Morphologic Changes of the Temporomandibular Joint in Pruzansky-Kaban Type IIa Hemifacial Microsomia Postmandibular Distraction Osteogenesis.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is a powerful tool for the correction of hemifacial microsomia (HFM). The temporomandibular joint (TMJ) is the focus of attention in the diagnosis and treatment of HFM. This observational retrospective cross-sectional study aimed to investigate morphologic changes in TMJ post-MDO in type IIa HFM. METHODS: We recruited 48 patients with unilateral type IIa HFM who had completed MDO and mandibular distractor extraction (MDE). Data relating to the length, distance, angle, and volume of the TMJ were measured on 3-dimension models created by the analysis of computed tomography data. Normality analysis was performed by using the Shapiro-Wilk test. Data were compared with the paired t test and Wilcoxon signed-ranks test. RESULTS: The spaces between the affected condyle and the affected glenoid fossa before MDO were all significantly larger than before MDE (P<0.05). The breadth of the affected glenoid fossa before MDO was significantly longer than before MDE (P<0.001). The height of the affected condyle before MDO was significantly longer than before MDE (P<0.001). The volume of the affected condyle before MDO was significantly larger than before MDE (P<0.001). The ratio between the volume of the affected condyle and unaffected condyle before MDO was 0.20±0.13. The ratio between the volume of the affected condyle before MDE and MDO was 0.65±0.32. The resorption rate of the affected condyle post-MDO was 0.35±0.32. CONCLUSION: Herein, we characterized anatomic changes of the TMJ in type- IIa HFM post-MDO. Condylar resorption and the compression of space between the condyle and the glenoid fossa on the affected side were 2 typical manifestations. Our findings enhanced the understanding of the application of MDO on HFM.

Three-Dimensional Measurement of the Temporomandibular Joint in Pruzansky-Kaban Type IIa Hemifacial Microsomia.

OBJECTIVE: This observational retrospective cross-sectional study aimed to investigate the morphological characteristics of the temporomandibular joint (TMJ) in type IIa hemifacial microsomia (HFM). METHODS: We recruited 88 patients with unilateral type IIa HFM. Data relating to the length, distance, and angle of the TMJ, were measured on 3-dimensional models created by the analysis of computed tomography data. Normality analysis was performed by using the Shapiro-Wilk test. Data were compared with the paired t test and Wilcoxon signed-rank test. RESULTS: The height, long axis, and short axis of the affected condyle were significantly shorter than the unaffected side ( P <0.001); the ratios were 0.41±0.15, 0.75±0.20, and 0.95±0.24, respectively. The spaces between the condyle and the glenoid fossa were significantly larger in affected TMJs ( P <0.001). The ratio between the ipsilateral and contralateral anterior space in the sagittal plane was 4.62±2.59; this was significantly different than the ratio of inner space (1.50±1.70), superior space (1.70±0.97), and lateral space (1.28±0.62) in the coronal plane ( P <0.001) and the ratio of superior space (1.43±1.05) and posterior space (1.47±0.98) in the sagittal plane ( P <0.001); there were no statistical differences between the 5 spaces ( P >0.05). The breadth and depth of the glenoid fossa were significantly shorter in affected TMJs ( P <0.001), the ratio of the breadth in the affected and unaffected glenoid fossa was between 0.5 and 1 and the depth of the affected glenoid fossa was almost half of that on the unaffected side. The ratio between the ipsilateral and contralateral height of the condyle was significantly different when compared with the length of the mandibular ramus ( P <0.001). The ratio between the ipsilateral height of the condyle and the length of the mandibular ramus was significantly different when compared with that of the contralateral side ( P <0.001). The height of the affected condyle were significantly different ( P =0.005) among different ages. CONCLUSIONS: We found that hypoplasia was more severe in terms of the height of the condyle than the long axis and short axis of the condyle. The degree of condyle deformity was more severe than the mandible. And the affected condyle still had growth potential in the vertical direction with age.

Cadaveric Study and Micro-Computed Tomography of the Anatomy of Palatine Aponeurosis and its Link to the Soft Palate Muscles and Pharyngeal Muscles.

