Identifying influencing factors of metabolic syndrome in patients with major depressive disorder: A real-world study with Bayesian network modeling.

BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.

Comparing short-term outcomes of robot-assisted and conventional laparoscopic total mesorectal excision surgery for rectal cancer in elderly patients.

BACKGROUND: Da Vinci Robotics-assisted total mesorectal excision (TME) surgery for rectal cancer is becoming more widely used. There is no strong evidence that robotic-assisted surgery and laparoscopic surgery have similar outcomes in elderly patients with TME for rectal cancer. AIM: To determine the improved oncological outcomes and short-term efficacy of robot-assisted surgery in elderly patients undergoing TME surgery. METHODS: A retrospective study of the clinical pathology and follow-up of elderly patients who underwent TME surgery at the Department of Gastrointestinal Oncology at the Affiliated Hospital of Nanjing University of Chinese Medicine was conducted from March 2020 through September 2023. The patients were divided into a robot-assisted group (the R-TME group) and a laparoscopic group (the L-TME group), and the short-term efficacy of the two groups was compared. RESULTS: There were 45 elderly patients (≥ 60 years) in the R-TME group and 50 elderly patients (≥ 60 years) in the L-TME group. There were no differences in demographics, conversion rates, or postoperative complication rates. The L-TME group had a longer surgical time than the R-TME group [145 (125, 187.5) vs 180 (148.75, 206.25) min, P = 0.005), and the first postoperative meal time in the L-TME group was longer than that in the R-TME (4 vs 3 d, P = 0.048). Among the sex and body mass index (BMI) subgroups, the R-TME group had better outcomes than did the L-TME group in terms of operation time (P = 0.042) and intraoperative assessment of bleeding (P = 0.042). In the high BMI group, catheter removal occurred earlier in the R-TME group than in the L-TME group (3 vs 4 d, P = 0.001), and autonomous voiding function was restored. CONCLUSION: The curative effect and short-term efficacy of robot-assisted TME surgery for elderly patients with rectal cancer are similar to those of laparoscopic TME surgery; however, robotic-assisted surgery has better short-term outcomes for individuals with risk factors such as obesity and pelvic stenosis. Optimizing the learning curve can shorten the operation time, reduce the recovery time of gastrointestinal function, and improve the prognosis.

Sociodemographic, clinical and treatment characteristics of current rapid-cycling bipolar disorder: a multicenter Chinese study.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway.

Ubiquitin-specific protease 7 inhibitors (USP7i) are considered a novel class of anticancer drugs. Cancer cells occasionally become insensitive to anticancer drugs, known as chemoresistance, by acquiring multidrug resistance, resulting in poor clinical outcomes in patients with cancer. However, the chemoresistance of cancer cells to USP7i (P22077 and P5091) and mechanisms to overcome it have not yet been investigated. In the present study, we generated human cancer cells with acquired resistance to USP7i-induced cell death. Gene expression profiling showed that heat stress response (HSR)- and unfolded protein response (UPR)-related genes were largely upregulated in USP7i-resistant cancer cells. Biochemical studies showed that USP7i induced the phosphorylation and activation of heat shock transcription factor 1 (HSF1), mediated by the endoplasmic reticulum (ER) stress protein kinase R-like ER kinase (PERK) signaling pathway. Inhibition of HSF1 and PERK significantly sensitized cancer cells to USP7i-induced cytotoxicity. Our study demonstrated that the ER stress-PERK axis is responsible for chemoresistance to USP7i, and inhibiting PERK is a potential strategy for improving the anticancer efficacy of USP7i.

Incidence and risk factors for pulmonary hemorrhage after percutaneous CT-guided pulmonary nodule biopsy: an observational study.

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.

Study on the lignin-derived sp2-sp3 hybrid hard carbon materials and the feasibility for industrial production.

