Effects of female bone marrow transplantation on male reproductive organs.

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function.

Dopamine Dynamics in the Amygdala Influence Emotional Changes in the Early Stage of Systemic Inflammatory Response Syndrome in Rats

SUMMARY: Systemic inflammatory response syndrome (SIRS) is a potentially fatal reaction to various forms of tissue damage and infections that cause damage to various organs. Furthermore, the brain is damaged earlier than other organs, resulting in diffuse brain dysfunction. The central clinical symptom of SIRS is delirium and emotional changes are involved in disease development. Although the amygdala is known to play a major role, the mechanisms underlying emotional changes in the early stages of SIRS have not been elucidated. Therefore, changes to dopamine levels in the amygdala were observed using an in vivo model of lipopolysaccharide (LPS)- induced SIRS to clarify the biochemical mechanisms activated in the early stages of SIRS. Extracellular dopamine was collected from the amygdala of free moving rats via microdialysis and then analyzed by high-performance liquid chromatography. In addition, emotional changes were assessed with the open field and sucrose preference tests. In the LPS group, dopamine release in the amygdala increased remarkably immediately after LPS administration, peaking at 120 min. Thereafter, dopamine release temporarily decreased, but then significantly increased again after 180 min. The present results suggest that diffuse brain dysfunction in the early stages of SIRS may involve altered dopamine levels in the amygdala.

El síndrome de respuesta inflamatoria sistémica (SRIS) es una reacción potencialmente fatal a diversas formas de daño tisular e infecciones que causan injuria a varios órganos. Además, el cerebro se daña antes que otros órganos, lo que provoca una disfunción cerebral difusa. El síntoma clínico central del SIRS es el delirio y los cambios emocionales están involucrados en el desarrollo de la enfermedad. Aunque se sabe que la amígdala desempeña un papel importante, no se han dilucidado los mecanismos que subyacen a los cambios emocionales en las primeras etapas del SRIS. Por lo tanto, en el estudio se provocaron cambios en los niveles de dopamina en la amígdala utilizando un modelo in vivo de SRIS inducido por lipopolisacáridos (LPS) para dilucidar los mecanismos bioquímicos activados en las primeras etapas del SRIS. La dopamina extracelular se recogió de la amígdala de ratas en movimiento libre mediante microdiálisis y luego se analizó mediante cromatografía líquida de alta resolución. Además, se evaluaron los cambios emocionales con las pruebas de campo abierto y de preferencia de sacarosa. En el grupo de LPS, la liberación de dopamina en la amígdala aumentó de manera notable inmediatamente después de la administración de LPS, alcanzando un máximo a los 120 minutos. A partir de entonces, la liberación de dopamina disminuyó temporalmente, pero luego volvió a aumentar significativamente después de 180 min. Los resultadosactuales sugieren que la disfunción cerebral difusa en las primeras etapas del SIRS puede implicar niveles alterados de dopamina en la amígdala.

Relationship between scapular elevation exercises with different alignments and activity of the trapezius and levator scapulae muscles.

[Purpose] This study aimed to examine whether scapular elevation exercises in sitting positions with different alignments lead to contractions of the trapezius and levator scapulae muscles. [Participants and Methods] The participants were 25 males, measured in four sitting positions with different alignments. Spine alignment was assessed by measuring the head protrusion, upper thoracic spine tilt, and pelvic tilt angles. Upper limb alignment was evaluated using the scapula tilt angle, scapula rotation angle, and distance between scapular spinous processes. Scapular elevation exercises were measured, and the thickness of the trapezius and levator scapulae muscles were measured in resting and elevated positions, with changes in muscle thickness. [Results] The trapezius muscle thickness was greater in the sitting position with less thoracic spine tilt and scapula tilt angles. Conversely, the levator scapulae muscle thickness was greater in the sitting position with more thoracic spine tilt and scapula tilt angles. [Conclusion] Scapular elevation exercises induce separate contractions of the trapezius and levator scapulae muscles by modifying the alignment of the spine and upper limbs.

Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.

