Factors affecting the intraoperative calculi excretion during flexible ureteroscopy lithotripsy: an in vitro analysis.

OBJECTIVE: To explore the parameters influencing intraoperative calculi excretion (ICE) during flexible ureteroscopy lithotripsy (fURL) using in vitro simulation experiments. METHODS: 3D-printed human kidney models were used to simulate the elimination of gravel during fURL. The factors influencing the ICE during fURL were analyzed by comparing the effects of different degrees of hydronephrosis (mild, moderate, and severe), surgical positions (supine and lateral position), ratios of endoscope-sheath diameter (RESD) (0.625, 0.725, and 0.825), gravel sizes (0.50-1.00 mm, 0.25-0.50 mm, and 0.10-0.25 mm), and ureteral access sheaths (UASs) (traditional UAS and negative-pressure UAS) on ICE. RESULTS: The impacts of various UAS, RESD, degree of hydronephrosis, surgical positions, and gravel sizes on ICE were all significant (p < 0.05). We found no evidence of multicollinearity for all the independent variables, and the linear regression equation fitted as ICE ( g / min ) = 0.102 + 0.083 ∗ UAS grade - 0.050 ∗ RESD grade - 0.048 ∗ hydronephrosis grade + 0.065 ∗ position grade - 0.027 ∗ gravel size grade (R2 = 0.569). CONCLUSION: Employing negative-pressure UAS, smaller RESD, milder hydronephrosis, lateral position, and smaller gravel size contribute to improved ICE during fURL. Among them, the adoption of negative-pressure UAS had the most substantial effects.

The optimal ratio of endoscope-sheath diameter with negative-pressure ureteral access sheath: an in vitro research.

PURPOSE: To maintain safe intrarenal pelvic pressure (IPP), the combination of flexible ureteroscope (fURS) and traditional ureteral access sheath (T-UAS) should maintain a basic rule that is the ratio of endoscope-sheath diameter (RESD) ≤ 0.75. However, the negative-pressure ureteral access sheath (NP-UAS) may break the rule of negative pressure suction. This study aimed to examine the effect of NP-UAS on IPP and flow rate (FR) with varying RESD. METHODS: In a 3D-printed renal model, flexible ureteroscopy lithotripsy (fURL) was replicated. Six sizes of fURS paired with 12Fr T-UAS and NP-UAS resulted in six distinct RESDs of 0.63, 0.78, 0.87, 0.89, 0.90, and 0.91. While the irrigation pressure (IRP) was set between 100 and 800 cmH2O and the sucking pressure (SP) was set between 0 and 800 cmH2O, the IPP and FR were measured in each RESD. RESULTS: NP-UASs can reduce the IPP and increase the FR at the same RESD compared to T-UASs. The IPP decreased with increasing SP with NP-UAS. When RESD ≤ 0.78, T-UAS and NP-UAS can maintain IPP < 40 cmH2O in most circumstances. When RESD = 0.87, it is challenging for T-UAS to sustain IPP < 40 cmH2O; however, NP-UAS can do so. When RESD ≥ 0.89, it is difficult to maintain an IPP < 40 cmH2O even with NP-UAS. CONCLUSION: NP-UAS can decrease IPP and increase FR compared with T-UAS. To maintain a safe IPP, it is recommended that RESD < 0.85 when utilizing NP-UAS.

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice.

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

The Influence of Donor/Acceptor Interfaces on Organic Solar Cells Efficiency and Stability Revealed through Theoretical Calculations and Morphology Characterizations.

End-groups halogenation strategies, generally refers to fluorination and chlorination, have been confirmed as simple and efficient methods to regulate the photoelectric performance of non-fullerene acceptors (NFAs), but a controversy over which one is better has existed for a long time. Here, two novel NFAs, C9N3-4F and C9N3-4Cl, featured with different end-groups were successfully synthesized and blended with two renowned donors, D18 and PM6, featured with different electron-withdrawing units. Detailed theoretical calculations and morphology characterizations of the interface structures indicate NFAs based on different end-groups possess different binding energy and miscibility with donors, which shows an obvious influence on phase-separation morphology, charge transport behavior and device performance. After verified by other three pairs of reported NFAs, a universal conclusion obtained as the devices based on D18 with fluorination-end-groups-based NFAs and PM6 with chlorination-end-groups-based NFAs generally show excellent efficiencies, high fill factors and stability. Finally, the devices based on D18: C9N3-4F and PM6: C9N3-4Cl yield outstanding efficiency of 18.53 % and 18.00 %, respectively. Suitably selecting donor and regulating donor/acceptor interface can accurately present the photoelectric conversion ability of a novel NFAs, which points out the way for further molecular design and selection for high-performance and stable organic solar cells.

