Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial.

Background: Postoperative sleep disturbance (PSD) is a common and serious postoperative complication and is associated with poor postoperative outcomes. Aims: This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on PSD in older patients undergoing lower limb major arthroplasty. Methods: In this prospective, double-blind, pilot, randomised, sham-controlled trial, patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS (a-tDCS) or sham tDCS (s-tDCS). The primary outcomes were the objective sleep measures on postoperative nights (N) 1 and N2. Results: 116 inpatients were assessed for eligibility, and a total of 92 patients were enrolled; 47 received a-tDCS and 45 received s-tDCS. tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups; the respective comparisons were as follows: the promotion of rapid eye movement (REM) sleep time on N1 (64.5 (33.5-105.5) vs 19.0 (0.0, 45.0) min, F=20.10, p<0.001) and N2 (75.0 (36.0-120.8) vs 30.0 (1.3-59.3) min, F=12.55, p<0.001); the total sleep time on N1 (506.0 (408.0-561.0) vs 392.0 (243.0-483.5) min, F=14.13, p<0.001) and N2 (488.5 (455.5-548.5) vs 346.0 (286.5-517.5) min, F=7.36, p=0.007); the deep sleep time on N1 (130.0 (103.3-177.0) vs 42.5 (9.8-100.8) min, F=24.4, p<0.001) and N2 (103.5 (46.0-154.8) vs 57.5 (23.3-106.5) min, F=8.4, p=0.004); and the percentages of light sleep and REM sleep on N1 and N2 (p<0.05 for each). The postoperative depression and anxiety scores did not differ significantly between the two groups. No significant adverse events were reported. Conclusion: In older patients undergoing lower limb major arthroplasty, a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures. However, this benefit was temporary and was not maintained over time.

A structure-functionality insight into the bioactivity of microbial polysaccharides toward biomedical applications: A review.

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

Effect of quercetin on the protein-substrate interactions in SIRT6: Insight from MD simulations.

SIRT6 is of interest for its promising effect in the treatment of aging-related diseases. Studies have shown quercetin (QUE) and its derivatives have varying degrees of effect on the catalytic effect of SIRT6. In the research, the effect of QUE on the protein-substrate interaction in the SIRT6-mediated mono-ADP ribosylation system was investigated by conventional molecular dynamics (MD) simulations combined with MM/PBSA binding free energy calculations. The results show that QUE can bind stably to SIRT6 with the binding energy of -22.8 kcal/mol and further affect the atomic interaction between SIRT6 and NAD+ (or H3K9), resulting in an increased affinity between SIRT6-NAD+ and decreased SIRT6-H3K9 binding capacity. At the same time, the binding of QUE can also alter some structural characteristics of the protein, with large shifts occurring in the residue regions involving the N-terminal (residues 1-27), Rossmann fold regions (residues 55-92), and ZBD (residues 164-179). Thus, QUE shows great potential as a scaffold for the design of novel potent SIRT6 modulators.

Compatibilization of Immiscible Polypropylene/Poly(methyl methacrylate) Blends by Silica Particles with Janus and Random Component-Selective Grafts.

Introducing component-selective polymer chains onto the surface of a particle is an effective approach to improve the compatibilization efficiency of a particle-based compatibilizer. In this study, two particles with different kinds of component-selective polymer chains that have the same length and similar density but different graft locations were synthesized and their compatibilization effects were comparatively investigated. It was found that compared with the particle with homogeneous PMMA and PP grafts (R-P), the particle with a hemisphere of poly(methyl methacrylate) (PMMA) grafts and other hemisphere of polypropylene (PP) chains (J-P) showed a better compatibilization effect under equal loadings, although both particles exhibited high efficiency. The better compatibilization effect of particles with Janus grafts may be attributed to the stronger entanglements between grafted polymer chains and selective individual components. This work suggests that optimizing the graft location of a particle is an effective strategy for improving its compatibilization efficiency and helpful for the design of advanced particle compatibilizers.

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

Biosafety consideration of nanocellulose in biomedical applications: A review.

