A Novel Sensor System for In Vivo Perception Reconstruction Based on Long Short-Term Memory Networks.

Monitoring bodily pressure could provide valuable medical information for both doctors and patients. Long-term implantation of in vivo sensors is highly desirable in situations where perception reconstruction is needed. In particular, for fecal incontinence, artificial anal sphincters without perceptions could not remind patients when to defecate and even cause ischemic tissue necrosis due to uncontrolled clamping pressure. To address these issues, a novel self-packaging strain gauge sensor system is designed for in vivo perception reconstruction. In addition, long short-term memory (LSTM) networks, which show excellent performance in processing time series-related features and fitting properties, are used in this article to improve the prediction accuracy of the perception model. The proposed system has been tested and compared with the traditional linear regression (LR) approach using data from in vitro experiments. The results show that the Root-Mean-Square Error (RMSE) is reduced by more than 69%, which demonstrates that the prediction accuracy of the proposed LSTM model is higher than that of the LR model to reach a more accurate prediction of the amount of intestinal content. Furthermore, outcomes of in vivo experiments show that the robustness of the novel sensor system based on long short-term memory networks is verified through experiments with limited data.

Design and evaluation of perception reconstruction with sensor system for artificial anal sphincter based on vector similarity.

BACKGROUND: Artificial organs are playing an increasingly important role in medical field. Artificial anal sphincter, as an example, is a widely used medical device for fecal incontinence. Though it could help patients maintain continence, the issue of perception reconstruction is still unsolved, which means that patients cannot control defecation as desired. METHODS: In this paper, a novel sensor system based on vector similarity has been analyzed and evaluated. The sensor system is a self-packaged strain gauge sensor with a small size 14.5 mm × 6 mm, especially for medical device implanted in body to reconstruct perception function. In order to overcome the disadvantages of single threshold judgment, a more accurate and reliable judgment standard for content pressure detection in rectum is developed by using vector similarity method. Therefore, in the novel sensor system, standard multi-parameters are comprehensive considered. Furthermore, weight-optimization of sensors are investigated since each sensor has played a different role in detection. Finally, sensor calibration, in vitro and in vivo experiments are established. RESULTS: In sensor calibration, the result R2 > 0.99 presents the strain gauge pressure sensor has a good linearity. After that, a series of in vitro experiments have been conducted. The optimized sensor system shows a high accuracy rate in perception reconstruction, which is 87.5% on early warning and 95% on the alarm. In the following in vivo experiments. The results indicate that the average accuracy of the proposed perception reconstruction module has increased by 17.7%, compared with that without optimized sensor system. CONCLUSIONS: All of these have proven that the novel perception reconstruction module with sensor system based on vector similarity is more acceptable and reliable.

Preliminary study of a novel artificial anal sphincter with perception reconstruction.

BACKGROUND: Artificial anal sphincter (AAS), as an advanced device, has been widely investigated by researchers around world. But the reliability of the structure is still unsatisfactory according to clinical results. What's more, the previous AAS systems are lack the ability of rectal perception as native anal sphincter, which fails to guarantee the safety of the blood supply. In addition, without it, the patient cannot determine when to defecate. METHODS: In order to improve the reliability and safety of current AAS systems, a novel structure AAS system with rectal perception function, based on pressure sensor module, is proposed in this article. The novel AAS system has a closed three-arm clamping mechanism, with transmission structure of cam-follower system. Then, the design, strength check, optimization and force analysis of the proposed mechanism are investigated. After that, to remodel rectal perception function, the novel sensor module system based on strain gauge is established. Finally, in vitro experiments are conducted. RESULTS: In vitro test, the sensor system could monitor the rectal pressure accurately. And when H = 24.6 cm (feeling the urge to have a bowel movement), the clamping pressure is 7.39 kPa. which is also less than the safe pressure 9.33 kPa. CONCLUSIONS: Good performance of the reliability and safety of both novel rectal perception function and new clamping mechanism have been showed.

Design and evaluation of puborectalis-like artificial anal sphincter that replicates rectal perception.

