Synthesis of Silver(I) Complexes through In Situ Reactions of dppeda with dmp in the Presence of Silver Halides for Photocatalysis.

Due to the unique photosensitivity of silver compounds, they exhibit good photocatalytic activity as photocatalysts in the degradation of water pollutants. However, silver compounds have poor cycling stability and are prone to decomposition and reaction under light to form metallic silver, which greatly limits their practical application. Herein, a (2-(2-(diphenylphosphaneyl)ethyl)-9-methyl-1.10-phenanthroline (PSNNP)) pincer ligand was designed for stabilizing the central metal. The in situ-formed PSNNP ligand could be readily generated in one pot with the participation of silver halides. The reaction of silver halides with dppeda (N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine) in the presence of dmp (2,9-dimethyl-1,10-phenanthroline) in acetonitrile afforded complexes Ag2X2 (PSNNP)2 (complexes 1, 2) (X = Cl, Br). Single-crystal X-ray diffraction shows that the tridentate coordination of the pincer ligand provides strong binding with metal centers and leads to high stability of the pincer metal unit. The removal rate of rhodamine B (RhB) by complexes 1 and 2 can reach up to 100%, demonstrating an excellent photocatalytic degradation performance for organic dyes. The important effect of PSNNP ligands on photocatalytic properties after coordination with central metals was studied through experiments and discrete Fourier transform (DFT) calculations. The photocatalytic reaction mechanism of complexes 1 and 2 was also studied. This result provides an effective pathway for the first synthesis of PSNNP and interesting insights into photocatalytic degradation chemistry.

Ormosianines A-P, Structurally Diverse Quinolizidine Alkaloids with AChE Inhibitory Effects from Ormosia yunnanensis.

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.

The relationship between childhood traumatic experience and suicidal tendency in non-suicidal self-injury behavior patients.

BACKGROUND: Individuals with non-suicidal self-injury (NSSI) behavior are usually prone to repeated, intentional, direct harm to their own bodies that is not allowed by society without suicidal ideation. Under this behavior guidance, childhood traumatic experience may easily cause a series of psychological comorbidity symptoms, such as anxiety and depression, finally leading to a suicidal tendency. METHODS: A total of 311 adolescent NSSI behavioral patients were recruited at the Ningbo Kangning hospital, Zhejiang Province according to the DSM-5 diagnostic criteria. Demographic data, childhood abuse and neglect, internet addiction, self-esteem, anxiety, and suicidal tendency were evaluated. A structural equation model with a path induction mechanism was constructed to evaluate the relationship between distal and proximal factors related to suicidal tendencies due to childhood traumatic experiences in NSSI behavioral individuals. RESULTS: Among the 311 subjects included in the survey, 250 (80.39%) suffered traumatic experiences, such as emotional abuse/physical abuse/sexual abuse/emotional neglect or physical neglect in their childhood, 303 (97.43%) had suicidal ideation, 271 (87.14%) showed the total score of self-esteem, 148 (47.59%) had different degrees of Internet addiction tendency, and 286 (91.96%) showed obvious anxiety. The established path model fit well (GFI = 0.996, RMSEA = 0.03), and the model showed that self-esteem, anxiety, and childhood traumatic experience had standardized coefficients of -0.235 (z = -4.742, p < 0.01), 0.322 (z = 6.296, p < 0.01), 0.205 (z = 4.047, p < 0.01), respectively, with suicidal ideation path, suggesting that self-esteem, Internet addiction, and anxiety showed significant mediating effects in the process of childhood traumatic experience affecting suicidal ideation. CONCLUSION: In the context of childhood traumatic experience, it is often accompanied by a series of regulatory behaviors such as Internet addiction, self-esteem, and so on, which finally leads to anxiety, mental symptoms, and even suicidal tendencies. The results provide effective support for the structural equation modeling to evaluate the multi-level influence of NSSI behavior individuals and emphasize that childhood familial factors may lead to psychiatric comorbidity symptoms and suicidal behavior.

Facile high yield, excellent catalytic performance of polyoxometalate-based lanthanide phosphine oxide complexes: Syntheses, structures, photocatalysis and THz spectra.

