The correlation between cumulative burden of mental disorders and self-harm, shame, and insight in young female patients with schizophrenia.

This study delves into the correlation between the cumulative burden of mental disorders and self-harm, shame, and insight in young female patients with schizophrenia. A prospective randomized controlled study was used to recruit 62 female schizophrenia patients who met the recruitment conditions from January 2022 to December 2023. The participants were randomly divided into an experimental group (31 cases) and a control group (31 cases) using a computer-based random number distribution method. The experimental group underwent an 8-week Mindfulness-Based Cognitive Therapy (MBCT) intervention, while the control group received conventional treatment. Data was collected using the Modified EI-SHS scale, the Link's Stigma Scale (LSS), the Five-factor Mindfulness Scale (FFMQ), and the Self-awareness and Therapeutic Attitude Questionnaire (ITAQ) before and after the intervention. One-way ANOVA and repeated measure ANOVA were used to compare and analyze the two groups of data. The experimental group exhibited a significant reduction in EI-SHS and LSS scores (100.26 ± 11.48 vs. 88.35 ± 10.09, 112.81 ± 12.30 vs. 100.50 ± 13.52, p < 0.01), coupled with significant increase in FFMQ and ITAQ scores (113.77 ± 12.25 vs. 128.31 ± 14.09, 14.03 ± 4.18 vs. 17.30 ± 2.96, p < 0.01). A positive correlation was found between overall stigma scores and mood disorder scores (r = 0.379, P < 0.011). Correlation analysis revealed a negative correlation between mindfulness (self-awareness) and stigma (r = -0.128, P = 0.025). MBCT effectively reduced stigma in young women with schizophrenia and improved coping tendencies, cognitive status, and attitudes toward mental illness, ultimately reducing the cumulative burden of mental disorders and self-harm in these patients. Increased levels of mindfulness correspond to improved cognitive status and a more positive attitude toward treatment for mental illness. It is of great value to promote MBCT in female patients with schizophrenia.

Gene expression profiling of peripheral blood in patients with steroid-induced osteonecrosis of the femoral head.

Aim: Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe complication following glucocorticoid therapy. This study aimed to identify the differential mRNA expression and investigate the molecular mechanisms of SONFH. Materials & methods: RNA sequencing was performed in eight SONFH patients, five non-SONFH patients and five healthy individuals. Results: A total of 1555, 3997 and 5276 differentially expressed mRNAs existed between the following combinations: SONFH versus non-SONFH, SONFH versus healthy subjects and non-SONFH versus healthy subjects. Increased ISM1 expression might contribute to a high risk of SONFH through antiangiogenesis. Decreased FOLR3 expression might affect the metabolism of homocysteine, leading to avascular necrosis of the femoral head. KCNJ2, which plays a pivotal role in regulating bone development, was also deregulated. Conclusion: ISM1, FOLR3 and KCNJ2 might be related to the occurrence of SONFH.

[Box: see text].

Will pay-per-view in the advanced charging model recover the business losses for online video companies in China?

The evolution of Internet technology is closely mirrored by the innovative business and profit models emerging within the platform economy. Integrating this economic framework, online video platforms are dynamically refining their pricing strategies to optimize profit margins. This paper, anchored in the theoretical construct of second-degree price discrimination, selects the Chinese online video platforms iQiyi and Tencent Video for in-depth case studies. It charts the progression of its pricing strategies and juxtaposes these with those of prominent international online video sites to highlight both congruities and divergences. The synthesis of theoretical models with real-world case studies culminates in strategic recommendations to foster the growth of Chinese online video platforms in the global Internet arena.

Modulating the Site Density of Mo Single Atoms to Catch Adventitious O Atoms for Efficient H2 O2 Oxidation with Light.

Coordination environment and site density have great impacts on the catalytic performance for single atoms (SAs). Herein, the site density of Mo-SAs on red polymeric carbon nitrides (RPCN) is modulated via a local carbonization strategy to controllably catch adventitious O atoms from open environment. The addition of melamine derivants with hydrocarbyl chains induces local carbonization during RPCN pyrolysis. These local carbonization regions bring abundant graphitic N3C to anchor Mo-SAs, and most of Mo-SAs catch the O atoms in air, forming the O2 -covered Mo-N3 coordination. The dopants of carbon source with different structures and amounts can modulate the site density of Mo-SAs, therefore controlling the amounts of coordinated O atoms. Furthermore, coordinated O atoms around Mo-SAs construct the catalytic environment with Lewis base and gather photo-generated electrons under light. Such O-covered Mo-SAs endow RPCN materials (Mo-RPCN) with a strong ability for hydrogen abstraction, leading to the 99.51% ratio (28.8 mmol min-1  g-1 ) rate for thioanisole conversion with H2 O2 assisted advance oxidation technology. This work brings a new sight on the coordinated atoms dominant oxidation process.