OBJECTIVE: There have been few studies on the anatomy of palatine aponeurosis (PA). Herein, we elucidated the relationship between the PA and soft palate muscles and pharyngeal muscles. DESIGN: Two cadaveric specimens were dissected to observe the gross anatomy of the PA. Six cadaveric specimens were processed and scanned by micro-computed tomography to determine the elaborate anatomy. Images were exported to Mimics software to reconstruct a three-dimensional model. RESULTS: The PA covered the anterior (32.1%-38.8%) of the soft palate, extending from the tensor veli palatini (TVP) and connecting to 3 muscles: palatopharyngeus (PP), uvula muscle, and superior pharyngeal constrictor (SC). The SC and PP are attached to the PA on the medial side of the pterygoid hamulus. SC muscle fibers were attached to the hamulus, forming a distinct gap between the hamulus. Some muscle fibers of the PP and uvula originated from the PA. The PA extended from the TVP to the midline and the posterior edge of the hard palate. The PA was not uniformly distributed, which was complementary to the attached muscles in thickness. CONCLUSIONS: PA, as a flexible fibrous membrane, maintains the shape of the soft palate. It extends from the TVP and covers anteriorly about one-third of the soft palate. The PA provides a platform for the soft palate muscles and pharyngeal muscles, connecting to the PP, uvula muscle, and SC. These muscles are important for palatopharyngeal closure and middle-ear function. It is necessary to minimize the damage to the PA during surgical interventions.

Three-dimensional Anatomy of the Velopharyngeal Muscles in the Cleft Palate.

OBJECTIVE: We have used micro-computed tomography (CT) to elucidate the relationship between the muscle fibers in specimens with cleft palate. These findings could be useful for muscle reconstruction in cleft palate repair and to better understand cleft palate speech. DESIGN: Cadaveric anatomical study. PARTICIPANTS: This study included three specimens with cleft palate. INTERVENTION: The specimens were stained with phosphomolybdic acid and scanned by Micro-CT. MAIN OUTCOME MEASURE(S): The anatomy of the muscles. RESULTS: Using 2D projection images and 3D reconstruction models, subtle anatomical structures could be observed in the muscles. The attachment of the levator veli palatini (LVP) was not at the posterior edge of the hard palate or palatine aponeurosis (PA), but at the anterior 21.71-44.2% of the cleft edge. The palatopharyngeal (PP) was composed of two bundles: inferior and superior heads, which clasped the LVP. The uvularis was unevenly distributed, and located on both sides of the cleft edge, originating at the edge. The palatoglossus, superior constrictor of pharynx and anatomical structure around the pterygoid hamulus, were normal. The PA, PP and LVP were attached to the cleft edge from front to back, in that order. The position of the uvularis was not fixed. CONCLUSIONS: With the help of Micro-CT technology, detailed anatomical features and the relationship between muscles could be visualized. In the specimen with cleft palate, muscles in the soft palate were associated with the pharyngeal muscles, which formed the 3D "velopharyngeal muscles complex." These findings provide anatomical evidence for muscle reconstruction in cleft palate repair.

Micro-Computed Tomography-Based Three-Dimensional Anatomical Structure of the Region Around the Pterygoid Hamulus.

OBJECTIVE: Palatoplasty would involve the structures around the pterygoid hamulus. However, clinicians hold different opinions on the optimal approach for the muscles and palatine aponeurosis around the pterygoid hamulus. The absence of a consensus regarding this point can be attributed to the lack of investigations on the exact anatomy of this region. Therefore, we used micro-computed tomography to examine the anatomical structure of the region surrounding the pterygoid hamulus. DESIGN: Cadaveric specimens were stained with iodine-potassium iodide and scanned by micro-computed tomography to study the structures of the tissues, particularly the muscle fibers. We imported Digital Imaging and Communications in Medicine images to Mimics to reconstruct a 3-dimensional model and simplified the model. RESULTS: Three muscles were present around the pterygoid hamulus, namely the palatopharyngeus (PP), superior constrictor (SC), and tensor veli palatini (TVP). The hamulus connects these muscles as a key pivot. The TVP extended to the palatine aponeurosis, which bypassed the pterygoid hamulus, and linked the PP and SC. Some muscle fibers of the SC originated from the hamulus, the aponeurosis of which was wrapped around the hamulus. There was a distinct gap between the pterygoid hamulus and the palatine aponeurosis. This formed a pulley-like structure around the pterygoid hamulus. CONCLUSIONS: Transection or fracture of the palatine aponeurosis or pterygoid hamulus, respectively, may have detrimental effects on the muscles around the pterygoid hamulus, which play essential roles in the velopharyngeal function and middle ear ventilation. Currently, cleft palate repair has limited treatment options with proven successful outcomes.