Water pollution, which continuously threatens human health and the sustainable development of society, has become a major concern. Photocatalytic degradation is an effective strategy to remove organic dyes from wastewater. For this strategy, it is crucial to select the appropriate catalyst. Using triphenylphosphine oxide (OPPh3) as the ligand, phosphomolybdic acid as the anion template, three new lanthanide complexes [Ln(OPPh3)4(H2O)3](PMo12O40)∙4C2H5OH (1-3) (Ln = Sm, Gd, Tb) were synthesized. The raw materials for the reaction are cheap and readily available. The convenient synthesis method is environmentally friendly, with high yield (70%-80%). Complexes 1-3 are all seven-coordinated mononuclear structures centered on lanthanide ions, [PMo12O40]3- anions and solvent molecules are not coordinated with metal ions. These mononuclear structures eventually form complicated 3D supramolecular structures through hydrogen bonds, Mo-O … π or C-H … π weak interactions. Complexes 1-3 photocatalytic degradation of MB have high removal rates, as catalysts have enough stability to be reused, and can be used as excellent catalysts for the degradation of dye molecules in sewage. Among them, the removal rate of MB by photodegradation of complex 2 was highest (99.50%). In addition, the effects of different initial concentrations of MB solution and different types of organic dyes on the photocatalysis experiment were investigated. The photocatalytic reaction mechanism of complexes 1-3 was also studied. Due to the similar structures of complexes 1-3, they have almost the same THz absorption spectra with different absorption intensity, which may be attributed to the difference of the number of weak interactions. Therefore, terahertz spectroscopy can be used as a sensitive method to distinguish and determine small differences between lanthanide-organic complexes. This is the first time that this spectrum has been used to characterize lanthanide phosphine oxide complexes modified by [PMo12O40]3-.

Intermolecular interactions, photocatalysis and THz-TDS interrelationships for lanthanide phosphine oxide complexes based on {PW12}.

A series of rare earth complexes containing (α-PW12O40)3- and PO ligand are synthesized by water bath in 70 °C, [Ln(OPPh3)4(H2O)3](PW12O40)·4CH3CN (Ln = La, Pr, Nd, Sm, Gd, Tb, Ho 1-7) (OPPh3 = Triphenylphosphine oxide, {PW12} = phosphotungstic acid). The precise structures are confirmed by X-ray single crystal diffraction and the result shows all complexes are isostructural. Complexes 1-7 are fully characterized by PXRD, FT-IR, TGA, UV diffuse reflectance spectra and terahertz time-domain spectroscopy (THz-TDS). Complex 3 exhibits the highest photocatalytic degradation efficiency for methylene blue (MB) in this series of complexes. The experimental results showed that the photodegradation efficiency can remain constant at the level of 95% after five consecutive cycles. The photocatalytic reaction kinetics and mechanism of complexes were investigated. Additionally, complexes also exhibit photocatalytic hydrogen evolution activity. THz-TDS was used to characterize the complexes and its raw materials, the characteristic peaks of OPPh3 (broad peak at 1.20 THz) and phosphotungstic acid (sharp peaks at 0.23, 0.32 THz) were obtained.

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia.

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of this study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins was measured by western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB), and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

Knockdown of POLQ interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration.

BACKGROUND: DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated. METHODS: In the present study, both the data collected from the Cancer Genome Atlas (TCGA) and our group's results showed higher POLQ expression in HCC tissues than the para-cancerous tissues, which was associated with higher malignancy and poor prognosis. POLQ knockdown HCC cell model (shPOLQ) was constructed along with the corresponding negative control (shCtrl) through lentivirus infection for loss-of-function study. RESULTS: We found that, upon knockdown of POLQ, the proliferation and migration of HCC cells decreased and apoptosis percentage increased. Moreover, the percentage of cells in G2 phase significantly increased in shPOLQ group compared with shCtrl group. Xenografts in mice grafted with shPOLQ cells grew much slower than that transplanted with shCtrl cells, and expressed lower Ki67 level. Furthermore, an apoptosis-related signaling array was used to explore the involvement of downstream signaling pathways, suggesting the enhanced phosphorylation of HSP27 and JNK, and the de-activation of mTOR, PRAS40, ERK1/2 and STAT3 pathways. CONCLUSIONS: Collectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC.

Neothalfine, a potent natural anti-tumor agent against metastatic colorectal cancer and its primary mechanism.

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 µM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.

Association of Elevated Cord Blood Oxidative Stress Biomarkers with Neonatal Outcomes in Mothers with Pre-Eclampsia: A Case-Control Study.

