Sex-based differences in brain morphometry under chronic stress: A pilot MRI study.

Background: Sex-based differences are known to be a significant feature of chronic stress; however, the morphological mechanisms of the brain underlying these differences remain unclear. The present study aimed to use magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to investigate the effects of sex on gray matter volume (GMV) changes under conditions of chronic stress. Methods: A total of 32 subjects were included for analysis in the present study: 16 participants experiencing chronic stress and 16 healthy controls. T1-weighted (T1WI) images from a 3 T MRI scanner were extracted from the OpenfMRI database. Images were segmented into gray matter using VBM analysis. A two-way analysis of variance (ANOVA) with a 2 × 2 full factorial design was used to evaluate the main and interaction effects of chronic stress and sex on GMV changes, and then post hoc testing was used to verify each simple effect. Results: Two-way ANOVA showed a chronic stress × sex interaction effect on GMV. Simple effects analysis indicated that the GMV of the bilateral pre- and post-central gyri, the right cuneus and superior occipital gyrus was decreased in males, whereas that of the bilateral pre- and post-central gyri, the right superior occipital gyrus and the left middle frontal gyrus and orbital middle frontal gyrus was increased in females, under chronic stress. Additionally, in the control group, the GMV of the bilateral pre- and post-central gyri, the right cuneus and superior occipital gyrus was greater in males than females. While in the chronic stress group, the above sex-based differences were no longer significant. Conclusions: This study preliminarily shows that there are significant differences in gray matter volume changes between males and females under chronic stress. These findings provide a basis for future studies investigating the volumetric mechanisms of sex differences under chronic stress.

Effects of electroacupuncture on treatment-resistant chronic migraine with medication overuse headache: A 12-month follow-up case report.

Background: Medication overuse headache (MOH) is a secondary headache disorder that leads to pronounced disability and decreased quality of life. Available therapeutic options for MOH are limited, and many are only effective in a subset of individuals. Although the existing evidence is limited, acupuncture may be an effective treatment option for MOH. Case presentation: A 45-year-old Chinese woman presented to the Medical Acupuncture Department of Sanming Integrated Traditional Chinese and Western Medicine Hospital on April 11, 2022. Thirty-five years ago, she had episodic migraines. The frequency increased over time, however, and for the past 10 years she has had daily headaches. These headaches were characterized by daily persistent throbbing pain on the left side of the patient's head, accompanied by photophobia, phonophobia, neck stiffness, dizziness, and fatigue. Without painkillers, the patient rated her headache intensity as 9 out of 10 on a visual analog scale (0 = no pain, 10 = intolerable pain), and reported that the headaches lasted for up to 7 days or more. With painkillers, the headaches had a reduced intensity (5 of 10), but persisted. The patient had taken 1-3.5 compound aminopyrine phenacetin tablets daily for more than 5 years. Standard conservative therapy (patient education, medication withdrawal, and behavioral intervention) for MOH had failed to improve her symptoms. Before her visit, the patient had headache and engaged in short-term medication use on 30 days per month. The total monthly headache intensity score was 90. The patient's Migraine-Specific Quality of Life Questionnaire (MSQ) score was 33 points, her Hamilton Depression Scale (HAMD) score was 24 points, and her Hamilton Anxiety Scale (HAMA) score was 20 points. Results: After 48 acupuncture sessions over 24 weeks, the patient completely discontinued short-term analgesic use and the monthly number of headache days and headache intensity score were both reduced by 96.67 % (from 30 to 1 and 90 to 3, respectively), with no adverse effect. Compared with baseline, the MSQ, HAMD, and HAMA scores improved by 45, 17, and 16 points, respectively. At 12 months, the patient's condition remained stable and her MOH had not relapsed. Conclusion: In the context of the current literature and the present case, electroacupuncture shows promise for the long-term relief of chronic migraine with MOH when other treatments fail.

The application of machine learning techniques in posttraumatic stress disorder: a systematic review and meta-analysis.