Comprehensive analysis of aberrantly expressed profiles of messenger RNA in alcoholic liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is one of the major cause of morbidity and mortality of clinical liver disease worldwide. Until today, although many general therapies are carried out and several molecular targets have been proposed to act as the potential therapeutic targets, more accurate molecular targets and more effective therapeutic methods remain needed. MATERIAL AND METHODS: In the study, we analyze the differential expression genes (DEGs) between the patients with ALD and healthy controls. Gene Ontology enrichment and KEGG signaling pathway analysis are performed to identify the function of DEGs. Some significant molecules are proposed to act as the potential therapeutic targets for ALD. RNA data of 15 ALD tissues and 7 normal tissues for RNA expression analysis were obtained. DEGs in ALD samples compared with normal tissues identified through the limma R package and subjected to network analysis. RESULTS: As a result, we obtained a total of 274 DEGs that mainly involved in biological processes related to the angiogenesis, stress reaction, synthesis, and metabolism of organic acids. Network analysis obtained several genes with high network degree and fold change. Some significant molecules are proposed to act as the potential therapeutic targets for ALD. CONCLUSIONS: Our research identified some new progression-related genes of alcohol liver diseases, which could be regarded as the new targets for the early diagnosis and therapeutic management in ALD.

[Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway].

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

A new water-soluble phosphorus-dipyrromethene and phosphorus-azadipyrromethene dye: PODIPY/aza-PODIPY.

PODIPY and aza-PODIPY have been successfully prepared by the treatment of dipyrromethene and azadipyrromethene with POCl3 in the presence of Et3 N. The new PODIPY and aza-PODIPY dyes are found to have photophysical properties. PODIPY and aza-PODIPY are water-soluble, and aza-PODIPY is suited for labeling living Hep-2 cells for imaging assays in the near-infrared region. Molecular orbital calculations show that the increase in the HOMO-LUMO band gap for the lowest energy absorption bands is observed in the new phosphorus-containing aza-PODIPY, and the HOMO and LUMO energies of aza-PODIPY are found to be higher than those of aza-BODIPY.

Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway. METHODS: A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis. RESULTS: QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01). CONCLUSION: The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway.

Condylar resorption post mandibular distraction osteogenesis in craniofacial microsomia: A retrospective study.

The aim of this study was to investigate the characteristics of condylar resorption in craniofacial microsomia (CFM) patients following mandibular distraction osteogenesis (MDO). Patients with unilateral type-IIa and type-IIb CFM, who had completed MDO and mandibular distractor extraction (MDE), were recruited. The height and volume of the condyle were measured on three-dimension models created by the analysis of computed tomography (CT) data. Normality analysis was performed using the Shapiro-Wilk test. Data for the affected and unaffected sides were compared using the paired t-test or Wilcoxon signed-rank test. Data for both type-IIa and type-IIb CFM were compared using the independent-samples t-test or Mann-Whitney U test. The Pearson or Spearman correlation was used to determine the correlations of condylar resorption rate with related measurements. In total, 48 type-IIa and 48 type-IIb CFM patients were included. The condylar resorption rate in type-IIa CFM (0.35 ± 0.32) was significantly associated with the height of the condyle (r = 0.776, p < 0.001) and distraction distance (r = 0.447, p = 0.001), while the condylar resorption rate in type-IIb CFM (0.49 ± 0.46) was significantly associated with the height of the condyle (r = 0.924, p < 0.001). However, there was no significant difference in condylar resorption rate between type-IIa and type-IIb CFM (p = 0.075). In addition to occlusal changes, no other negative symptoms of the TMJ were observed with condylar resorption. Condylar resorption was evident in CFM patients following mandibular distraction osteogenesis, and the condylar resorption rate showed a relationship with distraction distance and condylar height.

