The moderated-mediation role of risk perception and intolerance of uncertainty in the association between residual symptoms and psychological distress: a cross-sectional study after COVID-19 policy lifted in China.

BACKGROUND: A considerable number of individuals infected with COVID-19 experience residual symptoms after the acute phase. However, the correlation between residual symptoms and psychological distress and underlying mechanisms are scarcely studied. We aim to explore the association between residual symptoms of COVID-19 and psychological distress, specifically depression, anxiety, and fear of COVID-19, and examine the role of risk perception and intolerance of uncertainty in the association. METHODS: A cross-sectional survey was conducted by online questionnaire-based approach in mid-January 2023. Self-reported demographic characteristics, COVID-19-related information, and residual symptoms were collected. Depression, anxiety, fear, risk perception and intolerance of uncertainty were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Fear of COVID-19 Scale (FCV-19S), COVID-19 Risk Perception Scale and Intolerance of Uncertainty Scale-12 (IUS-12), respectively. Linear regression analyses were conducted to explore the associations. A moderated mediation model was then constructed to examine the role of risk perception of COVID-19 and intolerance of uncertainty in the association between residual symptoms and psychological distress. RESULTS: 1735 participants effectively completed the survey. 34.9% of the patients experienced residual symptoms after acute phase of COVID-19. Psychological distress was markedly increased by COVID-19 infection, while residual symptoms had a significant impact on psychological distress (Ps < 0.001), including depression (ß = 0.23), anxiety (ß = 0.21), and fear of COVID-19 (ß = 0.14). Risk perception served as a mediator between residual symptoms and all forms of psychological distress, while intolerance of uncertainty moderated the effect of risk perception on depression and anxiety. CONCLUSION: A considerable proportion of patients experience residual symptoms after acute phase of COVID-19, which have a significant impact on psychological distress. Risk perception and intolerance of uncertainty play a moderated-mediation role in the association between residual symptoms and depression/anxiety. It highly suggests that effective treatment for residual symptoms, maintaining appropriate risk perception and improving intolerance of uncertainty are critical strategies to alleviate COVID-19 infection-associated psychological distress.

Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

PURPOSE: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. METHODS: This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. RESULTS: Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. CONCLUSIONS: Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models.

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children. The orexigenic hormone ghrelin is important in neuroprotection and neurodevelopment, which may play an important role in psychopathogenesis of ADHD. This study aimed to systematically investigate the genomic and pharmacological manipulations of ghrelin functioning in ADHD-like symptoms in zebrafish models and validated the effects of ghrelin polymorphisms in human subjects with ADHD. We firstly generated ghrelinΔ/Δ zebrafish mutant, which displayed hyperactive, attention deficit-like and impulsive-like behaviors, as well as endophenotypes, mimicking human ADHD. GhrelinΔ/Δ zebrafish exhibited downregulated expression levels of wnt1, wnt3a, wnt5a that are critical for dopaminergic neuron development to possibly regulate their number and spatial organization. Pharmacological blockade of wnt signaling with XAV939 induced a reduced moving activity and less dopaminergic neurons; whereas, wnt agonist SB415286 rescued hyperactivity and dopaminergic neuron loss in ghrelinΔ/Δ zebrafish. In addition, we further identified and validated a SNP, rs696217, on orexigenic hormone preproghrelin/ghrelin (T408T, Met72Met) to be associated with a higher risk of ADHD in a case-controlled association study with 248 subjects with ADHD and 208 subjects of healthy controls. Together, our results reveal a novel endogenous role for orexigenic hormone ghrelin in ADHD, which provides insights into genetic regulation and drug screens for the identification of novel treatments of ADHD.

An updated meta-analysis: apolipoprotein E genotypes and risk of primary open-angle glaucoma.