Manipulating the Spin State of Spinel Octahedral Sites via a π-π Type Orbital Coupling to Boost Water Oxidation.

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7% via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

Airway Stents from Now to the Future: A Narrative Review.

Airway stent insertion is important for patients with airway stenosis. Currently, the most widely used airway stents in clinical procedures are silicone and metallic stents, which offer patients effective treatment. However, these stents composed of permanent materials need to be removed, subjecting patients to invasive manipulation once more. As a result, there is a growing demand for biodegradable airway stents. Biodegradable materials for airway stents are now available in two types: biodegradable polymers and biodegradable alloys. Polymers that include poly (l-lactic acid), poly (D, l-lactide-co-glycolide), polycaprolactone, and polydioxanone are the ultimate metabolites which are generally carbon dioxide and water. Magnesium alloys are the most often utilized metal biodegradable materials for airway stents. The stent's mechanical properties and rate of degradation vary as a result of the different materials, cutting techniques, and structural configurations. We summarized the information above from recent studies on biodegradable airway stents conducted in both animals and humans. There is great potential for clinical applications for biodegradable airway stents. They avoid damage to the trachea during removal and reduce complications to some extent. However, several significant technical difficulties slow down the development of biodegradable airway stents. The efficacy and safety of different biodegradable airway stents still need to be investigated and proved.

Rapid Determination of Bucinnazine in Blood by UPLC-MS/MS.

OBJECTIVES: To establish a rapid method for the analysis of bucinnazine in blood by UPLC-MS/MS and to apply the method to the practical case. METHODS: After the internal standard was added to blood, the protein was precipitated with 900 µL mixed solution (Vacetonitrile∶Vwater=8∶2). After vortex and centrifugation, the protein was measured through 0.22 µm filter membrane. The separation was performed on C18 chromatography column, with acetonitrile and 5 mmol/L ammonium acetate containing 0.1% formic acid aqueous as mobile phase gradient elution at the flow rate of 0.4 mL/min. Multiple reaction monitoring scan was performed in electrospray positive ion mode, quantitative measurement was performed by internal standard method, and methodological verification was carried out. RESULTS: The linear relationship of bucinnazine in blood was good in the range of 0.5-200 µg/L, the correlation coefficient (r) was 0.999 7, the limit of detection was 0.1 µg/L, the limit of quantitation was 0.5 µg/L, and the recovery was 78.3%-83.8% at 1, 10 and 100 µg/L mass concentration levels. The matrix effect was 69.4%-73.8%, the intra-day precision was 1.9%-2.8%, and the inter-day precision was 2.8%-3.2%, the accuracy was 3.1%-3.5%. The stability test results of 1 and 100 µg/L mass concentrations at -25 ℃ showed that the accuracy (bias) of 10 d was less than 4.5%. CONCLUSIONS: This method has the advantages of simple pre-treatment process, fast sample processing speed, high sensitivity of instrument analysis, good stability of content determination and reliable identification results, and can meet the needs of case identification.

Ultra Robust and Highly Efficient Flexible Organic Solar Cells with Over 18 % Efficiency Realized by Incorporating a Linker Dimerized Acceptor.

The wearable application of flexible organic solar cells (f-OSCs) necessitates high power conversion efficiency (PCE) and mechanical robustness. However, photoactive films based on efficient non-fullerene small molecule acceptors (NF-SMAs) are typically brittle, leading to poor mechanical stability in devices. In this study, we achieved a remarkable PCE of 18.06 % in f-OSCs while maintaining ultrahigh mechanical robustness (with a crack-onset strain (COS) of higher than 11 %) by incorporating a linker dimerized acceptor (DOY-TVT). Compared to binary blends, ternary systems exhibit reduced non-radiative recombination, suppressed crystallization and diffusion of NF-SMAs, and improved load distribution across the chain networks, enabling the dissipation of the load energy. Thus, the ternary f-OSCs developed in this study achieved, high PCE and stability, surpassing binary OSCs. Moreover, the developed f-OSCs retained 97 % of the initial PCE even after 3000 bending cycles, indicating excellent mechanical stability (9.1 % higher than binary systems). Furthermore, the rigid device with inverted structure based on the optimal active layer exhibited a substantial increase in efficiency retention, with 89.6 % after 865 h at 85 °C and 93 % after more than 1300 h of shelf storage at 25 °C. These findings highlight the potential of the linker oligomer acceptor for realizing high-performing f-OSCs with ultrahigh mechanical robustness.