Impact of CYP2C19 Phenotype and Drug-Drug Interactions on Voriconazole Concentration in Pediatric Patients.

Voriconazole (VRC), a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by human cytochrome P450 (CYP) 2C19. In this study, a retrospective analysis was performed to investigate the key factors that influence the plasma trough concentration (Cmin) of VRC, and an appropriate dosing regimen for pediatric patients was drafted subsequently. Overall, factors such as age, CYP2C19 phenotype, and combination medication with proton pump inhibitors accounted for 23.4% of variability in dose-normalized Cmin values of VRC by a multiple linear regression analysis. Dose-normalized Cmin values in the poor metabolizers (PMs) and intermediate metabolizers (IMs) were significantly higher than those in extensive metabolizers (EMs) (P < 0.001). To achieve therapeutic Cmin for CYP2C19 ultrarapid metabolizers (UMs) or EMs, patients aged no more than 12 and more than 12 years required doses of 6.53 ± 2.08 and 3.95 ± 0.85 mg/kg of body weight twice daily (P = 0.007). For CYP2C19 PMs or IMs, patients aged under 12 and over 12 years required doses of 5.75 ± 1.73 and 4.23 ± 0.76 mg/kg twice daily, respectively (P = 0.019). Furthermore, coadministration of rifamycin sodium or omeprazole exhibited significant effects on VRC Cmin. Taken together, it is necessary to pay attention to the impact of CYP2C19 phenotype and drug-drug interactions to achieve optimal therapy.

Expression and Function of WNT6: From Development to Disease.

WNT family member 6 (WNT6) is a member of the highly conserved WNT protein family. It plays an essential role in the normal development process, not only in embryonic morphogenesis, but also in post-natal homeostasis. WNT6 functions in mice and humans. This review summarizes the current findings on the biological functions of WNT6, describing its involvement in regulating embryogenesis, decidualization, and organ development. Aberrant WNT6 signaling is related to various pathologies, such as promoting cancer development, lung tuberculosis, and kidney fibrosis and improving the symptoms of Rett syndrome (RTT). Thus, due to its various functions, WNT6 has great potential for in-depth research. This work not only describes the signaling mechanism and function of WNT6 under physiological and pathological conditions, but also provides a theoretical basis for targeted therapy.

NUDT15 and TPMT Genetic Polymorphisms Are Related to Azathioprine Intolerance in Chinese Patients with Rheumatic Diseases.

Aims: Azathioprine (AZA) is commonly used to treat autoimmune diseases, but its applications have been limited due to significant adverse effects, particularly leukopenia. The aim of this study was to investigate the associations of NUDT15, TPMT, and inosine triphosphatase (ITPA) polymorphisms with AZA-induced toxicity. Materials and Methods: A total of 86 Chinese patients with autoimmune diseases were recruited, and the NUDT15*2-*6, TPMT*3C, and ITPA rs7270101 genotypes of these patients were characterized by Sanger sequencing. Sociodemographic data and clinical records over a period of 6 months were also collected. Results: The TPMT*3C and NUDT15*3 genotypes were significantly associated with AZA-induced leukopenia (p = 0.007 and 4.475 × 10-6, respectively). The p-value for the correlation between ITPA rs7270101 and leukopenia was 0.059. In addition, NUDT15*3 was significantly associated with gastrointestinal effects, erythropenia, hypochromia, and thrombocytopenia [p = 0.002, 1.109 × 10-5, 1.653 × 10-7, and 9.110 × 10-6, respectively; allelic odds ratio (95% confidence interval): 5.714 (1.56-20.95), 9.333 (2.96-29.47), 13.18 (4.15-41.87), and 20.13 (3.40-119.18), respectively]. The TPMT*3C genotypes were also significantly associated with gastrointestinal discomfort [p = 0.028, 12.08 (0.71-204.49)], alopecia [p = 2.864 × 10-4, 33 (1.80-606.47)], and hypochromia [p = 0.045, 10.33 (0.61-173.66)]. Conclusion: This study demonstrated that NUDT15*3 and TPMT*3C are both highly predictive genetic markers for AZA-induced toxicity in Chinese populations with rheumatic diseases.