PURPOSE: To study the association of apolipoprotein E (APOE) polymorphisms and primary open-angle glaucoma (POAG). METHODS: After a systematic literature search, all relevant studies evaluating the association between APOE polymorphisms and POAG were included. All statistical tests were calculated with Stata 11.0. RESULTS: Twelve independent studies on the APOE gene (1,971 cases, 1,756 controls) and POAG were included. A significant association between the APOE gene and POAG was found in the genetic model of ε4/ε4 versus ε3/ε3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12-3.88, p = 0.02). However, no association was detected in the models of ε2/ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2/ε4 versus ε3/ε3, ε3/ε4 versus ε3/ε3, allele ε2 versus allele ε3, and allele ε4 versus allele ε3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ε4/ε4 versus ε3/ε3 in Asians (OR = 3.55, 95% CI = 1.06-11.87, p = 0.04). No association was identified between the APOE gene and the risk of POAG in Caucasians. CONCLUSIONS: The present meta-analysis indicated that the ε4/ε4 genotype is associated with increased risk of POAG in Asians.

Deficiency of leap2 promotes somatic growth in zebrafish: Involvement of the growth hormone system.

Purpose: Liver-expressed antimicrobial peptide-2 (LEAP2) is identified as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor type 1a (GHSR1a), its effect on the GHSR1a is contrary to the role of GHRELIN. Growth hormone (GH) is a crucial hormone for early development. Previous studies report that LEAP2 dose-dependently attenuates ghrelin-induced GH secretion, and Leap2-knockout mice exhibit increased plasma GH levels after GHRELIN administration. Clinical data revealed a possible correlation between LEAP2 and height development. However, the role of LEAP2 in early development remains unclear. This study aimed to investigate the role of LEAP2 in early development using leap2 mutant zebrafish larvae as a model. Method: We analyzed the conservation of LEAP2 peptide across multiple species and generated leap2 mutants in zebrafish by CRISPR-Cas9, dynamically observed and measured the growth and development of zebrafish larvae from fertilization to 5 day post fertilization (dpf). In situ hybridization, transcriptome sequencing, quantitative real-time PCR and Western blot were used to detect the expression levels of GH and its signaling in early stage of embryonic development. Result: Our data demonstrate that zebrafish with a knockout of the leap2 gene display a significant increase in hatching rate, body length, and the distance between their eyes, all without visible developmental defects in the early stages of development. In addition, both RNA and protein analyses revealed a significant increase in GH expression in leap2 mutant. Conclusion: In general, this study demonstrates that LEAP2 regulates the expression of GH during early development, particularly influencing body length.

Nanopore-based sensors for DNA sequencing: a review.

Nanopore sensors, owing to their distinctive structural properties, can be used to detect biomolecular translocation events. These sensors operate by monitoring variations in electric current amplitude and duration, thereby enabling the calibration and distinction of various biomolecules. As a result, nanopores emerge as a potentially powerful tool in the field of deoxyribonucleic acid (DNA) sequencing. However, the interplay between testing bandwidth and noise often leads to the loss of part of the critical translocation signals, presenting a substantial challenge for the precise measurement of biomolecules. In this context, innovative detection mechanisms have been developed, including optical detection, tunneling current detection, and nanopore field-effect transistor (FET) detection. These novel detection methods are based on but beyond traditional nanopore techniques and each of them has unique advantages. Notably, nanopore FET sensors stand out for their high signal-to-noise ratio (SNR) and high bandwidth measurement capabilities, overcoming the limitations typically associated with traditional solid-state nanopore (SSN) technologies and thus paving the way for new avenues to biomolecule detection. This review begins by elucidating the fundamental detection principles, development history, applications, and fabrication methods for traditional SSNs. It then introduces three novel detection mechanisms, with a particular emphasis on nanopore FET detection. Finally, a comprehensive analysis of the advantages and challenges associated with both SSNs and nanopore FET sensors is performed, and then insights into the future development trajectories for nanopore FET sensors in DNA sequencing are provided. This review has two main purposes: firstly, to provide researchers with a preliminary understanding of advancements in the nanopore field, and secondly, to offer a comprehensive analysis of the fabrication techniques, transverse current detection principles, challenges, and future development trends in the field of nanopore FET sensors. This comprehensive analysis aims to help give researchers in-depth insights into cutting-edge advancements in the field of nanopore FET sensors.

New Endothelial Corneal Dystrophy in a Chinese Family.

