Exploring the nursing effect of application Albizia bark on autism in children based on network pharmacology and molecular docking.

OBJECTIVE: Autism is a disorder that manifests itself in early childhood. Early diagnosis of autism may not only help the affected children themselves, but also affect family well-being and social stability. The natural drug Albizia bark has been reported to have some effect in the prevention and treatment of autism in children. Therefore, we used network pharmacology and molecular docking to explore the possible mechanism. MATERIALS AND METHODS: TCMID and BATMAN-TCM was used to retrieve the chemical constituents of Albizia bark, and then obtained the relevant targets about autism by TTD, Gene Cards and OMIM. The resulting ingredients and targets were predicted, then a protein interaction network was constructed, and finally bioinformatics analysis was performed. Finally, molecular docking was used to verify the effective ingredients and targets obtained from the screening. RESULTS: Leucaena saponin B, luteolin, 3', 4', 7-trihydroxyflavone, which may be the key compounds for the treatment of autism. BP mainly involving signal transduction, G protein coupled receptor signal pathway, protein phosphorylation. CC, mainly involving plasma membrane, integral component of plasma membrane, MF, including protein binding, adenosine triphosphate binding, protein kinase activity. Molecular docking showed that AKT1, HRAS, PIK3CA, PIK3R1 and SRC, five potential targets, had good binding ability to Leucaena saponin B. CONCLUSIONS: The natural drug Albizia bark exerts pharmacological effects in a multi-component, multi-target and multi-channel manner, including neural regulation, inflammatory response and immune regulation.

[The clinical phenotype and gene analysis of syndromic deafness with PTPN11 gene mutation].

Objective: To analyze the clinical phenotype and screen the genetic mutations of hereditary deafness in three deaf families to clarify their molecular biology etiology. Methods: From January 2019 to January 2020, three deaf children and family members were collected for medical history, physical examination, audiology evaluation, electrocardiogram and cardiac color Doppler ultrasound, temporal bone CT examination, and peripheral blood DNA was obtained for high-throughput sequencing of deafness genes. Sanger sequencing was performed to verify the variant sites among family members. The pathogenicity of the variants was evaluated according to the American College of Medical Genetics and Genomics. Results: The probands in the three families had deafness phenotypes. In family 1, proband had multiple lentigines, special facial features, growth retardation, pectus carinatum, abnormal skin elasticity, cryptorchidism and other manifestations. In family 2, proband had special facial features, growth retardation and abnormal heart, and the proband in family 3 had growth retardation and abnormal electrocardiogram. Genetic testing of three families detected three heterozygous mutations in the PTPN11 gene: c.1391G>C (p.Gly464Ala), c.1510A>G (p.Met504Val), c.1502G>A (p.Arg501Lys). All three sites were missense mutations, and the mutation sites were highly conserved among multiple homologous species. Based on clinical manifestations and genetic test results, proband 1 was diagnosed with multiple lentigines Noonan syndrome, and probands 2 and 3 were diagnosed with Noonan syndrome. Conclusion: Missense mutations in the PTPN11 gene may be the cause of the disease in the three deaf families. This study enriches the clinical phenotype and mutation spectrum of the PTPN11 gene in the Chinese population.

Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression, by Y.-Q. Gao, H.-Y. Cheng, K.-F. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3621-3626-DOI: 10.26355/eurrev_201905_17785-PMID: 31114986" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17785.

[Introduction of joint model and its applications in medical research].

In medical follow-up studies, longitudinal data and survival data are often accompanied and associated with each other, thus respective analysis of longitudinal and survival data might lead to biased results. Joint model can correct deviations, improve the efficiency of parameter estimation and provide effective inferences by simultaneously processing longitudinal and survival data. It is a popular method in medical research. Joint model has made much progress, whereas the literature about the joint model and its application is limited in China. This paper summarizes the main idea, basic framework, parameter estimation methods of random effect joint model and introduces the analysis on AIDS data set based on the R software package 'JM' to clarify the advantages of the joint model in processing medical follow-up data and promote the use of the joint model in clinical research.

