Phenolic Ligand-Metal Charge Transfer Induced Copper Nanozyme with Reactive Oxygen Species-Scavenging Ability for Chronic Wound Healing.

Chronic wounds frequently arise as a complication in diabetic patients, and their management remains a significant clinical hurdle due to their nonhealing nature featured by heightened oxidative stress and impaired healing cells at the wound site. Herein, we present a 2D copper antioxidant nanozyme induced by phenolic ligand-metal charge transfer (LMCT) to eliminate reactive oxygen species (ROS) and facilitate the healing of chronic diabetic wounds. We found that polyphenol ligands coordinated on the Cu3(PO4)2 nanosheets led to a strong charge transfer at the interface and regulated the valence states of Cu. The obtained Cu nanozyme exhibited efficient scavenging ability toward different oxidative species and protected human cells from oxidative damage. The nanozyme enhanced the healing of diabetic wounds by promoting re-epithelialization, collagen deposition, angiogenesis, and immunoregulation. This work demonstrates the LMCT-induced ROS scavenging ability on a nanointerface, providing an alternative strategy of constructing metal-based nanozymes for the treatment of diabetic wounds as well as other diseases.

Diabetes mellitus in long-term survivors with colorectal, breast, or prostate cancer: Prevalence and prognosis. A population-based study.

BACKGROUND: Patients with cancer are at increased risk of diabetes mellitus (DM). Previous studies on the prevalence and prognostic impact of DM in cancer survivors were limited by small sample sizes or short follow-up times. We aimed to compare the patient-reported prevalence of DM in long-term cancer survivors (LTCS), who survived 5 years or more after cancer diagnosis, with that in cancer-free controls, and to estimate the mortality risk among LTCS according to DM status. METHODS: Our population-based cohort comprised 6952 LTCS diagnosed with breast, colorectal, or prostate cancer between 1994 and 2004, recruited in 2008-2011 (baseline), and followed until 2019. A total of 1828 cancer-free individuals served as controls. Multivariable logistic regression was used to compare the prevalence of DM in LTCS and controls, and according to covariates at baseline. Mortality among LTCS according to DM was assessed by Cox proportional hazards regression. RESULTS: A total of 962 (13.8%) LTCS at baseline reported DM. Prevalence of DM in LTCS was not higher than in cancer-free controls, both at baseline (odds ratio, 0.80; 95% CI, 0.66-0.97) and at follow-up (odds ratio, 0.83; 95% CI, 0.67-1.04). Prevalence of DM in LTCS was associated with cancer site, older age, lower education, higher socioeconomic deprivation, higher body mass index, physical inactivity, other comorbidities, and poorer prognosis (adjusted hazard ratio [all-cause mortality] = 1.29; 95% CI, 1.15-1.44). CONCLUSION: DM in LTCS is prevalent, but not higher than in cancer-free population controls. Cancer survivors with concurrent DM are at a potentially higher risk of death. PLAIN LANGUAGE SUMMARY: Cancer and diabetes mellitus (DM) are two serious threats to global health. In our study, prevalence of DM in long-term cancer survivors who survived 5 years or more after cancer diagnosis was not higher than in cancer-free controls. This should not be interpreted as an indication of a lower risk of DM in cancer survivors. Rather, it highlights the potentially poor prognosis in diabetic cancer survivors. Therefore, keeping a continuous satisfactory DM and hyperglycemia management is essential during long-term cancer survivorship.

Chinese Cancer Patients' Attitudes Toward Psychotherapy and Their Willingness to Participate in Clinical Trials of Psychotherapy.

INTRODUCTION: Psychotherapy is considered part of the standard treatment of cancer in Western countries. However, there is no literature on the attitudes of Chinese cancer patients toward psychotherapy. METHODS: In a multicenter, cross-sectional study in China, a homemade questionnaire was delivered to cancer patients. The targeted population was Chinese hospitalized cancer patients who were informed of their state of illness. RESULTS: Five hundred and fifty cancer patients received our questionnaire, and 83.3% completed the questionnaire. Among the 458 patients, 43.2% indicated that they had never heard of psychotherapy before the survey. However, after a brief introduction of psychotherapy, most (92.1%) cancer patients indicated that psychotherapy is essential for cancer patients, and over half of patients (57.4%) were willing to take psychotherapy on the advice of the oncologist in charge. Participants aged 45 years or younger, had a family income > 10000 yuan per month, and had an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 2-4 were more willing to receive psychotherapy. Of all patients, 59.2% and 57.6% were willing to participate in individual and group psychotherapy clinical trials, respectively. Participants who had a bachelor's degree or higher (odds ratio, OR = 2.09) and were aged 45 years or younger (OR = 1.67) were more willing to participate in individual and group psychotherapy clinical trials, respectively. CONCLUSION: The unmet psychological needs of cancer patients in China remain high, and doctors' advice is likely to positively impact the patients' acceptance of psychotherapy. Psychological education for Chinese cancer patients should be strengthened. More high-quality clinical trials of psychotherapy should be conducted in China to achieve greater benefits for cancer patients and their families.

