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Abstract: Nondopaminergic neurotransmitters such as adenosine, norepinephrine, serotonin, glutamate, and acetylcholine are all involved in Parkinson's disease (PD) and promote its symptoms. Therefore, nondopaminergic receptors are key targets for developing novel preparations for the management of motor and non-motor symptoms in PD, without the potential adverse events of dopamine replacement therapy. We reviewed English-written articles and ongoing clinical trials of nondopaminergic treatments for PD patients till 2014 to summarize the recent findings on nondopaminergic preparations for the treatment of PD patients. The most promising research area of nondopaminergic targets is to reduce motor complications caused by traditional dopamine replacement therapy, including motor fluctuations and levodopa-induced dyskinesia. Istradefylline, Safinamide, and Zonisamide were licensed for the management of motor fluctuations in PD patients, while novel serotonergic and glutamatergic agents to improve motor fluctuations are still under research. Sustained- release agents of Amantadine were approved for treating levodopa induced dyskinesia (LID), and serotonin 5HT1B receptor agonist also showed clinical benefits to LID. Nondopaminergic targets were also being explored for the treatment of non-motor symptoms of PD. Pimavanserin was approved globally for the management of hallucinations and delusions related to PD psychosis. Istradefylline revealed beneficial effect on daytime sleepiness, apathy, depression, and lower urinary tract symptoms in PD subjects. Droxidopa may benefit orthostatic hypotension in PD patients. Safinamide and Zonisamide also showed clinical efficacy on certain non-motor symptoms of PD patients. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs may lead to new approaches with positive clinical implications.

Renal ischemia-reperfusion (RIR)-induced acute kidney injury (AKI) is a common renal functional disorder with a high morbidity and mortality rate. Stimulator of interferon genes (STING) is the cytosolic DNA-activated signaling pathway responsible for mediating inflammation and injury. Extracellular cold-inducible RNA-binding protein (eCIRP) activates STING and exacerbates hemorrhagic shock. H151, a novel STING inhibitor, attenuated eCIRP-induced STING activation in vitro and inhibited RIR-induced AKI. H151 shows promise as a therapeutic intervention for RIR-induced AKI.

Changdong Wu,* Ping Wang,* Bin Wang, Muyesai Nijiati, Ming Hou Xinjiang Emergency Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Hou, Xinjiang Emergency Center, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91, Tian-chi Road, Tianshan District, Urumqi, 830001, People’s Republic of China, Tel +86-9918563596, Email houming199@sina.comPurpose: To investigate the optimal target temperature of cooling intervention in heat stroke (HS) rats and explore the potential mechanisms of cooling intervention in alleviating heat stroke-induced damage.Materials and Methods: A total of 32 Sprague-Dawley rats were randomly divided into 4 groups (n=8/group), including control, HS[core body temperature (Tc)], HS(Tc-1°C) and HS(Tc+1°C) group. Heat stroke model was established in rats of HS(Tc), HS(Tc-1°C) and HS(Tc+1°C) group. Rats in HS(Tc) group were cooled to baseline core body temperature after establishing heat stroke model, HS(Tc-1°C) group to baseline core body temperature minus 1°C and HS(Tc+1°C) group to baseline core body temperature plus 1°C. We compared the histopathological changes of lung, liver and renal tissue, as well as cell apoptosis and expression of critical proteins in phosphatidylinositol 3´-kinase (PI3K)/Akt signaling pathway.Results: Heat stroke caused the histopathological damage and cell apoptosis of lung, liver and renal tissue, which could be alleviated by cooling intervention to a certain extent. Notably, HS(Tc+1°C) group demonstrated a better effect on alleviating cell apoptosis although the differences were not significant. Heat stroke lead to the elevated expression of p-Akt, which subsequently induced the elevated expression of Caspase-3 and Bax, as well as the decreased expression of Bcl-2. Cooling intervention could reverse this trend. Notably, the expression level of Bax in lung tissue of HS(Tc+1°C) group was significantly lower than that of HS(Tc) and HS(Tc-1°C) group.Conclusion: The mechanisms of cooling intervention in alleviating heat stroke-induced damage were associated with the expression changes of p-Akt, Caspase-3, Bax and Bcl-2. The better effect of Tc+1°C might be associated with low expression of Bax.Keywords: heat stroke, cooling intervention, target temperature, histopathological damage, cell apoptosis, PI3K/Akt signaling pathway