While fecal incontinence (FI) is not fatal, it can dramatically decrease the patient's quality of life. An artificial anal sphincter (AAS) is an implantable device that treats FI by replacing a diseased or damaged anal sphincter, thus allowing the patient's continence to be maintained. Here, we report a novel implantable puborectalis-like artificial anal sphincter (PAAS) that replicates rectal perception and has a low risk of ischemia necrosis. Using the pressure sensors embedded in the PAAS, the relationship between the mass of feces and the pressure was determined, and a feces mass estimation model was developed based on in vitro studies. Rectal perception is provided through the real-time monitoring of rectal feces, and the feeling of defecation is quantified based on a comparison between the feces mass and a preset threshold mass. In vivo studies were performed for validation, and the accuracy of the model was determined to be as high as 90%. The performance of the PAAS in the real-time monitoring of rectal feces and its in vivo biocompatibility were also evaluated. The device should further the functionality of existing AAS systems while improving their biosafety and thus expand the applicability of implantable AAS systems in the treatment of FI.

Inhibition of hyperplasia during the implantation of the puborectalis-like artificial anal sphincter.

OBJECTIVES: This study aims to extend the implantation lifetime of the puborectalis-like artificial anal sphincter by inhibiting the occurrence of hyperplasia following the implantation process. METHOD: A new transmission structure was designed inside the puborectalis-like artificial anal sphincter to generate an adequate torque to maintain the feces, even if hyperplasia developed around the prosthetic sphincter. An outer shell was added to the prosthetic sphincter to decelerate the occurrence of hyperplasia on the outer shell side. Medical titanium alloy was tested to replace the nylon-12 prosthetic sphincter, while polyetheretherketone was used for the construction of the power supply unit in the puborectalis-like artificial anal sphincter system instead of nylon-12. In vivo experiments were conducted to evaluate all the methods presented in this study with 10 Pa Ma piglets, 1 domestic pig, and 1 beagle dog during the past 2 years. RESULTS: Compared with the previous prosthetic sphincter that was equipped with a fixed-axle gear transmission, the new transmission structure is equipped with a planet-gear train managed to generate a prosthetic sphincter output with a 53% larger torque but with the same size and type of motor as that used previously and increase the implantation lifetime by 56%. After the replacement of the nylon-12, the new prosthetic sphincter made of medical titanium alloy succeeded in extending the implanted lifetime by 83%. In addition, the lifetime was increased by 143%, when an outer shell was added to the prosthetic sphincter. Polyetheretherketone significantly decreased the growth rate of hyperplasia around the power supply unit by 44% after the replacement of the power supply unit material. After the combination of all the improvements, the longest implantation lifetime of the puborectalis-like artificial anal sphincter during the in vivo experiments was 7 months and 10 days, which reflected an improvement of 249%. CONCLUSION: All methods posted in this study were evaluated to be effective to prolong the implantation lifetime of the puborectalis-like artificial anal sphincter. Among the methods proposed, the most effective was the addition of the outer shell to the puborectalis-like artificial anal sphincter. The least effective method was the improvement of the transmission structure. Medical titanium alloy and polyetheretherketone were good replacements for nylon-12 that managed to extend the implantation lifetime and yield a moderate improvement.

A novel power supply system for puborectalis-like artificial anal sphincter.

Puborectalis-like artificial anal sphincter (PAAS) is an innovative new type of artificial anal sphincter (AAS). It overcomes many drawbacks and inadequacies of various previous AASs, and it has successfully been implanted in vivo for almost 3 weeks. During in vivo testing, PAAS shows its ability to retain continence with low risk of ischemia necrosis, and somehow truly helps to remodel rectal perception. However, there are still many defects that influence the long-term implantation of PAAS, especially in the power supply system (PSS). This article presents a new designed PSS which includes a new transcutaneous energy transfer (TET) system, a heat reduction system, and a safety usage system. The new PSS reduces the total size of PAAS by at least 30%. Newly designed TET system can satisfy the Qi standard, and render a power of 3W to fulfill the requirement of fast charging and normal use of PAAS at the distance of 15.5 mm when frequency of TET system is 110 kHz, which previous TET systems can hardly achieve. Heat reduction system helps to reduce the heat generated during TET charging. It can reduce heat by 40% during the same period of time of TET charging. Safety usage system helps the user control PAAS more properly which can reduce the rate of failure of PAAS system.

Decreased Expression of miR-138-5p by lncRNA H19 in Cervical Cancer Promotes Tumor Proliferation.

