Bone morphogenetic protein-2 and pulsed electrical stimulation synergistically promoted osteogenic differentiation on MC-3T3-E1 cells.

Electrical stimulation (ES) plays an important role in regulating cell osteoblast differentiation. As a noninvasive rehabilitation therapy method, Es has a unique role in postoperative recovery. Bone morphogenetic protein-2 (BMP-2) is the most commonly used bioactive molecule in in situ tissue engineering scaffolds, and it plays an important regulatory role in the whole process of bone injury repair. In this study, the osteogenic regulation of MC-3T3-E1 cells was studied by combining pulsed electrical stimulation (PES) and different concentrations of BMP-2. The results showed that PES and BMP-2 could synergically promote the proliferation of MC-3T3-E1 cells. The qPCR results of osteoblast-related genes showed that PES was synergistic with BMP-2 to promote osteoblast differentiation mainly through the regulation of the Smad/BMP and insulin like growth factor 1 (IGF1) signaling pathways. The expression level of alkaline phosphatase (ALP) and alizarin red staining further demonstrated the synergistic effect of PES and BMP-2 on promoting osteogenic differentiation and mineralization of cells. PES and BMP-2 could also synergically promote cell proliferation, expression of collagen I (COL-I) and ALP, and cell mineralization on the 3D-printed polylactic acid scaffold. These results suggest that the use of PES can enhance the osteogenic effect of in situ bone repair scaffolds containing BMP-2, reduce the dose of BMP-2 alone, and reduce the possible side effects of high-dose BMP-2 in vivo.

100Gb/s coherent optical secure communication over 1000†km based on analog-digital hybrid chaos.

In recent years, the transmission capacity of chaotic secure communications has been greatly expanded by combining coherent detection and multi-dimensional multiplexing. However, demonstrations over 1000 km fiber are yet to be further explored. In this paper, we propose a coherent optical secure transmission system based on analog-digital hybrid chaos. By introducing an analog-digital converter (ADC) and a bit extraction into the feedback loop of entropy source, the broadband analog chaos is converted into a binary digital signal. This binary digital signal is then mapped to a 65536-level pulse amplitude modulation (PAM) signal and injected into the semiconductor laser (SL) to regenerate the analog chaos, forming a closed loop. The binary digital signal from the chaos source and the encrypted signal are transmitted via wavelength division multiplexing (WDM). By using conventional digital signal processing (DSP) algorithms and neural networks for post-compensation, long-haul high-quality chaotic synchronization and high-performance secure communication are achieved. In addition, the probability density distribution of the analog chaotic signal is effectively improved by adopting the additional higher-order mapping operation in the digital part of the chaos source. The proof-of-concept experimental results show that our proposed scheme can support the secure transmission of 100 Gb/s quadrature phase shift keying (QPSK) signals over 1000 km of standard single-mode fiber (SSMF). The decrypted bit error rate (BER) reaches 9.88 × 10-4, which is well below the 7% forward error correction (FEC) threshold (BER = 3.8 × 10-3). This research provides a potential solution for high-capacity long-haul chaotic optical communications and fills the gap in secure communications based on analog-digital hybrid chaos.

DAC/ADC-free 4 × 12.9 Gbit/s 65,536-level quantum noise stream cipher secure optical WDM transmission based on delta-sigma modulation.

We propose and experimentally study a novel, to the best of our knowledge, quantum noise stream cipher (QNSC) secure transmission scheme based on the delta-sigma modulation (DSM) technique. The cooperation of the QNSC and DSM mechanisms makes it possible to transmit an ultrahigh-order encrypted signal in the non-return-to-zero (NRZ) on-off keying (OOK) format. The delivery of the NRZ OOK waveform over the fiber link allows us to send and receive signals using digital ports, instead of high-speed and high-resolution digital-to-analog converters (DACs) and analog-to-digital converters (ADCs) in conventional QNSC systems. Meanwhile, clock synchronization can be achieved by using a simple clock data recovery algorithm. The extra clock signal transmission link in conventional QNSC systems is no longer needed. The proposed scheme is also compatible with wavelength division multiplexing (WDM) systems. In this work, 4 × 12.9 Gbit/s plaintext is encrypted to a 65,536-level QNSC signal and then transmitted over a 10-km standard single-mode fiber. The transmitter and receiver are established by commercial 100G QSFP28 optical modules with clock data recovery. This proposed scheme can be easily deployed in commercial systems due to its minimalist implementation architecture and relatively low hardware cost.

