The distal tibiofibular syndesmosis is important for ankle mortise stability, weight transmission and walking. Incorrect treatment is correlate with chronicd ankle instability, long-term pain and the development of osteoarthritis. Some controversy still exists regarding the evaluation and treatment of syndesmotic injuries with screws. The goal of this review was to collect evidence on the technical aspects for the treatment of distal tibiofibular syndesmosis injuries with screw and to formulate some recommendations for clinical practices.
Ankle Injuries ; surgery ; Bone Screws ; Fibula ; injuries ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Joint Instability ; surgery ; Tibia ; injuries ; surgery

OBJECTIVETo investigate the difference in intracellular calcium ion [Ca2+]i concentration in prostate smooth muscle cells (PSMCs) between SD rat models of chronic abacterial prostatitis (CAP) and normal controls, and to evaluate the role of [Ca2+]i concentration in CAP.

METHODSWe established CAP models in SD rats using purified prostate protein and Freund's complete adjuvant, cultured in vitro and then purified the PSMCs of both the CAP models and normal controls. Continuous dynamic scanning was performed under the laser confocal scanning microscope after incubation of the cells with FLUO-3AM.

RESULTSThe fluorescence intensities of [Ca2+]i in the PSMCs were 80.39 +/- 9.00 and 27.95 +/- 10.04 in the CAP models and normal controls, respectively, with statistically significant differences between the two groups (P < 0.01).

CONCLUSIONThe concentration of [Ca2+]i increased in the PSMCs of the CAP rat models, which might enhance the constriction of PSMCs and subsequently increase the sensibility to pain and cause lower abdominal pain.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Chronic Disease ; Male ; Myocytes, Smooth Muscle ; metabolism ; Prostate ; metabolism ; Prostatitis ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the impact of the BKCa channel in prostate smooth muscle cells (PSMCs) on the membrane potential in SD rats with chronic abacterial prostatitis (CAP).

METHODSCAP models were established in 20 SD rats by castration and injection of 17 beta-estrogen, and another 20 were taken as normal controls. PSMCs were cultured and purified in vitro, and treated with DiBAC4, followed by quantitative observations on the dynamic changes of the cell membrane potential by laser confocal microscopy.

RESULTSThe extracellular calcium ion concentration ([Ca2+]o) was increased and the BKCa channel was activated, which induced the hyperpolarization of the PSMC membrane in both the CAP models and normal control rats. This effect was weakened with Iberiotoxin (IbTX), a specific blocker of the BKCa channel, but the amplitude of the hyperpolarization was obviously lower in the CAP than in the control group. The DiBAC4 fluorescence intensity induced by hyperpolarization was 18.78 +/- 2.92 in the former and 38.85 +/- 7.10 in the latter (P < 0.05), while that induced by IbTX was 1.61 +/- 0.46 and 6.12 +/- 1.32 (P < 0.05), respectively.

CONCLUSIONSignificant decrease of BKCa-mediated hyperpolarization in the CAP model can reduce its abilities of regulating the membrane potential and suppressing the excessive contraction of PSMCs, which may result in pelvic pain syndrome and lower urinary tract symptoms.

Animals ; Cells, Cultured ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits ; Male ; Membrane Potentials ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Potassium Channels ; metabolism ; Prostate ; cytology ; Prostatitis ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo construct a rat model of chronic nonbacterial prostatitis (CP) and investigate the difference in the quantitative expression of voltage-dependent calcium channels of prostate smooth muscle cells (PSMCs) between the models and controls.

METHODSWe established a CP rat model by estrogen induction, cultured and purified the PSMCs in vitro, and extracted total RNA by Trizol. Then we measured the mRNA expression of the cal subunit in the calcium channel subtypes by reverse transcription and SYBR Green I real time RT-PCR, and compared it with that of the controls.

RESULTSThe expressions of the L-, T- and P/Q-type calcium channels were found in both the CP and control groups, and that of the CaV1.2 L-type calcium channel was significantly increased in the former as compared with the latter (0.048 +/- 0.024 versus 0.031 +/- 0.015, t = 2.846, P = 0.007), but there were no statistically significant differences in the T- and P/Q-type calcium channels between the two groups.

CONCLUSIONThe number of CaV1.2 L-type calcium channels of PSMCs and calcium influx were increased in CP patients, which may be involved in the mechanism of CP.

