Huanglian Wendan Decoction Improves Insomnia in Rats by Regulating BDNF/TrkB Signaling Pathway Through Gut Microbiota-Mediated SCFAs and Affecting Microglia Polarization.

Insomnia is a typical type of sleep disorder. Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) with the effects of regulating Qi, drying dampness and resolving phlegm, calming the mind, and relieving irritation. This study aims to investigate the effect of HWD on insomnia in rats and its mechanism. Para-chlorophenylalanine (PCPA)-induced insomnia in rats was used for in vivo experiments and then treated with HWD. Behavioral tests, Western blot, real-time PCR, immunofluorescent staining, 16S rRNA sequencing were conducted. The content of SCFAs was determined by GC-MS. Acetic acid-pretreated rat hippocampal nerve cells were used for in vitro experiments. The results showed that HWD significantly improved the learning memory ability, decreased sleep latency, and prolonged sleep duration in insomniac rats. HWD reduced TNF-α and IL-6 levels and increased IL-10 and Foxp3 levels. HWD also promoted the polarization of macrophages from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, HWD increased the expression levels of BDNF and TrkB in the hippocampus. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone (7,8-DHF) confirmed the mechanism by which HWD activates BDNF/TrkB signaling to ameliorate insomnia. Furthermore, HWD restored gut microbiota richness and diversity and promoted short-chain fatty acid (SCFA) production in insomniac rats. In vitro experiments confirmed that the acetic acid-treated SCFA group could activate the BDNF/TrkB signaling pathway in neuronal cells, further promoting neuronal cell growth. In conclusion, HWD alleviated insomnia by maintaining gut microbiota homeostasis, promoting SCFA production, reducing neuroinflammatory response and microglia activation, and activating BDNF/TrkB signaling pathway.

Dietary Bacillus velezensis KNF-209 supplementation improves growth performance, enhances immunity, and promotes gut health in broilers.

This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1ß and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1ß and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels.

Modulating porous silicon-carbon anode stability: Carbon/silicon carbide semipermeable layer mitigates silicon-fluorine reaction and enhances lithium-ion transport.

Silicon-based material is regarded as one of the most promising anodes for next-generation high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity and low cost. Harnessing silicon carbide's robustness, we designed a novel porous silicon with a sandwich structure of carbon/silicon carbide/Ag-modified porous silicon (Ag-PSi@SiC@C). Different from the conventional SiC interface characterized by a frail connection, a robust dual covalent bond configuration, dependent on SiC and SiOC, has been successfully established. Moreover, the innovative sandwich structure effectively reduces detrimental side reactions on the surface, eases volume expansion, and bolsters the structural integrity of the silicon anode. The incorporation of silver nanoparticles contributes to an improvement in overall electron transport capacity and enhances the kinetics of the overall reaction. Consequently, the Ag-PSi@SiC@C electrode, benefiting from the aforementioned advantages, demonstrates a notably elevated lithium-ion mobility (2.4 * 10-9 cm2·s-1), surpassing that of silicon (5.1 * 10-12 cm2·s-1). The half-cell featuring Ag-PSi@SiC@C as the anode demonstrated robust rate cycling stability at 2.0 A/g, maintaining a capacity of 1321.7 mAh/g, and after 200 cycles, it retained 962.6 mAh/g. Additionally, the full-cell, featuring an Ag-PSi@SiC@C anode and a LiFePO4 (LFP) cathode, exhibits outstanding longevity. Hence, the proposed approach has the potential to unearth novel avenues for the extended exploration of high-performance silicon-carbon anodes for LIBs.

An improved Trizol method for extracting total RNA from Eleutherococcus senticosus (Rupr. & Maxim.) Maxim leaves.

INTRODUCTION: High-quality nucleic acids are the basis for molecular biology experiments. Traditional RNA extraction methods are not suitable for Eleutherococcus senticosus Maxim. OBJECTIVE: To find a suitable method to improve the quality of RNA extracted, we modified the RNA extraction methods of Trizol. METHODOLOGY: Based on the conventional Trizol method, the modified Trizol method 1 and modified Trizol method 2 were used as the control for extraction of RNA from E. senticosus Maxim leaves. The modified Trizol method 1 added ß-mercaptoethanol on the conventional Trizol method. After RNA was dissolved, a mixed solution of phenol, chloroform, and isoamyl alcohol was added to denature protein and inhibit the degradation of RNA. The modified Trizol method 2 adds PVPP to grind on the basis of modified Trizol method 1, so as to better remove phenols from leaves, and eliminates the step of incubation at -20°C to reduce extraction time and RNA degradation. Chloroform, CTAB, and CH3COONa were used instead of a phenol, chloroform, and isoamyl alcohol mixed solution to ensure complete separation of nucleic acid from plant tissues and to obtain high-purity RNA. RESULTS: The research results showed that the quality of RNA extracted by conventional Trizol method, modified Trizol method 1, was incomplete, accompanied with different degrees of contamination of polysaccharides, polyphenols, and DNA. The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. The ratio of A260/A280 was in the range of 1.8-2.0, and the yield of RNA was the highest, which was 1.68 and 1.15 times compared with that by conventional Trizol method and modified Trizol method 1 extraction, respectively. The reverse transcription cDNA was further tested through PCR with the specific primers. The amplified fragments are displayed in clear and bright bands in accordance with the expected size. CONCLUSION: The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. High-quality RNA has more advantages in molecular biology study of E. senticosus Maxim.