Posttraumatic stress disorder (PTSD) recently becomes one of the most important mental health concerns. However, no previous study has comprehensively reviewed the application of big data and machine learning (ML) techniques in PTSD. We found 873 studies meet the inclusion criteria and a total of 31 of those in a sample of 210,001 were included in quantitative analysis. ML algorithms were able to discriminate PTSD with an overall accuracy of 0.89. Pooled estimates of classification accuracy from multi-dimensional data (0.96) are higher than single data types (0.86 to 0.90). ML techniques can effectively classify PTSD and models using multi-dimensional data perform better than those using single data types. While selecting optimal combinations of data types and ML algorithms to be clinically applied at the individual level still remains a big challenge, these findings provide insights into the classification, identification, diagnosis and treatment of PTSD.

High-Entropy Alloy Electrocatalysts Bidirectionally Promote Lithium Polysulfide Conversions for Long-Cycle-Life Lithium-Sulfur Batteries.

High-entropy alloys (HEAs) have attracted considerable attention, owing to their exceptional characteristics and high configurational entropy. Recent findings demonstrated that incorporating HEAs into sulfur cathodes can alleviate the shuttling effect of lithium polysulfides (LiPSs) and accelerate their redox reactions. Herein, we synthesized nano Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs on hollow carbons (HCs; denoted as HEA/HC) by a facile pyrolysis strategy. The HEA/HC nanostructures were further integrated into hypha carbon nanobelts (HCNBs). The solid-solution phase formed by the uniform mixture of the five metal elements, i.e., Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs, gave rise to a strong interaction between neighboring atoms in different metals, resulting in their adsorption energy transformation across a wide, multipeak, and nearly continuous spectrum. Meanwhile, the HEAs exhibited numerous active sites on their surface, which is beneficial to catalyzing the cascade conversion of LiPSs. Combining density functional theory (DFT) calculations with detailed experimental investigations, the prepared HEAs bidirectionally catalyze the cascade reactions of LiPSs and boost their conversion reaction rates. S/HEA@HC/HCNB cathodes achieved a low 0.034% decay rate for 2000 cycles at 1.0 C. Notably, the S/HEA@HC/HCNB cathode delivered a high initial areal capacity of 10.2 mAh cm-2 with a sulfur loading of 9 mg cm-2 at 0.1 C. The assembled pouch cell exhibited a capacity of 1077.9 mAh g-1 at the first discharge at 0.1 C. The capacity declined to 71.3% after 43 cycles at 0.1 C. In this work, we propose to utilize HEAs as catalysts not only to improve the cycling stability of lithium-sulfur batteries, but also to promote HEAs in energy storage applications.

Fabrication and characterization of magnetic mesoporous nanoparticles for efficient determination and magnetic separation of sulfonamides in food samples.

A magnetic, mesoporous core/shell structured Fe3O4@SiO2@mSiO2 nanocomposite was synthesized and employed as a magnetic solid phase extraction (MSPE) sorbent for the determination of trace sulfonamides (SAs) in food samples. The synthesized nanocomposite was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, X-ray diffraction, N2 sorption analysis and vibrating sample magnetometry. The results showed that Fe3O4@SiO2@mSiO2 possessed a mesoporous structure with a large surface area. Batch experiments were carried out to investigate the adsorption ability for SAs. Fe3O4@SiO2@mSiO2 showed fast kinetics and high adsorption capacity, and the pseudo-second-order model and Langmuir adsorption isotherm are well fitted with the experimental data, indicating that chemical adsorption might be the rate-limiting step. Moreover, the high adsorption capacity can be maintained for at least 8 runs, indicating excellent stability and reusability. The proposed method exhibited good linearity in the range of 0.2-500 µg L-1, the R2 values of all the analytes were greater than 0.99 and the LODs were all lower than 0.2 µg L-1. Furthermore, real food samples were successfully analyzed with Fe3O4@SiO2@mSiO2 and high recoveries varying from 89.7% and 110.6% were obtained with low relative standard deviations ranging from 1.78% to 6.91%. The Fe3O4@SiO2@mSiO2 magnetic nanocomposite is a promising sorbent for the efficient extraction of SAs from complex food samples.

Real-world greenhouse gas emission characteristics from in-use light-duty diesel trucks in China.

