Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China.

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.

ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/ß-Catenin Signaling Pathway.

As a member of Rho GAPs family, Rho GTPase-Activating Protein 17 (ARHGAP17) regulates cytoskeletal recombination, cell polarity, cell proliferation and cell migration. ARHGAP17 is identified as a tumor suppressor in numerous cancer types. Current study intends to examine ARHGAP17 expression and its possible influence on the progression of hepatocellular carcinoma (HCC). ARHGAP17 expression in HCC cells was verified by RT-PCR and western blot. The proliferation and invasion of HCC cells were evaluated by CCK8 assay and transwell assay, respectively. The mRNA expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, GSK-3ß, Axin1, and APC were detected by RT-PCR. The protein expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, p-ß-catenin, GSK-3ß, p-GSK-3ß, Axin1, and APC were detected by western blot. ARHGAP17 staining was evaluated by immunohistochemistry and immunofluorescence. ARHGAP17 expression decreased significantly in HCC tumors and HCC cells after EMT. In response to overexpression of ARHGAP17, the capacities of HCC cell proliferation and invasion were reduced significantly, which were also confirmed by tumorigenesis experiments in vivo. With overexpression of ARHGAP17 in HCC cells, the p-GSK3ß/GSK3ß decreased, while the p-ß-catenin/ß-catenin, Axin1 and APC increased. In conclusion, ARHGAP17 inhibits HCC progression by inactivating the Wnt/ß-catenin signaling pathway.

Thrombin-targeted screening of anticoagulant active components from Polygonum amplexicaule D. Don var. sinense Forb by affinity ultrafiltration coupled with UPLC-Q-TOF-MS.

INTRODUCTION: Polygonum amplexicaule D. Don var. sinense Forb (PAF), a medicinal plant, has the effect of promoting blood circulation and removing blood stasis. However, the active compounds and targets of its anticoagulant effect are still unclear. OBJECTIVES: This study aims to establish an effective reversely thrombin-targeted screening method for anticoagulant active components in PAF by affinity ultrafiltration (AUF) coupled with ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC-Q-TOF-MS). METHODS: Different polar parts of PAF were screened for potential thrombin ligands by AUF-HPLC and identified by UPLC-Q-TOF-MS. After studying the affinity between ligands and thrombin by molecular docking, the antithrombotic activity of ligands was detected in vivo by zebrafish thrombus model, and in vitro by chromogenic substrate method. The mechanism of such ligands on thrombin was further studied by coagulation factor assay. RESULTS: Eleven potential thrombin ligands from PAF were screened by the AUF-UPLC-Q-TOF-MS method, and two compounds (butyl gallate and ß-sitosterol) with significant anticoagulant activity were discovered via in vitro and in vivo activity testing. CONCLUSION: A method system based on AUF-UPLC-Q-TOF-MS, molecular docking and in vivo and in vitro experiments also provided a powerful tool for further exploration of anticoagulant active components in PAF.

[Mechanism of Chaijin Jieyu Anshen Tablets in regulating abnormal ACC-vHPC glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats].