[Institutional delivery rate in minority inhabited areas of China from 1996 to 2017].

Objective: To describe the secular trends of institutional delivery (ID) rate in minority inhabited areas of China from 1996 to 2017 according to national health policies. Methods: The number of live births and IDs for each county/district in 31 provinces of China were derived from the datasets collected by the Office for National Maternal & Child Health Statistics of China. Information on health policies and ethnical areas was derived from official governmental websites. The calendar years were divided into three periods: pre-program period (1996 to 1999), program implementation period (2000 to 2008) and post-program period (2009 to 2017). Minority autonomous regions, autonomous prefectures, and autonomous counties were defined as minority inhabited areas. The ethnic that a county was classified into was determined by a principle of close proximity to the name of the county or its next higher level administrative division. A total of 700 counties in minority inhabited areas were included in the analysis. Results: A total of 45 684 265 live births including 35 098 855 delivered in institutions were analyzed. The ID rate in minority inhabited areas was 37.5% (696 221/1 856 164) in 1996 and 99.2% (2 371 209/2 390 131) in 2017, with an annual growth rate of 4.7%. During the 22-years period, the ID rates in the eastern, central and western regions increased simultaneously, with the annual growth rates of 3.1%, 4.2% and 4.9% respectively. The difference between the eastern and western regions decreased steadily from 16% in 1996 to <1% in 2017 and the difference between the urban and rural areas decreased from 32.1% in 1996 to <1% in 2017. Besides, the ID rates in Tibetan and Yi inhabited areas with lower baseline levels increased 73 and 63 percentage points respectively. The number of counties with the ID rate of <96% were substantially reduced from 589 in 1996 to 72 in 2017; the 71 counties were all located in national deep poverty-stricken areas named Three Districts and Three States, predominantly involving Tibetan (58), Yi (6), Uygur (2) and Lisu (2) ethnics. Conclusion: During the past 22 years, the ID rate in minority inhabited areas in China has dramatically increased, achieving the goal of 2 020 ahead of schedule, but there remains a few western counties where ID rates are still<96%, indicating that minority inhabited western areas should be focused in developing national policies concerning institutional delivery.

Risk factors and a predictive nomogram for non-sentinel lymph node metastases in Chinese breast cancer patients with one or two sentinel lymph node macrometastases and mastectomy.

Background: Two ongoing prospective randomized trials are evaluating whether omitting axillary lymph node dissection (alnd) in patients with breast cancer (bca) and sentinel lymph node (sln) macrometastases undergoing mastectomy is safe. Determining predictive risk factors for non-sln metastases and developing a model to predict the probability of those patients having non-sln metastases is also important. Methods: This retrospective study enrolled 396 patients with bca and 1-2 slns with macrometastases who underwent alnd and mastectomy between January 2012 and December 2016. Factors influencing the non-sln metastases were determined, and a predictive nomogram was formulated. Performance of the nomogram was evaluated by its area under the curve (auc). Results: We developed a predictive nomogram with an auc of 0.81 (cross-validation 95% confidence interval: 0.75 to 0.86) that included 4 factors (tumour size, histologic grade, and number of negative slns and axillary lymph nodes on imaging). Conclusions: Our predictive nomogram assesses the risk of non-sln metastases in patients with bca and 1-2 sln macrometastases undergoing mastectomy.

Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression.