PURPOSE: The aim of this study was to characterize the clinical presentation of atypical endothelial corneal dystrophy (ECD) and to identify possible associated genetic variants in a Chinese family. METHODS: Six affected members, 4 unaffected first-degree relatives, and 3 spouses who were enrolled in this study underwent ophthalmic examinations. Genetic linkage analysis was performed for 4 affected and 2 unaffected members, and whole-exome sequencing (WES) was performed for 2 patients to identify disease-causing variants. Candidate causal variants were verified using Sanger sequencing in family members and 200 healthy controls. RESULTS: The mean age at disease onset was 16.5 years. The early phenotype of this atypical ECD was characterized by multiple small white translucent spots located in Descemet membrane of the peripheral cornea. These spots coalesced to form opacities with variable shapes, and eventually merged along the limbus. Subsequently, translucent spots appeared in central Descemet membrane and accumulated, causing diffuse polymorphous opacities over time. Finally, significant endothelial decompensation led to diffuse corneal edema. A heterozygous missense variant in the KIAA1522 gene (c.1331G>A; p.R444Q) was identified by WES, which was present in all 6 patients but was absent in the unaffected members and healthy controls. CONCLUSIONS: The clinical features of atypical ECD are unique compared with those of known corneal dystrophies. Moreover, genetic analysis identified the c.1331G>A variant in KIAA1522 , which may be responsible for the pathogenesis of this atypical ECD. Thus, we propose this is a new form of ECD based on our clinical findings.

Analysis of Automated Clinical Depression Diagnosis in a Chinese Corpus.

Depression clinical interview corpora are essential for advancing automated depression diagnosis. While previous studies have used written speech material in controlled settings, these materials do not accurately represent spontaneous conversational speech. Additionally, self-reported measures of depression are subject to bias, making the data unreliable for training models for real-world scenarios. This study introduces a new corpus of depression clinical interviews collected directly from a psychiatric hospital, containing 113 recordings with 52 healthy and 61 depressive patients. The subjects were examined using the Montgomery-Asberg Depression Rating Scale (MADRS) in Chinese. Their final diagnosis was based on medical evaluations through a clinical interview conducted by a psychiatry specialist. All interviews were audio-recorded and transcribed verbatim, and annotated by experienced physicians. This dataset is a valuable resource for automated depression detection research and is expected to advance the field of psychology. Baseline models for detecting and predicting depression presence and level were built, and descriptive statistics of audio and text features were calculated. The decision-making process of the model was also investigated and illustrated. To the best of our knowledge, this is the first study to collect a depression clinical interview corpus in Chinese and train machine learning models to diagnose depression patients.

Serum total cholesterol levels associated with immediate memory performance in patients with chronic schizophrenia.

Cognitive impairments are common in patients with schizophrenia. Changes in total cholesterol (TC) may be involved in the development of schizophrenia and associated with cognitive function. This study aimed to investigate differences in serum TC level and cognitive function between schizophrenia patients and healthy controls and explore the relationship between serum TC level and cognitive function in patients with schizophrenia. A total of 105 schizophrenia patients and 105 healthy controls were recruited. Results showed that patients with schizophrenia had significantly lower scores on the overall RBANS scale and subscales (i.e., immediate memory, language, attention, and delayed memory) than those of healthy controls. Pearson's correlation analyses showed that in patients with schizophrenia, serum TC levels were positively associated with RBANS subscale scores of immediate memory and language. Furthermore, multivariate regression analyses showed that serum TC level was positively associated with the immediate memory index in patients with schizophrenia. However, no significant association was found between serum TC level and RBANS score in the healthy control group. Our results suggest that elevated serum TC level may be related to improved cognitive function in patients with schizophrenia, especially that of immediate memory.

Effects of astigmatic keratotomy combined with scleral tunnel incisions for the treatment of high astigmatism after penetrating keratoplasty.

