Uveitis is a blinding inflammatory disease that affects multiple structures within the eye, posing significant risks to patients' vision and mental health. Current treatments mainly involve glucocorticoids and immunosuppressants, which are associated with significant side effects, high relapse rates, and substantial costs. Recent research suggests that the gut microbiota may play a role in the development of uveitis through the gut-eye axis, with related metabolites also influencing disease progression. Modulating the gut microbiota or its metabolites could offer new therapeutic avenues for uveitis. This review explores the relationship between gut microbiota and various uveitis-associated diseases, such as systemic sarcoidosis, Vogt-Koyanagi-Harada syndrome, Behcet's disease, multiple sclerosis, and birdshot chorioretinopathy. It also discusses advancements in microbiota-related therapies, including probiotics and prebiotics, antibiotics, immunomodulators, phage therapy, and fecal microbiota transplantation. The aim is to provide a reference for the development of new therapies targeting specific microbial communities and genetic markers associated with uveitis, thereby promoting the realization of precision medicine.

The Keap1-Nrf2 pathway has been shown to be an important defense mechanism against oxidative stress, which may be an effective therapeutic strategy for many diseases. The research progresses on Keap1-Nrf2 pathway in inflammatory diseases were mainly reviewed. The basic components and activation mechanism of Keap1-Nrf2 pathway were introduced. The relationship between Keap1-Nrf2 pathway and the crosstalk between NF-κB pathway and HO-1 pathway, the expression of inflammatory mediators and enzymes, and inflammatory bodies were expounded. Natural product-derived inhibitors, small molecule inhibitors targeting Keap1-Nrf2 pathway and their clinical progress were introduced, and the potential application value of Keap1-Nrf2 pathway in the treatment of inflammation was discussed.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

BackgroundPatients with schizophrenia and depressive disorders exhibit abnormalities in perceptual processing. Previous perceptual studies are mainly based on asking participants to fill in a questionnaire， and little research has been undertaken on objective behavior in patients with schizophrenia and depressive disorders. ObjectiveTo explore the behavioral changes in vibrotactile sense among patients with schizophrenia and depressive disorders， so as to enrich relevant findings in objective behavioral research. MethodsFrom March 2021 to September 2023， 33 patients with schizophrenia and 31 patients with depressive disorders in the outpatient and inpatient departments of Beijing Huilongguan Hospital and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria were enrolled. And another 34 healthy controls were concurrently recruited at Beihang University and Beijing Huilongguan Hospital. Patients with schizophrenia were assessed using Positive and Negative Symptom Scale （PANSS）， and patients with depressive disorders were assessed using Hamilton Depression Scale-17 item （HAMD-17）. The vibrotactile sensitivity of the left hand in all participants was tested in a delay match-to-sample procedure， and the correct rate of vibrotactile delayed discrimination task was compared among the three groups. ResultsCompared with healthy controls， a reduction was found in the correct rates at index finger， middle finger and ring finger in patients with schizophrenia （P<0.01）， the average correct rate at five fingers in patients with schizophrenia （P=0.001）， and the correct rate at thumb in patients with depressive disorders （P=0.026）. No statistical difference was reported in correct rate of vibrotactile delayed discrimination task between patients with depression disorders and schizophrenia （P>0.05）. The average correct rate of vibrotactile sense in schizophrenia group was not significantly correlated with the duration of disease， age of onset， chlorpromazine equivalent doses and PANSS score （r=0.058、0.045、0.114、-0.194， P>0.05）. The average correct rate in depressive group was negatively correlated with age of onset （r=-0.415， P=0.020）， but not significantly correlated with the duration of disease and HAMD-17 score （r=-0.044， 0.142， P>0.05）. ConclusionPatients with schizophrenia and depressive disorders have impaired vibrotactile sense. The vibrotactile sense is impaired in index， middle and ring fingers among patients with schizophrenia， and in thumbs of patients with depressive disorders. Moreover， the impairment in patients with depressive disorders may be related to the age of onset. ［Funded by 2023 Hebei Provincial Graduate Innovation Funding Project （number， CXZZSS2023140）］

The NLRP3 inflammasome is a cellular multimeric protein complex that plays a crucial role in inflammation and immune responses. It consists of three main components: Nod-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing(ASC)and cysteine protease 1(caspase-1). Uveitis is a broad term encompassing a range of inflammatory diseases that primarily affect the iris, ciliary body, vitreous, retina and choroid. It is considered a major cause of blindness globally. Numerous studies have demonstrated the involvement of NLRP3 inflammasome in the onset and progression of uveitis, indicating its potential as a significant therapeutic target for uveitis in the future. This article provides an overview of the structure, biological functions and activation pathways of the NLRP3 inflammasome, as well as the current research progress on its association with different types of uveitis. Additionally, it discusses the application potential of the NLRP3 inflammasome in the treatment of uveitis.