OBJECTIVE: Recent studies have revealed the important role of long non-coding RNA (lncRNAs) in the development of malignant tumors. In this work, we explored the exact role of lncRNA DANCR in ovarian cancer progression and the underlying mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect DANCR expression in both ovarian cancer cells and tissue samples. Subsequently, cell proliferation assay and transwell assay were conducted. Furthermore, the underlying mechanism was explored via qRT-PCR and Western blot assay. RESULTS: The expression of DANCR in ovarian cancer samples was significantly higher than that of the corresponding normal tissues. After DANCR overexpression in vitro, the proliferation, invasion and migration of ovarian cancer cells were markedly promoted. In addition, both the mRNA and protein expression levels of insulin-like growth factor 2 (IGF2) were remarkably upregulated after DANCR overexpression. Furthermore, the results found that the expression level of IGF2 was positively correlated with DANCR expression in ovarian cancer tissues. CONCLUSIONS: In this study, we revealed that DANCR could enhance the proliferation, migration and invasion capacities of ovarian cancer cells by upregulating IGF2. Our findings might offer a potential therapeutic choice for patients with ovarian cancer.

[Research progress of single-nucleotide polymorphism in theTM6SF2 rs58542926].

Transmembrane 6 superfamily member 2 (TM6SF2) is a recently discovered gene, which is located on the chromosome 19 (19p12) and encodes a protein consisting of 351 amino acids. Presently, many studies have reported that the single-nucleotide polymorphism of TM6SF2 rs58542926 and plasma lipids are closely related to the incidence and development of diseases, such as non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), liver cancer, and hepatitis C. This review will summarize the research progress conducted in these areas.

[Clinical pathologic analysis on 3 724 cases of salivary gland tumors].

Objective: To investigate the incidence and proportion of salivary gland tumors in order to provide new thinking for clinical diagnosis and treatment. Methods: Collected 3 724 cases salivary gland tumors diagnosed by Pathology Department of Hospital of Stomatology, Jilin University from January 1961 to December 2016. The pathological diagnosis referred to the fourth edition of head and neck-salivary gland tumor histopathological classification standard of WHO. The database was established with Microsoft Excel and analyzed with SPSS 18.0. Made a retrospective analysis and comparison on the numbers of all cases in terms of types, site, gender and age and estimate the trend with the time interval of 8 years, and then make a judgement of the trend of salivary tumors. Results: The benign tumors were more common than the malignant among all periods, the proportion of all tumors was about 2.92∶1; The top three benign tumors were polymorphous adenoma [73.78% (2 046/2 773)], Warthin tumor [15.80% (438/2 773)] and base cell adenoma [8.37% (232/2 773)]. Polymorphous adenoma took up 54.94% (2 046/3 724) of all tumors. The top three malignant tumors were mucous epidermoid carcinoma [31.44% (299/951)], adenoid cystic carcinoma [26.92% (256/951)] and adenocarcinoma [11.88% (113/951)]. As for sex, male female ratio was 0.83∶1. As for site, the pathogenic site of tumors was mainly in parotid gland [63.75% (2 374/3 724)], followed by palatal gland [16.50% (615/3 724)], then submandibular gland [12.67% (472/3 724)]; As for age, the common age was between 51 and 60 years old [23.74% (884/3 724)], followed by 41 to 50 years old [21.56%(803/3 724)]. Conclusions: The incidence of benign and malignant salivary gland tumor increased in the 56 years. Females showed a higher incidence. The majority tumors occurred in parotid gland. The most common salivary gland tumor was pleomorphic adenoma and the most common malignant tumor was mucous epidermoid carcinoma. The most common age was in 51-60 years old period.

Circular RNA ITCH suppresses proliferation and promotes apoptosis in human epithelial ovarian cancer cells by sponging miR-10a-α.