All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy.

BACKGROUND: Conventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects. RESULTS: Herein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy. CONCLUSIONS: A nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.

Screening of the college students at clinical high risk for psychosis in China: a multicenter epidemiological study.

BACKGROUND: To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students. METHODS: An epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome. RESULTS: Twenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects. CONCLUSIONS: The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.

A comparative study of patients' satisfaction with different levels of hospitals in Beijing: why do patients prefer high-level hospitals?

BACKGROUND: To promote the integration of medical resources, Beijing has built medical alliances since 2012, but this reform has not changed the state of disordered medical treatment. Patients are still willing to go to high-level hospitals for medical treatment. What causes patients to prefer high-level hospitals? To explore the reasons behind this preference for high-level medical treatment among patients and to guide patients to make visits in an orderly manner, we conducted this study and compared patients' satisfaction with hospitals of different levels in the context of medical resource integration. METHODS: This study conducted a questionnaire survey among 1250 patients who were selected in 18 medical alliances in Beijing from October to December 2016. The study type is a comparative study based on cross-sectional data. Patient satisfaction was the main outcome, and descriptive analysis, chi-square tests, nonparametric tests and binary logistic regression analysis were used. The level of statistical significance was set at p < 0.05. RESULTS: The overall satisfaction score of the medical alliances was 3.375, and the satisfaction scores of core hospitals and cooperative hospitals were 2.77 and 3.07, respectively. The overall patient satisfaction rate was 44.62%, and the satisfaction rates of core hospitals and cooperative hospitals were 34.34 and 50.43%, respectively. The type of hospital and understanding of medical alliance policy were the factors associated with patient satisfaction with the medical alliance. CONCLUSIONS: The patients' satisfaction with cooperative hospitals was higher than their satisfaction with core hospitals. Although the patients were more satisfied with the service attitude of the cooperative hospitals, they still preferred core hospitals due to their higher expectations for their medical treatment and greater trust in their medical technology. It is necessary to explore the establishment of closed medical alliances under the unified management of human and financial resources to enable medical alliances to become a community of common interests and provide integrated medical services for patients.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

The long noncoding RNA Malat1 has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malat1 regulates autophagy in glioma is still unclear. In this study, we found that Malat1 expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malat1 level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malat1 significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malat1-induced cell proliferation. These data demonstrated that Malat1 activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells.

[The Diagnostic Value of Endobronchial Ultrasound-guided Needle Aspiration Biopsy for Lung or Mediastinal Lymph Node Cancer and Tuberculosis].

OBJECTIVES: To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing lung or mediastinal lymph node cancer and tuberculosis. METHODS: Clinical and pathological data of 553 patients who underwent EBUS-TBNA from January 2013 to September 2016 in West China Hospital of Sichuan University were reviewed. The sensitivity, specificity and accuracy of EBUS-TBNA for diagnosing lymph node tumor and tuberculosis of hilar and mediastinal lymph nodes were calculated. RESULTS: The sensitivity, specificity and accuracy of EBUS-TBNA in diagnosing hilar and mediastinal lymph node cancer were 89.2% (263/295), 100% (247/247) and 94.1% (510/542), respectively, compared with 70% (76/117), 97.2% (385/396) and 89.9% (461/513), respectively, for diagnosing tuberculosis identified though granulomatous biopsy. In the 102 cases with acid fast staining and TB-PCR, 63.7% accuracy (58/91), 90.9% (10/11) sensitivity and 66.7% (68/102) specificity were found for any positive findings from acid fast bacilli or TB-DNA. CONCLUSIONS: EBUS-TBNA has high sensitivity and specificity for diagnosing hilar and mediastinal tumor, which can be used in combination with acid fast staining and TB-PCR for diagnosing tuberculosis.