Nanocellulose-based biomaterials have gained significant attention in various fields, especially in medical and pharmaceutical areas, due to their unique properties, including non-toxicity, high specific surface area, biodegradability, biocompatibility, and abundant feasible and sophisticated strategies for functional modification. The biosafety of nanocellulose itself is a prerequisite to ensure the safe and effective application of biomaterials as they interact with living cells, tissues, and organs at the nanoscale. Potential residual endogenous impurities and exogenous contaminants could lead to the failure of the intended functionalities or even serious health complications if they are not adequately removed and assessed before use. This review summarizes the sources of impurities in nanocellulose that may pose potential hazards to their biosafety, including endogenous impurities that co-exist in the cellulosic raw materials themselves and exogenous contaminants caused by external exposure. Strategies to reduce or completely remove these impurities are outlined and classified as chemical, physical, biological, and combined methods. Additionally, key points that require careful consideration in the interpretation of the biosafety evaluation outcomes were discussed to ensure the safety and effectiveness of the nanocellulose-based biomaterials in medical applications.

MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients.

This study aimed to investigate the neurobiological mechanisms by which microRNA 124 (miR-124) is involved in major depressive disorder (MDD). We enrolled 53 untreated MDD patients and 38 healthy control (HC) subjects who completed behavior assessments and resting-state functional MRI (rs-fMRI) scans. MiR-124 expression levels were detected in the peripheral blood of all participants. We determined that miR-124 levels could influence depressive symptoms via disrupted large-scale intrinsic intra- and internetwork connectivity, including the default mode network (DMN)-DMN, dorsal attention network (DAN)-salience network (SN), and DAN-cingulo-opercular network (CON). This study deepens our understanding of how miR-124 dysregulation contributes to depression.

CRF regulates pain sensation by enhancement of corticoaccumbal excitatory synaptic transmission.

Both peripheral and central corticotropin-releasing factor (CRF) systems have been implicated in regulating pain sensation. However, compared with the peripheral, the mechanisms underlying central CRF system in pain modulation have not yet been elucidated, especially at the neural circuit level. The corticoaccumbal circuit, a structure rich in CRF receptors and CRF-positive neurons, plays an important role in behavioral responses to stressors including nociceptive stimuli. The present study was designed to investigate whether and how CRF signaling in this circuit regulated pain sensation under physiological and pathological pain conditions. Our studies employed the viral tracing and circuit-, and cell-specific electrophysiological methods to label the CRF-containing circuit from the medial prefrontal cortex to the nucleus accumbens shell (mPFCCRF-NAcS) and record its neuronal propriety. Combining optogenetic and chemogenetic manipulation, neuropharmacological methods, and behavioral tests, we were able to precisely manipulate this circuit and depict its role in regulation of pain sensation. The current study found that the CRF signaling in the NAc shell (NAcS), but not NAc core, was necessary and sufficient for the regulation of pain sensation under physiological and pathological pain conditions. This process was involved in the CRF-mediated enhancement of excitatory synaptic transmission in the NAcS. Furthermore, we demonstrated that the mPFCCRF neurons monosynaptically connected with the NAcS neurons. Chronic pain increased the protein level of CRF in NAcS, and then maintained the persistent NAcS neuronal hyperactivity through enhancement of this monosynaptic excitatory connection, and thus sustained chronic pain behavior. These findings reveal a novel cell- and circuit-based mechanistic link between chronic pain and the mPFCCRF → NAcS circuit and provide a potential new therapeutic target for chronic pain.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

The functional role of the visual and olfactory modalities in the development of socially transferred mechanical hypersensitivity in male C57BL/6J mice.

