Red/NIR-I-Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics.

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L-arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR-I fluorescent carbon dots based on rhein and doped with L-arginine (RA-CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA-CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR-I light for biological imaging. In vitro experiments show that RA-CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS-induced UC mouse model, both delayed and prophylactic treatment with RA-CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small-molecule drugs.

A common trajectory of gut microbiome development during the first month in healthy neonates with limited inter-individual environmental variations.

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Trends and hotspots related to traditional and modern approaches on acupuncture for stroke: A bibliometric and visualization analysis.

BACKGROUND: Acupuncture role in stroke treatment and post-stroke rehabilitation has garnered significant attention. However, there is a noticeable gap in bibliometric studies on this topic. Additionally, the precision and comprehensive methodology of cluster analysis remain underexplored. This research sought to introduce an innovative cluster analysis technique (called follower-leading clustering algorithm, FLCA) to evaluate global publications and trends related to acupuncture for stroke in the recent decade. METHODS: Publications pertaining to acupuncture for stroke from 2013 to 2022 were sourced from the Web of Science Core Collection. For the assessment of publication attributes-including contributing countries/regions (e.g., US states, provinces, and major cities in China) in comparison to others, institutions, departments, authors, journals, and keywords-we employed bibliometric visualization tools combined with the FLCA algorithm. The analysis findings, inclusive of present research status, prospective trends, and 3 influential articles, were presented through bibliometrics with visualizations. RESULTS: We identified 1050 publications from 92 countries/regions. An initial gradual rise in publication numbers was observed until 2019, marking a pivotal juncture. Prominent contributors in research, based on criteria such as regions, institutions, departments, and authors, were Beijing (China), Beijing Univ Chinese Med (China), the Department of Rehabilitation Medicine, and Lidian Chen (Fujian). The journal "Evid.-based Complement Altern" emerged as the most productive. The FLCA algorithm was effectively employed for co-word and author collaboration analyses. Furthermore, we detail the prevailing research status, anticipated trends, and 3 standout articles via bibliometrics. CONCLUSION: Acupuncture for stroke presents a vast research avenue. It is imperative for scholars from various global regions and institutions to transcend academic boundaries to foster dialogue and cooperation. For forthcoming bibliometric investigations, the application of the FLCA algorithm for cluster analysis is advocated.

First Report of Pseudocercospora paraguayensis Causing Leaf Spots on Bixa orellana from Chinese Mainland.

Bixa orellana L. is a traditional Chinese medicine. In December 2019, a leaf spot disease was observed on B. orellana from a field in Zhanjiang (21°18'12''N, 110°17'22''E), China. Disease incidence was around 85% (n = 100 investigated plants from about 30 hectares). Initial leaf spots were circular, and the center of the lesions was grayish-white with a purple black border. The coalescence of individual spots eventually led to leaf wilt. Ten symptomatic leaves from 10 plants were sampled. The margins of the samples were cut into 2 mm × 2 mm pieces, and the surfaces were disinfected with 75% ethanol for 30 sec, and 2% sodium hypochlorite for 60 sec. The the samples were then rinsed three times in sterile water, plated on potato dextrose agar (PDA), and incubated at 28 °C. Pure cultures were obtained by transferring the hyphal tips to new PDA plates. Three representative isolates (BOPP-1, BOPP-2, and BOPP-3) were used for further study. The colonies of isolates on PDA were dark olive green with off-white aerial mycelia after 7 days at 28 °C. Conidia were solitary, smooth to verrucous, olive to light brown, slightly curved, narrowly obclavate, apex obtuse, base obconic-truncate, had 2-4 septa, and 30.4-55.5×2.0-3.5 µm in size.. These morphological characteristics showed did not differ from the description of Pseudocercospora paraguayensis (Crous et al. 1997). For molecular identification, the internal transcribed spacer (ITS) region, the translation elongation factor 1-α (TEF1) gene, and actin (ACT) gene were amplified using primer pairs ITS1/ITS4 (White et al., 1990), EF1/EF2 ( O'Donnell et al. 1998), and ACT-512F/ACT-783R (Carbone and Kohn, 1999) and sequenced from DNA extracted from the three isolates, respectively. Sequences were deposited in GenBank under accession no. MZ363823-MZ363825 (ITS), MZ614954-MZ614956 (TEF1), and MZ614951-MZ614953 (ACT). A phylogenetic tree was generated on the basis of the concatenated data from the sequences of ITS, TEF1, and ACT that the three isolates were nested within the clade containing the type specimen of P. paraguayensis (CBS 111286) but not within P. bixae (the type specimen CPC 25244). Pathogenicity was tested through in vivo experiments. Inoculation and control seedlings (n = 5, 1-month-old) were sprayed with a spore suspension (1 × 105 per ml) of P. paraguayensis and sterile distilled water (control), respectively, until run-off (Fang. 1998). The plants were grown in pots in a greenhouse at 28°C, with at approximately 80% RH. The test was performed three times. Symptoms similar to those in the field were observed on the inoculated plants after two weeks. The control plants remained healthy. The fungus was re-isolated from the infected leaves and confirmed as the same isolates by morphological and comparison of ITS sequences with 100% identical to those of isolates. No original fungi were isolated from the control plants. A previous study reported that P. paraguayensis caused leaf spots on pistachio and eucalypts, and the fungus causing the leaf spots of B. orellana was redescribed as P. bixae (Crous et al. 2019). However, multilocus phylogenetic analyses differentiated P. paraguayensis from P. bixae. In the present study, P. paraguayensis was distinguished from P. bixae due to the absence of catenulate conidia and the presence of finely verruculose conidia (Crous et al. 2013). P. eucalypti as a synonyms was reported in Taiwan (www.MycoBank.org). The current study is the first to report P. paraguayensis causing leaf spots on B. orellana from Chinese Mainland. This finding will help to provide a scientific basis for the disease detection.