Relationship between ALDH2 genotype and in-stent restenosis in Chinese Han patients after percutaneous coronary intervention.

BACKGROUND: It is well known that the genotype of ALDH2 is associated with coronary artery disease (CAD), and in-stent restenosis (ISR) is a primary complication of percutaneous coronary intervention (PCI), a primary recommended treatment for CAD. The aim of this study was to identify the relationship between aldehyde dehydrogenase 2 (ALDH2) genotype and in-stent restenosis (ISR). METHODS: This study recruited 531 patients who were undergoing PCI at two Chinese hospitals from 2015 to 2017 and 183 were diagnosed with ISR after PCI during the one-year follow-up period. We used polymerase chain restriction fragment length polymorphism (PCR-RFLP) and sequencing to determine ALDH2 polymorphisms. RESULTS: Among all 531 patients (mean age = 59.4 ± 9.8; 65.9% male), 68.7% carried the wild-type genotype, 28.4% were heterozygous for the mutation, and 2.8% were homozygous for the mutation. Multiple logistical regression analyses indicated no correlation between ALDH2 genotype and the occurrence of restenosis after PCI (OR = 1.448, 95% CI: 0.965-2.168, p = 0.073), though a significant association was observed for patients with diabetes (OR = 4.053, 95% CI: 1.668-10.449, p = 0.003). CONCLUSION: In this study, we found that carrying an ALDH2*2 allele had no notable relationship with ISR one year after PCI but that it did have a significant association with complications in diabetic patients. Further studies with larger sample sizes will be necessary to reveal a consensus.

Mimicking π Backdonation in Ce-MOFs for Solar-Driven Ammonia Synthesis.

π Backdonation is the core process to break through the kinetically complex and energetic hurdle for catalyzing effectively the NH3 synthesis but only occurs on certain transition metals with empty and filled d orbitals. Herein, mimicking π backdonation enables MOF-76(Ce) materials to convert N2/NH3 effectively. Note that, by virtue of the intrinsic mechanism of ligand-to-metal charge transfer, metal cerium species in MOF-76(Ce) serve as an electron sink for accumulating the photogenerated electrons. Taken together, experimental and theoretical analyses reveal that such metal cerium species with coordination unsaturated state (Ce-CUS) on a MOF-76(Ce) nanorod surface can also provide unoccupied and occupied 4f orbitals to accept from and then donate electrons back to nitrogen molecules. Remarkably, it shows outstanding photocatalytic nitrogen reduction performance with high average NH3 yield (34 µmol g-1 h-1) under ambient conditions. This work provides fresh insights into rational designing and engineering highly active catalysts with rare earth elements.

Role of an external electric field on hybrid halide perovskite CH3NH3PbI3 band gaps.

The organic-inorganic perovskite CH3NH3PbI3 has attracted much attention due to their power conversion efficiency as a potential photovoltaic material, but the role of an external electric field has not been well understood. Based on first-principles calculations, the effects of an external electric field (E) applied along the [111] direction of the orthorhombic perovskite, CH3NH3PbI3, on its electronic structure and optical properties are investigated. Our results indicate that the electric field strength affects the band gap (Eg) of CH3NH3PbI3 (MAPbI3, MA = CH3NH3). The energy difference between the two peaks closest to the Fermi level in the density of states diagram decreases with increasing applied electric field strength along the [111] direction, indicating that the covalent character increases between A-sites cations and I-sites anions. Both the cell volume and the final energy show the same increasing trend. The absorption peaks move toward the visible-frequency range, with the optimal band gap of 1.1-1.45 eV and E = 0.04-0.06 eV/Å/e. In particular, the non-linear change of the second-order Stark effect causes a non-linear change in the band gap.

Effects of immuno-related gene polymorphisms on a bispecific antibody targeting colorectal cancer cell.