OBJECTIVE: To explore the effect of Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) on regulating epithelial ovarian cancer (EOC) cells proliferation and apoptosis, as well as its potential target microRNAs (miR) in vitro. MATERIALS AND METHODS: Circ-ITCH mimic, blank mimic, Circ-ITCH inhibitor and blank inhibitor plasmids were transfected into SKOV3 cells. Rescue experiments were carried out by transfecting blank mimic, miR-10a mimic, Circ-ITCH mimic and miR-10a mimic/Circ-ITCH mimic plasmids into SKOV3 cells. Quantitative polymerase chain reaction (qPCR) was performed to detect RNA expression. Cells proliferation was determined by Cell Counting Kit-8 (CCK-8) assay, and cells apoptosis rate was detected using Annexin V (AV) / propidium iodide (PI) assay. RESULTS: Circ-ITCH expression was decreased in Human EOC cell lines SKOV3, A-2780, OVCAR-3 and HO-8910 compared with human normal ovarian epithelial cell line IOSE80, and the most significant reduction of Circ-ITCH expression was presented in SKOV3 cells. Cells proliferation was suppressed by Circ-ITCH mimic transfection and promoted by Circ-ITCH inhibitor transfection in SKOV3 cells. Cells apoptosis was enhanced by Circ-ITCH mimic transfection and inhibited by Circ-ITCH inhibitor transfection in SKOV3 cells. In addition, Circ-ITCH adversely regulated miR-10a expression in SKOV3 cells but not miR-4251 or miR-6505. Rescue experiments were subsequently performed, which exhibited that Circ-ITCH adversely regulated miR-10a expression, whereas miR-10a did not affect Circ-ITCH expression. And most importantly, miR-10a mimic attenuated the effect of Circ-ITCH on reducing proliferation and promoting apoptosis in SKOV3 cells. CONCLUSIONS: Circ-ITCH suppresses cells proliferation and promotes cells apoptosis via sponging miR-10a in EOC cells.

[HIV epidemic among pregnant women in China, 2016: trend and spatial analysis].

Objective: To describe the spatial distribution characteristics of the HIV prevalence among pregnant women in mainland China in 2016, providing scientific evidence for the prevention of mother-to-child transmission of HIV. Methods: Data on pregnant women and those living with HIV in 2016 for all counties in mainland China is from the National Maternal & Child Health Statistics dataset. To obtain robust estimates, 2 964 counties were merged into 344 cities. Spatial autocorrelation analysis and trend analysis were performed based on the city-level dataset to detailedly describe the characteristics of the spatial distribution. Results: A total of 14 879 082 pregnant women were included in the analysis, among whom 5 051 were diagnosed to be infected with HIV, giving an overall prevalence of 34.0 per 100 000 pregnant women. The prevalence was higher in the south than in the north, and decreased from the west (93.5/100 000) to the east(8.6/100 000 ), more specifically, the prevalence in the West region was 11 times as high as that in the East region(χ(trend)(2)=68.61, P<0.01). Stratified analysis by provinces showed that there were 6 provinces whose prevalence was >50.0 per 100 000, and they (Yunnan, Xinjiang, Sichuan, Guangxi, Guizhou and Chongqing) were all located in the West Region; pregnant women in these provinces accounted for 21% of all pregnant women, but the HIV cases accounted for 76% of all cases diagnosed in mainland China. Stratified analysis by cities showed that there were 30 cities whose prevalence was >100.0 per 100 000, and 28 of these cities were also located in the western provinces above. Furthermore, the global Moran's I (0.5, P<0.01) indeed indicated a strong clustered distribution across mainland China; 2 hot spots were observed in the Midwest of Xinjiang, and Yunnan and its bordering areas (Sichuan, Guizhou, Guangxi and Chongqing), while 1 cold spot in the central and east China. The HIV prevalence in the hot spots (183.6/100 000) was 23 times as much as that in the cold spot (8.1/100 000). Conclusion: The overall HIV prevalence for pregnant women who lived in mainland China in 2016 (34.0/100 000) ranked at low-level worldwide, but varied markedly across the whole country with 2 high-prevalence-clustered areas: the Midwest of Xinjiang Uygur Autonomous Region, and Yunnan province along with its bordering areas, indicating comprehensive intervention strategies especially targeted to the areas with high HIV prevalence should be developed.

[Clinical analysis of hemorrhagic cystitis in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation].

Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.

The clinical effects of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty.

