Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

The role of corneal endothelium in macular corneal dystrophy development and recurrence.

Macular corneal dystrophy (MCD) is a progressive, bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6 (CHST6). Corneal transplantation is the ultimate therapeutic solution for MCD patients. Unfortunately, postoperative recurrence remains a significant challenge. We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK). Our results revealed that the recurrence rate was nearly three times higher in the DALK group (39.13%, 9/23 eyes) compared with the PKP group (10.89%, 11/101 eyes), suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence. Our experimental data confirmed the robust mRNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium. Selective knockdown of wild-type Chst5 in mouse corneal endothelium (ACsiChst5), but not in the corneal stroma, induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients. Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD, along with corneal endothelial abnormalities. Intracameral injection of wild-type Chst5 rescued the corneal impairments in ACsiChst5 mice and retarded the disease progression in Chst5 mutant mice. Overall, our study provides new mechanistic insights and therapeutic approaches for MCD treatment by high-lighting the role of corneal endothelium in MCD development.

Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.

AIMS: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). METHODS: Fifty of 71 patients completed this double-blind placebo-controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. RESULTS: Both Event-based PM (EBPM) and Time-based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. CONCLUSIONS: Our findings indicated that bilateral high-frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. SIGNIFICANCE: Our results provide one therapeutic option for PM in patients with SCZ.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.

Microbiological Characteristics and Risk Factors Involved in Progression from Fungal Keratitis with Hypopyon to Keratitis-Related Endophthalmitis.

PURPOSE: To investigate the differences in microbiological characteristics, risk factors, drug resistance, and visual outcomes in three infections: fungal keratitis with hypopyon (FKH), keratitis-related fungal endophthalmitis (FKE), and fungal endophthalmitis without keratitis (FE). METHODS: An analytical cross-sectional study. RESULTS: In total, 14.57% of eyes with FKH progressed to endophthalmitis. Hypopyon, pre-existence of lens problems, topical steroid use and sever keratitis were significantly associated with the development of FKE. The risk factors of the FKH and FE group were mainly plant trauma and open globe trauma, respectively. Keratitis-related endophthalmitis (FKE) showed a significantly higher resistance than the other two groups. The FKH group had the best final visual acuity, while the FKE group had the worst. CONCLUSION: Hypopyon height, pre-existing lens problems, topical steroid use and sever keratitis are risk factors for progression to endophthalmitis in eyes with fungal keratitis, and its progression is not affected by a single fungus. The antifungal drugs resistance in patients with endophthalmitis related to keratitis was significantly higher than that associated with other reasons. Timely diagnosis and risk factor assessment are essential for ensuring early treatment of FKE.

A pilot study on improvements in attention function in major depressive disorder after 12 weeks of escitalopram monotherapy or combined treatment with agomelatine.

Objective: This study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine. Methods: A total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale-17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline. Results: Compared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale-17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy. Conclusions: Patients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.

Development of sensory integration therapy in Mainland China: A comprehensive study with bibliometrics and visualization techniques.

Sensory integration therapy (SIT) is an intervention to improve the developmental and learning problems in children. It was introduced in China from late 1980 s to early 1990 s and has received considerable attention from scholars. However, due to its late development in China and its specialised nature, it is worth exploring in depth whether it is recognized by the general public and how it is researched by academics. Therefore, we used Internet survey approach to explore the actual feedback of users towards SIT through the Internet. At the same time, bibliometric method and visualization techniques were used to study 892 journal articles on SIT in CNKI, Wanfang Database and VIP Database to analyze the spatial and temporal distribution, subject distribution, keyword co-occurrence, and keyword clustering of SIT research in mainland China since it came to China mainland. We found that the research on SIT in mainland China has been fruitful. However, the public is less aware of its basic function, therapeutic effects, and necessity. Our findings point to the need to raise awareness of sensory integration disorder and sensory integration therapy among the general public, and to strengthen academic research on sensory integration therapy.

Photodegradation of glyphosate in water and stimulation of by-products on algae growth.