MicroRNAs (miRNAs) play important roles in the carcinogenesis of cervical cancer. However, the expression and underlying mechanisms of miRNA in cervical cancer progression remain unclear. In the present study, our data showed that the expression of miR-138-5p was significantly downregulated in cervical cancer tissues, and decreased expression of miR-138-5p was correlated with advanced FIGO stage, poor differentiation, lymph node metastasis, and poor overall survival of cervical cancer patients. Function assays showed that overexpression of miR-138-5p reduced cervical cancer cell proliferation, arrested cells in the G0/G1 phase, and induced cell apoptosis in vitro. Remarkably, SIRT1 was confirmed as a direct target of miR-138-5p in cervical cancer, and miR-138-5p exerted the reduced tumor functions by suppressing SIRT1 expression. Moreover, we further identified that lncRNA H19 could act as a molecular sponge of miR-138-5p in cervical cancer progression. Taken together, these results suggested that miR-138-5p could suppress cervical cancer cell progression by targeting SIRT1.

Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through Wnt/ß-catenin signaling pathway in cervical cancer.

BACKGROUND: Cervical cancer is the most common gynecological malignancies in women worldwide. The previous study showed that lncRNA NNT-AS1 could play an important role in tumor development and metastasis of colorectal cancer. However, little is known about the function of NNT-AS1 in cervical cancer. The aim of this study was to investigate the expression profile of NNT-AS1 in cervical cancer and assess its possible molecular mechanism. METHODS: Relative expression levels of NNT-AS1 in cervical cancer tissues were determined by qRT-PCR. The biologic functions of NNT-AS1 in cervical cancer were explored by MTT assay, transwell assay and flow cytometric analysis in vitro. The influence of NNT-AS1 on tumorigenesis was measured by mice xenograft model. In addition, we evaluated the activation of Wnt/ß-catenin signaling pathway by luciferase assay and western blot. RESULTS: Our results showed that NNT-AS1 expression in cervical cancer tissues compared with adjacent non-tumor tissues the overexpression of NNT-AS1 was positively associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poorer overall survival. Function assays showed that NNT-AS1 inhibition could suppress cervical cancer cells proliferation and invasion ability in vitro as well as the activation of Wnt/ß-catenin signaling pathway. In vivo mice xenograft model revealed that silencing NNT-AS1 could reduce tumor growth in nude mice. CONCLUSIONS: The results of the current study suggested that NNT-AS1 might play an important role in cervical carcinogenesis and might serve as a potentially therapeutic target and prognostic marker in the treatment of cervical cancer.

[Effects of small interfering RNA silencing MACC-1 expression on cell proliferation, cell cycle and invasion ability of cervical cancer SiHa cells].

OBJECTIVE: To investigate the expression of metastasis-associated in colon cancer-1 (MACC-1) mediated by siRNA, and to study the effects of its downregulation on cell proliferation, cell cycle and invasion ability of cervical cancer SiHa cells. METHODS: MACC-1 siRNA and control siRNA were transfected into cervical cancer SiHa cells, and the expression of MACC-1 protein after transfection with MACC-1 siRNA was detected by Western blotting. The changes of cell proliferation, cell cycle and invasion ability of the SiHa cells were determined by CCK-8 kit, flow cytometry and Boyden chamber assay. The expressions of cell cycle- and invasion-related proteins were analyzed by Western blotting. RESULTS: Compared with the untreated group (0.317 ± 0.023) and control siRNA group (0.309 ± 0.021), the expression of MACC-1 protein was downregulated in the MACC1 siRNA group (0.041 ± 0.006) (P < 0.05), and its downregulation significantly suppressed the cell proliferation, altered the cell cycle distribution and reduced the cell invasion ability of the SiHa cells (P < 0.05). Compared with the untreated group (0.217 ± 0.025 and 0.215 ± 0.024) and the control siRNA group (0.222 ± 0.023 and 0.207 ± 0.027), the expression of cyclin D1 and Cdk2 proteins were significantly decreased in the MACC1 siRNA group (0.076 ± 0.010 and 0.039 ± 0.007) (P < 0.05). Compared with the untreated group (0.099 ± 0.007) and control siRNA group (0.105 ± 0.012), the expression of p21 protein was significantly increased in the MACC1 siRNA group (0.676 ± 0.044) (P < 0.05). The downregulation of MACC-1 expression also evoked a decrease of expressions of MMP-2 and MMP-9 proteins and an increase of E-cadherin protein expression (P < 0.05). CONCLUSIONS: MACC-1 downregulation-mediated inhibition of proliferation and decreased invasion ability of tumor cells may be closely associated with the alterations of expressions of cell cycle- and invasion-related proteins.