Liquid-Based Cytology Preparation Can Improve Cytological Assessment of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

OBJECTIVE: This study investigated whether liquid-based cytology (LBC) can improve diagnostic values of cytological assessment of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). STUDY DESIGN: A cohort of 600 cases in West China Hospital was prospectively studied from June 2012 to September 2013. EBUS-TBNA was carried out in outpatients under local anesthesia and moderate sedation. The procedure was performed with an echobronchoscope (BF-UC160F-OL8, Olympus, Tokyo, Japan). Histological cores were stained with hematoxylin and eosin for further study. Additional immunohistological analysis was performed for establishing a reliable diagnosis when necessary. Aspirates were smeared on glass slides and separate aspirates were processed by the monolayer SurePath method. RESULTS: In total, 480 malignant tumors and 120 benign lesions were confirmed by histological examination. The sensitivity of SurePath liquid-based preparations and conventional smears was 82.1 and 56%, and the specificity was 87.5 and 82.5%, respectively. The combined specificity was 100%. Positive predictive values of the two groups were 96.3 and 92.8%, whereas negative predictive values were 54.9 and 31.9%, respectively. The difference between the two groups was significant (p < 0.001). CONCLUSIONS: LBC preparation can improve cytological assessment of EBUS-TBNA. Histological study is necessary in cases in which the cytological diagnosis is obscure.

Workplace violence against Chinese licensed doctors: a cross-sectional study.

Introduction: China has issued and implemented a series of policies aimed at preventing and controlling workplace violence (WPV) against licensed doctors. However, the prevalence of WPV has not been fundamentally curbed. The aim of this study was to present the prevalence of WPV, identify its influencing factors and propose responsive measures. Method: The online Chinese Physician Practice Survey was conducted with purposive sampling method among licensed doctors in China from January 2022 to June 2022. Data covered licensed doctors' sociodemographic characteristics, occupational characteristics, prevalence of WPV, and perception of effective countermeasures. Results: A total of 74,305 licensed doctors participated in this study. A total of 44.88% of respondents had experienced WPV, among them, either physical violence only (1.06%) or non-physical violence only (89.91%) or encountered both of them (9.03%). Age, gender, marital status, education level, professional title and registration type were all associated with WPV, being younger, non-married, more educated, and higher professional title are all risk factors for WPV. Male (OR = 1.396, 95CI%: 1.355 to 1.439), clinicians (OR = 1.342,95%CI: 1.177 to 1.529), who were single (OR = 1.174, 95%CI: 1.111 to 1.241), with master's degree (OR = 2.021, 95%CI: 1.739 to 2.349) and professional title were subsenior (OR = 1.194, 95%CI: 1.125 to 1.267) were most likely to occur WPV. WPV occurred mostly in provincial capitals, public hospitals, primary and community hospitals, and departments of internal medicine, surgery, pediatrics, emergency medicine and mental health. Overall, 44.24% of doctors perceived that strengthening crackdowns on criminal behaviors was the most effective measure to prevent WPV against healthcare staff. Conclusion: The frequency of WPV decreased after the implementation of relevant laws and policies. Future efforts should be made to strengthen crackdowns on illegal and criminal activities and to issue specific legal provisions on the prevention and control of WPV against doctors.

Electroacupuncture pretreatment alleviates spasticity after stroke in rats by inducing the NF-κB/NLRP3 signaling pathway and the gut-brain axis.

OBJECTIVE: Spasticity is one of the most prevalent ischemic stroke sequelae and the leading cause of disability after stroke. Although electroacupuncture pretreatment has been shown to be effective in the treatment of ischemic stroke, its therapeutic effect and mechanism on post-stroke spasm remain unknown. The purpose of this study was to look into the potential mechanism of electroacupuncture pretreatment in inducing the NF-κB/NLRP3 signaling pathway and the gut-brain axis in the therapy of spasm after stroke. METHODS: After electroacupuncture treatment at Baihui (DU20) and Qubin (G87), the rat model of middle cerebral artery occlusion (MCAO) was first established. HE, Nissl, and TUNEL staining were used to detect pathological alterations in the rat brain. The relative levels of IL-4, IL-6, TNF-α, and TMAO were determined by ELISA. qRT-PCR and Western blot were used to evaluate the mRNA and protein levels of NF-κB p65, NLRP3, caspase3 and caspase9. Gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of short-chain fatty acids (SCFAs) in rat gut. RESULTS: Hippocampal cells from rats with spasticity following stroke in the MCAO group were chaotic and loosely distributed with an unclear border, a blurred nucleolus, and vanished cytoplasm when compared to those from the sham operation group. Furthermore, the number of surviving neurons decreased while the number of apoptotic cells increased. In the I/R group, relative levels of IL-6, TNF-α, and TMAO increased considerably, while NF-κB p65, NLRP3, caspase3, and caspase9 were dramatically downregulated. The intestinal contents of n-propyl acetate and propyl butyrate were lowered in rats with spasticity following stroke. Electroacupuncture treatments miraculously remedied all of the foregoing pathogenic alterations. CONCLUSION: Pretreatment with electroacupuncture relieves spasticity after stroke by decreasing the inflammatory response, suppressing the NF-κB/NLRP3 signaling pathway, and modulating the gut-brain axis by increasing n-propyl acetate and propyl butyrate levels in the bowel. Our findings establish a new molecular mechanism and theoretical foundation for electroacupuncture therapy of ischemic stroke.

