Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression.

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model. Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed. Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2. Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

The formation and evolution of vulnerability risk of rural poor groups under the perspective of social support -- based on the analysis of "sensitivity-resilience".

The anticipated sensitivity and resilience practices of the poor groups expose them to significant vulnerability risks, with social support actions arising from the return to poverty posing additional interference. To comprehensively prevent and mitigate vulnerability risks, breakthroughs in corresponding social support are essential. This study, through questionnaire surveys and semi-structured interviews, collected original data from 750 impoverished households in Lantian County, northwest China. Using a bottom-up approach, it constructed a "sensitivity-resilience" framework to assess the vulnerability and resilience mechanisms of the relatively poor groups. The research reveals that vulnerability and resilience interact in response to risk shocks. The strong livelihood dependence, capital accumulation deficiency, and sensitivity characteristics of social marginalization among rural relatively poor groups, coupled with fragmented and inefficient social support, exacerbate the degree of vulnerability risks, leading to an amplification of sensitivity and a reduction in resilience. Based on these findings, targeted at the characteristics of vulnerability risks and the fatigue factors of social support, this study proposes policy recommendations at two levels: system reengineering to reduce sensitivity and long-term reengineering to enhance resilience, aiming to prevent large-scale return to poverty.

Comparison of Facial Aesthetic Evaluation Given by Patients with Cleft Lip and/or Palate and Professionals: A Systematic Review.

OBJECTIVE: To compare the differences of facial aesthetic evaluation between patients with Cleft Lip and/or Palate (CL/P) and professionals for the treatment outcome of CL/P. DESIGN: This systematic review was conducted on MedLine, Web of Science, Embase and Cochrane Library databases. The Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool was used to evaluate the included researches. SETTING: Not applicable. PATIENTS, PARTICIPANTS: Patients with CL/P and professionals. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The facial aesthetic evaluation of patients with CL/P and professionals. RESULTS: Among the 1695 literatures retrieved, 22 articles were included, including 974 patients with CL/P and 251 professionals. The bias risk assessment on 21 articles was rated "Moderate" and only one article was rated "Serious". Due to the high heterogeneity of the included studies, meta-analysis was not possible, so descriptive analysis was conducted. Among the included studies, two articles indicated similar views from both groups, 19 noted differences between the two groups, of which three articles indicated more positive evaluation by professionals and nine articles indicated more positive evaluation by patients. CONCLUSIONS: The available data indicate that there is a difference between patients with CL/P and professionals in the aesthetic evaluation, but it is not clear which group is more positive. During the treatment of patients with CL/P, apart from the objective aesthetic evaluation, professionals should fully consider subjective ideas and self-assessment of patients, in order to improve the quality of life for patients.

3D Gaussian Splatting as New Era: A Survey.

3D Gaussian Splatting (3D-GS) has emerged as a significant advancement in the field of Computer Graphics, offering explicit scene representation and novel view synthesis without the reliance on neural networks, such as Neural Radiance Fields (NeRF). This technique has found diverse applications in areas such as robotics, urban mapping, autonomous navigation, and virtual reality/augmented reality, just name a few. Given the growing popularity and expanding research in 3D Gaussian Splatting, this paper presents a comprehensive survey of relevant papers from the past year. We organize the survey into taxonomies based on characteristics and applications, providing an introduction to the theoretical underpinnings of 3D Gaussian Splatting. Our goal through this survey is to acquaint new researchers with 3D Gaussian Splatting, serve as a valuable reference for seminal works in the field, and inspire future research directions, as discussed in our concluding section.

Apigenin alleviates doxorubicin-induced myocardial pyroptosis by inhibiting glycogen synthase kinase-3ß in vitro and in vivo.

