Metalens for Accelerated Optoelectronic Edge Detection under Ambient Illumination.

Analog systems may allow image processing, such as edge detection, with low computational power. However, most demonstrated analog systems, based on either conventional 4-f imaging systems or nanophotonic structures, rely on coherent laser sources for illumination, which significantly restricts their use in routine imaging tasks with ambient, incoherent illumination. Here, we demonstrated a metalens-assisted imaging system that can allow optoelectronic edge detection under ambient illumination conditions. The metalens was designed to generate polarization-dependent optical transfer functions (OTFs), resulting in a synthetic OTF with an isotropic high-pass frequency response after digital subtraction. We integrated the polarization-multiplexed metalens with a polarization camera and experimentally demonstrated single-shot edge detection of indoor and outdoor scenes, including a flying airplane, under ambient sunlight illumination. The proposed system showcased the potential of using polarization multiplexing for the construction of complex optical convolution kernels toward accelerated machine vision tasks such as object detection and classification under ambient illumination.

The mechanosensitive ion channel Piezo1 contributes to podocyte cytoskeleton remodeling and development of proteinuria in lupus nephritis.

Piezo1 functions as a special transducer of mechanostress into electrochemical signals and is implicated in the pathogenesis of various diseases across different disciplines. However, whether Piezo1 contributes to the pathogenesis of lupus nephritis (LN) remains elusive. To study this, we applied an agonist and antagonist of Piezo1 to treat lupus-prone MRL/lpr mice. Additionally, a podocyte-specific Piezo1 knockout mouse model was also generated to substantiate the role of Piezo1 in podocyte injury induced by pristane, a murine model of LN. A marked upregulation of Piezo1 was found in podocytes in both human and murine LN. The Piezo1 antagonist, GsMTx4, significantly alleviated glomerulonephritis and tubulointerstitial damage, improved kidney function, decreased proteinuria, and mitigated podocyte foot process effacement in MRL/lpr mice. Moreover, podocyte-specific Piezo1 deletion showed protective effects on the progression of proteinuria and podocyte foot process effacement in the murine LN model. Mechanistically, Piezo1 expression was upregulated by inflammatory cytokines (IL-6, TNF-α and IFN-γ), soluble urokinase Plasminogen Activator Receptor and its own activation. Activation of Piezo1 elicited calcium influx, which subsequently enhanced Rac1 activity and increased active paxillin, thereby promoting cytoskeleton remodeling and decreasing podocyte motility. Thus, our work demonstrated that Piezo1 contributed to podocyte injury and proteinuria progression in LN. Hence, targeted therapy aimed at decreasing or inhibiting Piezo1 could represent a novel strategy to treat LN.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer.

Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

Potential profiling of self-management skills in older co-morbid patients.

BACKGROUND: Under the general trend of global aging, geriatric comorbidity is increasingly common, which may have some impact on the quality of life of the older people. Self-management can effectively improve patient compliance, subjective initiative, and improve patient quality of life. However, the present situation of self-management in different old people is different. Therefore, this study classifies older co-morbid patients through potential profiling analysis, understands the category characteristics of self-management level of older co-morbid patients, and discusses the influencing factors of self-management level of different categories of older co-morbid patients, which can provide reference for personalized intervention programs for different comorbidity characteristics of elderly people in the future.  METHOD: Through a cross-sectional study, 616 cases of older co-morbid patients in three districts of Zhengzhou City, Henan Province, were selected as survey subjects by using the whole cluster sampling method. The General Information Questionnaire, Chronic Disease Self-Management Scale, Health Literacy Scale, Electronic Health Literacy Scale, Collaborative Social Support Scale, and Health Empowerment Scale were used to conduct the survey. RESULTS: The result of LPA shows that the self-management characteristics of older co-morbid patients should be classified into 3 categories: good self-management (19.4%), medium self-management(27.9%), and low self-management (52.7%). The results of multivariate logistic regression analyses show that literacy, religiosity, health literacy, e-health literacy, appreciative social support, and health empowerment are influential factors for self-management among older co-morbid patients (p < 0.05). CONCLUSION: There is obvious heterogeneity in the self-management level of older co-morbid patients. It is recommended that healthcare professionals give targeted interventions for their weaknesses according to the self-management characteristics of different categories of patients in order to enhance the self-management level of this population and improve their quality of life.

Exploring anesthesiology nurse' presenteeism in China: cross-sectional study.