Glyphosate is the most widely used herbicide in global agricultural cultivation. However, little is known about the environmental risks associated with its migration and transformation. We conducted light irradiation experiments to study the dynamics and mechanism of photodegradation of glyphosate in ditches, ponds and lakes, and evaluated the effect of glyphosate photodegradation on algae growth through algae culture experiments. Our results showed that glyphosate in ditches, ponds and lakes could undergo photochemical degradation under sunlight irradiation with the production of phosphate, and the photodegradation rate of glyphosate in ditches could reach 86% after 96 h under sunlight irradiation. Hydroxyl radicals (•OH) was the main reactive oxygen species (ROS) for glyphosate photodegradation, and its steady-state concentrations in ditches, ponds and lakes were 6.22 × 10-17, 4.73 × 10-17, and 4.90 × 10-17 M. The fluorescence emission-excitation matrix (EEM) and other technologies further indicated that the humus components in dissolved organic matter (DOM) and nitrite were the main photosensitive substances producing •OH. In addition, the phosphate generated by glyphosate photodegradation could greatly promote the growth of Microcystis aeruginosa, thereby increasing the risk of eutrophication. Thus, glyphosate should be scientifically and reasonably applied to avoid environmental risks.

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis.

Purpose: Contact lens wear (CLW) is one of the leading risk factors for Pseudomonas aeruginosa keratitis (PAK). However, the intrinsic factors that contribute to the high susceptibility to keratitis during CLW remain to be elucidated. CLW over an extended period can elevate corneal norepinephrine (NE) concentration. In this study, we investigated the role of NE in promoting PAK. Methods: We constructed an injury-induced PAK model and a CLW-induced PAK model to confirm the impact of NE during corneal infection. Pharmacological blockage of NE and gene knockdown mouse were used to investigate the downstream effector of NE. RNA sequencing was performed to explore the cellular alterations during NE treatment. Non-parametric Mann-Whitney U test or Kruskal-Wallis test were used to ascertain the significance (P < 0.05). Results: Supplementation of NE led to PAK even without artificial corneal injury during CLW. The effect was mediated by the ß2-adrenergic receptor (ß2-AR) in the corneal epithelium. The ß2-AR blockage by the NE antagonist ICI118,551 (ICI) or by deleting of its encoding gene Adrb2 significantly alleviated infection during CLW. Conversely, ß2-AR activation compromised the integrity of the epithelium and significantly increased the cortical plaque marker ezrin. Transcriptome analysis identified that the protective effect of ICI on the keratitis was mediated by dual-specificity phosphatases. Suramin, a Dusp5 antagonist, abrogated the protective effect of ICI. Conclusions: These data reveal a new mechanism by which NE acts as an intrinsic factor that promotes CLW-induced PAK and provide novel therapeutic targets for treating keratitis by targeting NE-ß2-AR.

Association between thyroid autoimmunity and clinical characteristics in first-episode and drug-naive depressed patients with suicide attempts.

BACKGROUND: Previous reports had linked depression to thyroid function. However, the relationship between thyroid function and clinical characteristics in major depressive disorder (MDD) patients with suicidal attempts (SA) is still unclear. AIMS: This study aims to reveal the association between thyroid autoimmunity and clinical characteristics in depressed patients with SA. METHODS: We divided 1718 first-episode and drug-naive MDD patients into groups with suicide attempt (MDD-SA) and without suicide attempt (MDD-NSA). Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were assessed; thyroid function and autoantibodies were detected. RESULTS: The total scores of HAMD, HAMA and psychotic positive symptoms were significantly higher in patients with MDD-SA, accompanied by higher levels of TSH, TG-Ab and TPO-Ab, than in patients with MDD-NSA, without gender differences. Total scores of positive symptoms (TSPS) in MDD-SA patients with increased TSH or TG-Ab was significantly higher than in MDD-NSA patients and in MDD-SA patients with normal TSH and TG-Ab. The proportion of elevated-TSPS in MDD-SA patients was >4 times that in MDD-NSA patients. The proportion of MDD-SA patients with elevated-TSPS was >3 times that with not-elevated TSPS patients. CONCLUSIONS: Thyroid autoimmune abnormalities and psychotic positive symptoms may be the clinical features of MDD-SA patients. Psychiatrists should be more alert to the possibility of suicidal behaviors when they first encounter such a patient.