An increasing body of evidence suggests that the state of hyperalgesia could be socially transferred from one individual to another through a brief empathetic social contact. However, how the social transfer of pain develops during social contact is not well-known. Utilizing a well-established mouse model, the present study aims to study the functional role of visual and olfactory cues in the development of socially-transferred mechanical hypersensitivity. Behavioral tests demonstrated that one hour of brief social contact with a conspecific mouse injected with complete Freund's adjuvant (CFA) was both sufficient and necessary for developing socially-transferred mechanical hypersensitivity. One hour of social contact with visual deprivation could not prevent the development of socially-transferred mechanical hypersensitivity, and screen observation of a CFA cagemate was not sufficient to develop socially-transferred mechanical hypersensitivity in bystanders. Methimazole-induced olfactory deprivation, a compound with reversible toxicity on the nasal olfactory epithelium, was sufficient to prevent the development of socially-transferred mechanical hypersensitivity. Intriguingly, repeated but not acute olfactory exposure to the CFA mouse bedding induced a robust decrease in 50 % paw withdrawal thresholds (50 %PWTs) to mechanical stimuli, an effect returned to the baseline level after two days of washout with clean bedding. The findings strongly indicate that the normal olfactory function is crucial for the induction of mechanical hypersensitivity through brief empathetic contact, offering valuable insights for animal housing in future pain research.

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis.

CONTEXT: Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain. OBJECTIVE: To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR). RESULTS: Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively. CONCLUSIONS: The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Efficacy of transcranial direct current stimulation for improving postoperative quality of recovery in elderly patients undergoing lower limb major arthroplasty: a randomized controlled substudy.

Background: Previous studies have demonstrated improvements in motor, behavioral, and emotional areas following transcranial direct current stimulation (tDCS), but no published studies have reported the efficacy of tDCS on postoperative recovery quality in patients undergoing lower limb major arthroplasty. We hypothesized that tDCS might improve postoperative recovery quality in elderly patients undergoing lower limb major arthroplasty. Methods: Ninety-six patients (≥65 years) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to receive 2 mA tDCS for 20 min active-tDCS or sham-tDCS. The primary outcome was the 15-item quality of recovery (QoR-15) score on postoperative day one (Т2). Secondary outcomes included the QoR-15 scores at the 2nd hour (T1), the 1st month (Т3), and the 3rd month (Т4) postoperatively, numeric rating scale scores, and fatigue severity scale scores. Results: Ninety-six elderly patients (mean age, 71 years; 68.7% woman) were analyzed. Higher QoR-15 scores were found in the active-tDCS group at T2 (123.0 [114.3, 127.0] vs. 109.0 [99.3, 115.3]; median difference, 13.0; 95% CI, 8.0 to 17.0; p < 0.001). QoR-15 scores in the active-tDCS group were higher at T1 (p < 0.001), T3 (p = 0.001), and T4 (p = 0.001). The pain scores in the active-tDCS group were lower (p < 0.001 at motion; p < 0.001 at rest). The fatigue degree scores were lower in the active-tDCS group at T1 and T2 (p < 0.001 for each). Conclusion: tDCS may help improve the quality of early recovery in elderly patients undergoing lower limb major arthroplasty. Clinical trial registration: The trial was registered at the China Clinical Trial Center (ChiCTR2200057777, https://www.chictr.org.cn/showproj.html?proj=162744).

Assessing the role of residue Phe108 of cytochrome P450 3A4 in allosteric effects of midazolam metabolism.

Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more drugs in clinical use than any other xenobiotic-metabolizing enzyme. CYP3A4-mediated drug metabolism is usually allosterically modulated by substrate concentration (homotropic allostery) and other drugs (heterotropic allostery), exhibiting unusual kinetic profiles and regiospecific metabolism. Recent studies suggest that residue Phe108 (F108) of CYP3A4 may have an important role in drug metabolism. In this work, residue mutations were coupled with well-tempered metadynamics simulations to assess the importance of F108 in the allosteric effects of midazolam metabolism. Comparing the simulation results of the wild-type and mutation systems, we identify that the π-π interaction and steric effect between the F108 side chain and midazolam is favorable for the stable binding of substrate in the active site. F108 also plays an important role in the transition of substrate binding mode, which mainly induces the transition of substrate binding mode by forming π-π interactions with multiple aromatic rings of the substrate. Moreover, the side chain of F108 is closely related to the radius and depth of the 2a and 2f channels, and F108 may further regulate drug metabolism by affecting the pathway, orientation, or time of substrate entry into the CYP3A4 active site or product egress from the active site. Altogether, we suggest that F108 affects drug metabolism and regulatory mechanisms by affecting substrate binding stability, binding mode transition, and channel characteristics of CYP3A4. Our findings could promote the understanding of complicated allosteric mechanisms in CYP3A4-mediated drug metabolism, and the knowledge could be used for drug development and disease treatment.