The transportation sector is a significant contributor to greenhouse gas (GHG) emissions in China. However, real-world GHG emissions from in-use light-duty diesel trucks (LDDTs) are largely uncertain due to data paucity. In this study, we have conducted real driving emission (RDE) tests of real-world CO2, N2O, and CH4 emissions from 12 in-use LDDTs in China. Results reveal that China's CH4 emission rates from LDDTs are overestimated by 57.71 ±â€¯39.15 % if using the previous ratio method of CO2:CH4. Notably, under real-world driving conditions, such as speeds exceeding 60 km/h, maximum exhaust gas temperatures are reached, potentially impacting urea decomposition catalyst temperatures and subsequently influencing N2O production, which is highly sensitive to system temperature. Moreover, uphill roads can increase CO2 emissions by 51.93 % compared to downhill roads. Despite the tightening of vehicle emission standards, CO2 and N2O emissions from the LDDTs have not decreased linearly. However, LDDTs meeting the China VI standard exhibit the lowest average CO2, N2O and CH4 emission factors (EFs) of 335.26 ±â€¯21.72 g/km, 2.7 ±â€¯0.69 mg/km and 3.50 ±â€¯0.70 mg/km, respectively. At last, the uncertainties in the GHG EFs for the tested LDDTs through RDE tests were (-39 %, 82 %) in our study, while a significantly higher uncertainty (-85 %, 182 %) for GHG EFs of LDDTs were found in our study and other reported literature in China, largely due to the application of different non-native vehicle emission factor models and testing methods, as well as different vehicles of control emission standards. Our study highlights more urgent needs for direct RDE tests and the importance of considering real driving conditions, such as road grades, in special geographical regions when undertaking carbon accounting work in the transportation sector.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

GABAergic interneurons in the hippocampal CA1 mediate contextual fear generalization in PTSD rats.

Fear overgeneralization is widely accepted as a pathogenic marker of post-traumatic stress disorder (PTSD). Recently, GABAergic interneurons have been regarded as key players in the regulation of fear memory. The role of hippocampal GABAergic interneurons in contextual fear generalization of PTSD remains incompletely understood. In the present study, we established a rat model of PTSD with inescapable foot shocks (IFS) and observed the loss of GABAergic interneuron phenotype in the hippocampal cornu ammonis-1 (CA1) subfield. To determine whether the loss of GABAergic interneuron phenotype was associated with fear generalization in PTSD rats, we used adeno-associated virus (AAV) to reduce the expression of GAD67 in CA1 and observed its effect on fear generalization. The results showed that the reduction of GAD67 in CA1 enhanced contextual fear generalization in rats. We investigated whether the PERK pathway was involved in the GABAergic interneuron injury. Increased expression of p-PERK, CHOP, and Caspase12 in GABAergic interneurons of PTSD rats was observed. Then, we used salubrinal, an endoplasmic reticulum stress inhibitor, to modulate the PERK pathway. The salubrinal treatment significantly protected the GABAergic interneurons and relieved fear generalization in PTSD rats. In addition, the results showed that salubrinal down-regulated the expression of CHOP and Caspase12 in GABAergic interneurons of PTSD rats. In conclusion, this study provided evidence that the loss of GABAergic interneuron phenotype in CA1 may contribute to contextual fear generalization in PTSD. The PERK pathway is involved in the GABAergic interneuron injury of PTSD rats and modulating it can protect GABAergic interneurons and constrain contextual fear generalization.

Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections.

The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.

Paeoniflorin exerts anti-PTSD effects in adult rats by modulating hippocampus and amygdala histone acetylation modifications in response to early life stress.

Early life stress (ELS) can cause long-term changes by epigenetic factors, especially histone acetylation modification, playing a crucial role, affect normal cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood. It has been found that paeoniflorin (PF) can cross the blood-brain barrier to exert anti-PTSD effects on adult PTSD rats. However, whether PF can alleviate the harmful effects caused by ELS in adulthood has not yet been reported. Therefore, to explore the relationship between ELS and PTSD susceptibility in adulthood and its mechanism, in this study, SPS was used as a stressor of ELS, and the mathematical tool Z-normalization was employed as an evaluation criterion of behavioral resilience susceptibility. To investigate the regulatory mechanism of PF on histone acetylation in the hippocampus and amygdala of ELS rats in adulthood, using changes in HATs/HDACs as the entry point, meanwhile, the epigenetic marks (H3K9 and H4K12) in the key brain regions of ELS (hippocampus and amygdala) were evaluated, and the effects of PF on behavioral representation and PTSD susceptibility were observed. This study found that ELS lead to a series of PTSD-like behaviors in adulthood and caused imbalance of HATs/HDACs ratio in the hippocampus and amygdala, which confirms that ELS is an important risk factor for the development of PTSD in adulthood. In addition, paeoniflorin may improve ELS-induced PTSD-like behaviors and reduce the susceptibility of ELS rats to develop PTSD in adulthood by modulating the HATs/HDACs ratio in the hippocampus and amygdala.

