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Background and aim Chuanxiong Renshen decoction (CRD) is a traditional Chinese medicine compound used to treat Alzheimer's disease (AD). However, the effects and active ingredients of CRD and its mechanism have not been clarified. We aimed to determine the neuroprotective effects of CRD in a triple-transgenic mouse model of AD (3 × Tg-AD) and investigate the possible active ingredients and their mechanisms. Methods Morris water maze (MWM) tests were used to determine the protective effect of CRD on learning and memory ability. Afterward, we used brain tissue staining, immunofluorescent staining and western blotting to detect the neuroprotective effects of CRD. Ultraperformance liquid-chromatography-quadrupole–time-of-flight tandem mass spectrometry (UPLC-Q–TOF–MS) was applied to determine the ingredients of CRD, and the potential AD targets were obtained from DisGeNET and the GeneCards database. The protein‒protein interaction (PPI) network was built with the additional use of STRING 11.0. Metascape was used in the pathway enrichment analysis. Discovery Studio 2016 (DS) software was used to analyze the binding ability of CRD and AD-related genes. Finally, we verified the regulatory effect of CRD on the predicted core targets EGFR and CASP3 by western blotting. Results Our study indicated that CRD can significantly improve learning and memory, reduce the expression of Aβ and protect neurons. A total of 95 ingredients were identified in the CRD. Then, 25 ingredients were identified in serum, and 5 ingredients were identified in the brain tissue homogenate. PPI network analysis identified CASP3, EGFR, APP, CNR1, HIF1A, PTGS2 and MTOR as hub targets. KEGG and GO analyses revealed that the TNF signaling pathway and MAPK signaling pathway were enriched in multiple targets. The results of molecular docking proved that the binding of the ingredients with potential key targets was excellent. The western blotting results showed that CRD could significantly reduce the expression of CASP3 and EGFR in the hippocampus of 3 × Tg-AD mice. Combined with literature analysis, we assumed the neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway. Conclusion CRD significantly alleviated injury in 3 × Tg-AD mice. The possible active ingredients are ferulic acid, rutin, ginsenoside Rg1 and panaxydol. The therapeutic effect of CRD on AD is achieved through the downregulation of CASP3 and EGFR. The neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.

Objective: An assessment of functional gastrointestinal disorders (FGIDs) in premature infants in their first year of life and neonatal factors influencing the progression of FGIDs is conducted in this research. Methods: Subjects selected for the retrospective study involved preterm infants being hospitalized in the neonatal department of Northern Jiangsu People’s Hospital from September 2018 to September 2021. Data on neonatal risk factors such as gestational age, gender, birth weight, mode of delivery, feeding pattern, antibiotic administration and addition of probiotics, duration of hospitalization, maternal history of smoking, and mental condition, were all collected and analyzed. FGIDs were diagnosed as per Rome IV criteria and a multivariate logistic regression model has been applied for determining factors linked to it. Results: This study included 988 preterm infants, with 725 (73.4%) having at least one FGID, 449 (45.4%) having infant colic, 411 (41.6%) having infant regurgitation, 237 (24.0%) having infant dyschezia, 190 (19.2%) having functional constipation, and 34 (3.4%) having functional diarrhea throughout the first year of life. There was no evidence identified for infant rumination syndrome and recurrent vomiting syndrome. In total, 263 infants (26.6%) without FGID symptoms were included in the control group. Infant colic and infant regurgitation were found as the most prevalent FGIDs. Further, a higher prevalence of FGIDs was observed in preterm infants with infant colic as well as infant regurgitation in particular as being characterized by a low gestational age (Conclusion: Therefore, unnecessary antibiotic use in the neonatal period, cesarean delivery, passive smoking, lack of breastfeeding, along with inappropriate probiotics usage are major risk factors for FGIDs, and their systematic control may be effective in reducing the susceptibility to and prevalence of FGIDs in preterm infants in the first year of life.

