Parents' Experiences of Communicating With Children About Their Diagnosis of Nonterminal Cancer and Its Related Issues: A Systematic Review of Qualitative Studies.

BACKGROUND: Many children experience serious symptoms when they are diagnosed with and treated for cancer. Through appropriate parent-child communication, parents were able to identify children's physical and psychological problems, adjust their behavior, and help them cope with the disease. OBJECTIVE: This study aimed to systematically search for and integrate evidence from qualitative studies on communication between parents and children with nonterminal cancer from parents' perspectives. METHODS: A thorough systematic review and metasynthesis of qualitative studies were conducted. Articles were searched from PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, and PsycArticles from the database inception to November 6, 2022. After screening and quality appraisal, 14 articles were finally included in the metasynthesis. RESULTS: Three themes and 11 subthemes were identified: (1) communication content, including diagnosis, treatment, health management, health risk, and emotion; (2) factors influencing communication, including ages of children, parents' experience of communication, parents' awareness of protection, and culture; and (3) children's responses, including acceptance and resistance. CONCLUSIONS: This systematic review found that parents were influenced by various factors during the decision-making process of parent-child communication about childhood cancer and its related issues. Parents tended to adjust their communication content and style to protect their children. IMPLICATIONS FOR PRACTICE: Future research should be conducted to explore children's experiences of communicating with their parents and analyze the similarities and differences between the communication needs of parents and children. Healthcare professionals should provide professional communication guidance to facilitate the parent-child relationship and improve the mental health of both children and their parents.

5-Aminolevulinic acid combined with ferrous iron ameliorates scrotal heat stress-induced spermatogenic damage by enhancing HO-1 expression.

OBJECTIVE: To explore whether 5-Aminolevulinic acid combined with ferrous iron (5-ALA/Fe2+) could protect testicular tissues damage of mice subjected to heat stress (HS) and provide its underlying mechanisms. METHODS: 5-ALA/Fe2+ was administered intragastrically to mice for 10 days, then exposed to a scrotal heat stress at 43°C for 20 min on third day. Testes were harvested for morphologic and histopathological examination, oxidative stress, apoptosis, heme oxygenase-1 (HO-1) and inflammation detection. The mitogen-activated protein kinases (MAPK) signaling pathway in testis and CD4+FoxP3+regulatory T (Treg) cells in spleen were also investigated. RESULTS: Compared to control group, the testis weight decreased and histological damage severed in HS group. Besides, HS also increased the oxidative stress, apoptosis and inflammation in testis. However, these indicators were ameliorated after 5-ALA/Fe2+ treatment but deteriorated after receiving ZnPPIX. The expression of HO-1 was increased both in HS group and 5-ALA/Fe2+ group. The protein expression levels of MAPK proteins were activated by HS and inhibited by 5-ALA/Fe2+. The CD4+FoxP3+ Treg generation was reduced by HS and increased by 5-ALA/Fe2+. CONCLUSION: In this study, we have demonstrated that 5-ALA/Fe2+ ameliorated the spermatogenic damage induced by scrotal heat stress via up-regulating the expression of HO-1 and inhibiting MAPK mediated oxidative stress and apoptosis and inducing CD4+Foxp3+ Tregs to inhibit the inflammation induced by HS in mice.

A Cyclodiaryliodonium NOX Inhibitor for the Treatment of Pancreatic Cancer via Enzyme-Activatable Targeted Delivery by Sulfated Glycosaminoglycan Derivatives.

Pancreatic cancer renders a principal cause of cancer mortalities with a dismal prognosis, lacking sufficiently safe and effective therapeutics. Here, diversified cyclodiaryliodonium (CDAI) NADPH oxidase (NOX) inhibitors are rationally designed with tens of nanomolar optimal growth inhibition, and CD44-targeted delivery is implemented using synthesized sulfated glycosaminoglycan derivatives. The self-assembled nanoparticle-drug conjugate (NDC) enables hyaluronidase-activatable controlled release and facilitates cellular trafficking. NOX inhibition reprograms the metabolic phenotype by simultaneously impairing mitochondrial respiration and glycolysis. Moreover, the NDC selectively diminishes non-mitochondrial reactive oxygen species (ROS) but significantly elevates cytotoxic ROS through mitochondrial membrane depolarization. Transcriptomic profiling reveals perturbed p53, NF-κB, and GnRH signaling pathways interconnected with NOX inhibition. After being validated in patient-derived pancreatic cancer cells, the anticancer efficacy is further verified in xenograft mice bearing heterotopic and orthotopic pancreatic tumors, with extended survival and ameliorated systemic toxicity. It is envisaged that the translation of cyclodiaryliodonium inhibitors with an optimized molecular design can be expedited by enzyme-activatable targeted delivery with improved pharmacokinetic profiles and preserved efficacy.

