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Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the earliest and most commonly used anti-human immunodeficiency virus drugs and play an important role in high active antiretroviral therapy. However, NRTI drug therapy can cause peripheral neuropathic pain. In this study, we aimed to investigate the mechanisms of rapamycin on the pain sensitization of model mice by in vivo experiments to explore the effect of mammalian target of rapamycin (mTOR) in the pathogenesis of neuropathic pain caused by NRTIs., Methods: Male Kun Ming (KM) mice weighing 20-22 g were divided into control, 2 mg/kg rapamycin, 12 mg/kg stavudine, and CMC-Na groups. Drugs were orally administered to mice for 42 consecutive days. The von Frey filament detection and thermal pain tests were conducted on day 7, 14, 21, 28, 35, and 42 after drug administration. After the last behavioral tests, immunohistochemistry and western blotting assay were used for the measurement of mTOR and other biomarkers. Multivariate analysis of variance was used., Results: The beneficial effects of rapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 (mTORC1)-positive cells (70.80 ± 2.41 vs. 112.30 ± 5.66, F = 34.36, P < 0.01) and mTORC1 activity in the mouse spinal cord. Mechanistic studies revealed that Protein Kinase B (Akt)/mTOR signaling pathway blockade with rapamycin prevented the phosphorylation of mTORC1 in stavudine-intoxicated mice (0.72 ± 0.04 vs. 0.86 ± 0.03, F = 4.24, P = 0.045), as well as decreased the expression of phospho-p70S6K (0.47 ± 0.01 vs. 0.68 ± 0.03, F = 6.01, P = 0.022) and phospho-4EBP1 (0.90 ± 0.04 vs. 0.94 ± 0.06, F = 0.28, P = 0.646)., Conclusions: Taken together, these results suggest that stavudine elevates the expression and activity of mTORC1 in the spinal cord through activating the Akt/mTOR signaling pathway. The data also provide evidence that rapamycin might be useful for the treatment of peripheral neuropathic pain., Competing Interests: There are no conflicts of interest

Competing Interests: There are no conflicts of interest

Background: Sacral neuromodulation (SNM) has become an effective method for treating lower urinary tract voiding dysfunction during the past 20 years. Because of the expensive cost, the number of implantable pulse generator (IPG) implantations per year in China is far lower than that in Western developed countries since 2012. This study was to summarize the effects of the appropriate prolonged SNM testing time in improving the implantation rate of a permanent IPG in patients with refractory lower urinary tract symptoms (LUTS) in mainland China., Methods: From January 2013 to June 2016, 51 patients with refractory LUTS received SNM therapy. In this study, we compared the conversion rate 2 weeks after the Stage I test and final actual conversion rate. We also observed the complications (such as pain, infection, and electrode displacement) and effectiveness. We tried to improve an appropriate prolonged test time which was favorable for improving the SNM conversion rate while ensuring safety and effectiveness., Results: Among 51 patients receiving SNM therapy, 19 patients (mean age 45.0 ± 16.9 years) had poor Stage I test results, and on an average, the electrode was removed 27.4 ± 9.6 days after the surgery. In one patient, the electrode was removed within 2 weeks; when the remaining 18 patients were questioned 2 weeks after testing, none of the patients wanted to terminate the test, and all the 18 patients desired to prolong the testing time to further observe the treatment effect. The remaining 32 patients (mean age 46.7 ± 15.3 years) received Stage II permanent implantation at 19.6 ± 10.4 days after the surgery. The overall Stage I-II conversion was 62.7% (32/51) in this study. Within 2 weeks after the surgery, only eight patients received Stage II permanent implantation, and the conversion rate was only 15.7% (8/51), which was much lower than the overall conversion rate of 62.7%. Nearly 84.4% (27/32) of the patients received Stage II implantation within 4 weeks. None of the patients had incision infections. In one patient, the entire system was removed 1 month after Stage II implantation due to pain in the implantation site., Conclusions: Appropriate extension of the Stage I testing time of an SNM-barbed electrode could significantly improve the Stage II permanent implantation rate in Chinese refractory LUTS patients; there were no wound infections, and the postoperative complication rate was low. This study recommended that Stage I period of SNM therapy should be 4 weeks according to safety and successful conversion rate.

Background: Tumor intrinsic chemoradiotherapy resistance is the primary factor in concomitant chemoradiotherapy failure in advanced uterine cervical squamous cell carcinoma. This study aims to identify a set of genes and molecular pathways related to this condition., Methods: Forty patients with uterine cervical squamous cell carcinoma in International Federation of Gynecology and Obstetrics stage IIb or IIIb, treated with platinum-based concomitant chemoradiotherapy between May 2007 and December 2012, were enrolled in this trial. Patients included chemoradiotherapy resistant (n = 20) and sensitive (n = 20) groups. Total RNA was extracted from fresh tumor tissues obtained by biopsy before treatment and microarray analysis was performed to identify genes differentially expressed between the two groups., Results: Microarray analysis identified 108 genes differentially expressed between concomitant chemoradiotherapy resistant and sensitive patients. Functional pathway cluster analysis of these genes revealed that DNA damage repair, apoptosis, cell cycle, Map kinase signal transduction, anaerobic glycolysis and glutathione metabolism were the most relevant pathways. Platelet-derived growth factor receptor alpha (PDGFRA) and protein kinase A type 1A (PRKAR1A) were significantly upregulated in the chemoradiosensitive group, while lactate dehydrogenase A (LDHA), bcl2 antagonist/killer 1 (BAK1), bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), and cyclin-dependent kinase 7 (CDK7) were upregulated in the chemoradiotherapy resistant group., Conclusion: We have identified seven genes that are differentially expressed in concomitant chemoradiotherapy resistant and sensitive uterine cervical squamous cell carcinomas, which may represent primary predictors for this condition.