Animals ; Calcium Channels, L-Type ; metabolism ; Calcium Channels, Q-Type ; metabolism ; Calcium Channels, T-Type ; metabolism ; Estradiol ; pharmacology ; Male ; Myocytes, Smooth Muscle ; metabolism ; Prostate ; metabolism ; Prostatitis ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

OBJECTIVETo access the prevalence of menopause-like symptoms, and their related factors in old and middle-aged males in the area of Hefei.

METHODSThis study included 1 026 males aged over 45 years that came to the clinic for health examination. We collected their personal data, and evaluated their general health status and the results of the questionnaire investigation using the Aging Males' Symptoms (AMS) scale.

RESULTSThe total incidence of menopause-like symptoms was 64.7% among the old and middle-aged males in Hefei area, of which 58.1% were mild, 30.9% moderate and 11.0% severe. The average AMS score was 31.2 +/- 6.8, in which the scores on psychological, physical and sexual function symptoms were 8.3 +/- 2.1, 12.4 +/- 4.8 and 9.3 +/- 4.5, respectively. Sexual function symptoms were increased significantly with the increase of age (P < 0.05), but psychological and physical symptoms showed no obvious correlation with age (P > 0.05). The main risk factors of menopause-like symptoms included age, smoking, diabetes, cardiovascular diseases, and obesity, but physical exercise was an important protective factor against them.

CONCLUSIONWith the increase of age, the prevalence of male menopause-like symptoms rises and sexual function declines gradually, but psychological and physical scores are not affected significantly. Age, general health status and lifestyle are closely associated with the prevalence of menopause-like symptoms among old and middle-aged males.

Aged ; Aged, 80 and over ; Aging ; Andropause ; China ; epidemiology ; Humans ; Incidence ; Life Style ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires

OBJECTIVETo study the mechanism of hepatic carcinoma cell apoptosis induced by small interfering RNA (siRNA)-mediated nuclear factor-kappaB (NF-kappaB) P65 silencing.

METHODSHepatic carcinoma SMMC-7721 cells were exposed to liposome-mediated transfection with NF-kappaB P65 siRNA synthesized by in vitro transcription, and the cells with empty liposome transfection and those without particular treatment served as the control groups. The expression of NF-kappaB P65 in the cells was detected by Western blotting, the cell viability examined by MTT assay, and the cell apoptosis assessed by flow cytometry. Immunohistochemistry was used to examine the expressions of Bcl-2 and Bax.

RESULTSsiRNA transfection significantly inhibited the expression of NF-kappaB P65 in SMMC-7721cells, with inhibition rates of 64.74% compared with the untreated cells and of 34.52% compared with the liposome-treated cells. The siRNA-treated SMMC-7721 cells also exhibited significant decrease in cell proliferation by 33.39% and 27.23% in comparison with the untreated and liposome-treated cells, respectively. NF-kappaB P65 siRNA induced obvious cell apoptosis with down-regulated Bcl-2 and up-regulated Bax expressions.

CONCLUSIONNF-kappaB p65 siRNA can induce SMMC-7721 cell apoptosis via the Bcl-2/Bax pathway.

Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Liposomes ; Liver Neoplasms ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Small Interfering ; pharmacology ; Transcription Factor RelA ; metabolism ; Transfection ; bcl-2-Associated X Protein ; metabolism

In this study, the thermoresponsive micelles were synthesized with random copolymerization method and the photosensitizer indocyanine green (ICG) was loaded on micelles through the physical adsorption. The light energy was converted into heat energy to increase the temperature after irradiation with near-infrared light. When the phase transition temperature was reached, the micelle was disassembled and the targeted therapy was achieved. The nanoparticles were characterized with a transmission electron microscopy, Fourier transform infrared spectrometer, nuclear magnetic resonance spectrometer and other characterization were used to investigate. The critical micelle concentration (CMC), upper critical solution temperature, the photothermal properties of the carrier and the release of drug triggered by light were investigated after the doxorubicin (DOX) loaded. The carrier was evaluated for toxicity, cellular uptake, the effect of photothermal, the combination of photothermal and chemotherapy; the p(AAm-co-AN)-g-PEG (PAAP) was spherical in shape with a particle size of about 45 nm and a phase transition temperature was about 43℃. The critical micelle concentration was 24 μg·mL^-1. The particle size increased to 88 nm after loaded with ICG and DOX which the photothermal effect was obvious. The cumulative release of the drug under the irradiation of near-infrared light (808 nm, 2 W·cm^-2, 2 min·h^-1) was increased to 59.4% (pH 5.0) after 5 h. The results of the cell experiment indicated that ICG-PAAP was almost non-toxic and uptaken by the lysosomal pathway. The cell killing effect was stronger with combination of chemotherapy (DOX as 20 μg·mL^-1) with more than 70% of the cells killed. The results showed that the prepared micelle with low toxicity was thermoresponsive and could be used in combined therapy of tumor under the irradiation of near-infrared light.