One-Step Robot-Assisted Complete Urinary Tract Extirpation in Man with End-Stage Renal Disease on Dialysis: The First Case Report.

Urothelial carcinoma (UC) could be observed in urinary bladder (UBUC) and upper urinary tracts (UTUC). In the National Comprehensive Cancer Network guidelines for bladder cancer, extirpative surgery is indicated in certain cases. However, some extreme cases might also need the extirpation of the majority of the urinary tract, which is called complete urinary tract extirpation (CUTE). We present a patient diagnosed with high-grade UBUC and UTUC. He underwent dialysis for end-stage renal disease (ESRD) at the same time. Considering his non-functional kidneys and removing his high-risk urothelium at the same time, we performed robot-assisted CUTE to extirpate both his upper urinary tracts, urinary bladder, and prostate. In our experience, the console time was not significantly elongated, and the perioperative course was uneventful. To our knowledge, this is the first case report adopting a robotic system in such an extreme case. We conclude that robot-assisted CUTE is worth further study regarding its oncological survival outcomes and perioperative safety in patients with ESRD on dialysis.

[Re-thinking the acupoint-visceral correlation: evidence from clinical literature and its biological mechanism].

The regularity of acupoint-viscera correlation is a basic problem in the study of acupuncture and moxibustion. At present, there are two main theories of the regularities: (1) the law of acupoint effect determined by meridian circulation; (2) segmental dominance of acupoint effect. These two regularities belong to different paradigm systems, they are not complementary relations within the same conceptual system. Based on the evidence of clinical practice of acupuncture and moxibustion, combined with the research on biological mechanisms, this paper analyzed the objectivity and universality of the regularities of acupoint-visceral correlation. The law determined by meridian of acupoint effect does not manifests the universality guiding role in the clinical practice of modern acupuncture and moxibustion, which is obviously divorced from the needs of modern clinical practice. The segmental dominance of acupoint effect has been strongly supported by the clinical practice of modern acupuncture and moxibustion, which is highly consistent with the clinical practice. The regularity of acupoint effect needs to be tested and re-identified in practice.

Anti-Inflammatory and Anti-oxidative Effects of Puerarin in Postmenopausal Cardioprotection: Roles of Akt and Heme Oxygenase-1.