Controlled delivery of procyanidin through magnesium oxide nanoparticles (MgO NPs) to improve the activity and mineralization of osteoblasts under oxidative stress in vitro.

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), Dynamic Light Scattering (DLS), and Fourier Transform Infrared Spectroscopy (FTIR). After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate (DCFH-DA) probe, Cell Counting Kit-8 (CCK8), quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPS for at least 16 days. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.

Oxidative stress-induced hypermethylation and low expression of ANXA2R: Novel insights into the dysfunction of melanocytes in vitiligo.

BACKGROUND: Vitiligo is a skin disorder with melanocyte destruction caused by complex interplay between multiple genetic and environmental factors. Recent studies have suggested DNA methylation is involved in the melanocyte damage, but the underlying mechanism remains unknown. OBJECTIVE: To explore the abnormal DNA methylation patterns in vitiligo lesional and nonlesional skin, and the mechanism of DNA methylation involved in vitiligo pathogenesis. METHODS: Initially, the genome-wide aberrant DNA methylation profiles in lesional and nonlesional skin of vitiligo were detect via Illumina methylation EPIC 850k Beadchip. Subsequently, a comprehensive analysis was conduct to investigate the genomic characteristics of differentially methylated regions (DMRs). Furthermore, the effects of key aberrant methylated genes on cell apoptosis and function of both melanocytes and keratinocytes were further identified and validated by western bloting, ELISA, and immunofluorescence. RESULTS: Compared with nonlesional skins, we discovered 79 significantly differentially methylated CpG sites in vitiligo lesions. These DMRs were mainly located in the gene body and the TS1500 region. Annexin A2 receptor (ANXA2R), a crucial gene in cell apoptosis, was hypermethylated in vitiligo lesions. Furthermore, we showed that ANXA2R displayed hypermethylation and low expression levels in both keratinocytes and melanocytes of vitiligo patients, and the hypermethylated-triggered downregulation of ANXA2R under oxidative stress induced melanocyte apoptosis, and inhibited the secretion of stem cell factor (SCF) from keratinocytes thus impaired the survival of melanocytes. CONCLUSIONS: Our study illustrates the DNA methylation modification in vitiligo, and further demonstrates the molecular mechanism of hypermethylated ANXA2R in the dysfunction of melanocytes under oxidative stress.

Tannin-assisted interfacial polymerization towards COF membranes for efficient dye separation.

Membrane separation has been shown to have significant potential in addressing the global shortage of clean water. Covalent organic frameworks (COFs) have gained significant attention in the field of membrane separation due to their structural stability and controllable pore size. Here, a modification of polyethersulfone ultrafiltration membranes with TA-assisted COFs is prepared by interfacial polymerization and co-deposition. Intriguingly, in comparison to the conventional COF synthesis method, the interfacial polymerization reaction used n-butanol as the oil-phase monomer to prevent substrate corrosion. More importantly, the TA-assisted co-deposition not only introduces a large number of environmentally friendly hydrophilic groups to enhance the hydrophilicity of the membrane surface, but also the phenolic hydroxyl group contained in TA generates a quinone group upon oxidation. This group can undergo a Michael addition reaction with the amine group, followed by interfacial polymerization to regulate the COFs pore size. Consequently, the optimized membrane exhibited a high permeation flux of 122.03 L m-2 h-1 bar-1 without altering the pore size structure of the original membranes and demonstrated separation performance for various dyes (Mw: 300-1300 g mol-1), with a retention rate of over 98%. Despite multiple filtrations of methyl blue dye, the membrane prepared by simple rinsing still exhibited high retention rates (>98%) with exceptional stability and retention performance. The optimized membrane demonstrated good hydrophilicity and dye separation performance, indicated promising potential for dye separation applications.

Effective separation of dyes/salts by sulfonated covalent organic framework membranes based on phenolamine network conditioning.