Current research update on group B streptococcal infection related to obstetrics and gynecology.

Group B streptococcal (GBS) is a Gram-positive bacterium that is commonly found in the gastrointestinal tract and urogenital tract. GBS infestation during pregnancy is a significant contributor to maternal and neonatal morbidity and mortality globally. This article aims to discuss the infectious diseases caused by GBS in the field of obstetrics and gynecology, as well as the challenges associated with the detection, treatment, and prevention of GBS.

Cardiovascular disease burden in patients with urological cancers: The new discipline of uro-cardio-oncology.

Cancer remains a major cause of mortality worldwide, and urological cancers are the most common cancers among men. Several therapeutic agents have been used to treat urological cancer, leading to improved survival for patients. However, this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications. Here, we propose the novel discipline of uro-cardio-oncology, an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer. In this comprehensive review, we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers, including androgen deprivation therapy, vascular endothelial growth factor receptor tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapeutics. In addition, we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance, diagnosis, and effective management of cardiovascular complications. Finally, we provide an analysis of future perspectives in this emerging specialty, identifying areas in need of further research.

Phylogenomic analysis and dynamic evolution of chloroplast genomes of Clematis nannophylla.

Clematis nannophylla is a perennial shrub of Clematis with ecological, ornamental, and medicinal value, distributed in the arid and semi-arid areas of northwest China. This study successfully determined the chloroplast (cp) genome of C. nannophylla, reconstructing a phylogenetic tree of Clematis. This cp genome is 159,801 bp in length and has a typical tetrad structure, including a large single-copy, a small single-copy, and a pair of reverse repeats (IRa and IRb). It contains 133 unique genes, including 89 protein-coding, 36 tRNA, and 8 rRNA genes. Additionally, 66 simple repeat sequences, 50 dispersed repeats, and 24 tandem repeats were found; many of the dispersed and tandem repeats were between 20-30 bp and 10-20 bp, respectively, and the abundant repeats were located in the large single copy region. The cp genome was relatively conserved, especially in the IR region, where no inversion or rearrangement was observed, further revealing that the coding regions were more conserved than the noncoding regions. Phylogenetic analysis showed that C. nannophylla is more closely related to C. fruticosa and C. songorica. Our analysis provides reference data for molecular marker development, phylogenetic analysis, population studies, and cp genome processes to better utilise C. nannophylla.

Integrated transcriptome and microRNA analysis reveals molecular responses to high-temperature stress in the liver of American shad (Alosa sapidissima).

BACKGROUND: Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 â„ƒ (Low), 27 â„ƒ (Mid) and 30 â„ƒ (High) based on a high-throughput sequencing platform. RESULTS: The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 â„ƒ, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. CONCLUSIONS: In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.

Risk factors of postoperative airway obstruction complications in children with oral floor mass.

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

Small bowel adenocarcinoma of the jejunum detected by double contrast enhanced ultrasound: a case report of a novel ultrasound modality.

Background: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum. Case presentation: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma. Conclusion: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

Inadequate Glucagon Suppression During OGTT in prediabetes: A Systematic Review and Meta-Analysis.

CONTEXT: Glucagon plays a role in the development of type 2 diabetes, yet its role in prediabetes (preDM) remains uncertain. OBJECTIVE: To evaluate glucagon levels in fasting state and its response to glucose inhibition in preDM through meta-analysis. METHODS: A systematic search across Pubmed, Embase, Web of Science, and Cochrane Library identified studies assessing glucagon levels during 75g oral glucose tolerance test (OGTT) in both preDM and normal glucose tolerance (NGT) cohorts. Data on glucagon, glucose and insulin were pooled using random-effect model. RESULTS: Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0h, 0.5h, 1h and 1.5h in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0h, 1h, 1.5h and 2h during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay (RIA) method, glucagon levels in preDM were higher at 0.5h and 1h than NGT, while in studies using the Enzyme linked immunosorbent assay (ELISA) method, glucagon levels were similar to those of the NGT group despite higher glucose in preDM compared to NGT. Fasting glucagon level was inadequately suppressed in both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Responsiveness to glucose inhibition was preserved in IFG, while glucagon level in IGT group at 0.5h after glucose intake was not suppressed and was higher than NGT. CONCLUSION: Glucagon was not adequately suppressed during OGTT in preDM. Glucagon dysregulation is a contributing mechanism underlying both IFG and IGT.