This study was to investigate the relationship between the levels of Angiopoietin-Like Protein 4 (ANGPTL4) and Silent Mating-type Information Regulation 2 Homolog 1 (SIRT1) and the stability of carotid atherosclerotic plaque. For this purpose, 108 patients with coronary heart disease in our hospital from Jan 2021 to May 2022 were selected as the coronary heart disease (CHD) group and 80 patients with the healthy examination as the control group. Patients' serum levels of ANGPTL4 and SIRT1 were collected, and their stability of carotid atherosclerotic plaque was determined by carotid ultrasound. According to their stability results, patients were divided into three subgroups: No plaque, Stable plaque, and Unstable plaque. The serum ANGPTL4 and SIRT1 levels were analyzed in different groups, and the correlation between their serum levels and the stability of carotid atherosclerotic plaque was analyzed by rank correlation. Results showed that the CHD group's serum ANGPTL4 and SIRT1 levels were lower, with statistical significance (P<0.05); A statistically significant difference in serum ANGPTL4 and SIRT1 levels were observed among patients with No plaques, Stable plaques, and Unstable plaques (P<0.05); A negative correlation was observed between serum levels of ANGPTL4 and SIRT1 and the stability of carotid atherosclerotic plaque (r=-0.438, -0.717, P<0.001); Serum ANGPTL4 and SIRT1 can be used as the evaluation method of carotid atherosclerotic plaque stability. When ANGPTL4 ≤ 30.17mg/L and SIRT1 ≤ 6.91µg/L, patients were more likely to develop unstable plaques; When ANGPTL4 ≤ 30.40mg/L and SIRT1 ≤ 6.87µg/L, patients were more likely to develop plaques (instability and/or stability). In conclusion, the serum levels of ANGPTL4 and SIRT1 in patients with CHD decreased. ANGPTL4 and SIRT1 will participate in the formation and development of carotid plaque, which can be used as a serological evaluation index to evaluate the occurrence and carotid atherosclerotic plaque's stability.

Pathophysiological consequences and treatment strategy of obstructive jaundice.

Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

Morphological Classification of the Sagittal Tendon Plate in the Soleus Muscle in Japanese Cadavers / Clasificación Morfológica de la Lámina Tendinosa Sagital del Músculo Sóleo en Cadáveres Japoneses

SUMMARY: The human soleus muscle has attracted attention in the fields of sport science, rehabilitation medicine, etc. for improving exercise performance in training, preventing injuries, and rehabilitation. The sagittal tendon plate of the soleus muscle is particularly important in rehabilitation. Few studies, however, have evaluated the shape of the sagittal tendon plate in the human soleus muscle in detail and attempted to classify its variations based on its morphology. In this study, we conducted a detailed analysis of the morphology of the sagittal tendon plates in soleus muscle specimens from Japanese cadavers and constructed a morphology-based classification system and evaluated their frequencies of occurrence. First, the specimens were divided into those with a sagittal tendon plate that was visible on the anterior surface (pennate muscle group) and those without (non-pennate muscle group). Next, based on the "number" and "breadth" of the sagittal tendon plates, the pennate muscle group specimens were further classified into four classes: Class I (one tendon, thin), Class II (one tendon, slightly broad), Class III (one tendon, very broad), and Class IV (two tendons, thin). Subsequently, the specimens were further divided into three types based on the position where the sagittal tendon plate joined the Achilles tendon: median tendon type, lateral tendon type, and medial tendon type (a total 13 divisions). When 458 Japanese soleus muscle specimens were classified into these divisions, the occurrence frequencies of Class I-IV were 80.57 %, 4.59 %, 5.46 %, and 1.09 %, respectively. In Class I, the median tendon type was more frequent than the lateral and medial tendon types, accounting for 48.47 % overall. The classification types of the sagittal tendon plate and their respective occurrence frequencies shown in this study are expected to serve as fundamental data in implementing rehabilitation of soleus muscle.