Extracellular vesicles from human urine-derived stem cells merged in hyaluronic acid ameliorate erectile dysfunction in type 2 diabetic rats by glans administration.

BACKGROUND: The high prevalence of erectile dysfunction (ED) in patients with type 2 diabetes mellitus (DM2) is a challenging clinical problem. Researches on extracellular vesicles from urine-derived stem cells (USC-EVs) have shown that they have significant therapeutic effects in a variety of diseases by injection including ED. Hyaluronic acid (HA) is especially useful for delivering bioactive molecules. This study investigated the effects and related mechanisms of local administration of human USC-EVs combined with HA (USC-EVs-HA) on a rat model of DM2ED. METHODS: UCSs were extracted from human urine samples and identified for preparation of the corresponding USC-EVs. The effects of high glucose and USC-EVs on human umbilical vein endothelial cells (HUVECs) were assessed in vitro using a CCK-8 assay to determine cell proliferation and pick the most appropriate concentration for subsequent experiments. Scratch and tube formation assays were performed to assess the function of HUVECs. Quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of genes such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and superoxide dismutase-2 (SOD2). HA, USC-EVs, and USC-EVs-HA were prepared at concentrations and then administered topically to DM2ED rats multiple times. Intracavernous pressure and mean arterial pressure were measured to assess erectile function in rats. Masson, Tunel, Immunohistochemistry, and Western blot analysis were performed to assess the fibrosis and endothelial function in corpus cavernosum, respectively. RESULTS: Compared with the control group, the proliferation, migration ability, and tube-forming ability of HUVECs decreased in high glucose environment, while USC-EVs could optimize the function of HUVECs, reverse the expression of apoptotic genes, and enhance the antioxidant capacity. USC-EVs-HA showed improvement in ED compared to the HA and USC-EVs groups, and the 10-dose group was better than the 5-dose group. Histologically, the USC-EVs-HA group significantly improved apoptosis, angiogenesis, and smooth muscle regeneration in the corpus cavernosum compared to the HA group. CONCLUSIONS: The topical application of USC-EVs-HA in the treatment of DM2ED rats has been proved effective. The potential mechanism might to promote the proliferation of endothelial cells and smooth muscle in the corpus cavernosum, which leads to the remodeling of erectile function. And multiple dosing at intervals may make the effect more pronounced.

Conventional craniotomy versus conservative treatment in patients with minor spontaneous intracerebral hemorrhage in the basal ganglia.

BACKGROUND: The treatment for spontaneous intracerebral hemorrhage (ICH) is still controversial, especially for hematomas in the basal ganglia. A retrospective case-control study with propensity score matching was performed to compare the outcomes of conventional craniotomy and conservative treatment for patients with minor ICH in the basal ganglia. METHODS: We retrospectively collected the data of consecutive patients with minor basal ganglia hemorrhage from January 2018 to August 2019. We compared clinical outcomes of two groups using propensity score matching. The extended Glasgow outcome scale obtained by phone interviews based on questionnaires at a 12-month follow-up was used as the primary outcome measure. According to a previous prognosis algorithm, patients were divided into good and poor prognosis groups to obtain a dichotomized (favorable or unfavorable) outcome as the primary outcome. Secondary outcomes included hospitalized complications, mortality, and modified Rankin score at 12 months. RESULTS: A total of 54 patients were analyzed, and the baseline characteristics of patients in the surgery and conservative treatment groups were well matched. The primary favorable outcome at 12 months was significantly higher in the conservative treatment group than in the surgery group (81% vs 44%; OR 1.833, 95% CI 1.159-2.900; P=0.005). The incidence of pneumonia in the surgery group was significantly higher than that in the conservative treatment group (P=0.005). CONCLUSIONS: It is not recommended to undertake conventional craniotomy for patients with a minor hematoma (25-40 ml) in the basal ganglia. An open craniotomy might induce worse long-term functional outcomes than the conservative treatment.