60 Gb/s coherent optical secure communication over 100†km with hybrid chaotic encryption using one dual-polarization IQ modulator.

We propose and experimentally study a coherent optical secure transmission system based on one dual-polarization in-phase and quadrature modulator (IQM). One beam of the polarized light is used to generate broadband chaos by configuring a nonlinear opto-electronic oscillator while the other beam carries the encrypted signal. The encrypted signal is obtained through sequential encryption of the analog and digital chaos. The mutual mask of the hybrid chaotic signals can effectively enhance the security performance. Moreover, by varying the encryption depth of analog and digital vectors, the transmission performance can be flexibly adjusted. A commercial dual-polarization IQM could simultaneously generate a chaotic signal and a load message, which provides a high-integration solution. A fast independent component analysis (ICA) algorithm is adopted to compensate for the rotation of state of polarization (RSOP). 60 Gb/s encrypted quadrature phase shift keying (QPSK) signal transmission over 100 km single-mode fiber is realized, and the decrypted bit error rate (BER) performance is below the 7% forward error correction (FEC) threshold (BER = 3.8 × 10-3).

Capacity expansion of chaotic secure transmission system based on coherent optical detection and space division multiplexing over multi-core fiber.

We propose and experimentally study a coherent optical chaotic secure transmission system through a multi-core fiber (MCF). The messages are encrypted by the chaotic carrier and transmitted through the outer cores of the MCF, whereas the chaotic carrier signal is concealed by transmitting through the center core. The MCF provides large transmission capacity expansion and security enhancement against eavesdroppers due to its physical structure. In addition, the designed optical chaos self-homodyne coherent detection strategy has high detection sensitivity and simple physical structure. Due to the prevalence of devices and digital signal processing (DSP) algorithms used in this system, it can be well compatible with a commercial coherent optical communication system. Error free 40 Gb/s/core encrypted 16 quadrature amplitude modulation (QAM) signal transmission over 10 km 7-core fiber is achieved, and 20 Gb/s quadrature phase shift keying (QPSK) signal transmission over a 100 km standard single-mode fiber (SSMF) is demonstrated to verify the long-distance transmission capability. The sensitivity to the secret key is also studied.

Prenatal caffeine exposure caused H-type blood vessel-related long bone dysplasia via miR375/CTGF signaling.

Caffeine has developmental toxicity. Prenatal caffeine exposure (PCE) caused intrauterine growth retardation (IUGR) and multiple organ dysplasia. This study intended to explore the effect and mechanism of PCE on long bone development in female fetal rats. In vivo, the PCE group pregnant rats were given different concentrations of caffeine during the gestational Day 9-20. The mRNA expression of osteogenesis-related genes were significantly reduced in PCE group. In the PCE group (120 mg/kg·d), the length and primary center of fetal femur were shorter, and accompanied by H-type blood vessel abundance reducing. Meanwhile, connective tissue growth factor (CTGF) expression decreased in the growth plate of the PCE group (120 mg/kg·d). In contrast, the miR375 expression increased. In vitro, caffeine decreased CTGF and increased miR375 expression in fetal growth plate chondrocytes. After co-culture with caffeine-treated chondrocytes, the tube formation ability for the H-type endothelial cells was decreased. Furthermore, CTGF overexpression or miR375 inhibitor reversed caffeine-induced reduction of tube formation ability, and miR375 inhibitor reversed caffeine-induced CTGF expression inhibition. In summary, PCE decreased the expression of CTGF by miR375, ultimately resulting in H-type blood vessel-related long bone dysplasia.