Apigenin, a natural flavonoid compound found in chamomile (Matricaia chamomilla L.) from the Asteraceae family, has been shown in our previous study to possess antimyocardial hypertrophy and anti-cardiac fibrosis effects. However, its effects and mechanisms on the pyroptosis of cardiomyocytes induced by doxorubicin (DOX) are poorly understood. The objective of this study was to investigate the role of GSK-3ß and the effects of apigenin in DOX-induced cardiotoxicity. H9c2 cells stimulated with DOX were treated with SB216763 and apigenin. Additionally, a mouse model of DOX-induced cardiotoxicity was prepared and further treated with apigenin and SB216763 for 30 days. The findings revealed that treatment with SB216763 or apigenin resulted in a significant reduction in the levels of pyroptosis-related factors. Furthermore, the phosphorylation of GSK-3ß was enhanced while the phosphorylation of nuclear factor-kB (NF-κB) p65 was reduced following treatment with either SB216763 or apigenin. Conversely, the effects of apigenin treatment were nullified in siRNA-GSK-3ß-transfected cells. Results from computer simulation and molecular docking analysis supported that apigenin could directly target the regulation of GSK-3ß. Therefore, our study confirmed that the inhibition of GSK-3ß and treatment with apigenin effectively suppressed the pyroptosis of cardiomyocytes in both DOX-stimulated H9c2 cells and mice. These benefits may be attributed in part to the decrease in GSK-3ß expression and subsequent reduction in NF-κB p65 activation. Overall, our findings revealed that the pharmacological targeting of GSK-3ß may offer a promising therapeutic approach for alleviating DOX-induced cardiotoxicity.

SEC: A core hub during cell fate alteration.

Pol II pause release is a rate-limiting step in gene transcription, influencing various cell fate alterations. Numerous proteins orchestrate Pol II pause release, thereby playing pivotal roles in the intricate process of cellular fate modulation. Super elongation complex (SEC), a large assembly comprising diverse protein components, has garnered attention due to its emerging significance in orchestrating physiological and pathological cellular identity changes by regulating the transcription of crucial genes. Consequently, SEC emerges as a noteworthy functional complex capable of modulating cell fate alterations. Therefore, a comprehensive review is warranted to systematically summarize the core roles of SEC in different types of cell fate alterations. This review focuses on elucidating the current understanding of the structural and functional basis of SEC. Additionally, we discuss the intricate regulatory mechanisms governing SEC in various models of cell fate alteration, encompassing both physiological and pathological contexts. Furthermore, leveraging the existing knowledge of SEC, we propose some insightful directions for future research, aiming to enhance our mechanistic and functional comprehension of SEC within the diverse landscape of cell fate alterations.

Estrogen inhibits TGF­ß1­stimulated cardiac fibroblast differentiation and collagen synthesis by promoting Cdc42.

17ß­estradiol (E2) can inhibit cardiac fibrosis in female patients with heart failure (HF) and activate cell division cycle 42 (Cdc42), however it is unknown whether 17ß­estradiol (E2) can ameliorate differentiation and collagen synthesis in TGF­ß1­stimulated mouse cardiac fibroblasts (MCFs) by regulating cell division cycle 42 (Cdc42). The present study aimed to investigate the roles of estrogen and Cdc42 in preventing myocardial fibrosis and the underlying molecular mechanisms. An ELISA was used to measure the levels of E2 and Cdc42 in the serum of patients with heart failure (HF), and western blotting was used to measure the expression levels of Cdc42 in TGF­ß1­stimulated immortalized MCFs. MCFs were transfected with a Cdc42 overexpression (OE) lentivirus or small interfering RNA (siRNA), or treated with a Cdc42 inhibitor (MLS­573151), and the function of Cdc42 was assessed by western blotting, immunofluorescence staining, reverse transcription­quantitative PCR and dual­luciferase reporter assays. Western blotting and immunofluorescence staining were performed to verify the protective effect of E2 on TGF­ß1­stimulated MCFs, and the association between the protective effect and Cdc42. The results demonstrated that Cdc42 levels were increased in the serum of patients with HF and were positively correlated with the levels of E2; however, Cdc42 levels were decreased in TGF­ß1­stimulated MCFs. Cdc42 inhibited MCF differentiation and collagen synthesis, as indicated by the protein expression of α­smooth muscle actin, collagen I and collagen III. Mechanistically, Cdc42 inhibited the transcription of TGF­ß1 by promoting the expression of p21 (RAC1)­activated kinase 1 (Pak1)/JNK/c­Jun signaling pathway proteins and inhibiting the activity of the Tgfb1 gene promoter. In addition, E2 inhibited the differentiation and collagen synthesis of TGF­ß1­stimulated MCFs, and promoted the protein expression of Pak1, JNK and c­Jun, consistent with the effects of Cdc42, whereas the effects of E2 were abolished when Cdc42 was knocked down. The aforementioned findings suggested that E2 could inhibit differentiation and collagen synthesis in TGF­ß1­stimulated MCFs by regulating Cdc42 and the downstream Pak1/JNK/c­Jun signaling pathway.