El músculo sóleo humano ha atraído la atención de la ciencia del deporte, la medicina de rehabilitación, etc. para mejorar el rendimiento del ejercicio en el entrenamiento, prevenir las lesiones y rehabilitación. La lámina tendinosa sagital del músculo sóleo es particularmente importante en la rehabilitación. Sin embargo, pocos estudios han evaluado en detalle la forma de la placa lámina sagital en el músculo sóleo humano y han intentado clasificar sus variaciones en función de su morfología. Realizamos un análisis detallado de la morfología de las láminas de los tendones sagitales en muestras de músculo sóleo de cadáveres japoneses y construimos un sistema de clasificación basado en la morfología y, además, evaluamos su frecuencia de aparición. Los especímenes se dividieron en aquellos con una lámina de tendón sagital que era visible en la superficie anterior (grupo muscular pennado) y aquellos sin (grupo muscular no pennado). A continuación, según el "número" y el "ancho" de las láminas de los tendones sagitales, las muestras del grupo de músculos pennados se clasificaron en cuatro clases: Clase I (un tendón, delgado), Clase II (un tendón, ligeramente ancho), Clase III (un tendón, muy ancho) y Clase IV (dos tendones delgados). Posteriormente, las muestras se dividieron en tres tipos, según la posición donde la lámina del tendón sagital se unía al tendón calcáneo: tipo de tendón mediano, tipo de tendón lateral y tipo de tendón medial (un total de 13 divisiones). En estas divisiones se clasificaron 458 especímenes de músculo sóleo de indiviuos japoneses, las frecuencias de ocurrencia de Clase I-IV fueron 80,57 %, 4,59 %, 5,46 % y 1,09 %, respectivamente. En la Clase I, el tipo de tendón mediano era más frecuente que los tipos de tendón lateral y medial, representando el 48,47 % del total. Se espera que los tipos de clasificación de la lámina del tendón sagital y sus respectivas frecuencias de aparición, que se reportan en este estudio, sirvan como datos fundamentales para implementar la rehabilitación del músculo sóleo.

Structural and CBCT analysis of mandibular canal microvessels expressing neurotransmitters in human cadavers.

PURPOSE: This study focused on the detailed structure of microvessels of the neurotransmitter-positive vasa nervorum of the inferior alveolar nerve, vein, and artery in the mandibular canal (MC) to obtain information for improved safety in dental treatments. We also observed the detailed structure of the MC from the mental foramen to the mandibular foramen using cone-beam computed tomography (CBCT). METHODS: In this study, mandibles from 45 sides of 23 human cadavers aged 76-104 years were examined by microscopy, immunohistochemistry, and CBCT analysis. These data were further evaluated by principal component analysis (PCA). RESULTS: The microvessels of the vasa nervorum with calcitonin gene-related peptide- and neuropeptide Y-positive reactions were classified into 5 types: large (4.19%, 28/667); irregular large (7.35%, 49/667), numerous intermediate (29.23%, 195/667), irregular intermediate (29.23%, 195/667), and scattered fine (30.0%, 200/667) microvessels. The MC showed various structures from the 3rd molar to the premolars and was also classified into three types, including complete (57.0%, 228/400), partial (33.8%, 135/400), and unclear (9.2%, 37/400), from the mandibular foramen to the mental foramen. PCA results revealed that developed capillaries were mainly localized in the molar region. CONCLUSIONS: Fine microvessels of the vasa nervorum expressing neurotransmitters are present from the molar to premolar region, which is key information for mandibular dental treatments. The different microvessel structures also indicate differences in specific characteristics between dentulous and edentulous cadavers regarding oral surgical and implant treatments.

Synovium and blood capillaries at the femoral attachment of anterior cruciate ligament are significantly abundant than those at the tibial attachment / Sinovial y capilares sanguíneos en la inserción femoral del ligamento cruzado anterior son significativamente más abundantes que los de la inserción tibial

SUMMARY: The anterior cruciate ligament (ACL) is a ligament that mainly controls the anterior and rotational mobility of the knee joint, and its surface is covered by a synovial membrane with large number of blood vessels. In general, nutritional supply to the ligament is from many capillaries in the adjacent synovium. However, statistical studies of the capillaries distributed to the ACL are insufficient. In this study, we examined cross-sectional histological images of the femoral attachment (femoral level), middle level of the tendon (middle level), and tibial attachment (tibial level) of the ACL and statistically analyzed blood capillary distribution among the three levels. The ACLs of 10 cadavers were divided into 5 equal sections, and 4mm-thick paraffin sections were made at the femoral level, middle level, and tibial level, and then hematoxylin-eosin (HE) staining were performed. The area of each transverse section was measured using Image-J 1.51n (U. S. National Institutes of Health, Bethesda, MD, USA). Fiber bundles of the ACL were relatively small and sparse in cross-sectional area at the femoral level and became larger and denser toward the tibial level. Many blood levels. The synovium at the attachment of ACL covered the surface of the fiber bundle and also penetrated deeply between the fiber bundles. In particular, the blood capillaries were densely distributed in the synovium at the femoral attachment rather than another two levels. Indeed, the number of capillaries were also most abundant in the femoral level. The cross-sectional ACL area at the femoral level is significantly small, however, the blood capillaries were most abundant. Therefore, when the ACL is injured, its reconstruction with preservation of the femoral ligamentous remnant may be clinically useful for remodeling of the grafted tendon.