Effects of Mobile Intelligent Cognitive Training for Patients with Post-Stroke Cognitive Impairment: A 12-Week, Multicenter, Randomized Controlled Study.

Background: The current application effects of computerized cognitive intervention are inconsistent and limited to hospital rehabilitation settings. Objective: To investigate the effect of mobile intelligent cognitive training (MICT) on patients with post-stroke cognitive impairment (PSCI). Methods: This study was a multicenter, prospective, open-label, blinded endpoint, cluster-randomized controlled trial (RCT). 518 PSCI patients were stratified and assigned to four rehabilitation settings, and then patients were randomized into experimental and control groups in each rehabilitation setting through cluster randomization. All patients received comprehensive management for PSCI, while the experimental group additionally received MICT intervention. Treatment was 30 minutes daily, 5 days per week, for 12 weeks. Cognitive function, activities of daily living (ADL), and quality of life (QOL) were assessed before the treatment, at weeks 6 and 12 post-treatment, and a 16-week follow-up. Results: Linear Mixed Effects Models showed patients with PSCI were better off than pre-treatment patients on each outcome measure (p < 0.05). Additionally, the improvement of these outcomes in the experimental group was significantly better than in the control group at week 6 post-treatment and 16-week follow-up (p < 0.05). The rehabilitation setting also affected the cognitive efficacy of MICT intervention in improving PSCI patients, and the degree of improvement in each outcome was found to be highest in hospital, followed by community, nursing home, and home settings. Conclusions: Long-term MICT intervention can improve cognition, ADL, and QOL in patients with PSCI, with sustained effects for at least one month. Notably, different rehabilitation settings affect the cognitive intervention efficacy of MICT on PSCI patients. However, this still needs to be further determined in future studies.

A lysosomal-targeted and viscosity-ultrasensitive near-infrared fluorescent probe for sensing viscosity in cells and a diabetic mice model.

Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.

Association of serum interleukin-2 with severity and prognosis in hospitalized patients with community-acquired pneumonia: a prospective cohort study.

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

A ratiometric SERS aptasensor based on catalytic hairpin self-assembly mediated cyclic signal amplification strategy for the reliable determination of E. coli O157:H7.

A ratiometric SERS aptasensor based on catalytic hairpin self-assembly (CHA) mediated cyclic signal amplification strategy was developed for the rapid and reliable determination of Escherichia coli O157:H7. The recognition probe was synthesized by modifying magnetic beads with blocked aptamers, and the SERS probe was constructed by functionalizing gold nanoparticles (Au NPs) with hairpin structured DNA and 4-mercaptobenzonitrile (4-MBN). The recognition probe captured E. coli O157:H7 specifically and released the blocker DNA, which activated the CHA reaction on the SERS probe and turned on the SERS signal of 6-carboxyl-x-rhodamine (ROX). Meanwhile, 4-MBN was used as an internal reference to calibrate the matrix interference. Thus, sensitive and reliable determination and quantification of E. coli O157:H7 was established using the ratio of the SERS signal intensities of ROX to 4-MBN. This aptasensor enabled detection of 2.44 × 102 CFU/mL of E. coli O157:H7 in approximately 3 h without pre-culture and DNA extraction. In addition, good reliability and excellent reproducibility were observed for the determination of E. coli O157:H7 in spiked water and milk samples. This study offered a new solution for the design of rapid, sensitive, and reliable SERS aptasensors.

Correlation between motor function and health-related quality of life in early to mid-stage patients with Parkinson disease: a cross-sectional observational study.

