Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients.

The attitudes of psychiatric patients towards COVID-19 vaccination in China: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has become a global health catastrophe. By far, there has been no specific antiviral treatment for COVID-19. Developing a vaccine against COVID-19 appeared to be the most cost-effective strategy to stop the repeated outbreak. This study aimed to investigate the attitudes of psychiatric patients with regards to COVID-19 vaccination and potential factors that might influence their decision-making process. METHODS: Psychiatric patients participated in this cross-sectional survey in China. Family caregivers, usually a guardian or next of kin completed the questionnaire when the patient is unable to consent. Data was collected via an online self-administered questionnaire. This questionnaire focused on four main attributes: (1) sociology-demographic characteristics, such as age and sex; (2) questions relating to the COVID-19 pandemic, such as perceived risk of COVID-19; (3) Flu vaccination history; and (4) attitude towards COVID-19 vaccination and affected factors, such as preferred vaccine type and vaccination site. The associated factors that influenced vaccination acceptance were analyzed by Chi-square analysis and binary logistic regression. RESULTS: In total, 416 individuals were recruited, from which 408: 229 patients and 179 family caregivers completed the online survey (response rate: 98.1%). 78.7% of the participants (178 patients and 143 family caregivers) said they intended to receive vaccination once the COVID-19 vaccine became available on the market. Our results showed that participants would have a greater likelihood of joining the COVID-9 immunization programme if the people they knew (community residents or their friends and relatives) presented with high vaccine coverage (OR = 0.24; 95% CI:0.09-0.59). If the pandemic returns, participants were also more likely to accept vaccination (OR = 0.21; 95% CI:0.07-0.62). Moreover, those who believed that the vaccination was an important way to control the COVID-19 pandemic also showed a tendency to receive vaccination (OR = 0.21; 95% CI:0.11-0.40). For those who did not intend to get vaccinated either for themselves or their psychiatric family member, the safety of vaccine was their main concern (71.3%). CONCLUSIONS: This study showed a high acceptance rate for COVID-19 vaccination amongst psychiatric patients, while worries about the safety of vaccine led to refusal towards vaccination. To increase vaccination uptake amongst this vulnerable group, the public health messaging should include updated vaccination coverage in local communities, and the number of newly COVID-19 infected cases. Specific information about vaccine safety concerning psychiatric patients; as well as the importance of vaccination in controlling the pandemic should be explained in detail.

Mental Health During the Covid-19 Outbreak in China: a Meta-Analysis.

BACKGROUND: Covid-19 has started to spread within China since the end of December 2019. Despite government's immediate actions and strict control, more and more people were infected every day. As such a contagious virus can spread easily and rapidly between people, the whole country was put into lockdown and people were forced into isolation. In order to understand the impact of Covid-19 on mental health well-being, Chinese researchers have conducted several studies. However, no consistent results were obtained. Therefore, a meta-analysis was conducted. METHODS: We searched Embase, PubMed, and Web of Science databases to find literature from December 2019 to April 2020 related to Covid-19 and mental health, among which results such as comments, letters, reviews and case reports were excluded. The incidence of anxiety and depression in the population was synthesized and discussed. RESULTS: A total of 27,475 subjects were included in 12 studies. Random effect model is used to account for the data. The results showed that the incidence of anxiety was 25% (95% CI: 0.19-0.32), and the incidence of depression was 28% (95% CI: 0.17-0.38). Significant heterogeneity was detected across studies regarding these incidence estimates. Subgroup analysis included the study population and assessment tools, and sensitivity analysis was done to explore the sources of heterogeneity. CONCLUSIONS: Owing to the significant heterogeneity detected in studies regarding this pooled prevalence of anxiety and depression, we must interpret the results with caution. As the epidemic is ongoing, it is vital to set up a comprehensive crisis prevention system, which integrating epidemiological monitoring, screening and psychological crisis prevention and interventions.

[Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19)].

Adoptive immunotherapy based on chimeric antigen receptor-modified T cells (CAR-T) is one of the most promising strategies to treat malignant tumors, but its application in solid tumors is still limited. Glypican-3 (GPC3) is a meaningful diagnostic, therapeutic, and prognostic biomarker for hepatocellular carcinoma (HCC). The second/third generation GPC3-targeted CAR-T cells are generated to treat HCC. In order to improve the therapeutic effect, we constructed a fourth-generation lentiviral vector to express GPC3 CAR, human interleukin-7 (IL-7) and CCL19. Then the lentiviral vector and packaging plasmids were co-transfected into HEK293T cells to generate CAR lentiviral particles. Human T lymphocyte cells were transduced with CAR lentiviral to develop the fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19). In vitro, we used cell counting, transwell assay, luciferase bioluminescence assay and flow cytometry to compare the proliferation, chemotaxis, cytotoxicity and subtype distribution between GPC3-BBZ-7×19 CAR-T cells and the second generation GPC3-targeted CAR-T cells (GPC3-BBZ). In vivo, we established GPC3-positive HCC xenograft model in immunodeficient mice, then untransduced T cells (non-CAR-T) or GPC3-BBZ-7×19 CAR-T cells were injected. Tumor growth in mice was observed by bioluminescence imaging. Results showed that compared with GPC3-BBZ CAR-T, GPC3-BBZ-7×19 CAR-T cells had stronger proliferation, chemotactic ability, and higher composition of memory stem T cells (Tscm) (P values<0.05). However, there were no significant difference in cytotoxicity and cytokine secretion between them. In addition, GPC3-BBZ-7×19 CAR-T cells could significantly eliminate GPC3-positive HCC xenografts established in immunodeficient mice. Therefore, the fourth-generation GPC3-targeted CAR-T cells (secreting IL-7 and CCL19) are expected to be more durable and effective against HCC and produce tumor-specific memory, to provide a preclinical research basis for future clinical trials.