This study aims to reveal the molecular mechanism of Chaijin Jieyu Anshen Tablets(CJJYAS) in regulating the abnormal anterior cingulate cortex(ACC)-ventral hippocampus(vHPC) glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats. Firstly, the study used chemogenetics to localize glutaminergic adeno-associated virus(AAV) into the ACC brain region of rats. The model of depressed rats was established by chronic unpredictable mild stress(CUMS) combined with independent feeding. The rats were randomly divided into control group, model group, AAV empty group, AAV group, AAV+ glucocorticoid receptors(GR) blocker group, AAV+chemokine receptor 1(CX3CR1) blocker group, and AAV+CJJYAS group. Depressive-like behaviors of rats were evaluated by open-field, forced-swimming, and Morris water maze tests, combined with an animal behavior analysis system. The morphological and structural changes of ACC and vHPC neurons in rats were observed by hematoxylin-eosin(HE) staining. Immunofluorescence and nuclear phosphoprotein(c-Fos) were used to detect glutaminergic neural circuit activation of ACC-vHPC in rats. The changes in dendrites, synaptic spines, and synaptic submicrostructure of vHPC neurons were observed by Golgi staining and transmission electron microscopy, respectively. The expressions of synaptic remodeling-related proteins N-methyl-D-asprtate receptor 2A(GRIN2A), N-methyl-D-asprtate receptor 2B(GRIN2B), Ca~(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ), mitogen-activated protein kinase-activated protein kinase 2(MK2), and a ubiquitous actin-binding protein(cofilin) in vHPC glutaminergic neurons of rats were detected by immunofluorescence and Western blot, respectively. The results indicated that the activated glutaminergic AAV aggravated the depressive-like behaviors phenotype of rats in the model group and deteriorated the damage of morphology and structure of ACC and vHPC neurons and synaptic ultrastructure. However, both GR and CX3CR1 bloc-kers could reverse the abnormal changes to varying degrees, suggesting that the abnormal activation of ACC-vHPC glutaminergic neural circuit mediated by GR/CX3CR1 signals in gliocytes in the ACC brain region may be closely related to the occurrence and development of depression. Interestingly, CJJYAS significantly inhibited the activation of the ACC-vHPC glutaminergic neural circuit induced by AAV and the elevated Glu level. Furthermore, CJJYAS could also effectively reverse the aggravation of depressive-like behaviors and synaptic remodeling of vHPC neurons of rats in the model group induced by the activated AAV. Additionally, the findings suggested that the molecular mechanism of CJJYAS in improving synaptic damage of vHPC neurons might be related to the regulation of synaptic remodeling-related signals such as NR/CaMKⅡ and MK2/cofilin. In conclusion, this research confirms that CJJYAS effectively regulates the abnormal ACC-vHPC glutaminergic neural circuit and alleviates the synaptic remodeling of vHPC glutaminergic neurons in depressed rats, and the molecular mechanism might be associated with the regulation of synapse-related NR/CaMKⅡ and MK2/cofilin signaling pathways, which may be the crucial mechanism of its antidepressant effect.

Molecular surveillance reveals a potential hotspot of tick-borne disease in Yakeshi City, Inner Mongolia.

A molecular surveillance of tick-borne diseases was performed in Hulunbuir City, Inner Mongolia. A total of 149 ticks including three species (Ixodes persulcatus, Haemaphysalis concinna, and Dermacentor silvarum) were collected. As many as 11 tick-borne bacterial pathogens were identified in them. Some of them have high positive rates. For example, Candidatus Rickettsia tarasevichiae was detected with a high prevalence of 72.48%, while Candidatus Lariskella sp. was detected in 31.54% of ticks. For both Rickettsia raoultii and Anaplasma phagocytophilum, two distinct genotypes were identified based on their phylogenetic trees based on 16S rRNA, gltA, and groEL sequences. Remarkable genetic diversity was also observed for 16S and flaB genes of Borreliella garinii, an agent of Lyme disease. Rickettsia heilongjiangensis causing Far-Eastern spotted fever (2.68%, 4/149), Ehrlichia muris causing human ehrlichiosis (4.70%, 7/149), Borrelia miyamotoi causing relapsing fever (2.01%, 3/149), and Borreliella afzelii causing Lyme disease (2.01%, 3/149) were also detected. Additionally, a previously uncharacterized Anaplasma species closely related to Anaplasma ovis was identified. Herein we name it "Candidatus Anaplasma mongolica". Based on these results, we propose that Yakeshi City might be a potential hotspot of tick-borne diseases.

Circulation of multiple Rickettsiales bacteria in ticks from Sichuan province, Southwest China.