OBJECTIVE: We explored the clinical effect of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty. PATIENTS AND METHODS: From March 2012 to October 2015, 100 cases of children patients with central precocious puberty were enrolled in this study. Intramuscular injection of acetic acid triptorelin (50 to 100 pLg/kg) was made once every 4 weeks, and the treatment lasted for 4 months. Patients' bone age/height differentials (DBA/DCA), bone age (BA), growth velocity (GV) and predicted adult height (PAH) were determined before and after treatment (after 6, 12, 24, 36 months). Differences before and after treatment were analyzed. DBA/DCA, BA and PAH values 6, 12, 24, 36 months after treatment were significantly different compared with those before treatment. RESULTS: Sexual development symptoms in children patients were significantly improved 4 months after treatment (p<0.05). All patients completed the treatment, without any adverse drug reaction or severe complication. After one course of treatment (4 months), patients' uterus and ovarian volumes shrank, FSH level peaked, and LH level was reduced, compared to those before treatment. CONCLUSIONS: Acetate acid triptorelin is safe and reliable for treating central precocious puberty. We achieved the excellent clinical curative effect and were able to delay the growth rate in children patients. The predicted height and final height were improved.

[Current status and prospects of integrated traditional Chinese and Western medicine for treatment of portal hypertension].

Portal hypertension refers to a series of clinical manifestations caused by elevated pressure of the portal vein system, which can cause portal hypertension by causing portal venous obstruction and / or increased blood flow. A typical clinical manifestation in patients with decompensated cirrhosis is portal hypertension. A severe complication of portal hypertension is esophagogastric varices bleeding, refractory ascites, and hepatic encephalopathy. The effective reduction of portal pressure can reduce the incidence of complications, improve the prognosis and reduce the mortality. At present, the commonly used clinical methods for reducing portal hypertension include drug therapy, minimally invasive interventions, surgical treatment, and liver transplantation. This article reviews the current status of integrated traditional Chinese and Western medicine for portal hypertension.

[Secular trends of institutional delivery rate in China from 1996 to 2015].

Objective: To describe the secular trends of institutional delivery (ID) rate in China from 1996 to 2015, and to assess the impacts of national health policies on the ID rate. Methods: Data on the number of live births and IDs for districts/counties in 31 provinces of China was annually collected by the Office for National Maternal & Child Health Statistics of China. Information concerning the relevant policies was from official governmental websites, including the programme to reduce maternal mortality and eliminate neonatal tetanus (2000 to 2008), and ID subsidy programme in rural China (2009 to present). According to the programme to reduce maternal mortality and eliminate neonatal tetanus, the calendar years were categorized into three periods: pre-programme period (1996 to 1999), programme implementation period (2000 to 2008) and post-programme period (2009 to 2015). Results: A total of 244 398 010 live births were included in the analysis, in which 211 605 727 were delivered in institutions. During the 20 years, the ID rate steadily increased from 58.7% (6 309 255/10 739 816) in 1996 to 99.7% (13 583 658/13 626 948) in 2015, with a compound annual growth rate of 2.8%. Analyses stratified by economic regions or urban-rural areas showed notably consistent increases in ID rates, and the regional and urban-rural differences became nearly disappeared by 2015. The largest regional difference between East (71.6%, 2 540 896/3 547 423) and West (44.6%, 1 675 305/3 752 873) was 27% in 1996 and <1% in 2015 (East 99.9%[5 177 865/5 180 636]and West 99.0%[3 925 766/3 964 622]). The urban-rural difference was 22.7% in 1996 (urban 73.5%[2 756 531/3 748 703], rural 50.8%[3 552 724/6 991 113]) and 0.4% in 2015(urban 99.9%[6 257 853/6 262 763], rural 99.5%[7 325 805/7 364 185]). During the programme implementation period and the post-programme period, the ID rates in rural area increased faster than those in urban area, and the corresponding compound annual growth rates in rural area were 2.4 and 2.8 times of those in urban area; the ID rates in Middle and West regions increased faster than those in East region, and the corresponding compound annual growth rates in West region were 3.6 and 6.3 times of those in East region. By 2015, the ID rates in all provinces other than Tibet (90.5%[48 445/53 505]) and Qinghai (97.2%[60 836/62 600]) reached or were close to 100%. However, there were still 112 districts/counties with ID rates <96%, of which 39 with ID rates <80%; the 39 districts/counties were all located in four western provinces (Tibet 19, Sichuan 15, Qinghai 3, and Xinjiang 2). Conclusions: During the past 20 years, the ID rate in China has steadily increased and achieved the goal of the year 2020 ahead of schedule; the regional and urban-rural inequality in ID has nearly disappeared. Given universal two-child policy, it is of significance to strengthen existing achievements, focus on complicated pregnancies and comprehensively improve the capability and quality of ID services; meanwhile, it is also of significance to develop particular policies and explore the medical-aid model for the minority-inhabited western regions with lower ID rates.