Effect of downregulated histone deacetylase 2 expression on cell proliferation and cell cycle in cervical cancer.

PURPOSE: To investigate the effects and molecular mechanism of downregulated histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical cancer Hela cells. METHODS: HDAC2 small interfering (si)RNA and control siRNA were transfected into cervical cancer Hela cells. A cell proliferation assay using a cell counting kit-8 was applied to analyze the change in cell proliferation before and after transfection. Flow cytometry was used to detect the change in cell cycle distribution before and after transfection. Finally, Western blot was used to detect changes in the expression of cell proliferation and cell cycle-related proteins. RESULTS: HDAC2 siRNA significantly downregulated the expression of HDAC2 proteins in cervical cancer cells, markedly inhibiting their proliferation. In addition, the percentage of Hela cells in the G0/G1 phase in the HDAC2 siRNA group was 63.3±2.0%, significantly higher than those in the untreated group (29.3±1.7%) or the control siRNA group (29.4±1.7%) (F=354.181, p=0.000). Furthermore, Western blot analyses demonstrated that downregulated HDAC2 expression inhibited the expression of cyclin D1, cyclin E, and cdk2 proteins but elevated the expression of p21 protein. CONCLUSION: The proliferation inhibition and cell cycle arrest mediated by downregulated HDAC2 expression may be tightly associated with the decrease of cyclin D1, cyclin E, and cdk2 proteins expression and the increase in p21 protein expression.

Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis.

To examine if there is any correlation between ankylosing spondylitis (AS) and TNF-α gene promoter single-nucleotide polymorphisms (SNP) and their associated haplotypes. Using restriction fragment length polymorphism-polymerase chain reaction method, the polymorphism of TNF-α-238, -308, -850, -857, -863 locus, and TNF-ß +252 were analyzed in patients with progressive AS, stable AS and control. (1) Neither the genotypes nor the allele frequencies of TNF-α (-308), (-238), (-863), and TNF-ß +252 showed differences in each group. TNF-α (-850) CC genotype and C allele frequency distribution was significantly higher in healthy controls group than in the stable and progressive groups. TNF-α (-857) CT, CC genotype, and C, T allele frequency showed differences in all groups. (2) Polymorphism linkage equilibrium test revealed that association of six TNF-α, ß gene SNPs with haplotype GACTCG in progressive group is significantly higher than in the stable group and healthy control group (P < 0.05). TNF-α (-857), (-850) gene polymorphism may increase the susceptibility to AS, but do not reflect the disease active state. The CC genotype and C allele may play a protective role in the pathogenesis of AS. TNF-α (-308) may be a weak indicator reflecting the active state of AS. Haplotype GACTCG may indicate both the susceptibility and the activity of AS.

[Clinical observation on treatment of premature ovarian failure patients of shen deficiency gan stagnation syndrome by combination of bushui roumu recipe and medroxyprogesterone acetate tablet HUA].