The present study aimed to evaluate the efficacy, predictability and safety of astigmatic keratotomy (AK) combined with scleral tunnel incisions in the treatment of high astigmatism after penetrating keratoplasty (PKP). Paired AK combined with scleral tunnel incisions was performed at the steep astigmatic meridian in 8 eyes of 8 patients with high keratometric astigmatism [>5.0 diopters (D)] after PKP. Pre- and post-operative parameters, including uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction and keratometric astigmatism were evaluated. The Alpins method for vector analysis was used to evaluate the changes in keratometric astigmatism. The results indicated a statistically significant reduction in the mean keratometric astigmatism from 8.16±3.02 D pre-operatively to 2.28±1.07 D at 3 months postoperatively. The mean UCVA improved from 0.95±0.24 logarithm of the minimum angle of resolution (logMAR) pre-operatively to 0.61±0.17 logMAR at 3 months postoperatively (P<0.05). The mean BCVA improved from 0.41±0.18 logMAR pre-operatively to 0.26±0.12 logMAR at 3 months postoperatively (P>0.05). Between 3 and 6 months after the surgery, the keratometric astigmatism remained stable. Alpins vector analysis demonstrated the relative predictability of this combined surgical treatment. The surgically induced astigmatism was significantly correlated with the target induced astigmatism (r=0.76, P<0.05). None of the patients had any severe complications. The present study indicated that AK combined with scleral tunnel incisions is an effective, relatively predictable and safe treatment for high astigmatism after PKP.

Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio).

Reserpine is widely used for treatment of hypertension and schizophrenia. As a specific inhibitor of monoamine transporters, reserpine is known to deplete monoamine neurotransmitters and cause decreased movement symptoms. However, how zebrafish larvae respond to reserpine treatment is not well studied. Here we show that swimming distance and average velocity are significantly reduced after reserpine exposure under various stimulatory conditions. Using liquid chromatograph-mass spectrometer analysis, decreased levels of monoamines (e.g. dopamine, noradrenaline, and serotonin) were detected in reserpine-treated larvae. Moreover, reserpine treatment significantly reduced the number of dopaminergic neurons, which was identified with th (Tyrosine Hydroxylase) in situ hybridization in the preoptic area. Interestingly, dopaminergic neuron development-associated genes, such as otpa, otpb, wnt1, wnt3, wnt5 and manf, were downregulated in reserpine treated larvae. Our data indicates that 2 mg/L reserpine exposure induces dopaminergic neuron damage in the brain, demonstrating a chemical induced depression-like model in zebrafish larvae for future drug development.

Association of different susceptibilities to morphine with the expression of 5-HTT and 5-HT1AR mRNA in brain regions of SD rats.

OBJECTIVE: To investigate the possible mechanism for the different CPP susceptibilities. METHODS: Using a conditioned place preference (CPP) model, rats were selected into high and low preference groups. Using in situ hybridization, we examined the mRNA expression of 5-hydroxytryptamine transporter (5-HTT) and 5-hydroxytryptamine 1A receptor (5-HT1AR) in 3 crucial regions in addiction, namely the ventral tegmental area (VTA), the nucleus accumbens (NAc), and the medial prefrontal cortex (mPFC), during the dependence and withdrawal. RESULTS: During dependence state, the expression of 5-HTT mRNA in each of the regions in the high preference group was significantly lower than that of the low preference group, while higher expression of 5-HT1AR mRNA in each of the regions in the high preference group than that of the low preference group was found (P < 0.05). During withdrawal state, the expression of 5-HTT mRNA in each of the regions in high preference group was significantly higher than that of the low preference group, while lower expression of 5-HT1AR mRNA in each of the regions in the high preference group than that of the low preference group was found (P < 0.05). CONCLUSION: 5-HTT and 5-HT1AR may play a role in differences in susceptibility to morphine.

[Dopamine D2 receptor and transportor [corrected] in the medial prefrontal contex of morphine-induced conditioned place preference in Sprague-Dawley rats].