During menopause, the sharp decline in estrogen levels leads to an increased risk of cardiovascular disease in women. The inflammatory response and oxidative stress are reportedly involved in the development of cardiovascular disorders postmenopause. In this study, we evaluated the cardioprotective effects of puerarin, a phytoestrogen derived from the root of Pueraria lobate, and investigated its underlying molecular mechanisms. Puerarin alleviated cytotoxicity and the production of reactive oxygen species (ROS) in lipopolysaccharide (LPS)- and hydrogen peroxide-stimulated H9c2 cardiomyoblasts. Puerarin scavenges free radicals and reduces apoptosis, thereby suppressing NADPH oxidase-1 and Bax activation to attenuate the production of ROS and restore Bcl-2 expression. Additionally, puerarin inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nitric oxide production and decreased the hypertrophic phenotype under LPS stimulation. Treatment with puerarin reduced the levels of malondialdehyde and restored glutathione levels when facing oxidative stress. Mechanistically, puerarin inhibited both the LPS-induced Toll-like receptor 4/NF-[Formula: see text]B and mitogen-activated protein kinase signaling pathways. Furthermore, it reversed both the LPS-mediated downregulation of Akt activation and heme oxygenase-1 (HO-1) expression. The cardioprotective effects of puerarin were abolished by inhibitors of Akt and HO-1 and the estrogen receptor antagonist fulvestrant (ICI). This indicated that the estrogen receptor mediated by these two molecules plays important roles in conferring the anti-inflammatory and anti-oxidative functions of puerarin. These results demonstrate the therapeutic potential of puerarin for treating heart disease in postmenopausal women through Akt and HO-1 activation.

Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients.

Background: Rigid dietary controls and pill burden make a very-low protein (0.3−0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41−0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy.

Vitamin C (VitC) has shown great promise to promote cancer immunotherapy, however, its high hydrophilicity makes it quickly excreted, leading to limited therapeutic efficiency even with frequent high-dose administration. Herein, we provide a pioneering report about the employment of VitC amphiphile self-assembled nanofiber hydrogels for enhanced cancer immunotherapy. Specifically, driven by hydrogen bonding and hydrophobic interactions, the synthesized VitC amphiphile, consisting of a hydrophilic VitC headgroup and a hydrophobic alkyl chain, could self-assemble into an injectable nanofiber hydrogel with self-healing properties. The formed VitC hydrogel not only serves as a reservoir for VitC but also acts as an effective delivery platform for stimulator of interferon genes (STING) agonist-4 (SA). Interestingly, the VitC hydrogel itself exhibits antitumor effects by upregulating genes related to interferon (IFN) signaling, apoptotic signaling and viral recognition and defense. Moreover, the SA-encapsulated VitC hydrogel (SA@VitC hydrogel) synergistically activated the immune system to inhibit the progression of both local and abscopal tumors.

One-dimensional scanning multiphoton imaging reveals prolonged calcium transient and sarcomere contraction in a zebrafish model of doxorubicin cardiotoxicity.

Doxorubicin (DOX) is a potent chemotherapeutic agent known to induce cardiotoxicity. Here we applied one-dimensional scanning multiphoton imaging to investigate the derangement of cardiac dynamics induced by DOX on a zebrafish model. DOX changed the cell morphology and significantly prolonged calcium transient and sarcomere contraction, leading to an arrhythmia-like contractile disorder. The restoration phase of calcium transient dominated the overall prolongation, indicating that DOX perturbed primarily the protein functions responsible for recycling cytosolic calcium ions. This novel finding supplements the existing mechanism of DOX cardiotoxicity. We anticipate that this approach should help mechanistic studies of drug-induced cardiotoxicity or heart diseases.

Supplemented Low-Protein Diet May Delay the Need for Preemptive Kidney Transplantation: A Nationwide Population-Based Cohort Study.

BACKGROUND: Although several studies suggest the benefit of a low-protein diet supplemented with amino acids and keto acids (sLPD) in delaying the initiation of hemodialysis, evidence on whether these nutritional approaches could delay the timing of preemptive transplantation is lacking. METHODS: Retrospective nationwide cohort study, from Taiwan's National Health Insurance Research Database. Patients having undergone a first preemptive kidney transplantation between 2001 and 2017 were identified and divided into two groups according to the presence of sLPD treatment or not. The primary outcome was the time between the diagnosis of advanced CKD and transplantation. Secondary outcomes were post-transplantation adverse events. RESULTS: A total of 245 patients who received their first preemptive kidney transplantation were identified from the nationwide database; 63 of them had been on an sLPD prior to transplantation (sLPD group). The duration between the day of advanced CKD diagnosis and the day of transplantation was significantly longer in the sLPD group compared with the non-sLPD group (median duration: 345 vs. 220 days, p = 0.001). The risk of post-transplantation adverse events did not differ between the two groups. CONCLUSIONS: Within the limits of its observational, retrospective design, this is the first study to suggest that nutritional management with sLPDs can safely delay the timing of preemptive kidney transplantation.

Network pharmacology for the identification of phytochemicals in traditional Chinese medicine for COVID-19 that may regulate interleukin-6.