The present study explored the physiological mechanism of the effects of different pH treatments on the growth, physiological characteristics, and stachydrine biosynthesis of Leonurus japonicus to provide references for the cultivation and quality control of L. japonicus. Under hydroponic conditions, different pH treatments(pH 5,6,7,8) were set up. The growth, physiology, and the content of stachydrine and total alkaloids of L. japonicus, as well as the content of key intermediate products in stachydrine biosynthesis pathway(i.e., pyruvic acid, α-ketoglutaric acid, glutamic acid, and ornithine) were monitored to explore the physiological mechanism of the effects of pH on the growth and active components of L. japonicus. The results showed that L. japonicus. could grow normally in the pH 5-8 solution. The pH treatment of neutral acidity was more conducive to the accumulation of photosynthetic pigments and the increase in soluble protein in leaves of L. japonicus. to promote its growth and yield. However, since stachydrine is a nitrogen-containing pyrrolidine alkaloid, its synthesis involves the two key rate-limiting steps of nitrogen addition: reductive ammoniation reaction and Schiff base formation reaction. High pH treatments promote the synthesis and accumulation of substrates and products of the above two reactions, indicating that the alkaline environment can promote the nitrogen addition reaction, thereby promoting the biosynthesis and accumulation of stachydrine.

BACKGROUND Nasogastric tube (NG) insertion is one of the essential clinical skills. Unfortunately, it’s a blind procedure, as one cannot directly visualize the tip of the NG during the insertion process. Thus, the most significant risk was malposition. Suppose blind insertion can be broken through in teaching strategies so that learners can see through the internal structure of the human body when performing technology. In that case, students can have better memory and comprehension and simultaneously provide real-time feedback, both of which are conducive to conceptualizing invasive surgical execution. OBJECTIVE A mobile-based interactive simulation scheme (MISS) was proposed, and a MISS-based learning system was developed to investigate its effects on facilitating hands-on learning of nasogastric tube (NG) insertion in Taiwanese undergraduate medical students. METHODS A randomized controlled trial (RCT) design was adopted for this research, for which 73 grade-five medical students were recruited. An interactive simulation scheme with a hands-on learning design in a MISS model was built on a web-based application running on mobile devices equipped with the touchscreen. Learning performance including the conceptual knowledge, self-confidence scales, and practical skills (an OSCE-based test) were evaluated to investigate the differences between experimental and control groups. The MISS-based learning system was also evaluated in terms of learning satisfaction, system usability, and task load. The statistical methods used in this work included t-test, ANCOVA, and the Johnson-Neyman analysis. RESULTS he results showed significant differences between the experimental and control groups in terms of both knowledge and self-confidence (P < .001). The levels of image, perceived enjoyment, perceived usefulness, and intention to use scales in the technology acceptance model (TAM) were higher in the high progress group than in the low progress group. Besides, the score of the OSCE test in the experimental group were higher than those in the control group, which had significant difference (t=3.079, P=.003). CONCLUSIONS The proposed MISS-based learning system can efficiently assist students in hands-on learning of nasogastric tube insertion. Accordingly, the learning outcomes and self-confidence can be significantly improved. Moreover, experimental results also show that the useful diagnostic and enjoyment features in the system enhance learners' intention toward use.

BACKGROUND Mucosal-associated lymphoid tissue extranodal marginal zone (MALT) lymphoma is a low-grade tumor that rarely occurs in the urinary bladder. There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports. CASE SUMMARY A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria. Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder. The mass had an abundant blood supply. For further diagnosis, transurethral cystoscopic biopsy and bone marrow biopsy was performed, and the patient was finally diagnosed with primary MALT lymphoma of the bladder. R-CHOP chemotherapy was carried out. After three cycles of chemotherapy, the mass disappeared and the bladder wall thickness was only 4 mm, which indicated excellent therapeutic response to the chemotherapy. To date, the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles. CONCLUSION Primary MALT lymphoma of the bladder is rare, and there are certain characteristics in the ultrasonographic findings. Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway‐associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol‐mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.