OBJECTIVE Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage. METHODS In total, 222 consecutive patients who underwent endoscopic evacuation between July 2019 and April 2022 at four neurosurgical centers were enrolled prospectively. Patients were dichotomized into functionally independent (mRS score ≤ 3) and functionally dependent (mRS score ≥ 4) groups. Hematoma and perihematomal edema (PHE) volumes were calculated using 3D Slicer software. Predictors of functional dependence were assessed using logistic regression models. RESULTS Among the enrolled patients, the functional dependence rate was 45.50%. Factors independently associated with long-term functional dependence included female sex, older age (≥ 60 years), Glasgow Coma Scale score ≤ 8, larger preoperative hematoma volume (OR 1.02), and larger postoperative PHE volume (OR 1.03, 95% CI 1.01–1.05). A subsequent analysis evaluated the effect of stratified postoperative PHE volume on functional dependence. Specifically, patients with large (≥ 50 to < 75 ml) and extra-large (≥ 75 to 100 ml) postoperative PHE volumes had 4.61 (95% CI 0.99–21.53) and 6.75 (95% CI 1.20–37.85) times greater likelihood of long-term dependence, respectively, than patients with a small postoperative PHE volume (≥ 10 to < 25 ml). CONCLUSIONS A large postoperative PHE volume is an independent risk factor for functional dependence among basal ganglia hemorrhage patients after endoscopic evacuation, especially with postoperative PHE volume ≥ 50 ml.

Background: Positioning accuracy is the most important index of the reconnaissance positioning system. Positioning accuracy involves many factors, such as the position, attitude and motion state of the flight platform, the pointing accuracy of the stable platform, and various coordinate transformations. A reasonable fusion strategy can guarantee stable positioning accuracy, so it is very important to study the precise fusion of machine vision, 3D geographic data and UAV airborne positioning information to realize the optimal combination of positioning data and complete the accurate and rapid positioning of the ground target. Methods: In this paper, a location model based on stereo vision and spatial information fusion method is proposed. It fully integrates visual information, satellite positioning information and spatial geographic information, greatly improves positioning accuracy, and through a real-time processing algorithm, significantly improves real-time positioning. Results: Through the related experiments, positioning accuracy and real-time ability of positioning could reach about three meters. Conclusion: The proposed real-time and high-precision positioning method of the ground target through UAV stereo vision and spatial information fusion is proposed showing significant improvement compared to other traditional methods.

Objectives: To explore the immediate and retention effect of real-time tibial acceleration feedback on running biomechanics during gait retraining. Methods: Five electronic databases were searched to identify relevant studies published before May 2022. The included studies were evaluated for methodological quality and bias risk, and data were extracted. A meta-analysis was conducted on the primary outcomes, including peak tibial acceleration (PTA) and vertical ground reaction force. Subgroup analysis was performed by gender, feedback criterion, mode, dosage, fading, retention period, and running environment to evaluate the source of heterogeneity. Qualitative analysis was performed to describe other variables. Results: Fourteen studies (174 participants) were eligible. Meta-analysis showed that real-time tibial acceleration feedback reduced PTA (P P P = .004, P P P P P P = .005) and fading feedback (P = .005) conditions, and the retention effect of PTA was more noticeable with high feedback dosage (P P Conclusions: Real-time tibial acceleration feedback can reduce PTA and vertical ground reaction force during gait retraining, and for periods of 5 minutes to 12 months when the feedback is removed.

To characterize pathoetiologic associations of heritable thrombophilia-hypofibrinolysis with idiopathic (primary) multifocal osteonecrosis (ON) (≥3 ON anatomic sites), we prospectively studied 28 women and 12 men with primary multifocal ON compared with 27 women and 24 men with primary nonmultifocal ON (P =.002), G20210A prothrombin gene heterozygosity (6 of 40 [15%] vs 3 of 110 [3%], P =.011), and high (>150%) Factor VIII (8 of 40 [20%] vs 7 of 103 [7%], P =.031). These case-control familial coagulation differences paralleled those in 51 concurrently evaluated cases with primary nonmulti-focal ON, 7 of 51 (14%) of whom had Factor V Leiden heterozygosity vs 2% of controls ( P =.005) and 14 of 44 (32%) of whom had high Factor VIII vs 7 of 103 (7%) of controls ( P =.0002). Recognition of familial thrombophilia as a common pathoetiology of primary multifocal ON provides an opportunity for early anticoagulation (before joint collapse), allowing both prophylaxis and therapy aimed at relieving pain and slowing or stopping progression of the disease to joint collapse. [ Orthopedics . 2023;46(3):164–168.]