Effect of WenXin KeLi on Improvement of Arrhythmia after Myocardial Infarction by Intervening PI3K-AKT-mTOR Autophagy Pathway.

Background: Myocardial infarction (MI) is an acute and serious cardiovascular disease. Arrhythmia after MI can lead to sudden cardiac death, which seriously affects the survival outcome of patients. WenXin KeLi is a Chinese patent medicine for the treatment of arrhythmia in a clinic, which can significantly improve symptoms of palpitation and play an important role in reducing the risk of arrhythmia after MI. In this study, we aimed to explore the pharmacological mechanism of WenXin KeLi in protecting the heart. Methods: The MI model was established by ligating the left coronary artery and the ventricular fibrillation threshold (VFT) was measured by electrical stimulation. The expression of connexin43 (CX43) and autophagy-related protein were measured by Western Blot, and correlation analysis was conducted to study the relationship between cardiac autophagy, CX43, and arrhythmia in rats after MI. The effects of WenXin KeLi on arrhythmia, cardiac structure, and function in MI rats were respectively observed by electrical stimulation, cardiac gross section, Masson staining, and cardiac ultrasound. The effects of WenXin KeLi on the expression of phosphoinositide 3 kinase-protein kinase B-mammalian targets of rapamycin (PI3K-AKT-mTOR) autophagy pathway and CX43 were observed by Western Blot. Results: After 4 weeks of MI, the VFT in the model group was significantly reduced, the expression levels of yeast ATG6 homolog (Beclin1), microtubule-associated protein 1A/1B-light chain 3 (LC3II/LC3I), and p-CX43 (S368) significantly increased, the expression of sequestosome-1(P62) and CX43 significantly decreased. LC3II/LC3I and Beclin1 expression were significantly negatively correlated with the VFT, and the expression of P62 and CX43 were significantly positively correlated with the VFT. LC3II/LC3I and Beclin1 expression were negatively correlated with CX43 expression, while P62 expression was positively correlated with CX43 expression. WenXin KeLi could significantly increase the VFT, reduce the deposition of collagen fibers, and increase the index levels of the left ventricular end-diastolic anterior wall (LVEDAW), interventricular septum end-diastolic (IVSED), left ventricular end-systolic anterior wall (LVESAW), interventricular septum end-systolic (IVSES), left ventricular end-diastolic posterior wall (LVEDPW), left ventricular end-systolic posterior wall (LVESPW), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduce the index levels of the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). WenXin KeLi could increase the expression of CX43, P62, AKT, p-PI3K, p-AKT (308), p-AKT (473), and p-mTOR and decrease the expression of LC3II/LC3I and Beclin1. Conclusion: WenXin KeLi can activate the PI3K-AKT-mTOR signaling pathway, improve cardiac autophagy and Cx43 expression in rats after MI, reduce the risk of arrhythmia after MI, and play a cardioprotective role.

Three-Dimensional Anatomy of the Palatopharyngeus and Its Relation to the Levator Veli Palatini Based on Micro-Computed Tomography.

BACKGROUND: Although multiple studies have been reported on the palatopharyngeus and levator veli palatini, their subtle anatomy and functions remain unclear. The authors elucidated the relationship between these muscles and their functional implications based on three-dimensional digital techniques. METHODS: Cadaveric specimens were stained with iodine-potassium iodide and scanned using micro-computed tomography. The muscle fibers were drawn on the exported Imaging and Communications in Medicine images to reconstruct a three-dimensional model and further simplified. RESULTS: In the soft palate, the palatopharyngeus was divided into three bundles. The largest inferior head was found to attach to the palatine aponeurosis, soft palate, and the hard palate on the oral side, which occupied approximately the anterior 28.4 to 36.2 percent of the soft palate in the midline. The superior head was thin and attached to the palatine aponeurosis and the surrounding mucosa on the nasal side. The posterior head was located posterior to the levator veli palatini with fibers attaching to the levator veli palatini and the median portion of the uvula. The levator veli palatini was clasped by the three heads of the palatopharyngeus. The fasciculi of the palatopharyngeus converged into a bundle of muscles at the pharynx and inserted into the lateral and posterior pharyngeal wall. CONCLUSIONS: The palatopharyngeus is the largest muscle that connects the soft palate and pharyngeal wall; it closely coordinates with the levator veli palatini to control levator veli palatini overlifting, narrow the velopharyngeal port with the help of the superior constrictor, and elevate the pharynx. The palatopharyngeus and levator veli palatini help each other in velopharyngeal closure through coordination from other muscles.