Return to flight duty (RTFD) after posterior lumbar spine surgery for symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) in Chinese military pilots.

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

Effects of electroconvulsive therapy on functional brain networks in patients with schizophrenia.

BACKGROUND: Schizophrenia is a kind of intractable brain disorder. Electroconvulsive therapy (ECT) has been used to rapidly improve the clinical symptoms of patients with schizophrenia, but the effect of ECT on topological attributes of brain functional network in patients with schizophrenia has not been clear. The purpose of this study was to investigate the brain functional network mechanism of ECT against schizophrenia. METHODS: Thirty-one patients with schizophrenia and fifty healthy controls matching age, gender, and years of education were included. All participants underwent general data collection and magnetic resonance imaging scanning before ECT, and clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS). MRI and clinical symptoms were collected again after the first and eighth ECT application. The functional brain network was constructed on the basis of magnetic resonance imaging, and the global and node topological properties were analyzed. Repeated measure variance analysis was used to explore the changes of the topological attribute values and clinical symptom scores before and after ECT, and Bonferroni post hoc analysis was performed. The independent sample t-test was used to compare the differences in the topological attribute values between patients and healthy controls at three time points before and after ECT. Partial correlation analysis was performed for topological attribute values and clinical symptom scores of abnormal brain regions in the patient groups and their changes during ECT. A general linear regression model was used to predict the outcome after the final eighth ECT using the patient's response to the first ECT. RESULTS: (1) One ECT can restore the gamma(γ), lamuda(λ), sigma(σ), nodal global efficiency (Ne) of right insular gyrus ventral agranular insula (INS_R_vIa) and nodal local efficiency (NLe) of bilateral fusiform gyrus medioventral area37 (FuG_A37mv). Eight ECT can also restore the NLe of cortex rostral lingual gyrus (MVOcC _R_rLinG). Eight ECT did not improve the Ne of right superior parietal lobule rostral area 7 (SPL_R_A7r) and NLe of left superior frontal gyrus medial area 6 (SFG_L_A6m). (2) Even after only the first use of ECT, total PANSS scores began to decrease (mean ΔPANSSECT1 was 11.7%; Range, 2%-32.8%), decreased significantly after the eighth application (mean ΔPANSSECT8 was 86.0%; Range,72.5% to 97.9%). Five patients met the response criteria after ECT1 (20% reduction in PANSS total score), and all patients met the response criteria after ECT8. (3) Linear regression analysis showed that ΔPANSSECT1 was a significant predictor of ΔPANSSECT8 (F=5.387, P=0.028), and ΔPANSSECT1 explained 15.7% of the variance of ΔPANSSECT8 (R2=0.157). CONCLUSIONS: ECT was able to normalize γ, λ, σ, Ne of INS_R_vIa, NLe of bilateral FuG_A37mv in SZ patients after the first treatment, and NLe of MVOcC_R_rLinG after the eighth ECT. ECT significantly alleviates psychotic symptoms in patients with SZ, and its efficacy after eight sessions can be predicted by the patient's response to the first session of ECT.

Prognostic value of the fibrinogen-to-albumin ratio (FAR) in patients with chronic heart failure across the different ejection fraction spectrum.