El ligamento cruzado anterior (LCA) es un ligamento que controla principalmente la movilidad anterior y rotacional de la articulación de la rodilla, y su superficie está cubierta por una membrana sinovial con gran cantidad de vasos sanguíneos. En general, el suministro de nutrientes al ligamento proviene de muchos capilares en la sinovial adyacente. Sin embargo, los estudios estadísticos de los capilares distribuidos en el LCA son insuficientes. En este estudio, examinamos imágenes histológicas trans- versales de la inserción femoral (nivel femoral), el nivel medio del tendón (nivel medio) y la inserción tibial (nivel tibial) del LCA y analizamos estadísticamente la distribución de los capilares sanguíneos entre los tres niveles. Los LCA de 10 cadáveres se dividieron en 5 secciones iguales y se realizaron cortes en parafina de 4 µm de espesor a nivel femoral, medio y tibial, y luego se realizó tinción con hematoxilina-eosina (HE). El área de cada sección transversal se midió utilizando Image-J 1.51n (Institutos Nacionales de Salud de EE. UU., Bethesda, MD, EE. UU.). Los haces de fibras del LCA eran relativamente pequeños y escasos en el área de la sección transversal a nivel femoral y se hicieron más grandes y más densos hacia el nivel tibial. La membrana sinovial en la unión del LCA cubría la superficie del haz de fibras y también penetraba profundamente entre entre los haces de fibras. En particular, los capilares sanguíneos estaban densamente distribuidos en la unión femoral de la sinovial respecto a los otros dos niveles. De hecho, el número de capilares también fue más abundante a nivel femoral. El área transversal del LCA a nivel femoral era significativamente pequeña, sin embargo, los capilares sanguíneos fueron los más abundantes. Por lo tanto, cuando hay una lesión del LCA su reconstrucción con preservación del ligamento femoral remanente puede ser clínicamente útil para remodelar el tendón injertado.

The interrelationship between three-dimensional foot mobility and bodyweight bearing.

[Purpose] To clarify the three-dimensional nature of foot mobility and its interrelationships within the foot due to bodyweight bearing. [Participants and Methods] Data regarding left foot mobility due to body weight bearing were collected from 31 healthy adults. Foot shape differences while sitting and standing, and their interrelationship were examined. The same examiner reapplied the landmark stickers when misaligned during measurement position changes. [Results] The foot length, heel width, forefoot width, hallux valgus angle, and calcaneus eversion angle were significantly larger in the standing than in sitting position. The digitus minimus varus angle was significantly smaller in the standing than in sitting position. The medial and lateral malleoli, navicular, and dorsum of the foot were displaced medially and inferiorly; the other indices, except for the midfoot, were displaced anteriorly. The interrelationships within the foot showed a positive correlation between the calcaneus eversion angle and the medial displacement of the medial and lateral malleoli, navicular, and dorsum of the foot points. There was a negative correlation between the calcaneus eversion angle and inferior displacement of the medial malleolus, navicular, and dorsum of the foot. [Conclusion] The intra-foot coordination relationship in response to bodyweight bearing was clarified.

Relationship between the bilateral ratios of the thoracic shape and electromyographic activity of the thoracic and lumbar iliocostalis muscles during thoracic lateral translation.