During 2021, 403 ticks including Haemaphysalis qinghaiensis, Ixodes ovatus, Ixodes acutitarsus, and Rhipicephalus microplus were collected from three sites (590, 310, and 576 km away from each other) in Sichuan Province, China. A total of nine Rickettsiales species were identified in them, including three Rickettsia spp., five Anaplasma spp., and one Ehrlichia sp. Anaplasma ovis and a novel Rickettsia sp. named "Candidatus Rickettsia liangshanensis" were characterized in I. ovatus ticks from Liangshan, with positive rates of 11.11% and 45.56%, respectively. Anaplasma capra (13.33%) and Anaplasma bovis (15.33%) were detected in H. qinghaiensis ticks from Maerkang. Phylogenetic analysis based on 16S rRNA, gltA, and groEL gene sequences indicated that the A. bovis strains were divided into two groups. Additionally, a novel Ehrlichia species named "Candidatus Ehrlichia maerkangensis" was identified. It is closely related to "Candidatus Ehrlichia zunyiensis" which was previously reported in Berylmys bowersi rats from Zunyi City, Southwest China. In R. microplus from Mianyang, "Candidatus Rickettsia jingxinensis" was detected with a high prevalence (92.99%). Notably, a variant of R. raoultii was identified in I. acutitarsus (33.33%). This may be the first Rickettsiales bacterium reported in I. acutitarsus. Our results reveal the remarkable biodiversity of Rickettsiales in this area. Some of these bacteria are human pathogens, indicating the potential exposure risk to local people.

Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.

BACKGROUND: Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. METHODS: Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. RESULTS: HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. CONCLUSIONS: Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

Leonurine Regulates Hippocampal Nerve Regeneration in Rats with Chronic and Unpredictable Mild Stress by Activating SHH/GLI Signaling Pathway and Restoring Gut Microbiota and Microbial Metabolic Homeostasis.

Depression is a highly prevalent and heterogeneous disorder that requires new strategies to overcome depression. In this study, we aimed to investigate whether leonurine modulated hippocampal nerve regeneration in chronic and unpredictable mild stress (CUMS) rats through the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis. The CUMS rat model was constructed and treated with leonurine. The body weight of rats was recorded, and a series of tests were performed. Western blot was utilized to measure the expression of BDNF and 5-HT in the hippocampus. Then the expression of SHH, GLI, PTCH, and SMO were measured by qRT-PCR and western blot. The colocalization of BrdU+DCX and BrdU+NeuN was evaluated by IF. 16S rDNA high-throughput sequencing was applied to detect the composition and distribution of gut microbiota. The differential metabolites were analyzed by untargeted metabolomics. The correlation between gut microbiota and microbial metabolites was analyzed by Pearson correlation coefficient. After CUMS modeling, the body weight of rats was decreased, and the expression of BDNF and 5-HT were decreased, while the body weight was recovered, and the expression of BDNF and 5-HT were increased after leonurine treatment. Leonurine reversed the reduction in the colocalization of BrdU+DCX and BrdU+NeuN and the reduction in the levels of SHH, GLI, PTCH, and SMO induced by CUMS modeling. Leonurine also restored gut microbiota and microbial metabolites homeostasis in CUMS rats. Furthermore, Prevotellaceae_Ga6A1_group was negatively correlated with 3-Oxocholic acid, nutriacholic acid, and cholic acid. Collectively, leonurine regulated hippocampal nerve regeneration in CUMS rats by activating the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis.

Erdafitinib Inhibits Tumorigenesis of Human Lung Adenocarcinoma A549 by Inducing S-Phase Cell-Cycle Arrest as a CDK2 Inhibitor.