"Customized orthosis for non-surgical correction of congenital auricle deformities in newborns."

SUMMARY: A misshaped pinna, caused by extrinsic pressures such as birth canal extrusion or incorrect position, is typically one of congenital auricular deformities in newborns. As an approach to this deformity, surgery is a routine option, but it may lead to uncomfortable outcomes traumatically and aesthetically. Commercial ear mold orthosis with uniform size has achieved an effect of non-surgical orthotic treatment, but it is not applicable among all newborns in terms of the auricle morphologies. This research was to employ the CAD and 3D printing technology to develop a novel customized orthosis for congenital auricular deformities. The 3D models of the ears were reconstructed using CAD soft and a novel customized orthosis model was established after a process of correction, adjustment, and construction with simple wearing and precise matching to allow its tight attachment to the outer ear free from uneven skin pressing. After 3D printing customized orthosis injection mold, medical silicon injection molding was used to produce customized orthosis. Clinical application was conducted in three newborns and achieved satisfactory results. This novel customized auricle orthosis is expected to spread clinically for the purposes of improving the cure rate of non-surgical correction and reducing the occurrence of complications from surgery and anesthesia.

The senescence difference between the central and peripheral cornea induced by sutures.

INTRODUCTION: Cell senescence plays a regulatory role in tissue fibrosis. Corneal scarring is usually more severe in the central cornea based on clinical observation. In this study, we attempted to explore the senescence difference between the central and peripheral cornea in an in vivo mouse model with suture-induced senescence and in an in vitro model of senescence with hydrogen peroxide (H2O2)-induced rabbit corneal fibroblasts. METHODS: Male Balb/c mice (6-8 weeks) received sutures in the central, superior, inferior, nasal, and temporal cornea. The sutures were removed on the 14th day. Corneal neovascularization was observed under a slit lamp microscope with a digital camera. The fibroblasts isolated from the central and peripheral rabbit cornea were induced with H2O2 to establish the senescence model in vitro. Senescence was evaluated with SA-ß-gal staining and gene expression analysis of p21, p27, and p53. RESULTS: Senescent cells accumulated in the corneal stroma from the third day to the 14th day after the operation and peaked on the 14th day. More senescent keratocytes were observed in the peripheral cornea of the mouse model. In vitro, the peripheral corneal fibroblasts were more prone to senescence due to H2O2. The polymerase chain reaction results showed that the senescence-related genes p21, p27, and p53 were highly expressed in the peripheral corneal fibroblasts compared with the central corneal fibroblasts. CONCLUSIONS: Senescent fibroblasts can limit tissue fibrosis; hence, the senescence difference between the central and peripheral cornea may contribute to the difference in scarring.

Overactivation of Norepinephrine-ß2-Adrenergic Receptor Axis Promotes Corneal Neovascularization.

Purpose: To investigate the role of the sympathetic nervous system in corneal neovascularization (CNV) and to identify the downstream pathway involved in this regulation. Methods: Three types of CNV models were constructed with C57BL/6J mice, including the alkali burn model, suture model, and basic fibroblast growth factor (bFGF) corneal micropocket model. Subconjunctival injection of the sympathetic neurotransmitter norepinephrine (NE) was administered in these three models. Control mice received injections of water of the same volume. The corneal CNV was detected using slit-lamp microscopy and immunostaining with CD31, and the results were quantified by ImageJ. The expression of ß2-adrenergic receptor (ß2-AR) was stained with mouse corneas and human umbilical vein endothelial cells (HUVECs). Furthermore, the anti-CNV effects of ß2-AR antagonist ICI-118,551 (ICI) were examined with HUVEC tube formation assay and with a bFGF micropocket model. Additionally, partial ß2-AR knockdown mice (Adrb2+/-) were used to establish the bFGF micropocket model, and the corneal CNV size was quantified based on the slit-lamp images and vessel staining. Results: Sympathetic nerves invaded the cornea in the suture CNV model. The NE receptor ß2-AR was highly expressed in corneal epithelium and blood vessels. The addition of NE significantly promoted corneal angiogenesis, whereas ICI effectively inhibited CNV invasion and HUVEC tube formation. Adrb2 knockdown significantly reduced the cornea area occupied by CNV. Conclusions: Our study found that sympathetic nerves grow into the cornea in conjunction with newly formed vessels. The addition of the sympathetic neurotransmitter NE and activation of its downstream receptor ß2-AR promoted CNV. Targeting ß2-AR could potentially be used as an anti-CNV strategy.