BACKGROUND: The department of anesthesiology is the main battlefield for the treatment of acute and critical patients, with high work risk and high work pressure. Due to the particularity of the working environment and nature of work, medical staff have become a group with a high incidence of occupational exhaustion and presenteeism. OBJECTIVE: To investigate the current status of presenteeism among anesthesiology nurses in China and to analyze the related influencing factors. METHODS: Three hundred twelve anesthesiology nurses in Sichuan Province were surveyed by means of general data questionnaire, presenteeism scale, work-family conflict scale, perceived social support scale, occupational commitment scale and stress resistance scale from September to November 2023 by convenience sampling method. RESULTS: The total score of presenteeism was (14.67 ± 3.92), the score of work-family conflict was (45.44 ± 15.90), the score of professional commitment was (87.28 ± 14.30), and the score of perceived social support was (66.04 ± 12.78). The evaluation score of stress resistance was (73.35 ± 11.54). The results of multivariate analysis showed that age, education, mode of employment, position, overtime hours per week, work-family conflict, perceived social support and stress resistance were the factors that affected the presenteeism of anesthesiology nurses, which could explain 44.1% of the total variation. The position ( ß = 0.296, P < 0.001), overtime hours per week (h) ( ß = 0.271, P < 0.001), perceived social support ( ß = -0.279, P < 0.001) turned out as the stronger predictors of presenteeism. CONCLUSION: The presenteeism of anesthesiology nurses is at a high level and needs to be further improved. Clinical nursing managers should pay attention to the physical and mental health and special needs of anesthesiology nurses. Interventions are made according to the main influencing factors, so as to reduce the incidence of presenteeism and improve the quality and safety of surgery.

Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study.

BACKGROUND: This study aimed to investigate the effect of esketamine on the dose-effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol. METHODS: Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18-65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 µg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon's modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis. RESULTS: The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59-4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27-6.23 ng/mL) with TCI of propofol 3.0 µg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22-3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91-5.88 ng/mL). CONCLUSIONS: Combined with TCI of propofol 3.0 µg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trials Registry ( www.chictr.org.cn ; registration number: ChiCTR2200064932; date of registration:24/10/2022).

Safety and efficacy of stoma site selection in CT-guided percutaneous gastrostomy: a retrospective analysis.

PURPOSE: To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions. MATERIALS AND METHODS: This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded. RESULTS: The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P < 0.05). CONCLUSION: Rectus abdominis and intercostal stomas have similar safety and efficacy. However, intercostal stomas may result in greater short-term patient discomfort.

Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Treatment of silicosis with quercetin depolarizing macrophages via inhibition of mitochondrial damage-associated pyroptosis.

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.

[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

[Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects]. / 母亲MTRåŸºå› å¤šæ€æ€§åŠå ¶ä¸Žå›´å­•æœŸå¶é ¸è¡¥å çš„äº¤äº’ä½œç”¨ä¸Žå­ä»£å®¤é—´éš”ç¼ºæŸçš„å ³è”ç ”ç©¶.

OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

[A case-control study on the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease in offspring]. / çˆ¶æ¯å›´å­•æœŸå¸çƒŸå’Œé¥®é ’åŠå ¶äº¤äº’ä½œç”¨ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease (CHD) in offspring. METHODS: The parents of children with simple CHD aged 0 to 1 year (n=683) were recruited as the case group, while the parents of healthy children aged 0 to 1 year (n=740) served as the control group. A case-control study was conducted, and a questionnaire was used to collect information on perinatal exposures. After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching, the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined, as well as the cumulative effects of smoking and drinking on CHD risk. RESULTS: Maternal active smoking (OR=2.91, 95%CI: 1.60-5.30), passive smoking (OR=1.94, 95%CI: 1.56-2.42), and alcohol consumption (OR=2.59, 95%CI: 1.89-3.54), as well as paternal smoking (OR=1.52; 95%CI: 1.22-1.90) and drinking (OR=1.48, 95%CI: 1.19-1.84), were associated with an increased risk of CHD in offspring. There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring (P>0.05). The more parents' smoking and drinking behaviors during the perinatal pregnancy, the higher the risk of CHD in their offspring (OR=1.50, 95%CI: 1.36-1.65). CONCLUSIONS: Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring, and there is a cumulative effect on CHD risk, suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

miR-654-5p Suppresses Migration and Proliferation of Vascular Smooth Muscle Cells by Targeting ADAMTS-7.

Coronary artery disease (CAD) is the first leading cause of death worldwide. Therefore, novel therapeutic strategies need to be explored. Numerous publications reported that microRNA-654-5p (miR-654-5p) had anti-cancer activities in various cancers, and it was proven to modulate cell migration, invasion, and proliferation, which played critical roles in CAD. However, its role in CAD is unknown. Thus, we aimed to evaluate the role of miR-654-5p in vascular smooth muscle cells (VSMCs) involved in CAD. A total of 25 CAD patients and 19 healthy individuals were enrolled to evaluate their circulating miR-654-5p levels. miR-654-5p mimic or inhibitor were transfected into human VSMCs to assess their role on cell migration and proliferation. Target genes of miR-654-5p were predicted using TargetScan 7.2 and confirmed by the dual-luciferase reporter assay. miR-654-5p was significantly downregulated in the plasma of CAD patients and tumor necrosis factor-a/platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. miR-654-5p mimic inhibited the proliferation and migration of VSMCs, which could be promoted by miR-654-5p inhibitor. A disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) was identified as the direct target of miR-654-5p, whose expression could be induced by miR-654-5p inhibitor and decreased by its mimic. In addition, ADAMTS-7 overexpression blocked the inhibitory effect of miR-654-5p on the migration and proliferation of VSMCs. In summary, miR-654-5p inhibits the migration and proliferation of VSMCs by directly targeting ADAMTS-7, and miR-654-5p might serve as a novel therapeutic target for the treatment of CAD.