Lung adenocarcinoma (LADC) is the most prevalent lung cancer sub-type, and targeted therapy developed in recent years has made progress in its treatment. Erdafitinib, a potent and selective pan-FGFR tyrosine kinase inhibitor, has been confirmed to be effective for the treatment of LADC; however, the molecular mechanism responsible for this effect is unclear. The in vitro study showed that erdafitinib exhibited an outstanding anti-cancer activity in human LADC cell line A549 by inducing S-phase cell-cycle arrest and cell apoptosis. The mechanistic study based on the transcriptomic data revealed that erdafitinib exerted its anti-cancer effect by affecting the cell cycle-related pathway, and CDK2 was the regulatory target of this drug. In addition, CDK2 overexpression significantly attenuated the anti-cancer effect of erdafitinib by affecting the transcriptional activity and expression of E2F1, as well as the expression of CDK1. The in vivo study showed that erdafitinib presented an obvious anti-cancer effect in the A549 xenograft mice model, which was accompanied by the reduced expression of CDK2. Thus, this study demonstrates the anti-cancer effect of erdafitinib against LADC for the first time based on in vitro and in vivo models, whose activity is achieved by targeting CDK2 and regulating downstream E2F1-CDK1 signaling. This study may be helpful for expanding the clinical application of erdafitinib in treating LADC.

The molecular mechanism underlying mitophagy-mediated hippocampal neuron apoptosis in diabetes-related depression.

Diabetes-related depression (DD) is a major complication of diabetes mellitus. Our previous studies indicated that glutamate (Glu) and hippocampal neuron apoptosis are key signal and direct factor leading to diabetes-related depression, respectively. However, the accurate pathogenesis remains to be unclear. We hypothesized that diabetes-related depression might be associated with the mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-glutamate receptor2 (GluR2)-Parkin pathway. To testify this hypothesis, here the rat model of DD in vivo and in vitro were both established so as to uncover the potential mechanism of DD based on mitophagy and apoptosis. We found that DD rats exhibit an elevated glutamate levels followed by monoamine neurotransmitter deficiency and depressive-like behaviour, and DD modelling promoted autophagosome formation and caused mitochondrial impairment, eventually leading to hippocampal neuron apoptosis via aberrant Glu-GluR2-Parkin pathway. Further, in vitro study demonstrated that the simulated DD conditions resulted in an abnormal glutamate and monoamine neurotransmitter levels followed by autophagic flux increment, mitochondrial membrane potential reduction and mitochondrial reactive oxygen species and lactic dehydrogenase elevation. Interestingly, both GluR2 and mammalian target of rapamycin (mTOR) receptor blocker aggravated mitophagy-induced hippocampal neuron apoptosis and abnormal expression of apoptotic protein. In contrast, both GluR2 and mTOR receptor agonist ameliorated those apoptosis in simulated DD conditions. Our findings revealed that mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-GluR2-Parkin pathway, is responsible for depressive-like behaviour and monoamine neurotransmitter deficiency in DD rats. This work provides promising molecular targets and strategy for the treatment of DD.

Effects of different drying methods on the chemical constituents of Lilium lancifolium Thunb. based on UHPLC-MS analysis and antidepressant activity of the main chemical component regaloside A.

The Lilium lancifolium Thunb. is a herb with multiple functions in both medicine and food in China, and its extracts have shown antidepressant effects. In this study, fresh bulbs of Lilium lancifolium Thunb. were processed to study the effects of different drying processes on changes in its main chemical components. We found that different drying methods can affect the chemical constituents of the herb. Among these components, Regaloside A has been found as the characteristic component. Here, Cell Counting Kit-8 assay, and Western blotting were used to evaluate the neuroprotective antidepressant effects of Regaloside A. The results showed the cell survival rate was improved, the phosphorylation levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphatidylinositol 3 kinase, protein kinase B, and mammalian target of rapamycin were increased after Regaloside A treatment. In general, different drying methods have a significant influence on the chemical composition of the herb, and Regaloside A may be the main chemical component of the herb. It can alleviate the damage of corticosterone in SH-SY5Y cells, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling mediated by brain-derived neurotrophic factor/tyrosine kinase receptor B may play an important role in the neuroprotective antidepressant effects of Regaloside A.

[Effect of Baihe Dihuang Decoction on synaptic plasticity of hippocampus in rats with anxious depression].