Analog-digital hybrid chaos-based long-haul coherent optical secure communication.

We propose and numerically investigate a chaotic optical coherent secure communication scheme, which supports long-haul secure transmission for signals in advanced modulation formats. A hybrid optical chaos system is designed with coordination of digital and analog signals. The hybrid entropy source provides a broadband analog optical chaos signal, which could serve as the carrier to load quadrature amplitude modulation (QAM) data. Simultaneously, a digital binary signal generated from the entropy source is transmitted to establish long-haul chaotic synchronization. Coherent detection is utilized at the receiver, and a digital signal processing (DSP) algorithm is adopted to reduce transmission distortion. A 5 Gbaud 16QAM signal is encrypted by a phase chaos carrier with the effective bandwidth of 5.8 GHz. A bit error rate (BER) below forward error correction (FEC) can be achieved after transmitting over 1600 km based on digital-signal-induced chaos synchronization technology. Optimal launch power is investigated to minimize nonlinear effects of transmission links. System security is guaranteed by the high dynamical complexity of the chaotic source and the sensitive time delay as the secret key.

Experimental demonstration of a broadband optoelectronic chaos system based on highly nonlinear configuration of IQ modulator.

We experimentally investigated a novel broadband optoelectronic chaos generation scheme. The proposed system is achieved by adopting the highly nonlinear operation of an electro-optical exclusive-NOR (XNOR) logic gate and two delayed feedback loops that refer to the Boolean chaos model. The XNOR gate is established by a commercial use inphase and quadrature-phase (IQ) modulator that works at a specific bias point. The resulting power spectrum of the broadband chaos signal extends from DC to 29.1 GHz (10 dB bandwidth), and the probability density distribution is Gaussian distribution like. Owing to the strong nonlinearity of XNOR operation, the conditions to enter the chaos region are more relaxed compared to traditional optoelectronic oscillator (OEO) chaos systems, and the time delay signature (TDS) of the feedback loop is also suppressed. Moreover, to further enhance the performance of the generated chaos signal, we injected the optoelectronic chaotic signal into a semiconductor laser. Experimental results indicate that after the cascade optical injection, the bandwidth of the output chaos signal is extended to 38.4 GHz and the TDS is completely concealed; meanwhile, a perfect Gaussian distribution can be obtained.

Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats.

Epidemiologic studies showed that low birth weight is associated with high cholesterol and an increased risk of cardiovascular diseases in adulthood. This study aimed to elucidate the intrauterine programming mechanisms of adult hypercholesterolemia. The results showed that prenatal nicotine exposure (PNE) caused intrauterine growth retardation and hypercholesterolemia in male adult offspring rats. Hepatic cholesterol synthesis and output were deceased in utero but increased in adults; hepatic reverse cholesterol transport (RCT) persistently deceased before and after birth. Meanwhile, PNE elevated serum corticosterone level and decreased hepatic IGF1 pathway activity in male fetuses, whereas converse changes were observed in male adults. The chronic stress model and cortisol-treated HepG2 cells verified that excessive glucocorticoid (GC)-induced GC-IGF1 axis programming enhanced hepatic cholesterol synthesis and output. In addition, PNE decreased the expression of specific protein 1 and P300 enrichment and H3K27 acetylation at the promoter region of genes responsible for RCT both in fetal and adult, male livers and reduced expression of those genes, similar alterations were also confirmed in cortisol-treated HepG2 cells, suggesting that excessive GC-related programming induced continuous RCT reduction by epigenetic modification. Taken together, the "2-programming" approach discussed above may ultimately contribute to the development of hypercholesterolemia in male adult offspring.-Zhou, J., Zhu, C., Luo, H., Shen, L., Gong, J., Wu, Y., Magdalou, J., Chen, L., Guo, Y., Wang, H. Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats.