Inclusive education of elementary students with autism spectrum disorders in Shanghai, China: From the teachers' perspective.

Given an increasing number of children with ASD, the need for inclusive education has rapidly increased in China. Since 2011, children with ASD have been eligible for inclusive education. However, little is known of the implementation process by key personnel. The purpose of the current study was to qualitatively explore elementary school teachers' experiences and perspectives on an inclusive education policy and practice for students with ASD. Participants were from 5 elementary schools in 2 districts in Shanghai. This study consisted of data collection in 2 phases. First, semi-structured, in-depth interviews were conducted with school psychologists and vice principals responsible for students' mental health for implementation of general inclusive education at each school. Second, focus groups of frontline teachers were assembled to hear their firsthand experiences. A thematic analysis was performed. Findings indicated that although all 5 schools had some ASD-related support, training and resources varied depending on whether learning in regular classrooms (LRC) was implemented. Frontline teachers in particular faced challenges implementing LRC, including the limited extent of LRC, tedious implementation procedures, and parents' misconceptions of LRC. Regardless of these challenges, frontline teachers tried to support students with ASD as much as they could. The current findings should help to advance the inclusive education policy in Shanghai, including increasing the availability of inclusive education resources and training for teachers, issuing specific LRC guidance, and reducing ASD-related stigma. This study is among the first to explore the implementation of inclusive education in urban China.

Multidisciplinary approach to screening and management of children with Fabry disease: practice at a Tertiary Children's Hospital in China.

BACKGROUND: Fabry disease (FD) remains poorly recognized, especially in children in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children's hospital in China. METHODS: A multidisciplinary team (MDT) of pediatric FD experts was launched at Children's Hospital of Fudan University. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team. RESULTS: Before the establishment of the MDT, no case was diagnosed with FD in the hospital. However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Four of them started to receive enzyme replacement therapy. CONCLUSION: Screening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach. We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.

COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement Therapy.

BACKGROUND AND OBJECTIVES: During the coronavirus disease 2019 outbreak, the treatment of families with children on long-term KRT is challenging. This study was conducted to identify the current difficulties, worries regarding the next 2 months, and mental distress experienced by families with children on long-term KRT during the coronavirus disease 2019 outbreak and to deliver possible management approaches to ensure uninterrupted treatment for children on long-term KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter online survey was conducted between February 10 and 15, 2020, among the families with children on long-term KRT from five major pediatric dialysis centers in mainland China. The primary caregivers of children currently on long-term KRT were eligible and included. Demographic information, severe acute respiratory syndrome coronavirus 2 infection status, current difficulties, and worries regarding the next 2 months were surveyed using a self-developed questionnaire. The Patient Health Questionnaire-9 and the General Anxiety Disorder Scale-7 were used to screen for depressive symptoms and anxiety, respectively. RESULTS: Among the children in the 220 families included in data analysis, 113 (51%) children were on dialysis, and the other 107 (49%) had kidney transplants. No families reported confirmed or suspected cases of coronavirus disease 2019. Overall, 135 (61%) and 173 (79%) caregivers reported having difficulties now and having worries regarding the next 2 months, respectively. Dialysis supply shortage (dialysis group) and hard to have blood tests (kidney transplantation group) were most commonly reported. A total of 29 (13%) caregivers had depressive symptoms, and 24 (11%) had anxiety. After the survey, we offered online and offline interventions to address their problems. At the time of the submission of this paper, no treatment interruption had been reported. CONCLUSIONS: The coronavirus disease 2019 outbreak has had physical, mental, logistical, and financial effects on families with children on long-term KRT.

Highly Reactive Cyclic Monoaryl Iodoniums Tuned as Carbene Generators Couple with Nucleophiles under Metal-Free Conditions.