IMM0306 is a recombinant human signal regulatory protein α-anti-CD20 mouse chimeric antibody fusion protein, intended to treat refractory or recurrent CD20 positive B-cell non-Hodgkin lymphoma (B-NHL) in clinical. In this study, an ELISA method was established to evaluate the pharmacokinetics of IMM0306 in human serum. The experiment was approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences (No. CTR20192612). Recombinant human CD47 protein was coated with the plate overnight, blocking the plate with 5% skin milk for 2 h. After washing, 100 μL per well standard and unknown samples were added, and incubated for 1.5 h. After washing, the detection antibody Anti-IMM0306-Biotin was added and incubated for 1 h, and then HRP-labeled streptavidin was added for 1 h, and the color was detected. The optimal concentration of coating reagent was 2 μg·mL^-1 by ELISA method, and the optimal dilution of anti-IMM0306-biotin and SA-HRP were 1∶500 and 1∶5 000, respectively. The lower limit of quantitation was 4 ng·mL^-1, and the standard curve range was 4-100 ng·mL^-1. The verification results of the method meets the corresponding acceptance criteria, and can be used in IMM0306 clinical pharmacokinetic studies.

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca²⁺ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca²⁺]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca²⁺]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.
Acid Sensing Ion Channel Blockers/pharmacology* ; Acid Sensing Ion Channels/genetics* ; Animals ; Calcium/metabolism* ; Chelating Agents/pharmacology* ; Chronic Disease ; Cytokines/metabolism* ; Disease Models, Animal ; Egtazic Acid/pharmacology* ; Gene Knockdown Techniques ; Imidazoles/pharmacology* ; Inflammation/metabolism* ; MAP Kinase Signaling System/genetics* ; Male ; Pain/genetics* ; Peptides/pharmacology* ; Phosphorylation/drug effects* ; Posterior Horn Cells/metabolism* ; Prostatitis/complications* ; Protein Kinase Inhibitors/pharmacology* ; Pyridines/pharmacology* ; Rats ; Spider Venoms/pharmacology* ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/metabolism*

MicroRNAs (miRNAs) are considered to be involved in the pathogenic initiation and progression of chronic nonbacterial prostatitis (CNP); however, the comprehensive expression profile of dysregulated miRNAs, relevant signaling pathways, and core machineries in CNP have not been fully elucidated. In the current research, CNP rat models were established through the intraprostatic injection of carrageenan into the prostate. Then, next-generation sequencing was performed to explore the miRNA expression profile in CNP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatical analyses were conducted to reveal the enriched biological processes, molecular functions, and cellular components and signaling pathways. As a result, 1224, 1039, and 1029 known miRNAs were annotated in prostate tissues from the blank control (BC), normal saline injection (NS), and carrageenan injection (CAR) groups (n = 3 for each group), respectively. Among them, 84 miRNAs (CAR vs BC) and 70 miRNAs (CAR vs NS) with significantly different expression levels were identified. Compared with previously reported miRNAs with altered expression in various inflammatory diseases, the majority of deregulated miRNAs in CNP, such as miR-146b-5p, miR-155-5p, miR-150-5p, and miR-139-5p, showed similar expression patterns. Moreover, bioinformatics analyses have enriched mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), endocytosis, mammalian target of rapamycin (mTOR), and forkhead box O (FoxO) signaling pathways. These pathways were all involved in immune response, which indicates the critical regulatory role of the immune system in CNP initiation and progression. Our investigation has presented a global view of the differentially expressed miRNAs and potential regulatory networks containing their target genes, which may be helpful for identifying the novel mechanisms of miRNAs in immune regulation and effective target-specific theragnosis for CNP.
Animals ; Computational Biology ; Databases, Genetic ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Male ; MicroRNAs/metabolism* ; Prostate/metabolism* ; Prostatitis/metabolism* ; Rats ; Rats, Wistar