Quercetin nanocrystals for bioavailability enhancement: Impact of different functional stabilizers on in vitro/in vivo drug performances.

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant difference in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC0～t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the Cmax showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with Tmax at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same Tmax at 5.33 h. The longest MRT0～t (11.72 h) and t1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro, oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

Blueberry anthocyanin based active intelligent wheat gluten protein films: Preparation, characterization, and applications for shrimp freshness monitoring.

The aim of this study was to prepare active intelligent gluten protein films using wheat gluten protein (WG) and apple pectin (AP) as film-forming matrices, and blueberry anthocyanin extract (BAE) as a natural indicator. SEM and FT-IR analyses demonstrated the successful immobilization of BAE in the film matrix by hydrogen bonding interactions and its compatibility with WG and AP. The resultant WG-AP/BAE indicator films demonstrated notable antioxidant activity, color stability, barrier qualities, pH and ammonia response sensitivity, and mechanical properties. Among them, WG-AP/BAE5 exhibited the best mechanical properties (TS: 0.83 MPa and EB: 242.23%) as well as the lowest WVP (3.92 × 10-8 g.m/m2.Pa.s), and displayed high sensitivity to volatile ammonia. In addition, WG-AP/BAE5 showed a color shift from purplish red to green to yellowish green, demonstrating the monitoring of shrimp freshness in real time. Consequently, this study offers a firm scientific foundation for the development of active intelligent gluten protein films and their use in food freshness assessments.

Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Magnetic Nanoparticle-Based Microfluidic Platform for Automated Enrichment of High-Purity Extracellular Vesicles.

Extracellular vesicles (EVs) are available in various biological fluids and have highly heterogeneous sizes, origins, contents, and functions. Rapid enrichment of high-purity EVs remains crucial for enhancing research on EVs in tumors. In this work, we present a magnetic nanoparticle-based microfluidic platform (ExoCPR) for on-chip isolation, purification, and mild recovery of EVs from cell culture supernatant and plasma within 29 min. The ExoCPR chip integrates bubble-driven micromixers and immiscible filtration assisted by surface tension (IFAST) technology. The bubble-driven micromixer enhances the mixing between immunomagnetic beads and EVs, eliminating the need for manual pipetting or off-chip oscillatory incubation. The high-purity EVs were obtained after passing through the immiscible phase interface where hydrophilic or hydrophobic impurities nonspecifically bound to SIMI were removed. The ExoCPR chip had a capture efficiency of 75.8% and a release efficiency of 62.7% for model EVs. We also demonstrated the powerful performance of the ExoCPR in isolating EVs from biological samples (>90% purity). This chip was further employed in clinical plasma samples and showed that the number of GPC3-positive EVs isolated from hepatocellular carcinoma patients was significantly higher than that of healthy individuals. This ExoCPR chip may provide a promising tool for EV-based liquid biopsy and other fundamental research.

Bispectral Index Monitoring in the Nursing of Patients With Paroxysmal Sympathetic Hyperactivity.

AIM: To investigate the clinical nursing effect of bispectral index (BIS) monitoring for paroxysmal sympathetic hyperactivity (PSH) patients in the neurosurgical intensive care unit (NICU). METHODS: From January 2022 to June 2023, a total of 30 patients with PSH secondary to moderate to severe craniocerebral injury in the NICU were monitored for BIS. The patients' paroxysmal sympathetic hyperactivity-assessment measure (PSH-AM) scores were recorded. PSH patients generally appear in 3 states: calm state, seizure state, and postmedication state. Thirty PSH patients' BIS values were recorded during the calm period, during the seizure state, and postmedication state, and these 3 different stages' BIS values were divided into groups A, B, and C, using the Kruskal-Wallis H test to compare groups. RESULTS: The Kruskal-Wallis H test yielded a value of H=22.599, P<0.001. H0 was rejected against the test standard of α=0.05, and the BIS values of groups A, B, and C differed. The BIS values of group A and group B differed after a pairwise comparison, and the difference was statistically significant (adjusted P=0.001). Group B and group C had different BIS values, and the difference was statistically significant (adjusted P=0.001); group A and Group C had no difference in BIS values, and the difference was not statistically significant (adjusted P=1.00). CONCLUSIONS: Taking BIS value as the nursing observation index for PSH patients can make nursing work more objective, reasonable, and accurate, reduce the inducing factors of PSH attack, further reduce the attack of PSH, save nursing resources, and help guide the safety assessment of sedative use.