Aim: To investigate the correlation between motor function and health-related quality of life (HrQOL) in early to mid-stage patients with Parkinson disease (PwP). Methods: This cross-sectional study recruited PwP from April 2020 to December 2023 at the outpatient clinic of Peking Union Medical College Hospital in Beijing, China. The motor symptoms were assessed using Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3. Balance function was evaluated using the Berg Balance Scale (BBS), and the risk of fall using Timed Up-and-Go test (TUG), and Five Times Sit-to-Stand test (FTSST). Freezing of gait questionnaire (FOGQ) was used to evaluate the severity of gait. The Intelligent Device for Energy Expenditure and Physical Activity (IDEEA) recorded gait cycle parameters, and the isokinetic dynamometer measured muscle strength. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure HrQOL. All assessments were tested during the on state. Spearman correlation was conducted to evaluate the correlation between motor function and HrQOL. Results: 243 patients with mean age of 69.33 years were enrolled. The PDQ-39 score was strongly correlated with FOG in H&Y stage III (r = 0.653, p < 0.001) and moderately correlated in H&Y stage I (r = 0.471, p < 0.001) and H&Y stage II (r = 0.386, p < 0.001). Furthermore, the FOG was strongly correlated with mobility domain at H&Y stage III (r = 0.694, p < 0.001) and moderately correlated at H&Y stage I (r = 0.431, p < 0.001) and H&Y stage II (r = 0.434, p < 0.001). All motor function scores were correlated with PDQ-39 scores at H&Y stage III (p < 0.05). Conclusion: Motor function correlated with HrQOL in early to mid-stage PwP, and FOG was the main factor, especially affecting mobility, activities of daily life and communication. HrQOL in patients at different disease stages were variously affected by motor function, and HrQOL and multiple dimensions was significantly associated with motor function in patients at H&Y stage III.

Investigational Treatment of Congenital Hypogonadotropic Hypogonadism in Infants.

The aim of the study was to investigate whether the administration of gonadotropins to mimic the physiological development of infants with congenital hypogonadotropic hypogonadism (CHH) after birth can facilitate testicular descent, penile growth, and ultimately preserve fertility. This study included eight infants with CHH who received a gonadotropin-releasing hormone (GnRH) pump or human chorionic gonadotropin (HCG) combined with human menopausal gonadotropin (HMG) therapy at Beijing Children's Hospital from August 2018 to March 2023. The age of the infants ranged from 6 months to 2 years. 2. For literature review, a search was conducted in the PubMed database using the keywords "congenital hypogonadotropic hypogonadism," "infants," and "mini-puberty" up until June 2023. After 1-3 months of treatment, significant increases were observed in PL and TV. The testes descended from the inguinal region to the scrotum. Serum T and INH-B levels increased from being undetectable to 737.1±409.5 ng/dl and from 47.88±23.03 to 168.94±59.34 pg/ml, respectively. In a comparative literature review of 22 infants with CHH, the age at treatment initiation ranged from 0.5 to 7.9 months. Treatment involved various dosages and durations, ranging from 2 to 6 months of subcutaneous injections of LH and FSH. Both therapies successfully improved PL, TV, and testicular descent; reduced the need for surgery; and were safe. This is the first report of the use of a GnRH pump for the treatment of infant CHH.

SMARCA4 (BRG1)-deficient carcinoma invading the skull base: report of two cases and literature review.

Introduction and importance: SMARCA4 (BRG1)-deficient carcinomas in the head and neck are a rare and highly aggressive group of malignant tumors. They lack typical clinical and imaging features and are often misdiagnosed. Case presentation: The authors report two male patients with a history of smoking. Case 1 presented with nose bleeding as the first symptom, whereas case 2 presented with headache with blurred vision. Preoperative computed tomography (CT) and MRI suggested a highly aggressive malignant tumor of the head and neck with invasion of the skull base. Case 1 could not be operated on because of the large size of the punctured tumor. Case 2 underwent the surgery. The final pathological diagnosis was SMARCA4 (BRG1)-deficient carcinoma. At the 6-month follow-up, case 1 died. After completing the full course of chemotherapy, case 2 reported progressively worsening headaches and hearing loss. Discussion and conclusion: SMARCA4 (BRG1)-deficient carcinoma in the head and neck is a rare and highly aggressive malignant tumor that is advanced at diagnosis, prone to invasion of adjacent structures, difficult to operate on, and has a poor prognosis. CT and MRI play a vital role in evaluating the size and extent of the tumor, invasion of adjacent structures, and distant metastasis. It provides a significant reference for clinical diagnosis and therapeutic decision-making. Different patients of SMARCA4 (BRG1)-deficient carcinoma in the head and neck respond differently to radiotherapy and chemotherapy. Early use of next-generation sequencing (NGS) or immunohistochemistry(IHC) techniques is helpful in guiding treatment planning.

[Mechanism study of 6-shogaol alleviating cerebral ischemia/reperfusion injury by regulating microRNA-26a-5p/death-associated protein kinase 1].