Background: In order to simplify the complicated procedure of nerve-sparing radical hysterectomy, a novel technique characterized by integral preservation of the autonomic nerve plane has been employed for invasive cervical cancer. The objective of this study was to introduce the nerve plane-sparing radical hysterectomy technique and compare its efficacy and safety with that of nerve-sparing radical hysterectomy., Methods: From September 2006 to August 2010, 73 consecutive patients with International Federation of Gynecology and Obstetrics stage IB to IIA cervical cancer underwent radical hysterectomy with two different nerve-sparing approaches. Nerve-sparing radical hysterectomy was performed for the first 16 patients (nerve-sparing radical hysterectomy group). The detailed autonomic nerve structures were identified and separated by meticulous dissection during this procedure. After January 2008, the nerve plane-sparing radical hysterectomy procedure was developed and performed for the next 57 patients (nerve plane-sparing radical hysterectomy group). During this modified procedure, the nerve plane (meso-ureter and its extension) containing most of the autonomic nerve structures was integrally preserved. The patients' clinicopathologic characteristics, surgical parameters, and outcomes of postoperative bladder function were compared between the two groups., Results: There were no significant differences between the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups regarding age, International Federation of Gynecology and Obstetrics stage, pathological type, preoperative treatment, or need for intraoperative blood transfusion. The nerve plane-sparing radical hysterectomy group had a higher body mass index than that of the nerve-sparing radical hysterectomy group (P = 0.028). The mean surgical duration in the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups were (262 ± 46) minutes and (341 ± 36) minutes (P < 0.01). On the 8th postoperative day, 41 (71.9%) patients in the nerve plane-sparing radical hysterectomy group and nine (56.3%) patients in the nerve-sparing radical hysterectomy group had a postvoid residual urine volume of < 100 ml (P = 0.233). The median duration of catheterization was eight days (range 8 - 23 days) for the nerve plane-sparing radical hysterectomy group and eight days (range 8 - 22 days) for the nerve-sparing radical hysterectomy group (P = 0.509). Neither surgery-related injury nor pathologically positive margins were reported in either group., Conclusion: Nerve plane-sparing radical hysterectomy is a reproducible and simplified modification of nerve-sparing radical hysterectomy, and may be preferable to nerve-sparing radical hysterectomy for treatment of early-stage invasive cervical cancer.

Background: In general, sentinel lymph node (SLN) can reflect the whole state of the entire drainage area. The present study evaluated the clinical significance of sentinel lymph node identification in the treatment of early stage cervical cancer., Methods: Twenty-eight patients with early stage (Ia-IIa) cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were included in this study. At two locations 8 hours before operation, 0.4 ml 37 Mbq technicium-99 labeled dextran was injected intracervically. After that, preoperative lymphoscintigraphy was performed to detect SLNs. During the operation, lymph nodes were detected ex vivo by a gamma-counter to identify SLNs. The samples of SLNs and non-SLNs were used for pathological examination separately and compared with the final results., Results: SLNs were identified in 27 of 28 (96.4%) patients. A total of 123 SLNs were identified from 814 nodes. Six patients had altogether 11 positive lymph nodes, which were all SLNs. No patient had false-negative sentinel node., Conclusion: SLNs can successfully predict the lymphatic metastasis in patients with cervical cancer. The clinical validity of this technique should be evaluated prospectively.

Purpose: To promote the systematic development, interests, practice, research and clinical applications of health psychology in general hospitals in Hong Kong and the mainland of China., Data Sources: The targets and aims of therapeutic work with patients in pain, cancer patients, child and adolescent patients, patients with chronic illnesses, the elderly, and patients requiring organ transplantation are highlighted., Study Selection: The psychological interventions described are experiences derived from routine clinical services carried out in the Clinical Health Psychology Unit where the authors are affiliated, and can be seen as an example of a more comprehensive psychological intervention program for physically ill patients in Hong Kong., Results: Psychological interventions have intrinsic values in reducing patients' distress and sufferings. The services are also an integral part of modem day comprehensive patient care with positive effects on treatment effectiveness and eventual illness outcome., Conclusions: Physical illnesses affect a person physically as well as psychologically. Psychological care in general hospitals is cost effective and beneficial in reducing undue psychological complications precipitated by physical afflictions as well as in promoting better overall outcomes.

Using self-made special supporting tube, coloanal anastomosis was performed by intra-anal ligation for radical surgery in 48 patients with low rectal carcinoma. The anastomoses were completed without suturing, and the results were quite satisfactory. Follow-up after operation revealed that the bowel movement and the sphincteric function were excellent in all patients. The anal canal and the anal sphincter were all kept intact and abdominal colostomy was not required for decompression. Anastomosis without suturing, least trauma, and short operation time made blood transfusion unnecessary during the operation. This technique is actually derived from Park's operation, and is considered a promising procedure for coloanal anastomosis in the radical surgery for low rectal carcinoma.

We treated 52 patients with anal and low rectal carcinomas by orthotopic reconstruction of the anus, using an unilateral split gluteus maximum (GM) muscle flap to form the external anal sphincter and levator ani together with invagination of the colon to form the internal sphincter after radical resection of carcinoma. Among the 36 patients who were followed up for over 6 months, 34 (94.4%) exhibited good to excellent continence.