[Purpose] This study aimed to determine the relationship between thoracic lateral deviation, the bilateral ratio of the thoracic shape, and the bilateral ratio of the thoracic and lumbar iliocostalis muscles during resting sitting and thoracic lateral translation. [Participants and Methods] We included 23 healthy adult males in the study. The measurement tasks were resting sitting and thoracic lateral translation relative to the pelvis. The thoracic lateral deviation and bilateral ratio of the upper and lower thoracic shapes were measured using three-dimensional motion capture. The bilateral ratio of the thoracic and lumbar iliocostalis muscles were measured using the surface electromyographic recording. [Results] The bilateral ratio of the lower thoracic shape was significantly positively correlated with the thoracic translation distance and the bilateral ratio of the thoracic and iliocostalis muscles. In addition, the bilateral ratio of the thoracic iliocostalis muscles was significantly negatively correlated with the bilateral ratios of the lower thoracic shape and lumbar iliocostalis muscles. [Conclusion] Our findings showed that the asymmetry of the lower thoracic shape is associated with left lateral deviation of the thorax at rest and thoracic translation distance. In addition, the thoracic and lumbar iliocostalis muscle activity differed between the left and right translations.

Expression of neurotransmitters, vasculogenesis markers and myosin heavy chain isoforms in the masseter muscle of senescence-accelerated mouse prone 8 mice.

BACKGROUND: Learning and memory deficits and pathologic changes in the hippocampus caused by toothlessness and soft diet feeding are related to reduced masseter muscle (MM) function. OBJECTIVE: Myosin heavy chain (MyHC) isoform expression in the MM also changes under different chewing conditions. The neurotransmitter calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor A (VEGF-A) are involved in MM formation. However, the relationship between CGRP, VEGF-A and MyHC isoforms in the MM in the senescence-accelerated mouse prone 8 (SAMP8) strain, a model of learning and memory deficits, remains unclear. METHODS: Changes in CGRP, VEGF-A, vasculogenesis marker and MyHC isoform mRNA expression in the MMs of ageing SAMP8 and senescence-accelerated mouse resistant 1 (SAMR1) mice was investigated through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. RESULTS: qRT-PCR revealed obviously high CGRP levels in the SAMP8 mouse MM (p < .001). MyHC-IId/x mRNA expression in the MM was higher in 24-week-old SAMP8 mice than 24-week-old SAMR1 mice (p < .001) but lower in slow-MyHC SAMP8 mice than SAMR1 mice (p < .001). CGRP mRNA was observed on the muscle fibres of the SAMP8 mouse MM but not the SAMR1 mouse MM through in situ hybridization. Principal component analysis (PCA) revealed strong positive contributions of SAMP8-MyHC-IId/x, SAMP8-CGRP, SAMR1-MyHC-emb, SAMR1-CGRP, SAMR1-VEGF-A, SAMR1-CD31, SAMP8-VEGF-A, and SAMP8-CD31 in the MM at 12 and 24 weeks. CONCLUSION: Calcitonin gene-related peptide is also key for the MyHC-IId/x and slow-MyHC patterns in the MMs of SAMP8 mice.

Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

Relationship between the thoracic asymmetry in standing position and the asymmetry of ankle moment in the frontal plane during gait.

[Purpose] We aimed to investigate the relationship of thoracic asymmetry in standing position with asymmetry of the internal ankle moment in the frontal plane during gait. [Participants and Methods] The following measurements were recorded in 22 healthy adult males using a 3D motion analyzer and force plates: thoracic lateral deviation, asymmetrical ratios of the upper and lower thoracic shape, internal ankle moment in the frontal plane, mediolateral deviations of the center of mass and center of pressure. [Results] In the standing position, the thorax was deviated to the left relative to the pelvis, and the upper and lower thoracic shapes were asymmetrical. During gait, significant lateralities were observed in the internal ankle moment in the frontal plane, mediolateral deviations of the center of mass and the center of pressure. Significant positive correlations were observed between the asymmetrical ratio of the lower thoracic shape and both the asymmetry of the internal ankle moment in the frontal plane and the mediolateral deviation of the center of pressure. [Conclusion] These results suggest that thoracic asymmetry is associated with mediolateral control of the ankle during gait.

Neonatal corticosterone administration increases p27-positive Sertoli cell number and decreases Sertoli cell number in the testes of mice at prepuberty.