Hard carbon has been widely used in anode of lithium/sodium ion battery, electrode of supercapacitor, and carbon molecular sieve for CO2 capture and hydrogen storage. In this study the lignin derived hard carbon products are investigated, and the conclusions are abstracted as follows. (1) The lignin derived hard carbon products consist of microcrystal units of sp2 graphene fragments, jointed by sp3 carbon atoms and forming sp2-sp3 hybrid hard carbon family. (2) From the lignin precursors to the sp2-sp3 hybrid hard carbon products, most carbon atoms retain their original electron configurations (sp2 or sp3) and keep their composition in lignin. (3) The architectures of lignin-derived hard carbon materials are closely dependent on the forms of their lignin precursors, and could be preformed by different pretreatment techniques. (4) The carbonization of lignin precursors follows the mechanism "carbonization in situ and recombination nearby". (5) Due to the high carbon ratio and abundant active functional groups in lignin, new activation techniques could be developed for control of pore size and pore volume. In general lignin is an excellent raw material for sp2-sp3 hybrid hard carbon products, a green and sustainable alternative resource for phenolic resin, and industrial production for lignin derived hard carbon products would be feasible.

Safety and efficacy of stoma site selection in CT-guided percutaneous gastrostomy: a retrospective analysis.

PURPOSE: To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions. MATERIALS AND METHODS: This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded. RESULTS: The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P < 0.05). CONCLUSION: Rectus abdominis and intercostal stomas have similar safety and efficacy. However, intercostal stomas may result in greater short-term patient discomfort.

Effects of Fermented Polygonum cuspidatum on the Skeletal Muscle Functions.

Plant extract fermentation is widely employed to enhance the nutritional and pharmaceutical value of functional foods. Polygonum cuspidatum (Pc) contains flavonoids, anthraquinones, and stilbenes, imparting protective effects against inflammatory diseases, cancer, diabetes, and cardiovascular diseases. However, the effects of fermented Pc on skeletal muscle strength remain unexplored. In this study, we generated fermented Pc using a complex of microorganisms containing Lactobacillus spp. (McPc) and assessed its effects on muscle strength and motor function in mice. Compared to unfermented Pc water extract, elevated levels of emodin and resveratrol were noted in McPc. This was identified and quantified using UPLC-QTOF/MS and HPLC techniques. Gene expression profiling through RNA-seq and quantitative RT-PCR revealed that McPc administration upregulated the expression of genes associated with antioxidants, glycolysis, oxidative phosphorylation, fatty acid oxidation, and mitochondrial biogenesis in cultured C2C12 myotubes and the gastrocnemius muscle in mice. McPc significantly improved skeletal muscle strength, motor coordination, and traction force in mice subjected to sciatic neurectomy and high-fat diet (HFD). McPc administration exhibited more pronounced improvement of obesity, hyperglycemia, fatty liver, and hyperlipidemia in HFD mice compared to control group. These findings support the notion that emodin and resveratrol-enriched McPc may offer health benefits for addressing skeletal muscle weakness.

Pneumothorax after percutaneous CT-guided lung nodule biopsy: a prospective, multicenter study.

Background: Pneumothorax is a common complication induced by computed tomography (CT)-guided percutaneous needle biopsy, with a frequency of 17-40.4%. It remains debatable how to predict and prevent the occurrence of post-biopsy pneumothorax. In a real-world setting, we investigated the characteristics associated with pneumothorax in primary lung nodule biopsy. Methods: This clinical registry cohort study recorded patients with newly diagnosed pulmonary nodules from 10 medical centers from April 2021 to April 2022, and the data were input into the electronic data capture (EDC) system. The eligibility criteria for participants included being within the age range of 18 to 80 years and expressing a willingness to undergo percutaneous puncture biopsy, among other requirements. Conversely, the exclusion criteria included an inability to cooperate throughout the biopsy process and the emergence of new health issues during the study duration resulting in attendance delays, among other factors. This study collected data from 924 patients, out of which 593 were included after exclusion. The essential characteristics, imaging features of pulmonary nodules, and technical factors associated with percutaneous biopsy were recorded. T-tests or one-way analysis of variance (ANOVA) were performed for continuous variables and Pearson's χ2 test, likelihood ratio, or Fisher's exact test were applied for categorical variables for comparison as appropriate, followed by multivariate logistic regression. Results: The overall incidence of pneumothorax was 13.0% (77/593), among which timely pneumothorax was 10.3% (61/593), delayed pneumothorax was 2.7% (16/593), and the rate of chest tube placement was 3.4% (20/593). There was no significant difference in the incidence of pneumothorax in a needle size range of 16-19 G (P=0.129), but the incidence of pneumothorax was lower with 17 G needles than with 18 G. An increased morbidity of pneumothorax was correlated with age (P=0.003), emphysema (P=0.006), and operation time (P=0.002). There was no significant increase in the incidence of pneumothorax between 1 or 2 passes through the pleura (P=0.062). However, multiple pleural passes (3 times) increased the chances of pneumothorax significantly (P=0.022). These risk factors have a certain clinical value in predicting the incidence of post-biopsy pneumothorax, and the area under the curve (AUC) was 0.749. Conclusions: The most common post-biopsy complication, pneumothorax, was managed conservatively in most cases. A maximum of two pleural passes does not increase the incidence of pneumothorax, and the 17 G needle is more suitable for percutaneous biopsy of pulmonary nodules in the real world.