Background A case of isolated growth hormone deficiency type IA (IGHD IA) caused by novel compound heterozygous mutation in the GH1 gene was reported in this study, which aimed to provide insights that will benefit future diagnosis and treatment. Case presentation We analyzed and summarized the clinical data and genetic test results from a patient with IGHD admitted in March 2019 to the Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We described the results from a 1-year-9-months old female, whose chief complaint was “growth retardation for more than one year”. Her birth length was 49.0 cm, and her birth weight was 3.05 kg. Suboptimal intake (breastfeeding) jaundice lasted for approximately two months following birth. When evaluated at the age of 1-year-9-months old, the patient’s height was 61.0 cm (− 7.24 SD), and her weight was 6.4 kg (− 1.50 SD). The patient’s physical characteristics included yellowish hair, large and unclosed anterior fontanelles, raised forehead, and a low and flat nose. The major abnormalities observed from the auxiliary examinations included low GH (T, inherited from her mother) in intron 1 of the GH1 gene and a deletion that encompassed the same gene (chr17: 61973811–61996255, inherited from her father). After hormone replacement therapy with L-thyroxine and recombinant human GH (rhGH), the patient’s thyroid function returned to normal, and her serum IGF-1 level significantly improved, which resulted in an accelerated increase in height. Conclusion This study described a case of IGHD caused by novel compound heterozygous mutations in the GH1 gene. This study suggested that closer attention should be directed to genetic testing and diagnosis based on clinical characteristics to avoid misdiagnosis.

Electrical conductivity and dielectric parameters are general inherent features of materials. Controlling these characteristics through applied bias will add a new dimension to regulate the dynamic response of smart materials. Here, a fascinating electrical transport behavior is observed in topological insulator (TI) Bi

The growing demands of supramolecular hyperbranched polymers integrating noncovalent interaction and unique topological structure merits had received considerable interest in the fabrication of novel materials for advanced applications. Herein, we prepared A2B6-type POSS-containing supramolecular hyperbranched polymers with multiple morphologies including lamellar-like, branched, hollow, core-shell and porous spherical structures through regulating self-assembling monomer concentrations and solvent polarities. The incorporation of appropriate emulative guest molecules would further trigger morphological transformations (such as vesicles and spherical micelles) by synergistic effects of unique POSS aggregation ability, supramolecular complexations and hydrophilic-hydrophobic interactions. Thus, this facile and universal strategy may enable a modular nanofabrication of supramolecular hyperbranched polymers with diversiform topological structure and sophisticated multifunctionality for their potential applications.

Toxoplasma gondii can cross the blood-brain barrier and infect different regions of the brain including the hippocampus. In the present study, we examined the impact of Toxoplasma gondii infection on the metabolism of the hippocampus of female BALB/c mice compared to control mice using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariate analysis revealed significant differences between infected and control hippocampi and identified 25, 82, and 105 differential metabolites (DMs) in the infected hippocampi at 7, 14, and 21 days post-infection (dpi), respectively. One DM (sphingosyl-phosphocholine in the sphingolipid metabolism pathway) and 11 dysregulated pathways were detected at all time points post-infection, suggesting their important roles in the neuropathogenesis of T. gondii infection. These pathways were related to neural activity, such as inflammatory mediator regulation of TRP channels, retrograde endocannabinoid signaling, and arachidonic acid metabolism. Weighted correlation network analysis and receiver operating characteristic analysis identified 33 metabolites significantly associated with T. gondii infection in the hippocampus, and 30 of these were deemed as potential biomarkers for T. gondii infection. This study provides, for the first time, a global view of the metabolic perturbations that occur in the mouse hippocampus during T. gondii infection. The potential relevance of the identified metabolites and pathways to the pathogenesis of cognitive impairment and psychiatric disorders are discussed.

Ling Hou, Zhou Zhang, Yue Du, Xiuli Wang, Chengguang Zhao Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Yue DuDepartment of Pediatrics, Shengjing Hospital of China Medical University, No. 36 of Sanhao Street, Heping District, Shenyang, 110004, People’s Republic of ChinaTel +86 18940251606Fax +86 024 23892617Email drduyue24@163.comObjective: This study aims to investigate the risk factors of extraordinary daytime only urinary frequency (EDOUF) and propose a form of clinical treatment.Methods: Correlation and binary logistic regression analyses were carried out on the medical records of children with EDOUF, including their history of eczema, urticaria, allergic rhinitis or allergic cough, and pruritus (eye rubbing, etc.).Results: A total of 266 children with EDOUF, 127 boys and 139 girls, were enrolled in the present study; their average age was 5.60 ± 2.04 years. Binary logistic regression analysis revealed that the risk factors of EDOUF in children were eczema (odds ratio [OR] = 8.393), allergic rhinitis or allergic cough (OR = 4.459), pruritus (eye rubbing, etc.; OR = 3.879), and elevated total serum IgE level (OR = 7.927). The efficacy rate of oral administration of antihistamine (desloratadine) was 89.1%.Conclusion: Systemic or local allergic conditions, such as eczema, allergic rhinitis or allergic cough, and pruritus (including eye rubbing), and elevated total serum IgE level, are risk factors for the occurrence of EDOUF in children. The oral administration of antihistamine (desloratadine) can alleviate the symptoms.Keywords: extraordinary daytime only urinary frequency, children, allergy, risk factor, loratadine