Wenxin Granules Regulate Endoplasmic Reticulum Stress Unfolded Protein Response and Improve Ventricular Remodeling on Rats with Myocardial Infarction.

Background. Arrhythmia after myocardial infarction is the leading cause of death in clinical heart disease. Increasing studies have shown that the response to endoplasmic reticulum (ER) stress (ERS) caused by myocardial infarction is related to prognosis and the development of arrhythmias. The unfolded protein response (UPR) could serve as an important regulatory signaling pathway following myocardial infarction. The traditional Chinese medicine Wenxin Granules improve arrhythmias following myocardial infarction, which may be related to ERS intervention and the activation of the UPR and apoptosis. We aimed to investigate the involvement of Wenxin Granules in the activation of the UPR and apoptosis following myocardial infarction. Left coronary artery ligation was established as a rat model of myocardial infarction. The rats were randomly divided into the model group, low-dose Wenxin Granule group, high-dose Wenxin Granule group, and metoprolol group. Rats with only wire insertion and no ligature were used as the sham group. Small animal ultrasound systems were used to detect changes in heart structure and function, and the electrical stimulation threshold for ventricular fibrillation was detected. The expression of glucose-regulated protein (GRP)78, activating transcription factor (ATF)6, X-box binding protein (XBP)1, protein kinase-like ER kinase (PERK), phosphorylated (p)-PERK, Bax, Bcl2, C/EBP homologous protein (CHOP), caspase 12, caspase 8, and caspase 3 were detected by western blot, and terminal deoxynucleotidyl transferase dUTP Nick end labeling (TUNEL) was used to determine the cardiomyocyte apoptosis index. Compared with the sham group, rats in the model group displayed immediate ST-segment elevation and pathological Q waves after 24 hours. After 2 weeks, the left ventricular (LV) anterior wall thickness (LVAW) became thinner, and the inner diameter (LVID) increased. The end-diastolic LVAW (LVAWd), end-systolic LVAW (LVAWs), ejection fraction (EF), and fractional shortening (FS) were significantly reduced (P < 0.01), whereas the LVIDd, LVIDs, diastolic LV volume (LV Vold), and systolic LV volume (LV Vols) significantly increased (P < 0.01). The ventricular fibrillation threshold decreased significantly (P < 0.01). ERS proteins GRP78, p-PERK, PERK, ATF6, and XBP1 and apoptotic proteins CHOP, Bax, caspase 12, caspase 8, and caspase 3 significantly increased (P < 0.01, P < 0.05), whereas Bcl-2 expression and the Bcl-2/Bax ratio decreased (P < 0.01). Compared with the sham group, LVAWd, LVAWs, FS, and Bcl-2 protein expression were significantly increased in the low-dose Wenxin Granule group (P < 0.01, P < 0.05), and p-PERK and ATF6 decreased (P < 0.01, P < 0.05). Compared with the sham group, LVAWd, LVAWs, EF, FS, and the ventricular fibrillation threshold significantly increased in the high-dose Wenxin Granule and metoprolol groups (P < 0.01, P < 0.05), whereas LVIDs, LV Vols, and ERS proteins were significantly decreased (P < 0.01, P < 0.05). CHOP, Bax, caspase 12, caspase 8, and caspase 3 protein expression decreased in the Wenxin Granule group (P < 0.01, P < 0.05), whereas Bcl-2 and the Bcl-2/Bax ratio increased (P < 0.01, P < 0.05). LVIDd and Bax decreased in the metoprolol group (P < 0.01, P < 0.05), and the Bcl-2/Bax ratio increased (P < 0.05). The cardiomyocyte apoptosis index values for the low- and high-dose Wenxin Granule and metoprolol groups were significantly reduced (P < 0.05). This study suggested that the UPR is an essential mechanism underlying pathological injury after myocardial infarction. Wenxin Granule treatment can improve ventricular remodeling and cardiac function and inhibit arrhythmia by preventing excessive ERS from activating the UPR and apoptosis.