Long-term effects of climate factors on dengue fever over a 40-year period.

BACKGROUND: Dengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series. METHODS: By utilizing monthly dengue fever cases and climate data spanning four decades (1978-2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects. RESULTS: Our findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%. CONCLUSIONS: Consequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

Nano-flow cytometry unveils mitochondrial permeability transition process and multi-pathway cell death induction for cancer therapy.

Mitochondrial permeability transition (mPT)-mediated mitochondrial dysfunction plays a pivotal role in various human diseases. However, the intricate details of its mechanisms and the sequence of events remain elusive, primarily due to the interference caused by Bax/Bak-induced mitochondrial outer membrane permeabilization (MOMP). To address these, we have developed a methodology that utilizes nano-flow cytometry (nFCM) to quantitatively analyze the opening of mitochondrial permeability transition pore (mPTP), dissipation of mitochondrial membrane potential ( Δ Ψm), release of cytochrome c (Cyt c), and other molecular alternations of isolated mitochondria in response to mPT induction at the single-mitochondrion level. It was identified that betulinic acid (BetA) and antimycin A can directly induce mitochondrial dysfunction through mPT-mediated mechanisms, while cisplatin and staurosporine cannot. In addition, the nFCM analysis also revealed that BetA primarily induces mPTP opening through a reduction in Bcl-2 and Bcl-xL protein levels, along with an elevation in ROS content. Employing dose and time-dependent strategies of BetA, for the first time, we experimentally verified the sequential occurrence of mPTP opening and Δ Ψm depolarization prior to the release of Cyt c during mPT-mediated mitochondrial dysfunction. Notably, our study uncovers a simultaneous release of cell-death-associated factors, including Cyt c, AIF, PNPT1, and mtDNA during mPT, implying the initiation of multiple cell death pathways. Intriguingly, BetA induces caspase-independent cell death, even in the absence of Bax/Bak, thereby overcoming drug resistance. The presented findings offer new insights into mPT-mediated mitochondrial dysfunction using nFCM, emphasizing the potential for targeting such dysfunction in innovative cancer therapies and interventions.

Analysis of factors impacting postoperative pain and quality of life in patients with mixed hemorrhoids: A retrospective study.

BACKGROUND: Hemorrhoids are among the most common and frequently encountered chronic anorectal diseases in anorectal surgery. They are venous clusters formed by congestion, expansion, and flexion of the venous plexus in the lower part of the rectum. Mixed hemorrhoids bleed easily and recurrently, and this can result in severe anemia. Hence, they may have a negative effect on the health of the patient and surgical treatment is required. Milligan-Morgan hemorrhoidectomy has been widely used since 1937 for the treatment of grade III and IV hemorrhoids. However, most patients experience different degrees of postoperative pain that may cause anxiety. AIM: To assess the factors influencing pain scores and quality of life (QoL) in patients with mixed hemorrhoids post-surgery. METHODS: The clinical data of patients with mixed hemorrhoids who underwent Milligan-Morgan hemorrhoidectomy were collected retrospectively. The basic characteristics of the enrolled patients with mixed hemorrhoids were recorded, and based on the Goligher clinical grading system, the hemorrhoids were classified as grades III or IV. The endpoint of this study was the disappearance of pain in all patients. Quantitative data were presented as mean ± SD, such as age, pain score, and QoL score. Student's t-test was used to compare the groups. RESULTS: A total of 164 patients were enrolled. The distribution of the visual analog scale pain scores of all patients at 3, 7, 14 and 28 d after surgery showed that post-surgery pain was significantly reduced with the passage of time. Fourteen days after the operation, the pain had completely disappeared in some patients. Twenty-eight days after the surgery, none of the patients experienced any pain. Comparing the World Health Organization Quality of Life - BREF self-reporting questionnaire scores of patients between 14 and 28 d after surgery, we observed that the quality-of-life scores of the patients post-surgery had significantly improved. There were six items that were compared at 14- and 28-d post-surgery. The mean QoL score 28 d after surgery (4.79 ± 0.46) was higher than that at 14 d post-surgery (3.79 ± 0.57). The mean health condition score 28 d after surgery (4.80 ± 0.41) was also higher than that at 14 d post-surgery (4.01 ± 0.62). The mean physical health score 28 d after surgery (32.10 ± 2.96) was significantly higher than that at 14 d post-surgery (23.41 ± 2.85). The mean psychological health score 28 d after surgery (27.22 ± 1.62) was significantly higher than that at 14 d post-surgery (21.37 ± 1.70). The mean social relations score 28 d after surgery (12.21 ± 1.59) was significantly higher than that at 14 d post-surgery (6.32 ± 1.66). The mean surrounding environment score 28 d after surgery (37.13 ± 2.88) was significantly higher than that at 14 d post-surgery (28.42 ± 2.86). The differences in quality-of-life scores at day 14 and day 28 post-surgery were observed to be statistically significant (P < 0.001). CONCLUSION: Milligan-Morgan hemorrhoidectomy can significantly improve the postoperative QoL of patients. Age, sex, and the number of surgical resections were important factors influencing Milligan-Morgan hemorrhoidectomy.