Nocardia infection following ocular surface surgery.

OBJECTIVE: To investigate the clinical characteristics and treatment outcomes of Nocardia infection after ocular surface surgery. METHODS: This is a retrospective study. Eight cases of culture-proven Nocardia infection, which developed within 1 month after ocular surface surgery were included. Demographics and clinical history of patients were investigated. RESULTS: There were 8 eyes (2 left and 6 right) of 8 patients (5 males and 3 females), aged 27-65, with a median age of 52.9 years. Three cases underwent pterygium excision, three were subjected to conjunctival flap covering, and two were treated with lamellar corneal transplantation. The time interval between previous surgery and the onset of symptoms varied from 7 to 28 days (mean = 20.5 ± 7.13 days). All the cases presented grey-white infiltrates at the surgical incision site while appearing with six corneal ulcers and two conjunctival ulcers. Filaments of Nocardia were founded by confocal microscopy in two of the five cases. All responded poorly to medical therapy. Seven of the eight cases were treated with reoperation. Nocardia infection recurred in three cases after reoperation, and one was eviscerated. CONCLUSIONS: Surgical trauma is a risk factor for ocular Nocardia infection. Nocardia infection should be suspected when secondary infection occurs in a surgical incision with an atypical clinical presentation. The use of corticosteroids may influence the efficacy of drugs. Complete removal of lesions may lower the recurrence of Nocardia infection with poor drug treatment effects.

Peripheral ulcerative keratitis, nodular episcleritis, and pulmonary nodules as the initial signs of rheumatic arthritis: A Case Report.

Background: Rheumatoid vasculitis (RV) is a rare but potentially devastating complication of rheumatoid arthritis (RA). It typically occurs in patients with extra-articular manifestations. Here we reported a case of PUK with nodular episcleritis and pulmonary nodules that occurred in the same patient without joint involvement. Case presentation: A 43-year-old Chinese woman, exhibited a partial crescent-shaped marginal corneal ulcer in the right eye at admission and the ulcer developed rapidly into nearly 360-degree ulcers in both eyes within one week. Nodular episcleritis was observed in the right eye. Conjunctival biopsy revealed vasculitis. Her rheumatoid factor (RF) and anti-cyclic citrullinated protein antibody were positive, while anti-neutrophilic cytoplasmic antibody (c-ANCA) and anti-protease 3 were negative. Pulmonary nodules were found, without joint involvement. The ocular condition did not relieve under the topical and systemic use of corticosteroids, or under other immunosuppressive agents until the infliximab therapy. PUK recurrence was observed after the discontinuation of infliximab. Conclusions: Rapidly deteriorated PUK with nodular episcleritis and pulmonary nodules occurred in the same patient is a special case of RA without joint involvement. This case reinforces the concept that RV may be the initial sign of RA. Infliximab can be used to prevent further progress of RA-related PUK in some refractory cases.

MnASI1 Mediates Resistance to Botrytis cinerea in Mulberry (Morus notabilis).