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

Evaluating an Intervention Program Using WeChat for Patients With Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.

BACKGROUND: The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results. OBJECTIVE: This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media. It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD. METHODS: The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components. A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]). Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months. The primary outcome was patient quality of life measured with the COPD assessment test (CAT). The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George's Respiratory Questionnaire (SGRQ). RESULTS: The intention-to-treat analysis was used in the study. A total of 94 participants completed the 6-month pulmonary rehabilitation program. No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency. The Ex-SRES score had a significant effect on the CAT score (P=.03). The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24. CONCLUSIONS: The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy. Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3.

Ionization controls for biomineralization-inspired CO2 chemical looping at constant room temperature.

Living organisms such as corals can carry out CO2 looping efficiently via biomineralization under ambient conditions. Inspired by this natural process, we establish a solution system of calcium acetate-ethanol-water (Ca(Ac)2-C2H5OH-H2O) for CO2 chemical looping at constant room temperature. The CO2 capture is achieved by its reaction with Ca(Ac)2 to form calcium carbonate (CaCO3) mineral and HAc in the binary solvent with a high C2H5OH content. However, an increase in the H2O content in the system triggers acetic acid (HAc)-induced CaCO3 dissolution to release CO2. The system can be recovered for CO2 capture readily by the replenishment of C2H5OH. This biomimetic mineralization-based CO2 capture/release is controlled by the ionization states of the electrolytes, and is precisely regulated in the C2H5OH-H2O binary solvent. Our attempt highlights the fundamental principle of solution chemistry in reaction control and provides a bioinspired strategy for CO2 capture/release with very low cost and easy availability.

[Efficiency and outcome of Boari bladder flap plasty surgery for the treatment of middle and lower ureteral carcinoma].

OBJECTIVE: To study the effect and outcome of Boari bladder flap plasty surgery for the treatment of kidney-sparing strategy for patients with middle and lower ureteral carcinoma. METHODS: Database at the department of urology in the Second Xiangya Hospital from 2002-2007 was screened and all cases of primary solitary lower ureteral carcinoma treated with Boari bladder flap plasty surgery or radical nephroureterectomy were collected. We performed a retrospective review of the clinical data including sex, age, smoking history, tumor site, size, stage, grade, bladder recurrence, renal function et al and evaluated survival rate. The Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time. RESULTS: Thirty nine patients in total were enrolled, including 16 cases underwent Boari bladder flap plasty surgery and 23 cases underwent radical nephroureterectomy. The median follow-up time was 53 months (range 10-84 months). During the follow-up time, 18 patients died, including 6 patients treated with Boari bladder flap plasty surgery and 12 patients treated with radical nephroureterectomy. The estimated bladder recurrence-free survival rate and cancer-specific survival rate at 5 years were 63% vs 59% and 73.8% vs 73.5%, respectively (P>0.05). The survival rate at 5 years and the overall survival rate were 61% vs 57 % and 64.8% vs 58.1% respectively in the 2 groups (P>0.05). There was no significant difference in renal function before surgery between the two groups [creatinine clearance 57 (32-104 ) mL/ min vs 55 (30-102) mL/ min, P>0.05]. Patients underwent Boari bladder flap plasty showed better renal function than patients underwent radical nephroureterectomy [creatinine clearance 55 (35-102) mL/ min vs 43 (30-89) mL/min, P<0.05]. In multivariate Cox regression analysis, the tumor size, pT stage, tumor cell grade and the estimated glomerular filtration rate level were independent factors that affected the overall survival rate of the patients (P<0.05). The tumor size, pT stage and tumor cell grade were positively correlated to the survival time, and the estimated glomerular filtration rate was negatively correlated to the survival time. CONCLUSION: Boari bladder flap plasty surgery could be used to treat lower ureteral carcinoma. Compared with radical nephroureterectomy, Boari bladder flap plasty surgery has equal survival rate and shows superior postoperative renal function.