Overall quality changes and deterioration mechanism of fragrant rapeseed oils during 6-Month storage.

The strong-fragrant rapeseed oil (SFRO) is a popular rapeseed oil in China with a low refining degree only degumming with hot water, which remarkably affects its storage stability. The present study compared the overall changes of physical/chemical/nutrient quality of FROs at various temperatures, light wavelengths and headspace volumes. Results showed that red light (680 nm) had a most significant adverse effect on the overall quality of SFRO with the higher correlation coefficients to PV and TOTOX of 0.71 and 0.70, and lower correlation coefficients to chlorophyll and tocopherol of -0.95 and -0.53, respectively. Further studies revealed that red light accelerated the oxidation of fragrant rapeseed oils by degrading chlorophyll to initiate the photo-oxidation process and synthesize high amount of secondary oxidation products including aliphatic and aromatic oxidized compounds from linolenic acid. These findings provided a reference to control the deterioration of FROs by preventing the transmittance of red light.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Study on the microcrystal cellulose and the derived 2D graphene and relative carbon materials.

Microcrystal cellulose (MCC) is a green and sustainable resource that widely exists in various lignocellulose species in percentage 10% to 30%. The fine powder of MCC is often discarded in industrial productions that use lignocellulose as feedstock. The crystal structure of two types of MCC (sugarcane pith and bamboo pith) and their derived carbon materials are studied, and the key findings are summarized as follows. (1) In the MCC refined from sugarcane pith, there are large amount of cellulose 2D crystal, which can be converted to valuable 2D graphene crystal. (2) In the MCC refined from bamboo pith there are large amount of cluster microcrystal cellulose, which can be converted to soft and elastic graphene microcrystal (GMC). (3) The 2D cellulose in MCC of sugarcane pith has large surface area and is easily to be degraded to sugars by acid-base hydrolysis reaction, which can be carbonized to Fullerenes-like carbon spheres. (4) The crystal structures of MCC derived carbon materials are strongly impacted by the crystal structures of MCC, and the carbonization reaction of MCC follows "in situ carbonization" and "nearby recombination" mechanism. In general, the results from this study may open a new way for value-added applications of microcrystal cellulose.

Iodine-125 brachytherapy for a desmoid tumor in the abdomen-thorax: A retrospective study.

PURPOSE: To investigate the safety and efficacy of iodine-125 seed implantation in the treatment of abdomen-thorax desmoid tumors (DTs). METHODS AND MATERIALS: Data from 14 DT patients who received brachytherapy with iodine-125 seeds were retrospectively collected from 2014 to 2020. The operation was completed using CT guidance and the treatment plan system (TPS). The number of lesions and the target dosimetry parameters were recorded. After brachytherapy, the lesions were evaluated using response evaluation criteria in solid tumors (RECIST). RESULTS: Fourteen patients with 18 lesions were enrolled in this study; eleven lesions were in the thorax, seven were in the abdomen, and the lesion gross tumor volume (GTV) was 82.10 cc (interquartile range [IQR]: 40.37, 203.42 cc). The median number of seeds was 88 (IQR: 35, 158), and the median prescription dose was 120 Gy (IQR: 115, 120 Gy). The D90 was 123 ± 16.7 Gy, the V90 was 97% (IQR: 95.00, 97.25%), and the V200 was 27% (IQR: 14.50, 33.00%). The median follow-up time for each lesion was 34 (IQR: 23, 67) months, and the local response rate was 100%. Following brachytherapy, the overall survival was 52.3 ± 30.72 months. One year after brachytherapy, one patient experienced persistent worsening of a brachial plexus injury; another received a ureteral stent. No brachytherapy-related complications were observed in the remaining patients. CONCLUSIONS: Iodine-125 brachytherapy is a novel treatment option for DT of the abdomen and thorax. Although it is a safe and effective treatment, the radiation dose of iodine-125 brachytherapy for DT-embedded organs at risk must be investigated further.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Controlling Radiation Beams by High-Efficiency Metasurfaces with Enhanced Refractive Index Elements.