Background In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder. Methods All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors. Results The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively). Conclusions In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.

Background The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the immunomodulatory effects of a recombinant tegumental calcium-binding EF-hand protein 4 of F. gigantica (rFg-CaBP4) on goat monocytes. Methods The rFg-CaBP4 protein was induced and purified by affinity chromatography. The immunogenic reaction of rFg-CaBP4 against specific antibodies was detected through western blot analysis. The binding of rFg-CaBP4 on surface of goat monocytes was visualized by immunofluorescence assay. The localization of CaBP4 within adult fluke structure was detected by immunohistochemical analysis. The cytokine transcription levels in response to rFg-CaBP4 were examined using ABI 7500 real-time PCR system. The expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) in response to rFg-CaBP4 protein was analyzed using Flow cytometry. Results The isopropyl-ß-D-thiogalactopyranoside-induced rFg-CaBP4 protein reacted with rat sera containing anti-rFg-CaBP4 polyclonal antibodies in a western blot analysis. The adhesion of rFg-CaBP4 to monocytes was visualized by immunofluorescence and laser scanning confocal microscopy. Immunohistochemical analysis localized native CaBP4 to the oral sucker, pharynx, genital pore, acetabulum and tegument of adult F. gigantica. Co-incubation of rFg-CaBP4 with concanavalin A-stimulated monocytes increased the transcription levels of interleukin (IL)-2, IL-4, interferon gamma and transforming growth factor-β. However, a reduction in the expression of IL-10 and no change in the expression of tumor necrosis factor-α were detected. Additionally, rFg-CaBP4-treated monocytes exhibited a marked increase in the expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) and a decrease in MHC-I expression, in a dose-dependent manner. Conclusions These findings provide additional evidence that calcium-binding EF-hand proteins play roles in host-parasite interaction. Further characterization of the immunomodulatory role of rFg-CaBP4 should expand our understanding of the strategies used by F. gigantica to evade the host immune responses. Graphical abstract

Background Recombinant human growth hormone (rhGH) was approved for the therapy of pediatric patients with growth hormone deficiency (GHD) by the Food and Drug Administration (FDA) of the United States in 1985. This study aims to evaluate the effects of rhGH therapy on thyroid function in pediatric patients with GHD. Methods A total of 55 pediatric patients, who had been diagnosed with GHD and received rhGH therapy for 6-24 months, and who could regularly come to our hospital for outpatient visits from May 1, 2014 to April 30, 2017, were selected for the study. All of the patients were treated for at least six months, among which 44 patients were treated for 12 months, and 32 patients were treated for 18 months, and 16 patients were treated for 24 months. Results (I) During the course of the rhGH therapy, none of the patients had a free thyroxine (FT4) level lower than the normal lower limit. (II) The FT4 level decreased during the course of the therapy, when compared to the level at baseline, and the difference was statistically significant after 24 months of therapy. In the puberty group, the FT4 level had significantly decreased by the 12th month of therapy, when compared to the baseline, but there was no significant change in the FT4 and thyroid-stimulating hormone (TSH) levels at the remaining observation time points of treatment. Conclusions Growth hormone (GH) replacement therapy may affect the metabolism of the thyroid hormone in pediatric patients with GHD. During the course of treatment, the changes in thyroid function in pediatric patients with GHD should be regularly monitored in order to identify any abnormal thyroid function in its early stages.