Aminophylline use and the association between clinical outcomes and therapy timing have been less investigated. The objective of this study was to determine the efficacy of early aminophylline use (within the first two days of life) in premature infants.A retrospective observational cohort of infants weighing1500 g and30 weeks of gestational age at Kaohsiung Veterans General Hospital received aminophylline either within the first two days of life (EA, early aminophylline group), after the third day of life (LA, late aminophylline group), or without aminophylline during the first month of life (WA, without aminophylline group). Demographic data and neonatal clinical outcomes were compared among the three groups.This study included 89 preterm infants (EA = 33, LA = 38, WA = 18). The EA group had a lower incidence of bronchopulmonary dysplasia (BPD) than the WA group (adjusted odds ratio [aOR] = 8.86(1.56-59.32); P = 0.024). Although there was no significant difference in BPD incidence between the EA and LA groups (aOR = 2.66(0.51-13.81), P = 0.244), a trend remained. Birth body weight less than 1000 g was also a significant risk factor for BPD (aOR = 8.86(1.32-47.41), P = 0.014). The duration of mechanical ventilation was shorter in the infants in the EA group compared to the WA group (estimated beta = -11.344(-19.57-3.12); P = 0.008).Early aminophylline administration may be associated with a decreased incidence of BPD in preterm infants. However, the clinical benefits of aminophylline treatment require further investigation. In addition, a birth body weight of less than 1000 g was a crucial risk factor for BPD.

In recent years, contrastive learning has been very successful in unsupervised tasks of representation learning and has received a lot of attention in supervised tasks. In supervised tasks, the discrete nature of natural language makes the construction of sample pairs difficult and the models are poorly robust to adversarial samples, so it remains a challenge to make contrastive learning effective for text classification tasks and to guarantee the robustness of the models. This paper presents a contrastive adversarial learning framework built using data augmentation with labeled insertion data. Specifically,By adding perturbation to the word-embedding matrix, adversarial samples are generated as positive examples of contrastive learning, and external semantic information is introduced to construct negative examples. Contrastive learning is used to improve the sensitivity and generalization ability of the model, and adversarial training is used to improve robustness, thereby improving the classification accuracy. In addition, the momentum contrast from unsupervised tasks is also introduced into the text classification task to increase the number of sample pairs. Experimental results on several datasets show that the proposed approach outperforms the baseline comparison approach, and in addition some experiments are conducted to verify the effectiveness of the proposed framework under low-resource conditions.

Ideological and Political Education in Curriculum is a new requirement to strengthen the ideological and political education in colleges and universities in the new era and is important for cultivating people with morality. In recent years, it has been gradually implemented in colleges and universities, but there are still some problems in practice especially in the specialized courses in engineering. A practical path of Ideological and Political Education in Curriculum for specialized courses is promoted in this paper and is then illustrated by the case of “Operating System”.

Toll-gates are crucial points of management and key congestion bottleneck for the freeway. In order to avoid traffic deterioration and alleviate traffic congestion in advance, it is necessary to predict and evaluate the congestion in toll-gates scattering in large-scale region of freeway network. In this paper, traffic volume and operational delay time are selected from various traffic indicators to evaluate congestion considering the particular characteristics of the traffic flow within the toll-gate area. The congestion prediction method is designed including two modules: a deep learning (DL) prediction and a fuzzy evaluation. We propose a modified deep learning method based on graph convolutional network (GCN) structure in the fusion of dilated causal mechanism and optimize the method for spatial feature extraction by constructing a new adjacency matrix. This new AI network could process spatiotemporal information of traffic volume and operational delay time, that extracted from large-scaled toll-gates spontaneously, and predict key indicators in 15/30/60 min future time. The evaluation module is proposed based on these predicted results. Then, fuzzy C-means algorithm (FCM) is further modified by determining coupling weight for these two key indicators to detect congestion state. Original traffic data are obtained from the current 186 toll-gates served on the freeway network in Shaanxi Province, China. Experimental tests are carried out based on historical data of four months after preprogressing. The comparative tests show the proposed CPT-DF (congestion prediction on toll-gates using deep learning and fuzzy evaluation) outperforms the current-used other models by 6-15%. The successful prediction could extend to the real-time prediction and early warning of traffic congestion in the toll system to improve the intelligent level of traffic emergency management and guidance on the key road of disasters to some extent.

Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibiotics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users compared to non-users. Further experiments showed that macrolides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibiotic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.