Cross-coupling reactions between aryl iodide and nucleophiles have been well developed. Iodoniums equipped with a reactive C-I(III) bond accelerate cross-coupling reactions of aryl iodide. Among them, cyclic diaryliodoniums are more atom economical; however; they are often in the trap of metal reliance and encounter regioselectivity issues. Now, we have developed a series of highly reactive cyclic monoaryl-vinyl iodoniums that can be tuned to construct C-N, C-O, and C-C bonds without metal catalysis. Under promotion of triethylamine, coupling reactions with aniline, phenol, aromatic acid, and indole proceed rapidly and regioselectively at room temperature. The carbene species is conceptualized as a key intermediate in our mechanism model. Furthermore, the coupling products enable diversity-oriented synthesis strategy to further build up a chemical library of diverse heterocyclic fragments that are in demand in the drug discovery field. Our current work provides a deep insight into the synthetic application of these highly reactive cyclic iodoniums.

Ligand- and structural-based discovery of potential small molecules that target the colchicine site of tubulin for cancer treatment.

Small molecules targeting the colchicine site of tubulin represent an attractive cancer treatment strategy. In this study, a total of 468 models derived from 1076 diverse inhibitors binding to the tubulin colchicine site were constructed based on fingerprints using three machine learning approaches: 1) naive Bayesian (NB); 2) single tree (ST); and 3) random forest (RF). The overall predictive accuracy of the best models exceeded 85.12% for both the training and test sets. We designed an integrated virtual screening (VS) strategy for identifying new tubulin inhibitors by combining established models, molecular docking, and similarity-based analog searching. Through two rounds of VS, compound 23g was identified as a novel potent anticancer agent exhibiting activity against MDA-MB-231, HeLa, A549, HepG2, CNE2, and HCT116 tumor cell lines with IC50 values of 5.45, 8.61, 7.47, 2.29, 2.91, and 4.10 µM, respectively. Compared with taxol, colchicine, and adriamycin, 23g also displayed potent cytotoxicity against the drug-resistant tumor cell lines, HepG2/ADR, A549/CDDP, and A549/TAX cells, with IC50 values of 4.12, 6.58, and 6.38 µM, respectively. Further mechanistic studies revealed that 23g inhibited microtubule polymerization by binding to the colchicine site of tubulin, arrested the cell cycle at the G2/M phase, induced cell apoptosis, and exhibited potent in vitro anti-metastasis activity. Finally, molecular docking, molecular dynamics, and free energy analyses were employed to explore the detailed binding interaction between 23g and tubulin. Collectively, these findings indicated that 23g should be further investigated as a potential novel potent antitumor agent targeting tubulin.

Heterocyclic iodoniums as versatile synthons to approach diversified polycyclic heteroarenes.

Polycyclic heteroarenes are important scaffolds in the construction of pharmaceuticals. We have previously developed a series of novel heterocyclic iodoniums. In our current work, these unique iodoniums were employed to construct various complex polycyclic heteroarenes with structural diversity via tandem dual arylations. As a result, indole, thiophene and triphenylene motifs were fused into these heterocycles with high molecular quality, which might provide promising fragments in drug discovery. Moreover, these heterocycles could be diversified at a late stage.

Heterocyclic Iodoniums for the Assembly of Oxygen-Bridged Polycyclic Heteroarenes with Water as the Oxygen Source.

A diverse set of novel heterocyclic iodoniums was synthesized for the first time. The reactions of these unique iodoniums with environmentally benign water as the oxygen source provided structurally complex oxygen-incorporated heteropolycycles that are essential motifs in natural products and biologically active compounds. The transformation only required low-cost copper acetate. Further derivatization of the obtained polycycles expanded the structural diversity, which is important in the building of chemical libraries for drug discovery.

Domino Carbopalladation/C-H Activation as a Quick Access to Polycyclic Frameworks.

A new type of domino reaction for synthesis of heterocycles fusing the important bioactive cores, such as oxindole, indoline, and isoquinoline, is presented. Upon exposure to the very common palladium catalyst, the conceptually designed N-alkenyl iodobiaryls undergo a sequential carbopalladation/C-H activation to build polycyclic frameworks. These novel unique frameworks may provide structure sources in fragment-based drug discovery.