The efficient manipulation of the electromagnetic wavefront using metasurfaces (MSs) has attracted a continuous amount of attention in recent years. MSs with arbitrarily controllable amplitude and phase are highly desirable in many emerging fields. However, in previous research, the resonance effect has mainly been used to accomplish the task. This article presents a nonresonant metamaterial element with stronger capacitive coupling. The broadband sandwich-structured meta-atom achieves an enhanced refractive index ranging from 2.44 to 8.90. By using the enhanced refractive index elements, the proposed transmissive MS has an ultrathin thickness (0.23 free-space wavelength). It consists of a specially designed gradient index MS placed on top of the transmitting antenna. The MS is designed to convert the spherical surface wave into a plane wave with high efficiency. One core layer (CL) gradient index MS and two impedance matching layers (IMLs) have been designed to transform the magnitude and phase of the radiation beam from the transmitting antenna. An efficient transmissive MS has been designed and experimentally evaluated with a maximum measured efficiency of over 85%. The proposed control strategy increases the design flexibility of the MS and shows great potential for broadband applications in the realization of efficient functional devices.

Gender specific sexual dysfunction in patients with depression.

Background: This study aims to investigate the factors associated with sexual dysfunction (SD), with a particular focus on the influence of sex on the occurrence and severity of this condition in patients with major depressive disorder (MDD). Method: Sociodemographic and clinical assessments were conducted on 273 patients with MDD (female = 174, male = 99), including the ASEX, QIDS-SR16, GAD-7, and PHQ-15. Univariate analyses, independent samples t-test, Chi-square test, and Fisher's exact test were used as appropriate, and logistic regression analysis was used to identify correlation factors for SD. Statistical analyses were performed using the Statistical Analysis System (SAS 9.4). Result: SD was reported in 61.9% of the participants (ASEX score = 19.6 ± 5.5), and the prevalence of it in females (75.3%, ASEX score = 21.1 ± 5.4) was significantly higher than that in males (38.4%, ASEX score = 17.1 ± 4.6). Factors associated with SD included being female, being aged 45 years or above, having a low monthly income (≤750 USD), feeling more sluggish than usual (a QIDS-SR16 Item 15 score of 1 or above), and having somatic symptoms (evaluated with the total score of PHQ15). Limitation: The use of antidepressants and antipsychotics might be a confounding factor affecting sexual function. Also, the lack of information in the clinical data regarding the number, duration, and time of onset of the episodes limits the richness of the results. Conclusion: Our findings reveal the sex differences in the prevalence and severity of SD in patients with MDD. Evaluated with the ASEX score, female patients showed significantly worse sexual function than male patients. Being female, having a low monthly income, being aged 45 years or above, feeling sluggish, and having somatic symptoms may increase the risk of SD in patients with MDD.

Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors.

To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 µM for the binding of Λ-[1]Cl2 to αIIbß3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.

Clinicodemographic correlates of psychotic features in bipolar disorder - a multicenter study in China.

BACKGROUND: Psychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China. METHOD: A total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients' sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann-Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis. RESULTS: A total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups. CONCLUSIONS: Differences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration. TRIAL REGISTRATION: This study was first registered on the website of the ClinicalTrials.gov ( https://clinicaltrials.gov/ ) on 18/01/2013. Its registration number is NCT01770704.

In vivo metallophilic self-assembly of a light-activated anticancer drug.

Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (over 12 h) and efficient tumour accumulation rate (up to 10.2% of the injected dose per gram) in a skin melanoma tumour model. Green light activation leads to efficient tumour destruction due to the type I photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to 96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited to generating stable supramolecular nanotherapeutics in vivo with exceptional tumour-targeting properties.