Report on Pseudoaneurysm Caused by Injury of Internal Carotid Artery During Endoscopic Pituitary Surgery and Rebleeding After Treatment With Willis Covered Stent.

OBJECTIVE: Report on a case of pseudoaneurysm which was caused by injury of the internal carotid artery (ICA) during endoscopic endonasal surgery (EES), which was followed by rebleeding after treatment with a Willis covered stent. METHODS: A woman, aged 68, underwent EES for the treatment of a pituitary adenoma. During the surgery, the right ICA was injured, and successfully hemostasis by packed with cottonoid and gelatin sponge. Besides, cerebral angiography was performed in the interventional operating room for the purpose of discovering the formation of a pseudoaneurysm in the cavernous sinus segment of ICA, which was treated with a covered stent. After successfully placing the covered stent, the patient was promptly transferred to the general operating room for the removal of the cottonoid and to address the bleeding once again. The authors employ crushed muscles and cottonoid to locally compress and stop bleeding. Owing to concerns about the risk of rebleeding in the patient, after stent implantation, the patient did not utilize antiplatelet drugs. After the surgery, the patient developed occlusion of the right ICA and massive cerebral infarction in the right hemisphere. Dehydration, anti-infection, rehabilitation, hyperbaric oxygen, as well as related treatments, were given. The cottonoid was removed in EES 2 months postsurgery, and no instances of bleeding were observed. Six months after surgery, the patient had clear consciousness and hemiplegia in the left limb, with a Glasgow Outcome Scale score of 4. RESULTS: The ICA was injured during EES, which resulted in the formation of a pseudoaneurysm, the Willis stent was adopted for treatment, and there was a risk of rebleeding after the nasal packing (cottonoid, crushed muscles) was removed immediately. CONCLUSIONS: The ICA was injured during EES after bleeding was controlled by packing with cottonoid, crushed muscles, etc, subsequently, the patient was given intravascular treatment, it is advised to make thorough preparations and, after a suitable period, remove nasal packing in the hybrid operating room to address unexpected situations and unforeseen circumstances.

Aqueous Dispersion of Aramid Nanofibers Achieved by Using Tannic Acid for Ultrahigh Strength Films.

Polymer nanofibers have established a robust foundation and possess immense potential in various emerging fields such as sensors and biotechnology. In this study, aqueous dispersions of aramid nanofibers (ANFs) were successfully prepared by using tannic acid (TA). Morphological analysis revealed that TA effectively prevented self-aggregation of ANFs, and preserved the nanofiber structure during TA-assisted solvent exchange. Subsequently, the ANF and TA/ANF films were fabricated using casting and vacuum-assisted filtration techniques. Notably, the tensile strength of the casting TA/ANF film reached 393.8 MPa, exhibiting a remarkable improvement of 41.3% compared to that of the pure ANF film. These exceptional mechanical properties can be attributed to the well-dispersed nanostructures, hydrogen-bonding interactions, zigzag structures, and fiber-bridging effects. Furthermore, the TA/ANF film demonstrated superior ultraviolet (UV) shielding capabilities, visible transparency properties, and excellent resistance to chemical reagents. The above-mentioned interesting findings demonstrate its potential as a nanofiber-reinforced material for poly(vinyl alcohol) (PVA) composites.

Diagnosis and management of intraspinal tuberculoma with osseous involvement: a case report.