OBJECTIVE: To investigate whether 6-shogaol (6-SH) alleviates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal autophagy and calcium overload by promoting the expression of microRNA-26a-5p (miR-26a-5p) and inhibiting death-associated protein kinase 1 (DAPK1), and to explore its potential mechanisms. METHODS: Primary cultured logarithmic growth phase mouse hippocampal neurons HT22 cells were taken and cell counting kit-8 (CCK-8) was used to detect cell viability, searching for the optimal concentration of Na2S2O4. HT22 cells were divided into blank control group (NC group), OGD/R group (sugar-free culture medium + 10 mmol/L Na2S2O4 treatment for 1.5 hours followed by normal culture medium for 4 hours), 6-SH intervention group (cultured with 10 µmol/L 6-SH for 4 hours after OGD), negative control inhibitor pretreatment group (transfected with negative control inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours), and miR-26a-5p inhibitor pretreatment group (transfected with miR-26a-5p inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours). Cell viability of each group was detected by CCK-8 method; cell ultrastructure was observed under transmission electron microscopy; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of DAPK1 and miR-26a-5p; molecular docking were used to verify the interaction between 6-SH and miR-26a-5p; dual-luciferase assay was used to verify the targeting relationship between DAPK1 and miR-26a-5p; flow cytometry was used to determine the levels of intracellular Ca2+; Western blotting was used to detect the protein expressions of phosphorylated-glutamate receptor 2B (p-NMDAR2B) Ser1303, DAPK1, autophagy related protein Beclin1, light chain 3 (LC3), and p-DAPK1 Ser308; immunofluorescence was used to detect the expression of LC3 and Beclin1. RESULTS: The results of the CCK-8 assay showed that the cell viability of the 6-SH intervention group was significantly increased compared to the OGD/R group, while the cell viability of the miR-26a-5p inhibitor pretreatment group was significantly decreased compared to the 6-SH intervention group. Transmission electron microscopy revealed that the number of autophagosomes in the 6-SH intervention group was significantly reduced compared to the OGD/R group, while the number of autophagosomes in the miR-26a-5p inhibitor pretreatment group was significantly increased compared to the 6-SH intervention group. RT-qPCR results showed that compared with the OGD/R group, the expression of miR-26a-5p was significantly upregulated and the expression of DAPK1 mRNA was significantly downregulated in the 6-SH intervention group; compared with the 6-SH intervention group, the expression of miR-26a-5p was significantly downregulated and the expression of DAPK1 mRNA was significantly upregulated in the miR-26a-5p inhibitor pretreatment group. Molecular docking verified the interaction between 6-SH and miR-26a-5p. Dual-luciferase reporter gene assay showed that compared with the negative control group, mmu-miR-26a-5p significantly downregulated the luciferase expression of m-DAPK1-3UTR-WT, indicating a binding interaction between them. Flow cytometry results showed that compared with the OGD/R group, the level of intracellular Ca2+; was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the level of Ca2+ was significantly increased in the miR-26a-5p inhibitor pretreatment group. Western blotting results showed that compared with the OGD/R group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly decreased in the 6-SH intervention group (p-NMDAR2B Ser1303/ß-actin: 2.34±0.27 vs. 4.78±0.39, DAPK1/ß-actin: 1.40±0.13 vs. 2.37±0.21, Beclin1/ß-actin: 2.61±0.32 vs. 4.32±0.29, LC3/ß-actin: 2.52±0.45 vs. 5.09±0.18, all P < 0.05), while the protein expression of p-DAPK1 Ser308 was significantly increased (p-DAPK1 Ser308/ß-actin: 0.66±0.09 vs. 0.40±0.02, P < 0.05); compared with the 6-SH intervention group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly increased in the miR-26a-5p inhibitor pretreatment group (p-NMDAR2B Ser1303/ß-actin: 4.08±0.14 vs. 2.34±0.27, DAPK1/ß-actin: 1.96±0.15 vs. 1.40±0.13, Beclin1/ß-actin: 3.92±0.31 vs. 2.61±0.32, LC3/ß-actin: 4.33±0.33 vs. 2.52±0.45, all P < 0.05), while the expression of p-DAPK1 Ser308 protein was significantly decreased (p-DAPK1 Ser308/ß-actin: 0.33±0.12 vs. 0.66±0.09, P < 0.05); immunofluorescence staining showed that compared with the OGD/R group, the fluorescence intensity of LC3 and Beclin1 was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the fluorescence intensity of LC3 and Beclin1 was significantly increased in the miR-26a-5p inhibitor pretreatment group. CONCLUSIONS: 6-SH can alleviate neuronal damage by regulating miR-26a-5p/DAPK1 to reduce autophagy and calcium overload in cells.