The ratio of fibrinogen to albumin (FAR) is considered a new inflammatory biomarker and a predictor of cardiovascular disease risk. However, its prognostic value for patients with chronic heart failure (CHF) with different ejection fractions (EFs) remains unclear. A total of 916 hospitalized patients with CHF from January 2017 to October 2021 in the First Affiliated Hospital of Kunming Medical University were included in the study. Death occurred in 417 (45.5%) patients out of 916 patients during a median follow-up time of 750 days. Among these patients, 381 patients suffered from HFrEF (LVEF <40%) and 535 patients suffered from HFpEF or HFmrEF (HFpEF plus HFmrEF, LVEF ≥ 40%). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR (9.06) obtained from receiver operating characteristic (ROC) curve analysis. Upon analysing the Kaplan - Meier plots, the incidence of death was significantly higher in all patients with FAR-H and patients in both HF subgroups (p < 0.001). The multivariate Cox proportional hazard analyses indicated that the FAR was an independent predictor of all-cause mortality, regardless of heart failure subtype. (HR 1.115, 95% CI 1.089-1.142, p < 0.001; HFpEF plus HFmrEF, HR 1.109, 95% CI 1.074-1.146, p < 0.0001; HFrEF, HR 1.138, 95% CI 1.094-1.183, p < 0.0001) The optimal cut-off value of FAR in predicting all-cause mortality was 9.06 with an area under the curve value of 0.720 (95% CI: 0.687-0.753, p < 0.001), a sensitivity of 68.8% and a specificity of 65.6%. After adjusting for the traditional indicators (LVEF, Lg BNP, etc.), the new model with the FAR had better prediction ability in patients with CHF. Elevated FAR is an independent predictor of death in CHF and is not related to the HF subtype.

A Silicon-Rhodamine-Based Heavy-Atom-Free Photosensitizer for Mitochondria-targeted Photodynamic Therapy.

Silicon-xanthene derivatives (SiXs) have gained popularity in the field of bioimaging due to their advantageous far-red to near-infrared (NIR) absorption and emission wavelengths, notable brightness (ε × Φ), inherent mitochondrial targeting properties and high photo-stability, making them an excellent candidate for photodynamic therapy (PDT). Nevertheless, the utilization of SiXs as photosensitizers (PSs) for PDT in cancer treatment remains largely unexplored, primarily due to their limited capacity to generate cytotoxic reactive oxygen species (ROS). However, the potential of SiXs in PDT warrants further investigation. In this study, utilizing the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC) mechanism, we reported one novel heavy-atom-free, mitochondria-targeted, silicon-rhodamine-based photosensitizer (SiR-PXZ), which demonstrated excellent biocompatibility, minimal dark toxicity, favorable water-solubility and stability, and considerable singlet oxygen quantum yield under 660 nm light irradiation (ΦΔ = 0.16 in air-saturated PBS). Moreover, SiR-PXZ could be rapidly taken up by the mitochondria and efficiently induced apoptosis of cancer cells with an IC50 value of 1.2 µM. The in vivo studies showed that SiR-PXZ exhibited excellent anti-tumor effects, making it potentially valuable for clinical application. This study offers a source of ideas for the construction of SiXs-based photosensitizers for photodynamic cancer treatment in the future.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

AIM: Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. METHODS: A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. RESULTS: MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. CONCLUSIONS: These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

Abnormal caudate nucleus activity in patients with depressive disorder: Meta-analysis of task-based functional magnetic resonance imaging studies with behavioral domain.

During task-based functional magnetic resonance imaging (t-fMRI) patients with depressive disorder (DD) have shown abnormal caudate nucleus activation. There have been no meta-analyses that are conducted on the caudate nucleus using Activation Likelihood Estimation (ALE) in patients with DD, and the relationships between abnormal caudate activity and different behavior domains in patients with DD remain unclear. There were 24 previously published t-fMRI studies included in the study with the caudate nucleus as the region of interest. Meta-analyses were performed using the method of ALE. Included five ALE meta-analyses: (1) the hypoactivated caudate nucleus relative to healthy controls (HCs); (2) the hyper-activated caudate nucleus; (3) the abnormal activation in the caudate nucleus in the emotion domain; (4) the abnormal activation in cognition domain; (5) the abnormal activation in the affective cognition domain. Results revealed that the hypo-/hyper-activity in the caudate subregions is mainly located in the caudate body and head, while the relationships between abnormal caudate subregions and different behavior domains are complex. The hypoactivation of the caudate body and head plays a key role in the emotions which indicates there is a positive relationship between the decreased caudate activity and depressed emotional behaviors in patients with DD.