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Efficacy of recombinant human epidermal growth factor in pressure injury healing: evidence from Chinese randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of recombinant human epidermal growth factor (rhEGF) in healing pressure injuries (PIs). METHODS: A meta-analysis was conducted of randomized controlled trials (RCTs) involving rhEGF in the treatment of PIs that were identified in PubMed, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI). The population, intervention, comparison, outcomes, study design (PICOS) strategy was applied to determine analysis eligibility. The Cochrane risk of bias tool was used, and statistical analysis, including sensitivity analysis, was performed of 3 outcomes indicators: the primary outcome was total efficacy of rhEGF in treating PIs, and the secondary outcomes were the proportion of complete healing and the time to complete healing. Total efficacy refers to the proportion of cases that have been cured, obviously effective, or effective. Complete healing refers to cases where the wound has healed, scabbed, and the scab has sloughed off. RESULTS: Sixteen RCTs were included, comprising a total of 1,206 patients. Study and control group size varied by outcomes. The total effective healing rate in rhEGF group was 97.18%, which was significantly higher than 83.38% in control group (OR: 5.69, [95% CI: 3.61, 8.97], z=7.49, P < .001). The proportion of complete healing in the rhEGF group was 73.30%, which was higher than 39.52% in control group (OR: 3.88, [95% CI: 3.01, 5.01], z=10.39, P < .001). Furthermore, the healing time using rhEGF was shorter (SMD: -2.14 days, [95% CI: -2.60, -1.67], z=9.07, P < .001). Sensitivity analyses indicated that the results were robust. CONCLUSIONS: The meta-analysis indicated that rhEGF was effective in healing PIs with few negative effects. Further research beyond Chinese populations involving larger studies and studies that distinguish between results found in using rhEGF alone or in combination are recommended.

An improved technology for monitoring groundwater flow velocity and direction in fractured rock system based on colloidal particles motion.

The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.

Physicochemical and functional properties of carboxymethylated insoluble dietary fiber of Lycium barbarum seed dreg.

Lycium barbarum seed dregs (LBSDs) were used for carboxymethyl modification, resulting in three degree of substitution samples (DS). Based on the substitution degree, samples were designated as low degree of substitution insoluble dietary fiber (L-IDF), medium degree of substitution insoluble dietary fiber (M-IDF) and high degree of substitution insoluble dietary fiber (H-IDF). Physicochemical and functional properties of IDFs were examined in relation to carboxymethylation degree. Infrared Fourier transform spectroscopy (FT-IR) confirmed the carboxymethyl group. According to the results, IDF, L-IDF, M-IDF, and H-IDF acquired higher enthalpy changes, and their thermal stability improved significantly. A higher DS resulted in an increase in hydration properties such as water retention capacity and water swelling capacity, as well as functional properties such as glucose adsorption capacity, nitrite ion adsorption capacity, and cholesterol adsorption capacity. As a result, carboxymethylation could effectively enhance the biological properties of L. barbarum seed dreg insoluble dietary fiber (LBSDIDF).

Mortality of children and adolescents co-infected with tuberculosis and HIV: a systematic review and meta-analysis.

OBJECTIVE: Children and adolescents with HIV infection are well-known to face a heightened risk of tuberculosis. However, the exact mortality rates and temporal trends of those with HIV-TB co-infection remain unclear. We aimed to identify the overall mortality and temporal trends within this population. METHODS: PubMed, Web of Science, and Embase were employed to search for publications reporting on the mortality rates of children and adolescents with HIV-TB co-infection from inception to March 2, 2024. The outcome is the mortality rate for children and adolescents with HIV-TB co-infection during the follow-up period. In addition, we evaluate the temporal trends of mortality. RESULTS: During the follow-up period, the pooled mortality was 16% (95% CI 13-20). Single infection of either HIV or TB exhibit lower mortality rates (6% and 4%, respectively). We observed elevated mortality risks among individuals aged less than 12 months, those with EPTB, poor adherence to ART, and severe immunosuppression. In addition, we observed a decreasing trend in mortality before 2008 and an increasing trend after 2008, although the trends were not statistically significant (P = 0.08 and 0.2 respectively). CONCLUSIONS: Children and adolescents with HIV-TB co-infection bear a significant burden of mortality. Timely screening, effective treatment, and a comprehensive follow-up system contribute to reducing the mortality burden in this population.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.

