Analgesic Effect of Intrathecal 2R， 6R-HNK on Neuropathic Pain in Female Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.

Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF / 中山大学学报(医学科学版)

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 10 mice/group, half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

Neoadjuvant chemotherapy for patients with locally advanced penile cancer: an updated evidence / 亚洲男科学杂志(英文版)

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.

Lienal polypeptide injection attenuates lipopolysaccharide-induced acute lung injury in rats by metastasis-associated protein 1 / 中国胸心血管外科临床杂志

@#Objective To analyze the role of lienal polypeptide injection in acute lung injury induced by lipopolysaccharide (LPS) in rats. Methods Eighty male SD rats were randomly allocated into 4 groups: a LPS group, a control group, a lienal polypeptide group and a LPS+ lienal polypeptide group (20 rats in each group). Lienal polypeptide or normal saline was given with an intramuscular injection 30 min after an intraperitoneal injection of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 4 h after LPS challenge by enzyme-linked immunosorbent assay (ELISA), wet-to-dry weight ratio, hematoxylin and eosin (HE) staining, TUNEL and Western blotting. Results Lienal polypeptide injection treatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Moreover lienal polypeptide injection significantly suppressed LPS-induced activation of metastasis-associated protein-1 (MTA1). Conclusion Lienal polypeptide injection is demonstrated to protect rats from LPS-induced acute lung injury by the expression of MTA1.

Prostate cancer incidentally discovered at the time of radical cystoprostatectomy does not decrease overall survival: Results from a large Chinese medical center

ABSTRACT Purpose To investigate the incidence and pathologic characteristics of prostate cancer (PCa) incidentally discovered at the time of radical cystectomy and its impact on overall survival. Materials and Methods A single center retrospective study of 762 male patients who underwent radical cystoprostatectomy from Jan 1994 to Dec 2012. Results Of all included patients, 132 (17.3%) were found to have PCa. Patients with incidental PCa had a significantly higher mean age (69.2 vs. 62.2 years, P=0.015). Among the 132 patients with PCa, prostate specific antigen (PSA) analysis was available in 76 patients (57.6%), with a median value of 1.06ng/mL, and 61 (80.3%) patients had a PSA value below 4ng/mL. Four hundred and thirty-six patients (57.1%) were successfully followed, with a median duration of 46.5 months. The overall 5-year survival rate was 62.1%, and the 5-year cancer-specific survival rate was 72%. PCa recurrence was defined by two consecutive PSA values of >0.2 ng/mL and rising, and no PCa recurrence occurred. According to a univariate analyses, incidental PCa was not associated with cancer-specific survival (P=0.192) or overall survival (P=0.493). According to univariate analyses, the overall survival of patients with PCa was not associated with prostate cancer staging, PSA value, or Gleason score (All P values>0.05). Conclusions Prostate cancer incidentally discovered at the time of radical cystectomy does not decrease overall survival. Patients with incidental PCa were older than those without. The PSA value before operation is not helpful for predicting incidental prostate cancers.

Construction of a three-dimensional visualization model of arteries supplying the extrahepatic bile duct based on submillimeter CT data / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a three-dimensional (3D) model of arteries supplying the extrahepatic bile duct with a new segmentation algorithm based on submillimeter CT data.</p><p><b>METHODS</b>The new image segmentation algorithm based on interactive volume rendering was integrated into Medical Image Three-Dimensional Visualization System (MI-3DVS) as an intersected plug-in. The abdominal submillimeter CTA data of 10 patients were imported into MI-3DVS and the 3D model of the extrahepatic bile duct and its supplying arteries were constructed. The 3D model was zoomed in, zoomed out and spinned for observation and analysis of the arteries supplying the extrahepatic bile duct.</p><p><b>RESULTS</b>The 3D models of the blood supply to extrahepatic bile duct allowed stereoscopic, and accurate display of the fourth- and fifth-level branches of the hepatic artery, the second-level branches of the cystic artery, the pancreatic duodenal artery arch and the retroportal artery. The 3D models also provided a clear vision of the biliary structures including the hepatobiliary tract, the left and right hepatic ducts, gallbladder, the liver duct, and the common bile duct.</p><p><b>CONCLUSION</b>Based on the segmentation method of interactive volume rendering, the CT data of the arterioles supplying the extrahepatic bile duct can be extracted and segmented for 3D reconstruction to display the three-dimensional anatomical structures of the extrahepatic bile duct and its supplying arteries.</p>