OBJECTIVE: ´Three formulas and three medicines,' namely, Jinhua Qinggan Granule, Lianhua Qingwen Capsule, Xuebijing Injection, Qingfei Paidu Decoction, HuaShi BaiDu Formula, and XuanFei BaiDu Granule, were proven to be effective for coronavirus disease 2019 (COVID-19) treatment. The present study aimed to identify the active chemical constituents of this traditional Chinese medicine (TCM) and investigate their mechanisms through interleukin-6 (IL-6) integrating network pharmacological approaches. METHODS: We collected the compounds from all herbal ingredients of the previously mentioned TCM, but those that could down-regulate IL-6 were screened through the network pharmacology approach. Then, we modeled molecular docking to evaluate the binding affinity between compounds and IL-6. Furthermore, we analyzed the biological processes and pathways of compounds. Finally, we screened out the core genes of compounds through the construction of the protein-protein interaction network and the excavation of gene clusters of compounds. RESULTS: The network pharmacology research showed that TCM could decrease IL-6 using several compounds, such as quercetin, ursolic acid, luteolin, and rutin. Molecular docking results showed that the molecular binding affinity with IL-6 of all compounds except γ-aminobutyric acid was < -5.0 kJ/mol, indicating the potential of numerous active compounds in TCM to directly interact with IL-6, leading to an anti-inflammation effect. Finally, Cytoscape 3.7.2 was used to topologize the biological processes and pathways of compounds, revealing potential mechanisms for COVID-19 treatment. CONCLUSION: These results indicated the positive effect of TCM on the prevention and rehabilitation of COVID-19 in at-risk people. Quercetin, ursolic acid, luteolin, and rutin could inhibit COVID-19 by down-regulating IL-6.

Effectiveness and Safety of Umbilicus Treatment with Modified Dinggui Powder () in Patients with Chronic Nonbacterial Prostatitis: A Randomized, Double-blind, Placebo-controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP).@*METHODS@#A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial.@*RESULTS@#The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial.@*CONCLUSION@#A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).

Efficacy of Exercise on Fall in Old Adults: A Network Meta-analysis / 中国康复理论与实践

Objective:To evaluate the efficacy of exercise on preventing falls in the elderly. Methods:Literatures of randomized controlled trials about exercises for prevention of falls in the elderly were retrieved from Web of Science, PubMed, Cochrane Library and CNKI from 1980 to July, 2020. The qualities were evaluated with Review Manager 5.3, and the data were analyzed with R-Studio and Addis 1.16.6. Results:A total of 172 randomized controlled trials were finally included, with nine kinds of exercise intervention. The cognition and movement multitask training was the most effective to decrease fall rate (OR = 0.26, 95%CI 0.14 to 0.49, P < 0.05). The combined physical and whole body vibration training was the most effective to improve the score of Berg Balance Scale (d = 6.3, 95%CI 3.5 to 9.2, P < 0.05) and the time of Timed 'Up & Go' Test (d = -4.5, 95%CI -6.8 to -2.1, P < 0.05). The blood flow restriction training was the most effective to increase the lower limb muscle strength (d = 12, 95%CI 7.4 to 16, P < 0.05). Conclusion:The cognition and movement multitask training is the first recommended exercise to prevent falls in the elderly, followed by Taiji Quan and multimodal training. Gait practice or resistance training are the least effective. A variety of new intervention methods (blood flow restriction training, combined physical and whole body vibration training, Wit Fit training, etc.) may improve the physical function of the elderly, and need further researches.

Risk factors of acute renal impairment after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Acute renal impairment (ARI) is a major complication after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for cancer patients with peritoneal metastases. This study aimed to investigate the incidence and identify the risk factors of post-HIPEC creatinine increased. METHODS: From April 2015 to December 2019, demographic and perioperative data of 169 patients undergoing CRS/HIPEC with a preoperative creatinine level <1.5 mg/dL were retrospectively reviewed. Renal impairment was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The risk factors of creatinine increased were analyzed using univariate and multiple logistic regression analyses. RESULTS: Among the 169 enrolled patients, 21 (12.4%) had postoperative creatinine increased (ARI group) and 148 (87.6%) did not (non-ARI group). Significantly more of the ARI group received a cisplatin HIPEC regimen than the non-ARI group (71.4 vs. 37.8%, p = 0.004). Multiple logistic regression analysis revealed that the patients who received a cisplatin HIPEC regimen (adjusted odds ratio [AOR] = 11.38, p < 0.001) and peritoneal dialysis solution as HIPEC perfusate (AOR = 7.07, p = 0.002) were more likely to develop post-HIPEC creatinine increased. CONCLUSIONS: Identifying the risk factors of post-HIPEC creatinine increased can help to improve patient selection, a dose of HIPEC regimens modification and perioperative care. We also identified the detrimental renal effect of peritoneal dialysis solution as HIPEC perfusate. More prospective studies are warranted to confirm these findings.

