the addition of VED to regular use of Tadalafil preserved more penile length statistically (0.4 ± 0.9 vs -0.8 ± 0.7 cm, P < 0.01). IIEF-5 score and QEQ score in Group 1 were higher than Group 2 (both P < 0.05). After treatment, 21/36 (58.3%) Group 1 patients and 19/42 (45.2%) Group 2 patients could complete vaginal penetration. Group 1 patients also had markedly improved testosterone levels (P = 0.01). Unexpectedly, there was no significant difference in NPT testing between two therapies. For PFUI patients with ED after posterior urethroplasty, the addition of VED to regular use of Tadalafil could significantly improve their conditions - improving erection and increasing penile length - thus increasing patient satisfaction and confidence in penile rehabilitation.

Penile sensory thresholds in subtypes of premature ejaculation: implications of comorbid erectile dysfunction.

Penile hypersensitivity plays an important role in premature ejaculation (PE), but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes of lifelong and acquired PE, PE with and without erectile dysfunction (ED), PE with an intravaginal ejaculation latency time ≤1 min and >1 min, and PE with and without orgasmic pleasure perceptual dysfunction. During August 2014 to January 2016, 136 patients with PE were included. Penile warm, cold, and vibratory thresholds were measured. Data of clinical characteristics, sexual life, Premature Ejaculation Diagnostic Tool (PEDT) score, and the 5-item version of the International Index of Erectile Function (IIEF-5) score were collected. Vibratory thresholds of the PE with ED group were higher in the right coronal sulcus (median amplitude: 4.92 vs 3.65 µ m, P = 0.02) and the right penile shaft (median amplitude: 3.87 vs 3.30 µ m, P = 0.03), while differences in penile sensory thresholds between other subtypes were not significant. The median PEDT score was lower in the PE without ED group (12 vs 14, P < 0.001). The IIEF-5 and PEDT scores were negatively correlated (r = -0.29, P < 0.001). Patients with orgasmic pleasure perceptual dysfunction had a lower median IIEF-5 score (20 vs 21, P = 0.02). Patients with PE and ED had lower penile sensitivity, and ED was associated with more severe symptoms and weaker orgasmic pleasure perception. In men with PE, management of comorbid ED is necessary. In case of side effects in erectile function, topical anesthetics should be cautiously used in men with PE and ED.

KIF-2C expression is correlated with poor prognosis of operable esophageal squamous cell carcinoma male patients.

To determine the prognostic significance of Kinesin family member 2C (KIF-2C) expression in patients with operable esophageal squamous cell carcinoma (ESCC), we conducted an immunohistochemical analysis of KIF-2C expression in 415 surgically resected primary tumor tissues and 40 adjacent non-cancerous tissues from patients with operable ESCC. The median duration of postoperative follow-up was 76.0 months. Higher KIF-2C expression was associated with significantly increased risks of higher pathologic tumor (pT) status (P=0.038) and poorer tumor differentiation (P=0.022). For the entire cohort, KIF-2C expression was not an independent factor significantly associated with overall survival (OS) (P=0.097) or disease-free survival (DFS) (P=0.152). In female patients, KIF-2C expression had no effect on OS (P=0.880) and DFS (P=0.864). However, OS (hazard ratio (HR)=1.480, P=0.013) and DFS (HR=1.418, P=0.024) were worse for male patients with high KIF-2C expression compared with male patients with low KIF-2C expression. Moreover, the OS and DFS of male patients with high KIF-2C expression were also significantly shorter compared with female patients with low KIF-2C expression (P=0.022, P=0.029) and female patients with high KIF-2C expression (P=0.014, P=0.018). Based on these findings, KIF-2C expression in tumor tissues promises to serve as an independent prognostic marker for male, but not female, patients with operable ESCC. Prognosis was worse for male patients with high KIF-2C expression compared with patients with the same pathologic tumor-node-metastasis (pTNM) stage.

Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma.