Estradiol and raloxifene as adjunctive treatment for women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials.

OBJECTIVES: We conducted a comprehensive meta-analysis of all available trials to evaluate the efficacy and safety of estrogen and selective estrogen receptor modulators as adjunctive treatment for women with schizophrenia. METHODS: Multiple databases were searched from the inception until March 2022. Only randomized, double-blind, placebo-controlled studies (randomized controlled trials) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: The meta-analysis included six estradiol versus placebo studies (n = 724) and seven raloxifene versus placebo studies (n = 419), covering a total of 1143 patients. Adjunctive estradiol outperformed the placebo in terms of the Positive and Negative Syndrome Scale (PANSS) total score (MD = -7.29; 95% CI = -10.67 to -3.91; I2  = 59.1%; p < 0.001; k = 9; N = 858), positive symptom score (MD = -1.54; 95% CI = -3.04 to -0.72; I2  = 45.8%; p < 0.001; k = 7; N = 624), negative symptom score (MD = -1.9; 95% CI = -1.77 to -0.34; I2  = 37.6%; p < 0.05; k = 14; N = 1042), and general psychopathology score (MD = -4.27; 95% CI = -7.14 to -1.41; I2  = 76.3%; p < 0.005; k = 7; N = 624). Adjunctive raloxifene outperformed the placebo in terms of the PANSS total score (MD = -6.83; 95% CI = -11.69 to -1.97; I2  = 67.8%; p = 0.006; k = 8; N = 432) and general psychopathology score (MD = -3.82; 95% CI = -6.36 to -1.28; I2  = 65.3%; p < 0.005; k = 8; N = 432). CONCLUSIONS: Our meta-analysis showed that estradiol and raloxifene are effective and safe adjunctive treatments that improve schizophrenia symptoms in women. Moreover, the effects of estradiol and raloxifene differed in terms of timing and dosage. Both are promising adjunctive treatments that merit further study.

Regenerative Effect of Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Established Limb Ischemia.

BACKGROUND: Although regenerative cell therapy is expected to be an alternative treatment for peripheral artery disease (PAD), many regenerative cell therapies have failed to show sufficient efficacy in clinical trials. Most preclinical studies have used acute ischemia models, despite PAD being a chronic disease. In addition, aging and atherosclerosis decrease the quality of a patient's stem cells. Therefore, using a non-acute ischemic preclinical model and stem cells with high regenerative potency are important for the development of effective regenerative therapy. In this study, we assessed the tissue regenerative potential of umbilical cord-derived mesenchymal stromal cells (UCMSCs), which could potentially be an ideal cell source, in a rat model of established ischemia.Methods and Results: The regenerative capacity of UCMSCs was analyzed in terms of angiogenesis and muscle regeneration. In vitro analysis showed that UCMSCs secrete high amounts of cytokines associated with angiogenesis and muscle regeneration. In vivo experiments in a rat non-acute ischemia model showed significant improvement in blood perfusion after intravenous injection of UCMSCs compared with injection of culture medium or saline. Histological analysis revealed UCMSCs injection enhanced angiogenesis, with an increased number of von Willebrand factor-positive microcapillaries, and improved muscle regeneration. CONCLUSIONS: These results suggest that intravenous administration of UCMSCs may be useful for treating patients with PAD.

The association of air pollutants with hospital outpatient visits for child and adolescence psychiatry in Shenzhen, China.

BACKGROUND: Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. METHODS: A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO2, PM2.5, SO2 and O3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. RESULT: A total of 94,660 cases aged 3-18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M0) showed that in the single lag effect result, when the average daily concentration of NO2 at 24 µg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO2 M0 value to the outpatient visits were 1.438 (1.137-1.818) over lag 0-2, 1.454 (1.120-1.887) over lag 0-3, 1.466 (1.084-1.982) over lag 0-4, 1.680 (1.199-2.354) over lag 0-5, 1.993 (1.369-2.903) over lag 0-6, and 2.069 (1.372-3.119) over lag 0-7. However, PM2.5, SO2, O3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO2 increases by 10 units or when the maximum concentration of NO2 is reached. CONCLUSION: Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP.

Laser-triggered intelligent drug delivery and anti-cancer photodynamic therapy using platelets as the vehicle.

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals.

What is the context?1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro.2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets.3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm).4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells.What is new?1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug.2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets.3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo.4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions.What is impact?The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.