Six α-amylase/subtilisin inhibitor genes (MnASIs) were identified from mulberry (Morus notabilis). In this study, bioinformatics and expression pattern analysis of six MnASIs were performed to determine their roles in resistance to B. cinerea. The expression of all six MnASIs was significantly increased under Botrytis cinerea infection. MnASI1, which responded strongly to B. cinerea, was overexpressed in Arabidopsis and mulberry. The resistance of Arabidopsis and mulberry overexpressing MnASI1 gene to B. cinerea was significantly improved, the catalase (CAT) activity was increased, and the malondialdehyde (MDA) content was decreased after inoculation with B. cinerea. At the same time, H2O2 and O2- levels were reduced in MnASI1 transgenic Arabidopsis, reducing the damage of ROS accumulation to plants. In addition, MnASI1 transgenic Arabidopsis increased the expression of the salicylic acid (SA) pathway-related gene AtPR1. This study provides an important reference for further revealing the function of α-amylase/subtilisin inhibitors.

Childhood social isolation causes anxiety-like behaviors via the damage of blood-brain barrier in amygdala in female mice.

Social interaction plays an essential role in species survival for socialized animals. Previous studies have shown that a lack of social interaction such as social isolation, especially in the early-life phase, increases the risk of developing mental diseases in adulthood. Chronic social stress alters blood-brain barrier (BBB) integrity and increases peripheral cytokines to infiltrate the brain, which is linked to the development of depressive-like behaviors in mice, suggesting that BBB function is crucial in environmental stimuli-driven mood disorders via increased neuroinflammation in the brain. However, the precise mechanisms of inflammation and BBB integrity underlying the behavioral profiles induced by social isolation remain poorly understood. Here we showed that chronic childhood social isolation from post-weaning for consecutive 8 weeks in female but not male C57BL/6J mice induces anxiety-like behaviors. The levels of peripheral inflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the plasma of socially isolated female mice were increased. Importantly, we found decreased expression of the endothelial cell tight junction protein Claudin-5, increased BBB breakdown and microglial activation in the amygdala of isolated but not group-housed female mice. Moreover, the neuronal activity in the amygdala was increased as evidenced by c-fos positive cells, and the levels of IL-1ß in the amygdala, a critical brain region for regulating social processing and interaction, were also higher in female mice exposed to social isolation. Finally, down-regulation of Claudin-5 induced anxiety-like behaviors in group-housed females and overexpression of Claudin-5 with adeno-associated virus in the amygdala to restore BBB integrity decreased subsequent anxiety-like behaviors. Together, these findings suggest that chronic childhood social isolation impaired BBB permeability and caused neuroinflammation in the amygdala by recruiting peripheral cytokines into the brain and activating microglia, consequently triggering the development of anxiety-like behaviors in female mice.

Cross-sectional survey following a longitudinal study on mental health and insomnia of people with sporadic COVID-19.

BACKGROUND: In the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact of sporadic cases of COVID-19 and isolation measures on mental health and sleep in different groups of people need to be analyzed. AIM: To clarify the severity of psychological problems and insomnia of staff and community residents around a hospital with sporadic cases of COVID-19, and their relationship with quarantine location and long-term changes. METHODS: A cross-sectional survey was conducted on community residents and medical staff. Many of these medical staff had been subjected to different places of quarantine. Community residents did not experience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale (ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acute stress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-year follow-up study on medical staff, with related scales measurement immediately after and one year after the 2-wk quarantine period. RESULTS: We included 406 medical staff and 226 community residents. The total scores of ISI and subscale in HADS of community residents were significantly higher than that of medical staff. Further analysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels, 70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scores above normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logistic regression analysis found that subjects with higher total ASDS scores had a greater risk to develop anxiety and depression. The total ISI score for medical staff in hotel quarantine was significantly higher than those in home quarantine. Total 199 doctors and nurses who completed the 1-year follow-up study. Compared with baseline, HADS and ASDS scores decreased significantly one year after the end of quarantine, while ISI scores did not change significantly. CONCLUSION: Sporadic COVID-19 cases had a greater psychological impact on residents in surrounding communities, mainly manifested as insomnia and depressive symptoms. Hotel quarantine aggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.