[Research progress in surgical treatment of avascular necrosis of talus].

Objective: To summarize the surgical treatment methods for avascular necrosis of the talus. Methods: The recent domestic and international literature related to avascular necrosis of the talus was extensively conducted. The pathogenesis, surgical treatment methods, and prognosis were summarized. Results: The clinical symptoms of avascular necrosis of the talus at early stage are not obvious, and most patients have progressed to Ficat-Arlet stages Ⅲ-Ⅳ and require surgical treatment. Currently, surgical treatments for this disease include core decompression, vascularized bone flap transplantation, arthroplasty, and arthrodesis, etc. Early avascular necrosis of the talus can be treated conservatively, and if treatment fails, core decompression can be considered. Arthrodesis is a remedial surgery for patients with end-stage arthritis and collapse, and in cases of severe bone loss, tibiotalocalcaneal arthrodesis and bone grafting are required. Vascularized bone flap transplantation is effective and plays a role in all stages of avascular necrosis of the talus, but the appropriate donor area for the flap still needs further to be studied. Conclusion: The surgical treatment and the system of treatment for different stages of avascular necrosis of the talus still need to be refined.

Control of polymers' amorphous-crystalline transition enables miniaturization and multifunctional integration for hydrogel bioelectronics.

Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.

Enhancing Built-in Electric Fields via Molecular Symmetry Modulation in Supramolecular Photocatalysts for Highly Efficient Photocatalytic Hydrogen Evolution.

Nature-inspired supramolecular self-assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built-in electric field by symmetry breaking. Herein, an unsymmetric protonation, N-heterocyclic π-conjugated anthrazoline-based supramolecular photocatalyst SA-DADK-H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50-fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA-DADK-H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA-DADK-H+ exhibits an outstanding hydrogen evolution rate of 278.2 mmol g-1 h-1 and a remarkable apparent quantum efficiency of 25.1 % at 450 nm, placing it among the state-of-the-art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533 times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar-to-fuel production.

Generation time-out grows up: young adults' reports about childhood time-out use and their mental health, attachment, and emotion regulation.

Time-out (TO) is a widely utilised parental discipline technique with a strong evidence-base that nonetheless has attracted controversy regarding potential adverse effects on mental health in developing children. Associations between TO implementation and mental health outcomes have rarely been investigated, especially through the eyes of children who grew up experiencing TO. This study recruited 407 university students (Study 1) and a community sample of 535 young adults (Study 2); both samples aged 18-30 years. Young adults were surveyed on their retrospective reports of childhood TO experience, childhood experiences of adversity, perceived parenting style and parental attachment, and their current mental health outcomes (attachment style, emotion regulation and mental health). In Study 1, 334 (82.1%) young adults reported experiencing TO in childhood, but with widely varied implementation that differed considerably from its evidence-based ideal. Reports of more TO appropriate implementation were associated with less avoidant attachment, better mental health, and emotion regulation, over and above the effects associated with authoritative parenting and secure attachment in childhood. While exposure to childhood adversity was associated with poorer adulthood outcomes, TO implementation did not moderate the association. Study 2 replicated most findings from Study 1, except that appropriate TO implementation displayed a positive association with mental health and no associations with anxious and avoidant attachment and emotion regulation. These findings suggest the safety of TO use with young children, including those who experienced childhood adversity, and highlight the importance of disseminating sufficient parenting information on TO in the community.