BACKGROUND: Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the "opposite" voltage-sensing properties of hERG and HCN remains unknown. RESULTS: We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y. CONCLUSIONS: Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.

Diagnosis and Treatment of Sylvian Aqueduct Syndrome.

BACKGROUND: Sylvian aqueduct syndrome is a rare complication after ventriculoperitoneal (V-P) shunt surgery and is not easily diagnosed. METHODS: A 26-year-old male with obstructive hydrocephalus due to tectal glioma was treated with a V-P shunt surgery in another hospital. After the surgery, the patient developed an intractable disturbance of consciousness. When the V-P shunt pressure was raised or lowered, the patient's consciousness disorder still could not be improved. The patient was diagnosed with Sylvian aqueduct syndrome, a rare complication after V-P shunt operation. RESULTS: The paper clarifies the treatment experience with simultaneous endoscopic third ventriculostomy (ETV) and tectum gliomas biopsy, postoperative pathology suggestive of fibrillary astrocytoma; after surgery, the Sylvian aqueduct syndrome was cured and the patient recovered well. CONCLUSIONS: The preferred treatment for obstructive hydrocephalus caused by tumors in the Pineal region is the ETV operation. If an ETV operation and biopsy operation are performed simultaneously, more details need to be noted.

Lateral root primordium: Formation, influencing factors and regulation.

Roots are the primary determinants of water and nutrient uptake by plants. The structure of roots is largely determined by the repeated formation of new lateral roots (LR). A new lateral root primordium (LRP) is formed between the beginning and appearance of LR, which defines the organization and function of LR. Therefore, proper LRP morphogenesis is a crucial process for lateral root formation. The development of LRP is regulated by multiple factors, including hormone and environmental signals. Roots integrate signals and regulate growth and development. At the molecular level, many genes regulate the growth and development of root organs to ensure stable development plans, while also being influenced by various environmental factors. To gain a better understanding of the LRP formation and its influencing factors, this study summarizes previous research. The cell cycle involved in LRP formation, as well as the roles of ROS, auxin, other auxin-related plant hormones, and genetic regulation, are discussed in detail. Additionally, the effects of gravity, mechanical stress, and cell death on LRP formation are explored. Throughout the text unanswered or poorly understood questions are identified to guide future research in this area.

Restoration of the Mucosal IgA Response by Improving CD4+ T Pyroptosis Fails to Attenuate Gut Bacterial Translocation and Organ Damage After LPS Attack.

BACKGROUND: Currently, the mechanisms of impaired gut mucosal immunity in sepsis remain unclear. Gut immunoglobulin A (IgA) is an important defense mechanism against invasive pathogens, and CD4+ T cells regulate the IgA response. AIM: We aimed to verify the hypothesis indicating that CD4+ T pyroptosis induced by lipopolysaccharide (LPS) leads to an impaired gut IgA response and subsequent bacterial translocation and organ damage. METHODS: Cultured CD4+ T cells and mice were manipulated with LPS, and pyroptosis was improved by A438079 or adoptive CD4+ T cell transfer. The changes demonstrated in pyroptosis-related molecules, cytotoxicity and CD4+ T cells were examined to determine CD4+ T pyroptosis. The changes demonstrated in IgA+ B cells, AID (key enzyme for immunoglobulins) and IgA production and function were examined to evaluate the IgA response. Serum biomarkers, bacterial colonies and survival analysis were detected for bacterial translocation and organ damage. RESULTS: LPS attack induced CD4+ T pyroptosis, as evidenced by increased expression of P2X7, Caspase-11 and cleaved GSDMD, which elevated cytotoxicity and decreased CD4+ T cells. Decreased CD4+ T subsets (Foxp3+ T and Tfh cells) influenced the IgA response, as evidenced by lower AID expression, which decreased IgA+ B cells and IgA production and function. A438079 or cell transfer improved the IgA response but failed to reduce the translocation of gut pathogens, damage to the liver and kidney, and mortality of mice. CONCLUSION: LPS attack results in CD4+ T pyroptosis. Improvement of pyroptosis restores the mucosal IgA response but fails to ameliorate bacterial translocation and organ damage.