AIM: To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio (NLR) in esophageal squamous cell carcinoma (ESCC). METHODS: Data from 371 eligible patients with ESCC who had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ(2) test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival (CSS) and recurrence-free survival (RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied. RESULTS: The median age of the patients was 57.0 years, and 276/371 (74.4%) patients were male. The NLR was ≤ 3.0 in 80.1% (297/371) of the patients, and the remaining 19.9% (74/371) had an NLR > 3.0. Median postoperative follow-up was 66.0 mo [interquartile range (IQR): 49.0-76.0 mo], with a follow-up rate of 94%. Follow-up was not significantly different between patients with an NLR ≤ and > 3.0 (63.13 ± 1.64 vs 61.52 ± 3.66, P = 0.711). However, higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status (P = 0.007). A significant, independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS (HR = 1.591; P = 0.007) and RFS (HR = 1.525; P = 0.013). Moreover, when patients were stratified by pathological tumor-node-metastasis (TNM) staging, the adverse effects of preoperative serum NLR on CSS (HR = 2.294; P = 0.008) and RFS (HR = 2.273; P = 0.008) were greatest in those patients with stage IIIA disease. CONCLUSION: Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients, particularly in patients with stage IIIA disease.

Prognostic value of bone marrow micrometastasis in patients with operable esophageal squamous cell carcinoma: a long-term follow-up study.

INTRODUCTION: Detection of bone marrow micrometastasis (BMM) has been focused on as a prognostic parameter in various malignant neoplasms recently. This study was designed to evaluate the prognostic significance of BMM detection in patients with operable esophageal squamous cell carcinoma (ESCC) after long-term follow-up. METHODS: In 61 consecutive patients with ESCC who had undergone radical surgical resection, BMM was detected through reverse transcriptase-polymerase chain reaction (RT-PCR). Correlation between BMM detection and prognosis of the 61 patients was analyzed. RESULTS: BMM was found in 13 patients (21.3%). No significant correlation between BMM detection and tumor, node, metastasis (TNM) stage was found. The median survival time, 5-year overall survival rate, 5-year disease-free survival rate, and 5-year distant disease-free survival rate for cases with positive BMM were 13.0 months, 15.4%, 7.7%, and 34.2%, respectively, compared with that of 66.0 months, 59.7%, 49.1%, and 60.6% for cases with negative BMM (p < 0.05). In multivariate analysis, BMM were found to be an independent factor in the prediction of overall survival (odds ratio [OR] 3.928, p = 0.001), disease-free survival (OR 4.285, p < 0.001), and distant disease-free survival (OR 3.270, p = 0.013). CONCLUSIONS: BMM is an independent prognostic factor in the prediction of the subsequent development of metastatic disease and disease outcome for operable ESCC patients, and may be a useful adjunct to conventional tumor staging. Further studies are required to evaluate the value of neoadjuvant or adjuvant systemic therapy in ESCC patients with BMM.

[Changes in phototaxical index of Daphnia carinata under electric field of direct current in response to Cr6+ and Hg2+].

In order to detect toxicants sensitively in water by phototaxity of Daphnia, we studied the influence of DC electric field on phototaxity of self-bred Daphnia carinata, a mono-clone with high phototaxity, and the changes of their phototaxity in response to Cr6+ and Hg2+ after the treatment of DC electric field. The result indicated that the treatment of DC electric field changed their phototaxical indexes from positive to negative as the electric density increased and the time prolonged. The criteria values that showed no sign of changes in the phototaxical index of Daphnia carinata were 0.01 mA for 5 min. However, the limit for detecting Cr6+ and Hg2+ by their phototaxical index decreased significantly after treatment with 0.01 mA/5 min. The detection limits were only 32 microg x L(-1) for Cr6+ and 4.2 microg x L(-1) for Hg2+ after this treatment, much lower than those without pretreatment (56 microg x L(-1) for Cr6+ and 5.6 microg x L(-1) for Hg2+, respectively). Therefore, appropriate DC electric field to pre-treat Daphnia could decrease the detection limit, widen the concentration range of detection, and increased the sensibilities in water monitoring.

[Progress in diagnosis of neurogenic erectile dysfunction].

Recently, with application of evoked potentials technology in the test of somatic and autonomic nerves, quantitative sensory testing in the detection of small nerve fiber function, and functional magnetic resonance imaging in the detection of senior central function, the detection of neural function has become more accurate. This article reviews the progress and application of diagnostic methods about neurogenic erectile dysfunction in order to provide a reference for forensic diagnosis and research in the future.

[Application of quantitative temperature testing in diagnosis of neurogenic erectile dysfunction].