OBJECTIVES: The objective of this study was to determine the relationship between the levels of stress biomarkers in cord blood and pre-eclampsia (PE) in a hospital-based population of pregnant patients and evaluate the effects on pregnancy outcomes. DESIGN: This was an observational, case-control study. Participants/Materials, Setting, Methods: This case-control study included 282 patients with severe PE and 534 women with normal pregnancy. The umbilical cord was collected at delivery and tested for malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, and homocysteine (Hcy) analysis. We performed a univariate general linear regression model analysis to control potential confounders and determined the underlying influencing factors for high MDA and ROS. A receiver operating characteristic curve analysis was conducted to determine the cutoff values for identifying severe PE. Further, the severe PE group was divided into the low- or high-MDA and low- or high-ROS subgroups according to the cutoff values. Finally, we created logistic regression models to estimate the adjusted odds ratio for each perinatal outcome in the high-MDA and high-ROS subgroup. RESULTS: The levels of MDA and ROS levels were higher in women with severe PE than in normotensive pregnant patients. However, when adjusted for cord blood Hcy levels, the difference was insignificant. Additionally, both MDA (r = 0.359, p < 0.001) and ROS (r = 0.473, p < 0.001) were positively correlated with the cord blood Hcy level. The areas under the curve of MDA and ROS levels were 0.65 (95% confidence interval [CI]: 0.60-0.69) and 0.88 (95% CI: 0.86-0.90), respectively. Higher MDA and ROS levels were associated with increased risks of a low Apgar score, admission to the NICU, and assisted ventilation for the newborn. LIMITATIONS: The study design led to the exclusion of several participants. CONCLUSIONS: Increased levels of oxidative stress markers in the cord blood might be significantly associated with negative effects on newborns. High levels of Hcy in the cord blood might be associated with elevated MDA and ROS concentrations in women with severe PE.

Survey of factors influencing women's selection of the delivery method of their second child in Shanxi Province, China.

OBJECTIVE: To explore the factors influencing women's selection of the delivery method of their second child. METHODS: A questionnaire survey was administered among 431 women in the age range of interest from January 2015 to January 2017, and the survey results were evaluated and analyzed statistically. The experts evaluating the questionnaire are professionals in the Department of Obstetrics and Gynecology, Heji Hospital Affiliated to Changzhi Medical College. RESULTS: A total of 70.99% of subjects were 28-35 years old. Approximately 82.35% wished to undergo vaginal delivery, and the remaining 17.65% expressed to undergo cesarean delivery. The reasons for cesarean delivery included the following: fetal factors: worry about fetal health (33.33%), birth trauma (12.90%), and fetal macrosomia (38.17%); maternal factors: advanced age (36.56%), inability to bear uterine contraction pains (21.51%), worry about uracratia after vaginal delivery (10.75%), worry about perineum laceration (8.60%) and the impacts on sexual gratification after delivery (5.38%); social factors: faster delivery mode (54.84%), selection of birth time (27.96%), and better planning of maternity leave (17.20%). CONCLUSION: Most women tend to undergo vaginal delivery. However, due to the influence of age, educational level and other factors, an increasing number of women prefer cesarean delivery. Medical institutions have the responsibility for providing overall and fair medical information to women of childbearing age to help them make informed choices regarding mode of delivery.

POSTERIOR FUNDUS HEMORRHAGES: Frequency and Associated Factors: The Beijing Eye Study.

PURPOSE: To examine frequency and associations of retinal hemorrhages. METHODS: The population-based Beijing Eye Study included 3,468 individuals. Monoscopic fundus photographs were examined for hemorrhages. RESULTS: Retinal hemorrhages were detected in 515 eyes (429 individuals) (prevalence: 7.6%; 95% confidence interval [CI]: 7.0-8.0 per eye; 12.7%; 95% CI: 11.7-13.7 per person). Higher prevalence of retinal hemorrhages was correlated (multivariate analysis) with higher systolic blood pressure (P < 0.001; odds ratio: 1.02; 95% CI: 1.01-1.03), higher prevalence of diabetic retinopathy (P < 0.001; odds ratio: 121; 95% CI: 61-240), and higher prevalence of retinal vein occlusions (P < 0.001; odds ratio: 27; 95% CI: 17-42). Retinal hemorrhages were due to diabetic retinopathy (189 [36.7%] eyes), retinal vein occlusions (n = 65 [12.6%]), posterior vitreous detachment (n = 23 [4.5%]), glaucoma (n = 14 [2.7%]), exudative age-related macular degeneration (n = 8 [1.6%]), hypertensive retinopathy (n = 10 [1.9%]), and exudative myopic maculopathy (n = 1 [0.2%]). Retinal hemorrhages without evident ocular cause ("NOH") were detected in 204 (3.0%) eyes (or 39.6% of all retinal hemorrhages). Higher prevalence of NOHs was correlated with higher systolic blood pressure (P < 0.001; odds ratio: 1.02; 95% CI: 1.01-1.03) after adjusting for blood glucose concentration and prevalence of cortical cataract. CONCLUSION: In a population-based recruited cohort of individuals aged 50+ years, prevalence of any fundus hemorrhage was about 8% per eye and 13% per individual. Approximately 60% of the hemorrhages were due to ocular reasons, mainly diabetic retinopathy, retinal vein occlusions, and posterior vitreous detachment, whereas 40% of the bleedings were not evidently associated with ophthalmologic causes but strongly with elevated systolic blood pressure.