Non-pharmacological interventions for preventing suicide attempts: A systematic review and network meta-analysis.

Suicide attempts can cause serious physical harm or death. It would be crucial to gain a better understanding of the comparative efficacy of non-pharmacological interventions. We aimed to identify which non-pharmacological interventions are more effective in preventing suicide attempts. PubMed, Web of Science, and EMBASE databases were searched systematically from their inception until 3 April 2023. To be eligible for inclusion, randomized controlled trials (RCTs) had to meet the following criteria: Participants were individuals who had suicidal ideation or a history of severe self-harm or attempted suicide. A network meta-analysis was performed using a random effects model to estimate the treatment effect of various non-pharmacological interventions. (PROSPERO registration number: CRD42023411393). We obtained data from 54 studies involving 17,630 participants. Our primary analysis found that Cognitive therapy (CT) (OR=0.19, 95%CI =0.04-0.81), Dialectical Behavior Therapy (DBT) (OR=0.37, 95%CI =0.13-0.97), Cognitive-behavioral therapy (CBT) (OR=0.42, 95%CI =0.17-0.99), and Brief intervention and contact (BIC) (OR=0.65, 95%CI=0.44-0.94) were superior to TAU (within the longest available follow-up time) in preventing suicide attempts, while other intervention methods do not show significant advantages over TAU. Secondary analysis showed that the two intervention measures (CT and BIC) were effective when follow-up time did not exceed 6 months, but there was no effective intervention measure with longer follow-up times. CT, DBT, CBT, and BIC have a better effect in preventing suicide attempts than other non-pharmacological interventions. Additional research is necessary to validate which interventions, as well as which combinations of interventions, are the most effective.

Changes in Corneal Higher-Order Aberrations and Ocular Biometric Measurements after Phacoemulsification Combined with Goniosynechialysis in Primary Angle Closure/Glaucoma Patients.

Purpose: To compare corneal higher-order aberrations (HOAs), refractive error, and ocular biological parameters before and after phacoemulsification combined with goniosynechialysis (Phaco-GSL) in primary angle closure/glaucoma (PAC/PACG) patients with different axial lengths (ALs). Methods: In this prospective study, cataract patients diagnosed with PAC/PACG were categorized into two groups based on their ALs: the short AL group (AL ≤ 22.5 mm) and the normal AL group (22.5 < AL ≤ 24.5 mm). The pre- and postsurgery measurements of intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were conducted at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months. Additionally, the assessments included corneal HOAs, the number of antiglaucoma medications, visual field parameters, manifest refraction, and other ocular biological parameters before surgery and at the final follow-up. Results: Prior to surgery, the two groups exhibited no significant differences, except for AL, curvature value, and Z (4, 0) of the posterior corneal surface (all P < 0.01). Following surgery, BCVA improved, and IOP decreased significantly in both groups (P < 0.01). Both anterior and total corneal HOAs, along with Z (3, -3), increased in the two groups (all P < 0.05), with the normal AL group exhibiting a significantly greater increase in total cornea Z (3, -3) than the short AL group (P=0.047). The normal AL group also exhibited a slight tendency towards hyperopia (P < 0.01). Significant changes were observed in the visual field index and mean deviation in both groups (P < 0.05). Conclusions: Phaco-GSL resulted in an increased corneal HOAs, particularly trefoil, with variations based on the patient's AL. Patients with normal ALs tended to shift towards hyperopia after surgery.