Investigation of the Inhibitory Effect of Simvastatin on the Metabolism of Lidocaine Both in vitro and in vivo.

BACKGROUND: Lidocaine has cardiovascular and neurologic toxicity, which is dose-dependent. Due to CYP3A4-involved metabolism, lidocaine may be prone to drug-drug interactions. MATERIALS AND METHODS: Given statins have the possibility of combination with lidocaine in the clinic, we established in vitro models to assess the effect of statins on the metabolism of lidocaine. Further pharmacokinetic alterations of lidocaine and its main metabolite, monoethylglycinexylidide in rats influenced by simvastatin, were investigated. RESULTS: In vitro study revealed that simvastatin, among the statins, had the most significant inhibitory effect on lidocaine metabolism with IC50 of 39.31 µM, 50 µM and 15.77 µM for RLM, HLM and CYP3A4.1, respectively. Consistent with in vitro results, lidocaine concomitantly used with simvastatin in rats was associated with 1.2-fold AUC(0-t), 1.2-fold AUC(0-∞), and 20%-decreased clearance for lidocaine, and 1.4-fold Cmax for MEGX compared with lidocaine alone. CONCLUSION: Collectively, these results implied that simvastatin could evidently inhibit the metabolism of lidocaine both in vivo and in vitro. Accordingly, more attention and necessary therapeutic drug monitoring should be paid to patients with the concomitant coadministration of lidocaine and simvastatin so as to avoid unexpected toxicity.

Sodium valproate induced acute pancreatitis in a bipolar disorder patient: a case report.

BACKGROUND: Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis. CASE PRESENTATION: The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations. CONCLUSION: Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.

Genistein Improves the Major Depression through Suppressing the Expression of miR-221/222 by Targeting Connexin 43.

OBJECTIVE: Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. METHODS: The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. RESULTS: The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. CONCLUSION: Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.

Effect of Repetitive Transcranial Magnetic Stimulation on Cigarette Smoking in Patients with Schizophrenia.

BACKGROUND: The high smoking rate among patients with schizophrenia is an important public health problem, and researchers have been studying how to change the status quo. OBJECTIVE: We investigated the effects of high frequency (10Hz) repetitive transcranial magnetic stimulation on the amount of cigarette smoking in patients with schizophrenia. METHOD: This study enrolled 37 male patients with schizophrenia who were at a stable stage of treatment. Patients were randomly divided into a treatment group (n=19) and a control group (n=18). The treatment group received repetitive transcranial magnetic stimulation (rTMS) on the left prefrontal dorsolateral cortex (DLPFC), and the control group received placebo treatment. The number of cigarettes smoked were recorded at 7 days before treatment, during the course of treatment (i.e. for 21 days), and 3 weeks after treatment had ended. Assessments using the Positive and Negative Syndrome Scale (PANSS), Wisconsin Card Sorting Test (WCST), and Montgomery Asberg Depression Rating Scale (MADRS) were applied before and after treatment. RESULT: Compared to the control group, the number of cigarettes smoked in the treatment group showed a statistically significant reduction in the first week after treatment. However, there was no significant correlation between the scores on PANSS, WCST and MADRS and the number of cigarettes smoked before and after treatment in both groups. DISCUSSION: High frequency (10Hz) repetitive transcranial magnetic stimulation on the left prefrontal cortex can reduce the number of cigarettes smoked in patients with schizophrenia.

Risk factors for HIV/syphilis infection and male circumcision practices and preferences among men who have sex with men in China.

OBJECTIVE: To investigate factors associated with HIV infection and the frequency and willingness of male circumcision among men who have sex with men (MSM) in Chengdu city, China. METHODS: A cross-sectional survey provided information on participants' demographics, risk behaviors, circumcision, and uptake of HIV prevention services. RESULTS: Of 570 participants, 13.3% were infected with HIV and 15.9% with syphilis. An estimated 43.0% of respondents reported having unprotected receptive anal intercourse, and 58.9% reported having ≥2 male sexual partners in the past 6 months. Multivariable logistic regression revealed that syphilis, more male sex partners, predominantly receptive anal intercourse, and exclusively receptive male sex were associated with HIV infection. Higher level of education and peer education service were inversely associated with HIV infection. Nearly a fifth (18.0%) of participants were circumcised. More than half of uncircumcised participants expressed willingness to be circumcised. CONCLUSION: This study reveals a high prevalence of HIV and syphilis among MSM in Chengdu province of China. The frequency of unprotected receptive anal intercourse and multiple male sexual partnerships highlight the urgency for an effective comprehensive HIV prevention strategy. Although the willingness to accept male circumcision (MC) is high, further research is needed to assess the protective effective of MC among MSM.

Case report of adjunctive use of olanzapine with an antidepressant to treat sleep paralysis.

Sleep paralysis (SP) is a condition of unknown etiology that usually occurs when falling asleep or when awakening in which the individual remains conscious but is unable to control their voluntary movements. This case report is about a 68-year-old man with a 40-year history of symptoms of SP and associated panic attacks upon awakening. Neurological examination and neuroimaging identified no abnormalities. Five years before the current evaluation he had been diagnosed with depression and treated with various anti-depressants which ameliorated, but did not cure, his SP. However, this 40-year history of SP was abruptly terminated - and did not return over the subsequent two years - after adjunctive treatment with 2.5 mg olanzapine each night was added to his antidepressant.