Plasma-activated medium as adjuvant therapy for lung cancer with malignant pleural effusion.

This study compared effects of plasma-activated medium (PAM) with effects of conventional clinical thermal therapy on both lung cancer cells and benign cells for management of malignant pleural effusion (MPE). For MPE treatment, chemotherapy, photodynamic therapy, and thermal therapy are used but caused systemic side effects, patient photosensitivity, and edema, respectively. Recent studies show that plasma induces apoptosis in cancer cells with minor effects on normal cells and is cost-effective. However, the effects of plasma on MPE have not been investigated previously. This study applied a nonthermal atmospheric-pressure plasma jet to treat RPMI medium to produce PAM, carefully controlled the long-life reactive oxygen and nitrogen species concentration in PAM, and treated the cells. The influence of PAM treatment on the microenvironment of cells was also checked. The results indicated that PAM selectively inhibited CL1-5 and A549 cells, exerting minor effects on benign mesothelial and fibroblast cells. In contrast to selective lethal effects of PAM, thermal therapy inhibited both CL1-5 and benign mesothelial cells. This study also found that fibroblast growth factor 1 is not the factor explaining why PAM can selectively inhibit CL1-5 cells. These results indicate that PAM is potentially a less-harmful and cost-effective adjuvant therapy for MPE.

Glucosamine Enhancement of BDNF Expression and Animal Cognitive Function.

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.

Combined chelation with high-dose deferiprone and deferoxamine to improve survival and restore cardiac function effectively in patients with transfusion-dependent thalassemia presenting severe cardiac complications.

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.

Bacteria-triggered tumor-specific thrombosis to enable potent photothermal immunotherapy of cancer.

We discovered that attenuated Salmonella after intravenous injection would proliferate within various types of solid tumors but show rapid clearance in normal organs, without rendering notable toxicity. Bacteria-induced inflammation would trigger thrombosis in the infected tumors by destroying tumor blood vessels. Six types of tested tumors would all turn into darkened color with strong near-infrared absorbance, as observed by photoacoustic imaging. Under laser irradiation, those bacterial-infected tumors would be effectively ablated. Because of the immune-stimulation function, such bacteria-based photothermal therapy (PTT) would subsequently trigger antitumor immune responses, which could be further enhanced by immune checkpoint blockade to effectively suppress the growth of abscopal tumors. A robust immune memory effect to reject rechallenged tumors is also observed after bacteria-based PTT. Our work demonstrates that bacteria by themselves could act as a tumor-specific PTT agent to enable photoimmunotherapy cancer therapy to inhibit tumor metastasis and recurrence.

Integrative review of breast cancer survivors' transition experience and transitional care: dialog with transition theory perspectives.

The health of breast cancer survivors (BCSs) is an essential concern worldwide. This review summarizes current knowledge and proposes a novel framework for understanding BCSs' transition experiences and adopting a more holistic view of transitional care to ensure a successful shift from patient-to-survivor. An integrative review was applied whereby we searched CINAHL, MEDLINE, PubMed, and ProQuest. Eleven qualitative and 16 experimental articles were extracted and evaluated. Constant comparison and matrix classification were used for data analysis, extraction, and synthesizing, which were circulated between the study findings and transitions theory. The breast cancer survivors' incorporated transition theory (BCSITT) encompasses the concepts of transition nature, conditions, intervention strategies, and patterns of response as developed from the data analysis. Facilitators and inhibitors of BCSs' transition experience in the personal, interpersonal, organizational, communal, societal dimensions as well as an empirical intervention of BCSs' transitional care from micro to macro levels are proposed. In conclusion, the BCSITT could provide comprehensive insights for understanding the phenomenon of BCSs' transition from primary treatment completion to self-management and serve as a holistic framework to guide clinical practice and research for BCSs' transitional care. Health care professionals need to assess the readiness of BCSs for transition and provide early interventions for enhancing BCSs' mastering of new skills to manage the challenges of transition. Incorporating stakeholders at each level and providing a comprehensive continuum of care may successfully assist BCSs' patient-to-survivor transition.