OBJECTIVE: To explore the application of quantitative temperature testing (QTT) in forensic identification and clinical diagnosis of neurogenic erectile dysfunction (NED). METHODS: TSA-II-NeuroSensory Analyzer was used to measure the thresholds of four kinds of sensory, including cold, cold pain, heat, heat pain, in 22 normal and 35 NED patients at dorsal glans (DG), left thigh interior (LTI) and left thenar (LT). To calculate the relative thresholds of the sensory mentioned above between DG and LTI (DG/LTI), and between DG and LT (DG/LT). Then to analyze those thresholds and the relative thresholds. RESULTS: NED group showed significant higher threshold than the normal group in DG-heat, DG-heat pain, LTI-heat, LTI-heat pain, DG/LTI-heat, DG/LT-heat, DG/LT-heat pain (P < 0.05). CONCLUSION: The threshold of QTT at dorsal glans could be used as an accessory indicator in forensic medicine and clinical diagnosis of NED.

[Accurate determination of wound depth with ultrasound and its forensic significance].

Accurate determination of the wound depth has long been a difficult task in forensic medicine due to lack of technology. Nowadays, the depth of the wound can be accurately determined by using high frequency 2-D ultrasound and Color Doppler Flow Imaging (CDFI). Two typical cases with ultrasonic images were reported to show the importance of ultrasound technology in forensic medicine. The new technology provides scientific evidence of the injury assessment.

[Pathomorphologic study of the fibrous cap and fatty core of coronary arthrosclerotic plaque in sudden coronary death].

OBJECTIVE: The differences in the thickness of fibrous cap and the percentage of fatty core of the coronary atherosclerotic plaques between sudden coronary death (SCD) group and the control group were investigated. METHODS: Sixty-four autopsy cases were divided into SCD and control groups. Samples were taken from the most severely damaged portions of the coronary atherosclerotic plaques, sectioned, stained with HE, and the percentage of examined by light microscopy for morphologic changes and structural alternations. Image analysis system was adopted to compare the thickness of fibrous cap and percentage of fatty core in the whole plaque between the two groups, and allthe data were analyzed and calculated with SPSS 11.5 statistic software. RESULTS: There were 15 grade III and 21 grade IV atherosclerotic cases found in the SCD group, while there were 16 and 12 found in the control group, respectively. Although no significant differences on the severity of atherosclerosis were found between the two groups (P > 0.05), there were significant differences on the thickness of the fibrous cap and the percentage of fatty core found between the two groups (P < 0.01). CONCLUSION: Our study indicates that there are significant differences in the thickness of fibrous cap and the percentage of fatty core in atherosclerosis plaques between the SCD group and the control group. These observed differences may be helpful for morphological diagnosis of SCD.

[Dissection of cavernous nerves in rat and model of neurological erectile dysfunction].

OBJECTIVES: To identify rat cavernous nerve and establish a rat model of erectile dysfunction caused by injury of cavernous nerve. METHODS: Ten rats were undergone dissections. 30 experimental rats were randomized into 2 groups, cavernous nerve were identified by electrical stimulation. One month after surgery, rat models were evaluated by electrical stimulation. RESULTS: The anatomic structure of cavernous nerve in rats are highly similar to human beings, the erection can be evoked by stimulating cavernous nerves, and after cavernous nerve injury it can not be evoked (P < 0.05). CONCLUSION: Because of the highly similarity of cavernous nerve between rats and human beings, so as the suitable price, rat should be used as the ideal ED experimental animal. The model of ED caused by cavernous nerve injury is reliable.

[Forensic identification for 16 cases with lumbar sacralization and lumbarization].

Lumbar sacralization and lumbarization are congenital spine malformation. 16 cases with lumbar sacralization or lumbarization were reviewed. Through studying the etiopathogenisis and clinical manifestation we analyze the relationship between injury and disease. 6 cases of 16 have lumbar sacralization. 10 cases are attributed to lumbarization. Most of this cases have backleg pain more or less. As a forensic doctor we suggest that pay more attention to this problem in our identify practice and locate the sequence of vertebral body more exactly.

[The method and new advance in diagnosing erectile dysfunction].

Recently, we have a further understanding on the pathogeny of erectile dysfunction, and with the application of so many new technologies, such as color Doppler ultrasound, electrical impedance, evoked potential, sensor etc. The diagnosis of ED becomes more and more scientific and convenient. Today we make a review on all kinds of diagnosing methods in order to recognise it more clearly and to provide some more precise and practical way for forensic evaluation in future.