20.2% Efficiency Organic Photovoltaics Employing a π-Extension Quinoxaline-Based Acceptor with Ordered Arrangement.

Organic solar cells, as a cutting-edge sustainable renewable energy technology, possess a myriad of potential applications, while the bottleneck problem of less than 20% efficiency limits the further development. Simultaneously achieving an ordered molecular arrangement, appropriate crystalline domain size, and reduced nonradiative recombination poses a significant challenge and is pivotal for overcoming efficiency limitations. This study employs a dual strategy involving the development of a novel acceptor and ternary blending to address this challenge. A novel non-fullerene acceptor, SMA, characterized by a highly ordered arrangement and high lowest unoccupied molecular orbital energy level, is synthesized. By incorporating SMA as a guest acceptor in the PM6:BTP-eC9 system, it is observed that SMA staggered the liquid-solid transition of donor and acceptor, facilitating acceptor crystallization and ordering while maintaining a suitable domain size. Furthermore, SMA optimized the vertical morphology and reduced bimolecular recombination. As a result, the ternary device achieved a champion efficiency of 20.22%, accompanied by increased voltage, short-circuit current density, and fill factor. Notably, a stabilized efficiency of 18.42% is attained for flexible devices. This study underscores the significant potential of a synergistic approach integrating acceptor material innovation and ternary blending techniques for optimizing bulk heterojunction morphology and photovoltaic performance.

Recent development of microfluidics-based platforms for respiratory virus detection.

With the global outbreak of SARS-CoV-2, the inadequacies of current detection technology for respiratory viruses have been recognized. Rapid, portable, accurate, and sensitive assays are needed to expedite diagnosis and early intervention. Conventional methods for detection of respiratory viruses include cell culture-based assays, serological tests, nucleic acid detection (e.g., RT-PCR), and direct immunoassays. However, these traditional methods are often time-consuming, labor-intensive, and require laboratory facilities, which cannot meet the testing needs, especially during pandemics of respiratory diseases, such as COVID-19. Microfluidics-based techniques can overcome these demerits and provide simple, rapid, accurate, and cost-effective analysis of intact virus, viral antigen/antibody, and viral nucleic acids. This review aims to summarize the recent development of microfluidics-based techniques for detection of respiratory viruses. Recent advances in different types of microfluidic devices for respiratory virus diagnostics are highlighted, including paper-based microfluidics, continuous-flow microfluidics, and droplet-based microfluidics. Finally, the future development of microfluidic technologies for respiratory virus diagnostics is discussed.

Optimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA.

Lipid nanoparticles (LNPs) have demonstrated efficacy and safety for mRNA vaccine administration by intramuscular injection; however, the pulmonary delivery of mRNA encapsulated LNPs remains challenging. The atomization process of LNPs will cause shear stress due to dispersed air, air jets, ultrasonication, vibrating mesh etc., leading to the agglomeration or leakage of LNPs, which can be detrimental to transcellular transport and endosomal escape. In this study, the LNP formulation, atomization methods and buffer system were optimized to maintain the LNP stability and mRNA efficiency during the atomization process. Firstly, a suitable LNP formulation for atomization was optimized based on the in vitro results, and the optimized LNP formulation was AX4, DSPC, cholesterol and DMG-PEG2K at a 35/16/46.5/2.5 (%) molar ratio. Subsequently, different atomization methods were compared to find the most suitable method to deliver mRNA-LNP solution. Soft mist inhaler (SMI) was found to be the best for pulmonary delivery of mRNA encapsulated LNPs. The physico-chemical properties such as size and entrapment efficiency (EE) of the LNPs were further improved by adjusting the buffer system with trehalose. Lastly, the in vivo fluorescence imaging of mice demonstrated that SMI with proper LNPs design and buffer system hold promise for inhaled mRNA-LNP therapies.