A multifunctional flexible sensor based on PI-MXene/SrTiO3 hybrid aerogel for tactile perception.

The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications. Here, we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities. This sensor utilizes a novel PI-MXene/SrTiO3 hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments. Moreover, polyimide (PI) provides a high-strength skeleton, MXene realizes a pressure-sensing function, and MXene/SrTiO3 achieves both thermoelectric and infrared radiation response behaviors. Furthermore, via the pressure response mechanism and unsteady-state heat transfer, these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling. They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94% and 85%, respectively, using a decision tree algorithm. In addition, based on the infrared radiation-sensing function, a sensory array was assembled, and different shapes of objects were successfully recognized. These findings demonstrate that this PI-MXene/SrTiO3 aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand. This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility.

Parental Phubbing and Adolescent Smartphone Addiction: Depression and Perceived School Climate Matter.

This study investigated the association between parental phubbing and adolescents' smartphone addiction, the mediating role of depression, and the moderating role of perceived school climate in the association. Seven hundred forty-two Chinese adolescents (Mage = 12.97, SD = 0.64, 45.55 percent female) were recruited and self-reported questionnaires were administered. Results indicated that parental phubbing was positively associated with adolescents' smartphone addiction. Depression partially mediated the above relation. Further, perceived school climate moderated the relation between parental phubbing and depression, such that the positive association between parental phubbing and depression was stronger among adolescents who perceived their school climate as more negative (vs. positive). The findings deepened our understanding of the relation between parenting behaviors and adolescents' smartphone addiction and implications for interventions and practices were discussed.

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.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

[Inhibitory Effect of Ginsenoside Rg3 Combined With 5-Fluorouracil on Tumor Angiogenesis and Tumor Growth of Colon Cancer in Mice: An Experimental Study]. / 人参皂苷Rg3与5-æ°Ÿå°¿å˜§å•¶è”ç”¨å¯¹ç»“è‚ ç™Œå°é¼ è‚¿ç˜¤çš„è¡€ç®¡ç”Ÿæˆä¸Žè‚¿ç˜¤ç”Ÿé•¿æŠ‘åˆ¶æ•ˆæžœçš„å®žéªŒç ”ç©¶.

Objective: To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice. Methods: CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored. Results: After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started. Conclusion: Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.

Highly Active Frozen Nanovesicles Microneedles for Senile Wound Healing via Antibacteria, Immunotherapy, and Skin Regeneration.

Senile wound healing risks a variety of health complications and makes both economic and psychological burdens on patients greatly. Poor activity of aged dermal fibroblasts (A-FBs) and local disordered immunoreaction in the deep dermis contribute to delayed wound healing. Therefore, the locally complex microenvironment in deep requires additional processing. Herein, a novel double-layer hyaluronic acid methacrylate (HAMA)/polyvinyl alcohol (PVA) microneedle patch (MNP) coated by young fibroblast-derived exosomes (Y-EXOs) (Y-EXOs@HAMA/PVA MNP) is presented for deep drug delivery, aged wound healing and immunoregulation. A spraying and freeze-drying method is applied for keeping the bioactivity of the nanovesicles. An ideal loading of Y-EXOs and enhanced strength for penetration have realized after circulation for times. The Y-EXOs@HAMA/PVA MNP shows an excellent influence on delayed wound healing of aged skin with active A-FBs, more deposition of collagen and less production of IL-17A compared with application of aged fibroblast-derived exosomes (A-EXOs). Moreover, the content microRNAs in Y-EXOs and A-EXOs are sequenced for further study. This study initiatively demonstrates that Y-EXOs have effective function on both anti-aging and anti-inflammation and Y-EXOs@HAMA/PVA MNP is expected as a novel strategy for deep drug delivery for promoting hard wound healing in aged skin in future clinical application.