This study developed a modified polyacrylonitrile (PAN) membrane controlled by a phenol-amine network and enhanced with a sulfonated covalent organic framework (SCOF), aimed at improving the efficiency of textile wastewater treatment. Utilizing a phenol-amine network control strategy allows for precise manipulation of interfacial reactions in the synthesis of SCOF, achieving highly uniform modification on the surface of the PAN membrane. This modified membrane demonstrated high rejection of over 98% for various water-soluble dyes, including Alcian blue 8GX, Coomassie Brilliant Blue G250, methyl blue, congo red, and rose bengal, and also exhibited specific selectivity in processing salt-containing wastewater. By adjusting the deposition time of the phenol-amine and the concentration of SCOF monomers, optimal retention performance and permeate flux were achieved, effectively separating dyes and salts. This research provides a new and effective solution for treating textile wastewater, especially in separating and recovering dyes and salts, offering broad application prospects in environmental management and water resource management, and highlighting its significant practical implications.

Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease that affects over 30% of the world's population. For decades, the heterogeneity of non-alcoholic fatty liver disease (NAFLD) has impeded our understanding of the disease mechanism and the development of effective medications. However, a recent change in the nomenclature from NAFLD to MASLD emphasizes the critical role of systemic metabolic dysfunction in the pathophysiology of this disease and therefore promotes the progress in the pharmaceutical treatment of MASLD. In this review, we focus on the mechanism underlying the abnormality of hepatic lipid metabolism in patients with MASLD, and summarize the latest progress in the therapeutic medications of MASLD that target metabolic disorders.

Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis.

BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.

Revisiting the surgical table: An analysis of surgical dose-response in Asian exotropia.

BACKGROUND: Previous research on the factors associated with surgical dose-response in strabismus surgery for exotropia has yielded inconsistent results. This study determined the factors influencing surgical dose-response in exotropia patients who underwent recession and resection (R&R). METHODS: Exotropia patients who underwent unilateral R&R at the National Taiwan University Hospital between 2006 and 2021 were evaluated. Deviation-angle differences in prism diopters (PD) were measured preoperatively and at 1 month postoperatively. Surgical dose-response (PD/mm) was defined as the difference in deviation angle (in PD) divided by the surgical dose in millimeters. Linear and non-linear regression models were used to evaluate the influence of variables including age, sex, axial length, and preoperative deviation on surgical dose-response. RESULTS: Overall, 295 patients (162 children; 133 adults) were included. Average surgical dose-response in the pediatric and adult groups was 2.82 ± 0.60 PD/mm and 3.02 ± 0.62 PD/mm, respectively. Male sex was negatively correlated with surgical dose-response in children. The surgical dose-response was larger in adults with longer axial length (>25.64 mm) and patients with larger preoperative deviation (>42.6 PD and >38.7 PD in pediatric and adult groups, respectively). Surgical dose-responses peaked at 35.1 years. CONCLUSION: Age, axial length, and preoperative deviation have a nonlinear effect on surgical dose-responses in exotropia patients undergoing R&R. Surgical dose-responses were larger in patients in young adulthood, with longer axial length and larger preoperative deviation angle. A table with fitted values for surgical dose-response based on age, axial length, and preoperative deviation was established for clinical reference.

Intravenous injection of dexamethasone is non-inferior to perineural administration for popliteal sciatic nerve and saphenous nerve blocks: A randomized, controlled, triple-blind study.

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18-75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0-48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, -1.7; 95% CI, -3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P < 0.001). Conditions for establishing non-inferiority were met. Conclusions: Our findings indicate that a single 10-mg intravenous dose of dexamethasone was noninferior to the combined dose of ropivacaine plus deaxmethasone in terms of duration of analgesia for foot and ankle surgery.

Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats.

Quercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio and enhanced Cyanobacteria. At the genus level, quercetin downregulated 6 and upregulated 14 bacterial species. Metabolomics analysis revealed that quercetin regulated multiple metabolic pathways, including glycolysis/gluconeogenesis, sphingolipid metabolism, the pentose phosphate pathway, and coenzyme A biosynthesis. This modulation leads to improvements in depression-like phenotypes, anxiety-like phenotypes, and cognitive function, highlighting the therapeutic potential of quercetin in treating depression.

Interferon-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon-α (PEG-IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG-IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP-1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN-γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell-associated chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN-γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue-resident memory T cells with increased ALT levels. IFN-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.