Cortisol and corticosterone (CORT) are steroid, antistress hormones and one of the glucocorticoids in humans and animals, respectively. This study evaluated the effects of CORT administration on the male reproductive system in early life stages. CORT was subcutaneously injected at 0.36 (low-), 3.6 (middle-), and 36 (high-dosed) mg/kg body weight from postnatal day (PND) 1 to 10 in ICR mice. We observed a dose-dependent increase in serum CORT levels on PND 10, and serum testosterone levels were significantly increased only in high-dosed-CORT mice. Triiodothyronine levels were significantly higher in the low-dosed mice but lower in the middle- and high-dosed mice. However, testicular weights did not change significantly among the mice. Sertoli cell numbers were significantly reduced in low- and middle-dosed mice, whereas p27-positive Sertoli cell numbers increased in low- and middle-dosed mice. On PND 16, significant increases in testicular and relative testicular weights were observed in all-dosed-CORT mice. On PND 70, a significant decrease in testicular weight, Sertoli cell number, and spermatozoa count was observed. These results revealed that increased serum CORT levels in early life stages could induce p27 expression in Sertoli cells and terminate Sertoli cell proliferation, leading to decreased Sertoli cell number in mouse testes.

The mechanism of Yinchenhao decoction in treating obstructive-jaundice-induced liver injury based on Nrf2 signaling pathway.

BACKGROUND: Obstructive jaundice (OJ) is caused by bile excretion disorder after partial or complete bile duct obstruction. It may cause liver injury through various mechanisms. Traditional Chinese medicine (TCM) has a lot of advantages in treating OJ. The recovery of liver function can be accelerated by combining Chinese medicine treatment with existing clinical practice. Yinchenhao decoction (YCHD), a TCM formula, has been used to treat jaundice. Although much progress has been made in recent years in understanding the mechanism of YCHD in treating OJ-induced liver injury, it is still not clear. AIM: To investigate chemical components of YCHD that are effective in the treatment of OJ and predict the mechanism of YCHD. METHODS: The active components and putative targets of YCHD were predicted using a network pharmacology approach. Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes path enrichment analysis were carried out by cluster profile. We predicted the biological processes, possible targets, and associated signaling pathways that YCHD may involve in the treatment of OJ. Thirty male Sprague-Dawley rats were randomly divided into three groups, each consisting of 10 rats: the sham group (Group S), the OJ model group (Group M), and the YCHD-treated group (Group Y). The sham group only received laparotomy. The OJ model was established by ligating the common bile duct twice in Groups M and Y. For 1 wk, rats in Group Y were given a gavage of YCHD (3.6 mL/kg) twice daily, whereas rats in Groups S and M were given the same amount of physiological saline after intragastric administration daily. After 7 d, all rats were killed, and the liver and blood samples were collected for histopathological and biochemical examinations. Total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and aspartate transaminase (AST) levels in the blood samples were detected. The gene expression levels of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and the nucleus positive rate of NF-E2 related factor 2 (Nrf2) protein were measured. Western blot analyses were used to detect the protein and gene expression levels of Nrf2, Kelch-like ECH-associated protein 1, NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione-S-transferase (GST) in the liver tissues. One-way analysis of variance was used to evaluate the statistical differences using the statistical package for the social sciences 23.0 software. Intergroup comparisons were followed by the least significant difference test and Dunnett's test. RESULTS: The effects of YCHD on OJ involve biological processes such as DNA transcription factor binding, RNA polymerase II specific regulation, DNA binding transcriptional activator activity, and nuclear receptor activity. The protective effects of YCHD against OJ were closely related to 20 pathways, including the hepatitis-B, the mitogen-activated protein kinase, the phosphatidylinositol 3-kinase/protein kinase B, and tumor necrosis factor signaling pathways. YCHD alleviated the swelling and necrosis of hepatocytes. Following YCHD treatment, the serum levels of TBIL (176.39 ± 17.03 µmol/L vs 132.23 ± 13.88 µmol/L, P < 0.01), DBIL (141.41 ± 14.66 µmol/L vs 106.43 ± 10.88 µmol/L, P < 0.01), ALT (332.07 ± 34.34 U/L vs 269.97 ± 24.78 U/L, P < 0.05), and AST (411.44 ± 47.64 U/L vs 305.47 ± 29.36 U/L, P < 0.01) decreased. YCHD promoted the translocation of Nrf2 into the nucleus (12.78 ± 0.99 % vs 60.77 ± 1.90 %, P < 0.001). After YCHD treatment, we found a decrease in iNOS (0.30 ± 0.02 vs 0.20 ± 0.02, P < 0.001) and an increase in eNOS (0.18 ± 0.02 vs 0.32 ± 0.02, P < 0.001). Meanwhile, in OJ rats, YCHD increased the expressions of Nrf2 (0.57 ± 0.03 vs 1.18 ± 0.10, P < 0.001), NQO1 (0.13 ± 0.09 vs 1.19 ± 0.07, P < 0.001), and GST (0.12 ± 0.02 vs 0.50 ± 0.05, P < 0.001), implying that the potential mechanism of YCHD against OJ-induced liver injury was the upregulation of the Nrf2 signaling pathway. CONCLUSION: OJ-induced liver injury is associated with the Nrf2 signaling pathway. YCHD can reduce liver injury and oxidative damage by upregulating the Nrf2 pathway.