OBJECTIVE: To investigate the expression of dopamine D2 receptors (D2R) and dopamine transportors (DAT) located in the medial prefrontal contex (mPFC) in high and low conditioned place preference (CPP) rats, and to unveil the possible mechanism leading to different CPP susceptibilities. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly assigned into an experiment group (n = 130) and a control group (n = 30). The experiment group was re-classified into 2 groups according to CPP values:high preference group (HP group) and low preference group (LP group). According to the execution time-points after the last administration, the HP and LP group was classified into a 3-hour group (3 h), a 72-hour group (J3d), and a 14-day group (J14d), respectively. At 3 hours, 72 hours, and 14 days after the final injection, rats were killed and cardio-perfused, and the brains were removed and sliced up coronarily. The mRNA levels of D2R and DAT in mPFC were determined with in situ hybridization. RESULTS: There were no significant differences of pretest scores staying at the non-preference chamber among the groups(P = 0.470). However, the test scores of the CPP time stayed at pretest natural preference in the HP group were significantly higher than those of the LP group(P = 0.000). In 3h, J3d, and J14d groups,the expressions of D2R mRNA in the HP group (125.43 +/- 2.90 approximately 142.92 +/- 3.32) were lower than those of LP group (122.25 +/- 2.20 approximately 136.67 +/-5.39) (P = 0.000). In 3h and J3d,the expressions of DAT mRNA in the HP group (157.00 +/- 3.55 approximately 145.15 +/- 3.69) were significantly lower than those of the LP group (150.69 +/- 3.12 approximately 138.84 +/- 3.99) (P = 0.000). In J14d, there were no differences among 3 groups in mPFC (P = 0.458). CONCLUSION: D2R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.

Correlations of PTEN genetic polymorphisms with the risk of depression and depressive symptoms in a Chinese population.

OBJECTIVE: This study aimed to investigate the correlations of three common single nucleotide polymorphisms (SNPs) in the PTEN gene (rs701848 T>C, rs2735343 G>C and rs112025902 A>T) with the risk of depression and depressive symptoms in a Chinese population. METHODS: From July 2011 to June 2013, a total of 384 patients with depression and 400 healthy individuals were included in this study. These SNPs in the PTEN gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. The Hamilton Depression Rating Scale (HAMD) was used to evaluate the severity of depression. RESULTS: The C allele of rs701848, the C allele of rs2735343 and the T allele of rs112025902 were associated with an increased risk of depression (odds ratio [OR]=3.814, 95% CI: 3.093-4.703, P<0.001; OR=2.642, 95% CI: 2.152-3.242, P<0.001; OR=2.882, 95% CI: 2.347-3.539, P<0.001; respectively). Depression patients carrying C allele (TC+CC) of rs701848 and carrying T allele (AT+TT) of rs112025902 had higher HAMD total scores and HAMD anxiety factor scores than those carrying TT genotype of rs701848 and carrying AA genotype of rs112025902 (all P<0.05). Furthermore, depression patients carrying C allele (GC+CC) of rs2735343 had lower HAMD total scores and HAMD factors associated with depression scores than those carrying GG genotype (both P<0.05). Logistic regression analysis revealed that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be independent risk factors of depression (relative risk [RR]=1.807, 95% CI=1.023-3.193, P=0.042; RR=1.759, 95% CI=1.033-2.995, P=0.038; RR=1.646, 95% CI=1.018-2.663, P=0.042; respectively). CONCLUSION: Our findings provide evidence that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be correlated with the risk of depression and depressive symptoms in the Chinese population.

SMILE and Wavefront-Guided LASIK Out-Compete Other Refractive Surgeries in Ameliorating the Induction of High-Order Aberrations in Anterior Corneal Surface.

Purpose. To compare the change of anterior corneal higher-order aberrations (HOAs) after laser in situ keratomileusis (LASIK), wavefront-guided LASIK with iris registration (WF-LASIK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). Methods. In a prospective study, 82 eyes underwent LASIK, 119 eyes underwent WF-LASIK, 88 eyes underwent FS-LASIK, and 170 eyes underwent SMILE surgery. HOAs were measured with Pentacam device preoperatively and 6 months after surgery. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs, spherical aberration (SA), horizontal coma, and vertical coma over 6 mm diameter central corneal zone. Results. Six months postoperatively, all procedures result in increase of anterior corneal total HOAs and SA. There were no significant differences in the induced HOAs between LASIK and FS-LASIK, while SMILE induced fewer total HOAs and SA compared with LASIK and FS-LASIK. Similarly, WF-LASIK also induced less total HOAs than LASIK and FS-LASIK, but only fewer SA than FS-LASIK (P < 0.05). No significant difference could be detected in the induced total HOAs and SA between SMILE and WF-LASIK, whereas SMILE induced more horizontal coma and vertical coma compared with WF-LASIK (P < 0.05). Conclusion. FS-LASIK and LASIK induced comparable anterior corneal HOAs. Compared to LASIK and FS-LASIK, both SMILE and WF-LASIK showed advantages in inducing less total HOAs. In addition, SMILE also possesses better ability to reduce the induction of SA in comparison with LASIK and FS-LASIK. However, SMILE induced more horizontal coma and vertical coma compared with WF-LASIK, indicating that the centration of SMILE procedure is probably less precise than WF-LASIK.