OBJECTIVE: To study the therapeutic efficacy of bushui roumu recipe (BRR) combined medroxyprogesterone acetate tablet (MAT) in treating premature ovarian failure (POF). METHODS: Totally 90 POF patients of Shen deficiency Gan stagnation syndrome were assigned to 3 groups by random number table, 30 in each group. Patients in the treatment group were treated with BRR and MAT, those in the Chinese medicine group were treated with BRR, and those in the Western medicine group were treated with artificial period method. All patients were treated for 3 months. The menstrual improvement was observed before and after treatment. The therapeutic efficacy was assessed using modified Kupperman scoring standard. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were observed before and after treatment. RESULTS: (1) In aspect of the menstrual improvement: In the treatment group 20 patients had menstrual onset during the treatment course. Ten had normal menstruation after discontinued medication. Of them one got pregnancy one month after treatment. In the Chinese medicine group 6 patients had menstrual onset during the treatment course. Two had normal menstruation after discontinued medication. In the Western medicine group 26 patients had menstrual onset during the treatment course. Twelve had normal menstruation after discontinued medication. Better effects on the menstrual improvement were obtained in the treatment group than in the Chinese medicine group (P < 0.01), but with no statistical difference when compared with the Western medicine group (P > 0.05). (2) There was statistical difference in modified Kupperman scores of the 3 groups between before and after treatment (P < 0.01). The improvement of total modified Kupperman score was better in the treatment group than in the other two groups (P < 0.01). The improvement of palpitation was better in the treatment group than in the other two groups (P < 0.05). The improvement of tidal fever and sweat was better in the treatment group and the Chinese medicine group than in the Western medicine group (P < 0.05). (3) After treatment all patients' serum E2 was higher than before treatment, serum levels of FSH and LH were lower than before treatment. Compared pre- and post-treatment, there was statistical difference (P < 0.01). The serum E2 level in the 3 groups was higher after treatment than before treatment with statistical difference (P < 0.01). The levels of FSH and LH were lower in the 3 groups after treatment than before treatment with statistical difference (P < 0.01). The improvement of E2 was better in the treatment group than in the Chinese medicine group (P < 0.05). The improvement of FSH and LH was better in the treatment group than in the Western medicine group (P < 0.05). CONCLUSION: Combination of BRR and MAT could improve the clinical symptoms, menstruation, and serum reproductive hormones in POF patients of Shen deficiency Gan stagnation syndrome.

HDAC6 siRNA inhibits proliferation and induces apoptosis of HeLa cells and its related molecular mechanism.

OBJECTIVE: To investigate the effects of histone deacetylase 6 (HDAC6) siRNA on cell proliferation and cell apoptosis of the HeLa cervical carcinoma cell line and the molecular mechanisms involved. METHODS: Division was into three groups: A, the untreated group; B, the control siRNA group; and C, the HDAC6 siRNA group. Lipofectamine 2000 was used for siRNA transfection, and Western blot analysis was used to determine the protein levels. Cell proliferation and apoptosis were characterized using a CCK-8 assay and flow cytometry, respectively. RESULTS: HDAC6 protein expression in the HDAC6 siRNA-transfection group was significantly lower (P < 0.05) than in the untreated and control siRNA groups. The CCK-8 kit results demonstrated that the proliferation of HeLa cells was clearly inhibited in the HDAC6 siRNA transfection group (P < 0.05). In addition, flow cytometry revealed that the early apoptotic rate (26.0% ± 0.87%) was significantly elevated (P < 0.05) as compared with the untreated group (10.6% ± 1.19%) and control siRNA group (8.61% ± 0.98%). Furthermore, Western blot analysis indicated that bcl-2 protein expression in the HDAC6 siRNA-transfection group was down-regulated, whereas the expression of p21 and bax was up-regulated. CONCLUSION: HDAC6 plays an essential role in the occurrence and development of cervical carcinoma, and the down-regulation of HDAC6 expression may be useful molecular therapeutic method.

[Effect of down-regulation of histone deacetylase 2 protein expression on cell proliferation and cell cycle in cervical carcinoma].

OBJECTIVE: To study the effect of down-regulation of histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical carcinoma cell lines HeLa. METHODS: HDAC2 siRNA and control siRNA were transfected to HeLa cells. CCK-8 and flow cytometry were used to analyze the changes of cell proliferation and cell cycle, respectively. Western blot was employed to detect the changes of cell proliferation and cell cycle-related proteins. RESULTS: HDAC2 siRNA significantly down-regulated the expression of HDAC2 protein in HeLa cells, resulting in marked inhibition of cell proliferation. In addition, the percentage of cells in G(0)/G(1) phase in HDAC2 siRNA group (63.3% ± 2.0%) was significantly higher than that in untreated group (29.3% ± 1.7%) or control siRNA group (29.4% ± 1.7%), F = 354.181, P = 0.000. Furthermore, Western blot demonstrated that down-regulation of HDAC2 expression decreased the expression of cyclin D1, cyclin E and CDK2 proteins but increased the expression of p21 protein. CONCLUSIONS: Down-regulation of HDAC2 expression mediates proliferation inhibition and cell cycle arrest. It is associated with decrease in cyclin D1, cyclin E and CDK2 protein expression and increase in p21 protein expression.