BACKGROUND: Colorectal cancer (CRC) represents the third most common type of cancer and the third leading cause of death from cancer around the world. M701 is a CD3/EpCAM bispecific antibody that shows promising cytotoxicity toward CRC cells. AIM: To investigate the influence of immuno-related gene polymorphisms on M701 mediated cytotoxicity to CRC cell HCT116. METHOD: We analyzed the influence of the effect of M701 on the activation and cytotoxicity of peripheral mononuclear blood cells from 129 healthy volunteers with different genotypes. RESULT: When incubated with M701, peripheral mononuclear blood cells from CD247 rs2949655 AA homozygotes showed significantly lower cytotoxicity than those from AG/GG heterozygotes. CONCLUSION: CD247 rs2949655 was significantly associated with the cytotoxicity of M701 to HCT116, which might contribute to personalized medicine of M701.

Clinical effects of Ganglioside and fructose-1, 6-diphosphate on neonatal heart and brain injuries after Asphyxia.

OBJECTIVE: To study the clinical effect of ganglioside (GM) and fructose-1, 6-diphosphate (FDP) on neonatal heart and brain injuries after asphyxia. METHODS: Ninety-one neonates with asphyxia neonatal heart and brain injuries were randomly divided into an observation group and a control group. Both groups were given symptomatic treatment as soon as possible. On this basis, the observation group was given 200 mL of 5% glucose injection and 20 mg of GM and 250 mg/kg·d FDP by intravenous infusion. The above two drugs were given once a day for 14 days. The control group was given 20 mL of 5% glucose injection, 2 mL of cerebrolysin and 250 mg/kg·d FDP by intravenous infusion, once a day for 14 days. Both groups were administered on the first day after admission, and the course of treatment was 14 days. The treatment outcomes of the two groups were compared by detecting the levels of glycogen phosphorylase isoenzyme BB (GPBB), cTn-I and CK-MB, MRI results and Neonatal Behavioral Neurological Assessment (NBNA) scores before and after treatment. RESULTS: The levels of GPBB, cTn-I and CK-MB in the observation group were significantly higher than those of normal neonates. After treatment, the levels of cTn-I and CK-MB in the observation group were closer to those of normal neonates compared with the control group, with significant differences (P<0.05). There was a significant difference in the brain MRI examination between the two groups (P<0.05). The NBNA scores of the two groups were significantly different before and after treatment (P<0.05). The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). CONCLUSION: Neonatal heart and brain injuries after asphyxia can be well treated by combining GM with FDP.

Clinical effects of pulmonary surfactant in combination with nasal continuous positive airway pressure therapy on neonatal respiratory distress syndrome.

OBJECTIVE: To analyze the therapeutic effect of pulmonary surfactant (PS) in combination with nasal continuous positive airway pressure (NCPAP) therapy on neonatal respiratory distress syndrome (NRDS). METHODOLOGY: Forty-nine neonates who were diagnosed as NRDS and admitted in our hospital from May 2014 to June 2015 were selected and divided into an observation group and a control group. The observation group was treated with PS and NCPAP. The control group was treated only with NCPAP. The clinical symptoms, pulmonary X-ray, arterial partial pressure of oxygen (PaO2) and prognosis of the two groups were observed. RESULTS: Twelve hours after treatment, the partial pressure of carbon dioxide and oxygenation index decreased significantly (P<0.05), and PaO2 and ratio of arterial/pulmonary oxygen partial pressures increased significantly (P<0.05). Pulmonary X-ray examination showed that 78.3% of the observation group and 53.8% of the control group were relieved 12-24 hour after treatment, between which the difference was statistically significant (P<0.05). The improvement rate of the observation group was significantly higher than that of the control group (82.6% vs. 57.7%, P<0.05), the incidence of complications was significantly lower in the observation group (P<0.05), and the average length of stay in the observation group was significantly shorter (P<0.05). CONCLUSION: Both methods effectively treated NRDS, but PS in combination with NCPAP better improved oxygenation, reduced mortality and incidence of complications.

Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy.

Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs. The effects of POR variants on CYP activities are substrate dependent. In this review, recent research on the effects of POR genetic polymorphisms on drug metabolism and therapy has been summarized and discussed, which can contribute to the rational use of drugs in clinic and the development of personalized medicine.

Oxygen-Induced Bi5+-Self-Doped Bi4V2O11 with a p-n Homojunction Toward Promoting the Photocatalytic Performance.