Protective Effect of Rutin Against H2O2-Induced Oxidative Stress and Apoptosis in Human Lens Epithelial Cells.

PURPOSE: The aim of this study was to evaluate the effect of rutin on oxidative stress and apoptosis induced by H2O2 in human lens epithelial (HLE) cells and the associated mechanisms involved. METHODS: Cell viability was assessed by 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and cell apoptosis was determined by flow cytometry, TUNEL assay and DNA fragmentation assay after 24 h treatment of 100 µM H2O2 with or without rutin pretreatment at various concentrations. The level of reactive oxygen species (ROS) was examined using 2',7'-dichlorodihydrofluorescein diacetate by flow cytometry. The activity of superoxide dismutase (SOD) was measured by xanthinoxidase method and the contents of glutathione (GSH) and malondialdehyde (MDA) were quantified by enzyme-linked immunosorbent assay. The expression change of Bcl-2, Bax and caspase-3 at mRNA and protein levels were detected by real-time polymerized chain reaction (RT-PCR) and Western-blot analysis, respectively. Activation and translocation of nuclear factor-kappaB (NF-кB/p65) were examined by Western blot and immunocytochemistry. RESULTS: Rutin pretreatment protected HLE cells from H2O2-induced cell viability decrease and apoptosis. In addition, in the presence of rutin, H2O2-induced intracellular excessive ROS and MDA were attenuated, whereas intracellular SOD and GSH depletion were prevented. Moreover, rutin also inhibited the up-regulation of caspase-3 and Bax expression and rescued down-regulation of Bcl-2 expression. Lastly, rutin blocked the activation and translocation of NF-кB/p65 induced by H2O2. CONCLUSIONS: Our results demonstrated that rutin effectively protects HLE cells from H2O2-induced oxidative stress and apoptosis in a dose-dependent manner. The involved mechanisms may be related to the regulation of ROS production, the inhabitation of lipid peroxidation, the protection of intracellular antioxidant system and its modulation of Bcl-2/Bax family and NF-кB/p65 signaling pathway.

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma.

BACKGROUND: Glaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome 1q-linked open-angle glaucoma (GLC1A) in a Chinese family with primary open-angle glaucoma (POAG). METHODS: A total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations. RESULTS: Six members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene (MYOC). Furthermore, we also identified a novel mutation c.G322A in beta-1,4-galactosyltransferase 3 (B4GALT3) gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls. CONCLUSION: The mutations c.1456C < T (p.L486F) in MYOC and c.322G < A (p.V108I) in B4GALT3 are likely responsible for the pathogenesis of POAG in this family.

An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1 and GSTT1) Polymorphisms to Age-Related Cataract.

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057-1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598-0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137-1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.

Prevalence of tardive dyskinesia in chronic male inpatients with schizophrenia on long-term clozapine versus typical antipsychotics.

This study aimed to examine the prevalence and clinical associated variables of tardive dyskinesia (TD) in a large sample of Chinese inpatients with schizophrenia on long-term treatment with clozapine versus typical antipsychotics. A total of 584 male inpatients with schizophrenia on long-term clozapine (n=341) or typical antipsychotic (n=243) treatment were evaluated using the Abnormal Involuntary Movement Scale (AIMS). The patient's psychopathology was assessed using the Positive and Negative Syndrome Scale. The overall prevalence of TD was 44.5%, with rates of 48.7% in the clozapine group and 38.7% in the typical antipsychotic group (P=0.017). The AIMS score was significantly lower in typical than in clozapine groups (P<0.005). A multiple regression analysis showed that the following variables were significantly associated with the AIMS score: clozapine versus typical medication (P=0.008), Positive and Negative Syndrome Scale negative subscore (P=0.017), and age (P=0.04). There are significant differences in the prevalence and clinical correlates of TD in schizophrenia treated with clozapine versus typical antipsychotics.