GIT1 is an untolerized autoantigen involved in immunologic disturbance of spermatogenesis.

Male haploid cells, spermatids and spermatozoa, that appear after the establishment of immune tolerance express novel cell surface and intracellular proteins that can be recognized as foreign antigens by the self-immune system. However, these germ cells do not normally evoke a pathological immune response. The immune-privileged micro-circumstance in testis involving the blood-testis-barrier formed by Sertoli cells protects these germ cells from autoimmune attack. We recently found that immunization with heat shock protein family A member 4-like (HSPA4L), one of the new differentiation antigens of haploid cells, induced experimental autoimmune orchitis (EAO) in A/J male mice. In this study, we focused on G protein-coupled receptor kinase interacting protein-1 (GIT1), another haploid cell-specific differentiation antigen, to investigate whether GIT1 is a target autoantigen for EAO induction. GIT1 emulsified with complete Freund's adjuvant was injected subcutaneously into the mice inguinal region once on day 0 and again on day 14, and the optimum condition of EAO induction was determined. Mice immunized with 200 µg GIT1 showed significantly higher incidence of EAO than that of immunization with other concentrations. In particular, significant lymphocytic inflammation and extensive aspermatogenesis were observed in these mice at 120 days after the first immunization. These findings indicate that GIT1 is also a target antigen that induces EAO, like HSPA4L.

Characteristic expression of CGRP and osteogenic and vasculogenic markers in the proximal and distal regions of the rib during male mouse development.

BACKGROUND: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis and osteogenesis during bone formation and organ development. From the foetal period to the postnatal period, the thorax, which is necessary for lung respiration, forms. The thorax exhibits the same cartilage ossification as the bones of the extremities, but a specific system within the thorax exists as costal cartilage after birth. The relationship among CGRP, osteogenesis and vasculogenic markers in the two rib locations during thorax formation is not fully understood. MATERIALS AND METHODS: In our study, male mice were used to provide ribs under different development conditions on various embryonic days (E12. 5, E14.5, and E17.5) and postnatal days (P1 and P5). The mRNA expression levels of CGRP, vascular endothelial growth factor (VEGF-A), type 1 collagen (Col1a-1), type 2 collagen (Col2a1), neuropeptide Y (NPY), osteocalcin (OCN) and osteopontin (OPN) were analysed by qRT-PCR. We also analysed the mRNA expression of CGRP, VEGF-A and OPN by in situ hybridization. Multivariate modelling with principal component analysis (PCA) was performed to estimate the interactions among the quantitative real-time RT-PCR data. RESULTS: The mRNA expression levels of CGRP, VEGF-A, Col2a, Col1a-1, OCN, and NPY in the male mouse rib gradually increased during development. An antisense probe for CGRP mRNA was strongly detected in the central region of the mouse rib at E12.5 and the hypertrophic and ossification zones at E17.5 by in situ hybridization. VEGF-A was also located in the same region as CGRP at E12.5 and E17.5. OPN was strongly detected at the rib formation stage from E14.5 to E17.5. The expression of CGRP also differed between the proximal and distal regions of the rib at E17.5. As demonstrated by in situ hybridization, CGRP continuously participates in cartilage formation in the distal regions of the rib after birth. The PCA revealed that the mRNA expression of CGRP was related to that of Col1a-1 and VEGF-A during rib formation. CONCLUSION: This study shows that CGRP is involved in vascular and bone formation during rib development and may also be involved in cartilage formation after birth. The findings suggest that CGRP may temporarily participate in bone formation and continuously participate in cartilage formation in the rib, which may also be related to the formation of the anterior thoracic wall after birth.

The choice of operation timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis: a retrospective clinical analysis.