BACKGROUND: To compare the physical development status, level of blood glucose and lipid metabolism in small for gestational age (SGA) and appropriate for gestational age (AGA) groups with central precocious puberty (CPP). METHODS: This was a retrospective study. Three hundred and twenty-two girls with CPP were divided into the AGA group (304 cases) and the SGA group (18 cases). Physical index such as height, weight, and body mass index (BMI), as well as sex hormones, adrenal androgens, blood lipid levels, fasting blood glucose, insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between the two groups. RESULTS: Height, weight, and BMI in the SGA group were lower than those in the AGA group (P0.05). The fasting blood glucose, insulin level, HOMA-IR, high-density lipoprotein (HDL) and the average level of triglycerides were similar between these two groups (P>0.05). There was a statistically significant difference in total cholesterol and low-density lipoprotein (LDL) between the two groups (P

In this paper, we obtain the existence of at least two nontrivial solutions for a class of p(x)-curl systems arising in electromagnetism. Some new criteria to guarantee that the existence of at least two solutions for the considered problem is established by using the variational approach in critical point theory, which extend and complement previously known results in the literature.

Background Oxidative stress is a common cause of neurodegeneration and plays a central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) is a redox-regulated enzyme that is induced in neurodegenerative diseases and acts against oxidative stress but can also promote cell death, a phenomenon that is still unexplained in molecular terms. Here, we test whether HMOX1 has opposing effects during retinal degeneration and investigate the molecular mechanisms behind its pro-apoptotic role. Methods Basal and induced levels of HMOX1 in retinas are examined during light-induced retinal degeneration in mice. Light damage-independent HMOX1 induction at two different expression levels is achieved by intraocular injection of different doses of an adeno-associated virus vector expressing HMOX1. Activation of Müller glial cells, retinal morphology and photoreceptor cell death are examined using hematoxylin-eosin staining, TUNEL assays, immunostaining and retinal function are evaluated with electroretinograms. Downstream gene expression of HMOX1 is analyzed by RNA-seq, qPCR examination and western blotting. The role of one of these genes, the pro-apoptotic DNA damage inducible transcript 3 (Ddit3), is analyzed in a line of knockout mice. Results Light-induced retinal degeneration leads to photoreceptor degeneration and concomitant HMOX1 induction. HMOX1 expression at low levels before light exposure prevents photoreceptor degeneration but expression at high levels directly induces photoreceptor degeneration even without light stress. Photoreceptor degeneration following high level expression of HMOX1 is associated with a mislocalization of rhodopsin in photoreceptors and an increase in the expression of DDIT3. Genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration normally resulting from high level HMOX1 expression. Conclusion The results reveal that the expression levels determine whether HMOX1 is protective or deleterious in the retina. Furthermore, in contrast to the protective low dose of HMOX1, the deleterious high dose is associated with induction of DDIT3 and endoplasmic reticulum stress as manifested, for instance, in rhodopsin mislocalization. Hence, future applications of HMOX1 or its regulated targets in gene therapy approaches should carefully consider expression levels in order to avoid potentially devastating effects.

Most land plants associate with arbuscular mycorrhizal (AM) fungi to secure mineral nutrient acquisition, especially that of phosphorus. A phosphate starvation response (PHR)-centered network regulates AM symbiosis. Here, we identified 520 direct target genes for the rice transcription factor OsPHR1/2/3 during AM symbiosis using transcriptome deep sequencing and DNA affinity purification sequencing. These genes were involved in strigolactone biosynthesis, transcriptional reprogramming, and bidirectional nutrient exchange. Moreover, we identified the receptor-like kinase, Arbuscule Development Kinase 1 (OsADK1), as a new target of OsPHR1/2/3. Electrophoretic mobility shift assays and transactivation assays showed that OsPHR2 can bind directly to the P1BS elements within the OsADK1 promoter to activate its transcription. OsADK1 appeared to be required for mycorrhizal colonization and arbuscule development. In addition, hydroponic experiments suggested that OsADK1 may be involved in plant Pi starvation responses. Our findings validate a role for OsPHR1/2/3 as master regulators of mycorrhizal-related genes involved in various stages of symbiosis, and uncover a new RLK involved in AM symbiosis and plant Pi starvation responses.