Simulation Studies of Protein and Small Molecule Interactions and Reaction.

Computational studies of protein and small molecule (protein-ligand/enzyme-substrate) interactions become more and more important in biological science and drug discovery. Computer modeling can provide molecular details of the processes such as conformational change, binding, and transportation of small molecules/proteins, which are not easily to be captured in experiments. In this chapter, we discussed simulation studies of both protein and small molecules from three aspects: conformation sampling, transportations of small molecules in enzymes, and enzymatic reactions involving small molecules. Both methodology developments and examples of simulation studies in this field were presented.

Expression profiles of SMAD1 protein in lung cancer tissues and normal tissues and its effect on lung cancer incidence.

The aim of this study is to detect the expression profiles of SMAD1 protein in lung cancer tissues and normal tissues to investigate its effect on the incidence of lung cancer. The expression profiles of SMAD1 protein in 60 cases of lung cancer tissues (lung cancer group), 25 cases of normal alveolus tissues (alveolus control group) and 29 cases of normal bronchial tissues (bronchial control group) were detected by adopting immunohistochemical analyses, and their relationships with clinicopathologic data were analyzed. The expression of SMAD1 protein in the lung cancer group and the lung squamous cell carcinoma group was significantly lower than that in the alveolus control group and the bronchial control group (P < 0.01). The expression of SMAD1 protein in the lung adenocarcinoma group was significantly lower than that in the alveolus control group and the bronchial control group (P < 0.01); The expression SMAD1 protein showed a significant correlation with lung cancer differentiation and lymphatic metastasis (P < 0.05), but not with genders, ages, tumor sizes and histological types of lung cancer patients (P>0.05).

A flexible, transparent and super-long-life supercapacitor based on ultrafine Co3O4 nanocrystal electrodes.

Flexible and transparent supercapacitors, as advanced energy storage devices, are essential for the development of innovative wearable electronics because of their unique optical and mechanical qualities. However, all previous designs are based on carbon-based nanostructures like carbon nanotubes and graphene, and these devices usually have poor or short cycling lives. Here, we demonstrate a high-performance, flexible, transparent, and super-long-life supercapacitor made from ultrafine Co3O4 nanocrystals synthesized using a novel process involving laser ablation in liquid. The fabricated flexible and transparent pseudocapacitor exhibits a high capacitance of 177 F g(-1) on a mass basis and 6.03 mF cm(-2) based on the area of the active material at a scan rate of 1 mV s(-1), as well as a super-long cycling life with 100% retention rate after 20 000 cycles. An optical transmittance of up to 51% at a wavelength of 550 nm is achieved, and there are not any obvious changes in the specific capacitance after bending from 0° to 150°, even after bending over 100 times. The integrated electrochemical performance of the Co3O4-based supercapacitor is greatly superior to that of the carbon-based ones reported to date. These findings open the door to applications of transition metal oxides as advanced electrode materials in flexible and transparent pseudocapacitors.