RNA-Seq analysis of potential lncRNAs and genes for the anti-renal fibrotic effect of norcantharidin.

BACKGROUND: As a common phenotype in chronic kidney disease, renal interstitial fibrosis has been largely studied. Norcantharidin (NCTD), a derivative of naturally occurring cantharidin, has an anti-renal fibrotic effect. However, its underlying mechanisms of the protective role remain largely unknown. Long noncoding RNAs (lncRNAs) play vital parts in tissue homeostasis modulation under pathophysiological conditions. In this study, we discovered the underlying lncRNAs and genes, which may contribute to the anti-renal fibrotic effects of NCTD. METHODS: RNA-seq analysis was performed to evaluate profiling of lncRNAs and messenger RNAs (mRNAs) in kidney tissues of sham-control, and unilateral ureteral obstruction (UUO) mouse models with or without NCTD treatment. Systematic bioinformatic analysis of expression levels was used in lncRNAs and mRNAs of NCTD-treated UUO kidneys. Altered expression of lncRNAs and mRNAs levels was confirmed by quantitative real-time polymerase chain reaction analysis. RESULTS: 467 lncRNAs and 1502 mRNAs were differentially expressed between UUO- and sham-operated kidneys, and notably, these alterations in UUO-operated kidney were partially reversed following NCTD treatment. Interestingly, the up-regulation of lncRNA Gm16076, Gm26669, and down-regulation of Fam120aos were highly correlated with the up-regulation of mRNA levels of fibrosis-related gene ITGB1, STAT3 and reduction of Pink1 in UUO kidney, respectively. CONCLUSIONS: The result suggested lncRNAs-regulated genes may contribute to the anti-renal fibrotic effect under NCTD treatment, and thus targeting lncRNAs-controlled genes and their related molecular signaling pathways may serve as a promising therapeutic target in renal fibrosis treatment.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

Prenatal nicotine exposure intergenerationally programs imperfect articular cartilage via histone deacetylation through maternal lineage.

Accumulating evidence has shown that the impact of prenatal environmental factors on the organs of the offspring could last until the adulthood. Here, we aimed to investigate these effects and the potential mechanism of prenatal nicotine exposure (PNE) on the female adult cartilage of the first generation (PNE-F1) and the second generation (PNE-F2). Pregnant Wistar rats were injected with 2.0 mg/kg.d nicotine from gestational day (GD) 9 to 20. Then their F1 generation at GD20 and postnatal week (PW) 12, and F2 generation at PW12 were harvested. The expression of extracellular matrix (ECM) and transforming growth factor ß (TGFß) signaling genes were analyzed by real-time quantitative PCR, and the histone acetylation was examined by chromatin immunoprecipitation assay. The results showed that PNE reduced the ECM and TGFß signaling gene expressions in both PNE-F1 and PNE-F2 female adult articular cartilage. In the F1 generation, PNE inhibited the acetylation at H3K9 of TGFß, TGFß receptor 1 (TGFßR1), SRY-type high mobility group box 9 (SOX9), a1 chain of type II collagen (COL2A1) and aggrecan (ACAN) gene promoters at both GD20 and PW12. In PNE-F2 at PW12, the obvious deacetylation at H3K9 of the TGFßR1 and COL2A1 promoters still existed. Moreover, in rat fetal chondrocytes, corticosterone rather than nicotine directly induced the hypoacetylation of H3K9 of TGFßR1 and COL2A1 genes, which might be the main cause of imperfect cartilage for PNE-F2. This study may be helpful to elucidate the developmental variability of articular cartilage quality and useful for the early prevention of articular damage.

Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats.