Male workers' exposure characteristics of ΣPCDD/F from a municipal solid waste incinerator in south China through hair analysis.

Human hair, flue gas and fly ash from a municipal solid waste incinerator (MSWI) in south China were collected and analyzed for polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF). The ΣPCDD/F level in hair from male workers were higher than those from residents. The Principal Component Analysis (PCA) suggested that ΣPCDD/F in flue gas is an external source of male workers' hair ΣPCDD/F. Results of daily intake of ΣPCDD/F by inhaling flue gas suggested that the inhalation exposure of ΣPCDD/F was at a slight health risk. For the male workers directly exposed to the MSWI power plant, ΣPCDD/F levels in their hair were significantly higher than those who were non-directly exposed. Moreover, a significantly positive relationship was obtained between ΣPCDD/F levels in male workers' hair and the working time. The result of correlation analysis suggested that 1,2,3,4,6,7,8-HpCDD and OCDD could be level indicator congeners to estimate ΣPCDD/F levels. In addition, 2,3,7,8-TCDD could be applied as TEQ indicator congener to characterize the hair of MSWI male workers.

ALDH1A1 mediates resistance of diffuse large B cell lymphoma to the CHOP regimen.

Although there have been substantial advances in our knowledge of the resistance of diffuse large B cell lymphoma (DLBCL) to chemotherapy, there are few efficient treatment strategies for recurrent/refractory DLBCL. The aim of this study was to investigate the role of aldehyde dehydrogenase (ALDH) 1A1 in the resistance of diffuse large B cell lymphoma to the chemotherapeutic mixture consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The involvement of ALDH1A1 in DLBCL was elucidated by knockdown and pharmacologic inhibition; Cell Counting Kit-8 (CCK-8) and clone formation assays were used to determine its role in CHOP sensitivity and clone formation ability. Caspase colorimetric assay was used to measure the extent of apoptosis. Western blot analysis was used to measure signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signaling proteins, and quantitative real-time PCR (RT-PCR) was used to measure the differential expression of ALDH1A1 of DLBCL patients and healthy donors. ALDH1A1 showed a 5.64-fold higher expression in malignant B cells than in normal B cells. Diethylaminobenzaldehyde (DEAB) decreased the half maximal inhibitory concentration (IC50) of the CHOP regimen in Farage cells from 344.78 ± 65.75 to 183.88 ± 49.75 ng/ml (P = 0.004). Both knockdown and inhibition of ALDH1A1 reduced clonogenicity, increased caspase-3/caspase-9 activity, and attenuated the phosphorylation status of STAT3/NF-κB. The prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels of expression (P = 0.044). ALDH1A1 is a new mediator for resistance of DLBCL to CHOP; it is a predictor of clinical prognosis and may serve as a potential target to improve chemotherapy responsiveness of human DLBCL.

Mechanism of action of Taohong Siwu decoction in the alleviation of primary dysmenorrhea.

Background: As one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism. Purpose: The objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism. Methods: HPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway. Results: Gallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins. Conclusion: TSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

(±)-Involucrasin D, a pair of enantiomeric bisflavonoid from the roots of Shuteria involucrata and its anti-inflammatory activity.

An undescribed bisflavonoid, named involucrasin D (1), along with two known flavonoids, 2(S)7,3',5'-trihydroxydihydroflavone (2) and sigmone (3) were isolated from the roots of Shuteria involucrata. A further chiral separation of 1 to yielded a pair of enantiomers (+)-1 and (-)-1. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Among them, bisflavonoid 1 and its enantiomers displayed remarkable anti-inflammatory effects by inhibiting the production of TNF-α and IL-6 in a dose-dependent manner.

The effects of ambient temperature and feeding regimens on cecum bacteria composition and circadian rhythm in growing rabbits.

Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Retinal nerve fiber layer defects and chronic kidney disease: the Kailuan Eye Study.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].