Significant improvements in CO2 capture by pyridine-containing anion-functionalized ionic liquids through multiple-site cooperative interactions.

A strategy for improving CO2 capture by new anion-functionalized ionic liquids (ILs) making use of multiple site cooperative interactions is reported. An extremely high capacity of up to 1.60 mol CO2 per mol IL and excellent reversibility were achieved by introducing a nitrogen-based interacting site on the phenolate and imidazolate anion. Quantum-chemical calculations, spectroscopic investigations, and calorimetric data demonstrated that multiple-site cooperative interactions between two kinds of interacting sites in the anion and CO2 resulted in superior CO2 capacities, which originated from the π-electron delocalization in the pyridine ring.

Delayed Wound Healing in the Elderly and a New Therapeutic Target: CD271.

With the development of society, the global population is showing a trend of aging. It is well known that age is one of the factors affecting wound healing. Aging compromises the normal physiological process of wound healing, such as the change of skin structure, the decrease of growth factors, the deceleration of cell proliferation, and the weakening of migration ability, hence delaying wound healing. At present, research in adult stem cell-related technology and its derived regenerative medicine provides a novel idea for the treatment of senile wounds. Studies have confirmed that CD271 (P75 neurotropism receptor/P75NTR)-positive cells (CD271+ cells) are a kind of stem cells with a stronger ability of proliferation, differentiation, migration and secretion than CD271 negative (CD271- cells). Meanwhile, the total amount and distribution of CD271 positive cells in different ages of skin are also different, which may be related to the delayed wound healing of aging skin. Therefore, this article reviews the relationship between CD271+ cells and senile wounds and discusses a new scheme for the treatment of senile wounds.

A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.

Mesenchymal stem cells (MSCs) are extensively researched for therapeutic applications in tissue engineering and show significant potential for clinical use. Intrinsic or extrinsic factors causing senescence may lead to reduced proliferation, aberrant differentiation, weakened immunoregulation, and increased inflammation, ultimately limiting the potential of MSCs. It is crucial to comprehend the molecular pathways and internal processes responsible for the decline in MSC function due to senescence in order to devise innovative approaches for rejuvenating senescent MSCs and enhancing MSC treatment. We investigate the main molecular processes involved in senescence, aiming to provide a thorough understanding of senescence-related issues in MSCs. Additionally, we analyze the most recent advancements in cutting-edge approaches to combat MSC senescence based on current research. We are curious whether the aging process of stem cells results in a permanent "memory" and if cellular reprogramming may potentially revert the aging epigenome to a more youthful state.

Diagnosis and treatment intraorbital foreign body: A case report.

Key Clinical Message: Wooden foreign bodies inside the eye socket are an uncommon kind of eye injury that falls into a distinct category of intraorbital foreign bodies. Due to the wide range of clinical presentations and imaging features of intraorbital wooden foreign bodies, misinterpretation and failure to diagnose correctly often happen. Abstract: Wooden foreign bodies inside the eye socket are an uncommon kind of eye injury that falls into a distinct category of intraorbital foreign bodies. The condition mostly manifested in individuals of youthful and middle age. Due to the wide range of clinical presentations and imaging features of intraorbital wooden foreign bodies, misinterpretation and failure to diagnose correctly often happen during the first examination. The risk of orbital infection might greatly rise if there is a delay in diagnosing woody foreign substances inside the eye socket. The majority of patients need surgical intervention as the recommended course of therapy. Nevertheless, it is essential to avoid disregarding undetected diagnoses and the existence of foreign material remnants after prior surgical procedures. Hence, achieving a precise diagnosis relies on a comprehensive assessment of the patient's trauma history, meticulous examination of the eyes, vigilant monitoring of clinical symptoms, accurate imaging techniques such as magnetic resonance imaging (MRI) or computerized tomography (CT), and prompt and thorough removal of wooden foreign objects within the eye socket.

Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.

Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.