Bi5+-self-doped Bi4V2O11 (Bi5+-BVO) nanotubes with p-n homojunctions are fabricated via an oxygen-induced strategy. Calcinating the as-spun fibers with abundant oxygen plays a pivotal role in achieving Bi5+ self-doping. Density functional theory calculations and experimental results indicate that Bi5+ self-doping can narrow the band gap of Bi4V2O11, which contributes to enhancing light harvesting. Moreover, Bi5+ self-doping endows Bi4V2O11 with n- and p-type semiconductor characteristics simultaneously, resulting in the construction of p-n homojunctions for retarding rapid electron-hole recombination. Benefiting from these favorable properties, Bi5+-BVO exhibits a superior photocatalytic performance in contrast to that of pristine Bi4V2O11. Furthermore, this is the first report describing the achievement of p-n homojunctions through self-doping, which gives full play to the advantages of self-doping.

New Immunotherapy Strategies in Breast Cancer.

Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer.

Colorectal cancer (CRC) represents the third most common type of cancer in developed countries and one of the leading causes of cancer deaths worldwide. Personalized management of CRC has gained increasing attention since there are large inter-individual variations in the prognosis and response to drugs used to treat CRC owing to molecular heterogeneity. Approximately 15% of CRCs are caused by deficient mismatch repair (dMMR) characterized by microsatellite instability (MSI) phenotype. The present review is aimed at highlighting the role of MMR status in informing prognosis and personalized treatment of CRC including adjuvant chemotherapy, targeted therapy, and immune checkpoint inhibitor therapy to guide the individualized therapy of CRC.

Drug Resistance in Colorectal Cancer Cell Lines is Partially Associated with Aneuploidy Status in Light of Profiling Gene Expression.

A priority in solving the problem of drug resistance is to understand the molecular mechanism of how a drug induces the resistance response within cells. Because many cancer cells exhibit chromosome aneuploidy, we explored whether changes of aneuploidy status result in drug resistance. Two typical colorectal cancer cells, HCT116 and LoVo, were cultured with the chemotherapeutic drugs irinotecan (SN38) or oxaliplatin (QxPt), and the non- and drug-resistant cell lines were selected. Whole exome sequencing (WES) was employed to evaluate the aneuploidy status of these cells, and RNAseq and LC-MS/MS were implemented to examine gene expression at both mRNA and protein level. The data of gene expression was well-matched with the genomic conclusion that HCT116 was a near diploid cell, whereas LoVo was an aneuploid cell with the increased abundance of mRNA and protein for these genes located at chromosomes 5, 7, 12, and 15. By comparing the genomic, transcriptomic, and proteomic data, the LoVo cells with SN38 tolerance showed an increased genome copy in chromosome 14, and the expression levels of the genes on this chromosome were also significantly increased. Thus, we first observed that SN38 could impact the aneuploidy status in cancer cells, which was partially associated with the acquired drug resistance.

Effect of NADPH-cytochrome P450 reductase on all-trans-retinoic acid efficacy and cytochrome P450 26A1 expression in human myeloid leukaemia HL-60 cells.

OBJECTIVES: All-trans-retinoic acid (ATRA), a naturally occurring metabolite of vitamin A, has been shown to have great potential as an antitumorigenic drug to treat acute leukaemia by promoting cancer cell differentiation. Cytochrome P450 oxidoreductase (POR) is the only obligate electron donor for all of the microsomal cytochrome P450 enzymes including CYP26A1 which is highly specific for ATRA metabolism and efficacy in human myeloid leukaemia cells. In this study, we aimed to investigate the effect of POR on ATRA efficacy and CYP26A1 expression in human myeloid leukaemia HL-60 cells. METHODS: Stably expressed POR and POR-RNAi HL-60 cell lines were established by transfecting POR overexpression or RNAi (RNA interference) vectors mediated by lentivirus. The protein expression of POR and CYP26A1 was examined by Western blot. The potential roles of POR on ATRA efficacy in HL-60 cells were explored by cell viability assay, cell cycle distribution, cellular differentiation and apoptosis analysis. KEY FINDINGS: All-trans-retinoic acid treatment caused the expression of POR upregulation and CYP26A1 downregulation in dose- and time-dependent manners. POR overexpression decreased CYP26A1 expression in HL-60 cells. When POR gene was interfered, the downregulation of CYP26A1 expression by ATRA was abolished. In addition, POR overexpression in HL-60 cells significantly compromised ATRA-induced cell proliferation inhibition, cell cycle arrest, differentiation and apoptosis, whereas downregulation of POR significantly potentiated ATRA effects. CONCLUSIONS: Our study therefore suggested that POR played an important role in regulating ATRA efficacy and CYP26A1 expression in HL-60 cells.