Higher Incidence of Diabetes in Cancer Patients Compared to Cancer-Free Population Controls: A Systematic Review and Meta-Analysis.

Background: Diabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. Methods: A systematic electronic literature search was carried out from cohort studies regarding the incidence of diabetes in cancer patients, using the databases PubMed (MEDLINE), Embase, Web of Science, and the Cochrane Library. Random-effects meta-analyses were conducted to pool the estimates. Results: A total of 34 articles involving 360,971 cancer patients and 1,819,451 cancer-free controls were included in the meta-analysis. An increased pooled relative risk (RR) of 1.42 (95% confidence interval (CI): 1.30−1.54, I2 = 95, τ2 = 0.0551, p < 0.01) for diabetes in cancer patients was found compared with the cancer-free population. The highest relative risk was observed in the first year after cancer diagnosis (RR = 2.06; 95% CI 1.63−2.60). Conclusions: New-onset diabetes is positively associated with cancer, but this association varies according to cancer type. More prospective studies with large sample sizes and longer follow-up times are advocated to further examine the association and the underlying mechanisms.

Locally advanced malignant solitary fibrous tumour successfully treated with conversion chemotherapy, operation and postoperative radiotherapy: a case report.

Preoperative diagnosis of solitary fibrous tumour (SFT) may not provide a complete tumour picture and may be inaccurate. There is no standard treatment for locally advanced or metastasised malignant SFT (MSFT). Here, the case of a 17-year-old male patient with final pathology diagnosis of MSFT is reported. Preoperative biopsy pathology results suggested an Ewing sarcoma that was positive for CD99 antigen, vimentin, friend leukaemia integration 1 transcription factor, apoptosis regulator Bcl-2, and synaptophysin; and negative for CD34 antigen, S-100 protein (S-100), smooth muscle antigen, cytokeratin, and Wilms tumour 1 associated protein. The Ki67 positive rate was 8%, so the patient initially received eight cycles of conversion chemotherapy (vincristine, etoposide, ifosfamide and pirarubicin for one cycle, and vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide for 7 cycles in total). The tumour shrunk significantly and was surgically removed. The final pathology diagnosis was MSFT that was positive for CD99 and signal transducer and activator of transcription 6, and negative for CD34, tumour protein 63, S-100, desmin, and epithelial membrane antigen. Fluorescence in situ hybridization showed no gene translocation in EWS RNA binding protein 1, SS18 subunit of BAF chromatin remodelling complex or FUS RNA binding protein. The patient finally accepted adjuvant radiotherapy of 5600 cGy. Disease-free survival has been > 1 year, with no recurrence or metastasis detected to date. MSFT is rare and treatment for locally advanced or metastatic MSFT remains controversial. The efficacy of the present therapeutic strategy requires further research.

Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer.

Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.

Attitudes Of Chinese Cancer Patients Toward The Clinical Use Of Artificial Intelligence.

PURPOSE: Artificial intelligence (AI) plays a substantial role in many domains, including medical fields. However, we still lack evidence to support whether or not cancer patients will accept the clinical use of AI. This research aims to assess the attitudes of Chinese cancer patients toward the clinical use of artificial intelligence in medicine (AIM), and to analyze the possible influencing factors. PATIENTS AND METHODS: A questionnaire was delivered to 527 participants. Targeted people were Chinese cancer patients who were informed of their cancer diagnosis. RESULTS: The effective response rate was 76.3% (402/527). Most cancer patients trusted AIMs in both stages of diagnosis and treatment, and participants who had heard of AIMs were more likely to trust them in the diagnosis phase. When an AIM's diagnosis diverged from a human doctor' s, ethnic minorities, and those who had received traditional Chinese medicine (TCM), had never received chemotherapy, were more likely to choose "AIM", and when an AIM's therapeutic advice diverged from a human doctor's, male participants, and those who had received TCM or surgery, were more likely to choose "AIM". CONCLUSION: Most Chinese cancer patients believed in the AIM to some extent. Nevertheless, most still thought that oncology physicians were more trustworthy when their opinions diverged. Participants' gender, race, treatment received, and AIM related knowledge might influence their attitudes toward the AIM. Most participants thought AIM would assist oncology physicians in the future, while little really believed that oncology physicians would completely be replaced.

Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors.

Several groups have suggested that transplantation of marrow stromal cells (MSCs) promotes functional recovery in animal models of brain trauma. Recent studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit, as transplanted MSCs have only limited ability to replace injured central nervous system (CNS) tissue. To gain insight into the mechanisms responsible for such effects, we systematically investigated the therapeutic potential of MSCs for treatment of brain injury. Using in vitro studies, we detected the synthesis of various growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). Enzyme-linked immunosorbent assay (ELISA) demonstrated that MSCs cultured in Dulbecco's modified Eagle medium (DMEM) produced substantial amounts of NGF for at least 7 weeks, whereas the levels of BDNF, GDNF and NT-3 remained unchanged. In studies in mice, after intraventricular injection of MSCs, NGF levels were increased significantly in cerebrospinal fluid by ELISA, confirming our cell culture results. Further studies showed that treatment of traumatic brain injury with MSCs could attenuate the loss of cholinergic neuronal immunostaining in the medial septum of mice. These studies demonstrate for the first time that by increasing the brain concentration of NGF, intraventricularly transplanted MSCs might play an important role in the treatment of traumatic brain injury.

Reduced inflammatory reactions to the inoculation of helper-dependent adenoviral vectors in traumatically injured rat brain.

Traumatic brain injury (TBI) causes delayed neuronal deficits that in principle could be prevented by timely intervention with therapeutic genes. However, appropriate vectors for gene transfer to the brain with TBI remain to be developed. First-generation adenoviruses (fgAd) are usually associated with inflammatory and toxic effects when inoculated into brains, despite their high efficiency of gene transfer to these tissues. In this study the authors attempted to determine whether a less immunogenic gene-transfer protocol can be established in the traumatically injured rat brain using helper-dependent adenoviruses (hdAd), a novel adenoviral construct with full deletion of viral coding sequences. Their results show that transgene expression from intrahippocampally inoculated hdAd is maintained for at least 2 months after TBI, in contrast to the much shorter duration of fgAd-mediated gene expression. There was only minimal secretion of proinflammatory IL-1beta and TNF-alpha after inoculation of hdAd. Furthermore, the hdAd-mediated gene expression was associated with less microglial proliferation, astrocytic activation, and macrophage infiltration than observed in fgAd-inoculated brains. There was no additional tissue loss after hdAd inoculation compared with PBS injection. Although both anti-adenoviral and neutralizing antibodies were found in serum after brain inoculation of hdAd, they did not appear to affect transgene expression. The results suggest that hdAd are less immunogenic vectors than conventional adenoviral vectors, and offer improved vehicles for long-term therapeutic transgene transfer to traumatically injured brains.

Improvement of spatial learning and memory after adenovirus-mediated transfer of the nerve growth factor gene to aged rat brain.

Adenovirus-mediated transfer of the nerve growth factor gene promotes significant recovery of age-related cholinergic neuronal deficits in aged rats, but the effects of such treatment on cognitive dysfunction remain unclear. Herein we report a beneficial effect of first-generation adenovirus-mediated nerve growth factor gene transfer (AdNGF) on the spatial learning and memory of aged rats. The NGF protein was detected by enzyme-linked immunosorbent assay in cerebrospinal fluid as early as 3 days after gene transfer and was expressed for at least 30 days. Escape latency in the Morris water maze hidden-platform test was significantly improved on day 8 postinoculation in memory-impaired rats treated with AdNGF as well as at later testing intervals. Ultimately, the escape latency values for the AdNGF group become indistinguishable from those for aged rats with normal learning capacity. Immunohistochemical analysis of septal cholinergic neurons for choline acetyltransferase (ChAT) showed significant increases in both the number and somal distribution of ChAT-positive cells after inoculation of memory-impaired rats with AdNGF. Improvement in memory performance was positively correlated with increases in both NGF concentration in cerebrospinal fluid (r = 0.73, p = 0.005) and the number of ChAT-staining cells (r = 0.77, p = 0.0022). We conclude that AdNGF can improve cognitive function in memory-impaired aged rats and, with refinements in vector-driven expression of the transgene, may prove suitable for use in humans.