Design, synthesis and biological evaluation of N-arylsulfonyl carbazoles as novel anticancer agents.

In this work, a set of structurally diverse synthetic carbazoles was screened for their anticancer activities. According to structure-activity relationship studies, carbazoles with an N-substituted sulfonyl group exhibited better anticancer activity. Moreover, compound 8h was discovered to show the most potent anticancer effects on Capan-2 cells by inducing apoptosis and cell cycle arrest in G2/M phase. Finally, the in vivo study demonstrated that 8h prevented the tumor growth in PANC-1 and Capan-2 xenograft models without apparent toxicity.

Relayed Regioselective Alkynylation/Olefination of Unsymmetrical Cyclic Diaryliodonium Species Catalyzed by Cu and Pd: Affording Fluorescent Cytotoxic Benzoxazoles.

Although cyclic diaryliodonium species have the potential to act as valuable synthons for cascade transformations, they still remain largely unexplored. The regioselectivity associated with unsymmetrical cyclic diaryliodonium species has previously been known to pose a challenge. A regioselective relayed alkynylation and olefination of unsymmetrical cyclic diaryliodonium species has been achieved by installation of a directing amido group. These relayed transformations were delayed until an oxazole ring had formed, delivering a series of unique fluorescent benzoxazoles. Moreover, some of these synthetic benzoxazoles showed apparent inhibitory activity against malignant cancer cells. Further confocal visualization revealed that benzoxazoles targeted cell nuclei. These findings might provide a novel structural scaffold to develop desirable anticancer agents.

Pd catalyzed insertion of alkynes into cyclic diaryliodoniums: a direct access to multi-substituted phenanthrenes.

Cyclic diaryliodoniums remain unexplored compared to linear iodoniums. In our current work, internal alkynes were for the first time applied to react with cyclic iodoniums, catalyzed by Pd, resulting in a [4 + 2] benzannulation. Our work offers a new strategy to synthesize multi-substituted phenanthrene derivatives which are not easily accessed by conventional methods.

Mild Cu(I)-catalyzed cascade reaction of cyclic diaryliodoniums, sodium azide, and alkynes: efficient synthesis of triazolophenanthridines.

Linear iodoniums are widely used as arylating reagents. However, cyclic diaryl idodoniums are ignored despite their potential to initiate dual arylations, atom and step economically. In our current work, a three-component cascade reaction of cyclic diaryliodoniums, sodium azide, and alkynes has been successfully achieved under mild conditions, catalyzed by cheap copper species. The regioselectivity associated with unsymmetrical iodoniums was enhanced by installing two methyls ortho and para to the I(III) center. The reaction enables a rapid access to a variety of complex molecules, triazolophenanthridine derivatives.

Three-component Pd/Cu-catalyzed cascade reactions of cyclic iodoniums, alkynes, and boronic acids: an approach to methylidenefluorenes.

Linear diaryliodonium salts are widely used as arylating reagents for C-C and C-X bond formation. Meanwhile, synthetic applications of cyclic iodoniums are relatively rare although they offer the opportunity to set up reaction cascades. We demonstrate an atom and step economical three-component reaction involving cyclic diphenyleneiodoniums, alkynes, and boronic acids, resulting in the construction of methylidenefluorenes in a single operation. Our route enables facile access to both symmetrical and unsymmetrical methylidenefluorene derivatives, compounds that have attracted interest due to their optical properties.

Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity.

Carbazole moiety is an important scaffold with a variety of biological applications, for example, anti-oxidative stress. Our previous synthesized carbazoles were screened for their neuroprotective properties against two individual oxidative stresses. Some of the new carbazole derivatives were observed with modest to good neuroprotective effects on neuronal cells HT22 against cell injury induced by glutamate or homocysteic acid (HCA). Substituents introduced to the carbazole ring system play crucial roles in their biological activities. In particular, a bulky group favors the neuroprotective activity of the compounds. One of the new compounds, 6, showed the best neuroprotective effects, which might result from its anti-oxidative activity with a GSH-independent mechanism. These findings might provide an alternative strategy for the development of novel carbazole derivatives for the treatment of CNS diseases such as Alzheimer's disease.