BACKGROUND: This study aimed to evaluate the timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: Patients with acute moderate to severe cholecystitis treated by LC after PTGBD in the Department of Hepatobiliary and Pancreatic Surgery, Nankai Hospital (N-362) between January 2017 and August 2019were retrospectively enrolled into this study. According to the interval times from PTGBD to LC, the patients were divided into six groups, including group A (105 cases, within 1 week), group B (62 cases, 1-2 weeks), group C (34 cases, 3-4 weeks), group D (54 cases, 5-8 weeks), group E (24 cases, 9-12 weeks), and group F (83 cases, over 12 weeks). The gender, age, hospital stay, duration of operation, rate of conversion to laparotomy, incidence of complications, and hospitalization expenses of the six groups were evaluated and compared. RESULTS: Of the 362 cases of LC, 346 patients were operated successfully (95.6%), 10 were converted to laparotomy (2.8%), 16 had various complications (4.4%), and 2 died (0.6%). There were no significant differences between groups in the gender ratio, complication rate, and rate of conversion to laparotomy. The hospital stay and hospitalization expenses in group A were the least and significantly lower than those in other groups (P<0.01), and the duration of operation in group D was the longest and significantly higher than that in groups A, B, E, and F (P<0.05). CONCLUSIONS: For non-elderly patients diagnosed with acute moderate to severe cholecystitis with an anesthesia risk score [American Society of Anesthesiologists (ASA)] ≤2, LC is recommended to be performed within 1 week after PTGBD surgery. If delayed LC is performed within 2 to 8 weeks after PTGBD, the operation time will be longer due to inflammatory edema and fibrous adhesion of the gallbladder triangle. If PTGBD is performed for more than 2 months and the clinical circumstances are good, delayed LC can be considered to reduce the inconvenience of patients with a long-term catheter as much as possible.

Neonatal maternal separation increases the number of p27-positive Sertoli cells in prepuberty.

Neonatal maternal separation (NMS) is an experimental model for early life stress, which affects the growth and development of various organs, resulting in adverse health effects in humans and animals. In our previous study, we demonstrated that NMS [(0.5-, 1-, 2-h/day NMS, from postnatal day (PND) 1-10] induced morphological changes to the male reproductive system, including decreased Sertoli cell numbers in mouse testes at PND 70. To clarify the mechanism by which NMS decreases Sertoli cell numbers, we evaluated the effects of NMS on mouse testes at PNDs 10 and 16. At PND 10, the Sertoli cell number was not significantly different among experimental groups; however, it decreased in 0.5- and 2-h/day NMS mice at PND 16. The termination of Sertoli cell proliferation in prepuberty can be induced by p27, a cyclin-dependent kinase inhibitor. At PND 10, we observed an increase in the number of p27-positive Sertoli cells in 2-h/day NMS mice. The seminiferous tubule diameters decreased significantly in 1- and 2-h/day NMS mice, and the relative interstitial area increased in 2-h/day NMS mice. Serum corticosterone level significantly increased, and serum testosterone level significantly decreased in the 2-h/day NMS mice. At PND 16, the tubule diameters and height of seminiferous epithelium were significantly higher in 0.5- and 2-h/day NMS mice. Our results suggest that NMS disturbs serum corticosterone and testosterone levels and increases the number of p27-positive Sertoli cells at PND 10, resulting in a decrease in the number of Sertoli cells at PND 16.

Heat shock protein A4L is a potent autoantigen for testicular autoimmunity in mice.

Experimental autoimmune orchitis (EAO) may be used as a model to investigate immunological infertility in men. Murine EAO is induced via immunization with auto-immunogenic antigens (AIAgs) from testicular germ cells (TGCs). CD4 + T cells play a crucial role in EAO induction. However, whether AIAgs induce an immune response remains unclear. We aimed to identify self-antigens that induce EAO by screening a phage display library of random TGC peptides using IgG from EAO-induced A/J mice. Twenty TGC-specific AIAgs were detected, and G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) and heat shock protein A4L (HSPA4L) were identified as candidate AIAgs that induce EAO. Immunization with GIT1 or HSPA4L, emulsified in complete Freund's adjuvant, resulted in 66 % or 100 % incidence of EAO, respectively, indicating that HSPA4L is a most potent AIAg that induces EAO in mice. These findings may expectedly help improve the diagnostic procedures and treatment of immunological infertility in men.