BACKGROUND/AIMS: Prenatal ethanol exposure (PEE) could induce intrauterine programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolism, resulting in intrauterine growth retardation and susceptibility to adult hypercholesterolemia in offspring. This study aimed to analyse the effects and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the occurrence of adult hypercholesterolemia in offspring rats. METHODS: Wistar female rats were treated with ethanol (4 g/kg.d) at gestational days 11-20. The offspring were given a normal diet or HFD after weaning, and the blood cholesterol metabolism phenotype and expression of hepatic cholesterol metabolism related genes were detected in 24-week-old offspring. Furthermore, the interactions among PEE, HFD, and gender on hypercholesterolemia occurrence were analysed. RESULTS: PEE increased the serum total cholesterol (TCH) and low-density lipoprotein-cholesterol (LDL-C) levels and decreased the serum high-density lipoprotein-cholesterol (HDL-C) level in adult offspring rats; the changes in female offspring were greater than those in males. At the same time, the mRNA expression levels of hepatic cholesterol metabolic enzymes (apolipoprotein B (ApoB) and 7α-hydroxylase (CYP7A1))-were increased, while the mRNA expression levels of the scavenger receptor B1 (SR-B1) and LDL receptor (LDLR) were decreased. Furthermore, a three-way ANOVA showed there were interactions among PEE, post-weaning HFD and gender. For PEE offspring, a post-weaning HFD aggravated the elevated hepatic ApoB and CYP7A1 expression and reduced SR-B1 and LDLR expression; the changes in hepatic SR-B1 and CYP7A1 expression were greater in female HFD rats than in males. CONCLUSION: Our findings suggest that a post-weaning HFD could aggravate offspring hypercholesterolemia caused by PEE and that this mechanism might be associated with hepatic cholesterol metabolic disorders that are aggravated by a post-weaning HFD; hepatic cholesterol metabolism was more sensitive to neuroendocrine metabolic alterations by PEE and a post-weaning HFD in the female offspring than in the male offspring.

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism.

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30-120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8-20 µM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta.

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet.

Prenatal caffeine exposure (PCE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts.

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats.

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2.

Optimizing lower limb rehabilitation: the intersection of machine learning and rehabilitative robotics.

Lower limb rehabilitation is essential for recovery post-injury, stroke, or surgery, improving functional mobility and quality of life. Traditional therapy, dependent on therapists' expertise, faces challenges that are addressed by rehabilitation robotics. In the domain of lower limb rehabilitation, machine learning is progressively manifesting its capabilities in high personalization and data-driven approaches, gradually transforming methods of optimizing treatment protocols and predicting rehabilitation outcomes. However, this evolution faces obstacles, including model interpretability, economic hurdles, and regulatory constraints. This review explores the synergy between machine learning and robotic-assisted lower limb rehabilitation, summarizing scientific literature and highlighting various models, data, and domains. Challenges are critically addressed, and future directions proposed for more effective clinical integration. Emphasis is placed on upcoming applications such as Virtual Reality and the potential of deep learning in refining rehabilitation training. This examination aims to provide insights into the evolving landscape, spotlighting the potential of machine learning in rehabilitation robotics and encouraging balanced exploration of current challenges and future opportunities.

The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA). Method: The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022. Results: A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral vs. intravenous routes), 78 in the paracetamol group (oral vs. intravenous routes), and 72 in the ibuprofen group (rectal vs. oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; P < 0.0001, I2 = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; P = 0.71, I2 = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy. Conclusion: This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.

Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient: a case report and review of the literature.

Rhabdomyosarcoma of the prostate is a rare mesenchymal tumor that originates from undifferentiated mesenchymal cells. Spindle cell rhabdomyosarcoma is a variant of embryonal rhabdomyosarcoma. The vast majority of these two pathological types occur in children, with only a few adult cases reported to date, and both are associated with poor clinical outcomes. We herein report a case involving a man in his early 40s with spindle cell embryonal rhabdomyosarcoma of the prostate. His chief complaint was difficult urination. The diagnosis was confirmed by puncture biopsy of the prostate, and pelvic lymph node metastasis was already present at the time of diagnosis. The patient underwent three courses of chemotherapy. However, his response to the treatment was very poor, and he died of the disease 4 months after diagnosis.