Advances of Traditional Chinese Medicine Regulating Connexin43 in the Prevention and Treatment of Myocardial Infarction.

Gap junctions are the main form of interaction between cardiomyocytes, through which the electrochemical activities between cardiomyocytes can be synchronized to maintain the normal function of the heart. Connexins are the basis of gap junctions. Changes in the expression, structural changes (e.g., phosphorylation and dephosphorylation), and distribution of connexins can affect the normal electrophysiological activities of the heart. Myocardial infarction (MI) and concurrent arrhythmia, shock, or heart failure can endanger life. The structural and functional damage of connexin (Cx) 43 in cardiomyocytes is a central part of the pathological progression of MI and is one of the main pathological mechanisms of arrhythmia after MI. Therefore, increasing Cx43 expression has become one of the main measures to prevent MI. Also, intervention in Cx43 expression can improve the structural and electrical remodeling of the myocardium to improve MI prognosis. Here, research progress of Cx43 in MI and its prevention and treatment using Traditional Chinese Medicine formulations is reviewed.

Dynamic Changes in Brain Glucose Metabolism and Neuronal Structure in Rats with Heart Failure.

Patients with heart failure (HF) are more susceptible to cognitive impairment, but the mechanism is still unclear. This study aimed to observe the dynamic changes in brain glucose metabolism and neuronal structure in different stages of HF. An HF rat model was established by ligating the anterior descending branch of the left coronary artery. To simulate acute heart failure (AHF) and chronic heart failure (CHF) in the clinic, relevant laboratory indexes were detected 10 and 60 days after ligation. The results showed that the model rats had systolic HF. Cognitive function was not obviously impaired in 10-day rats with HF, while the memory and learning functions were significantly impaired in 60-day rats with HF. The brain glucose metabolism in 10-day rats compensatorily increased in the prefrontal cortex (PFC), medial PFC (mPFC), cingulate gyrus, and basal ganglia (BG). In contrast, the metabolism of 60-day rats reduced in the PFC and BG. Meanwhile, the neuronal structure slightly changed in 10-day rats with HF, but neuronal karyopyknosis, reduced Nissl bodies, and swollen organelles were found in 60-day rats with HF. In conclusion, brain glucose metabolism and neuronal structure showed a dynamic evolution. Rats with AHF were in a compensatory state for increased glucose metabolism and slight neuronal damage. As a result, no significant cognitive impairment was observed. However, rats with CHF had significantly decreased cerebral glucose metabolism and neuronal degeneration, contributing to the cognitive function after HF.

Chlorogenic acid induces apoptosis to inhibit inflammatory proliferation of IL-6-induced fibroblast-like synoviocytes through modulating the activation of JAK/STAT and NF-κB signaling pathways.

Chlorogenic acid (CGA) is the primary constituent of Caulis Lonicerae, a Chinese herb used for the treatment of rheumatoid arthritis (RA). The present study aimed to investigate whether CGA was able to inhibit the proliferation of the fibroblast-like synoviocyte cell line (RSC-364), stimulated by interleukin (IL)-6, through inducing apoptosis. Following incubation with IL-6 or IL-6 and CGA, the cellular proliferation of RSC-364 cells was detected by MTT assay. The ratio of apoptosed cells were detected by flow cytometry. Western blot analysis was performed to observe protein expression levels of key molecules involved in the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT) signaling pathway [phosphorylated (p)-STAT3, JAK1 and gp130] and the nuclear factor κB (NF-κB) signaling pathway [phosphorylated (p)-inhibitor of κB kinase subunit α/ß and NF-κB p50). It was revealed that CGA was able to inhibit the inflammatory proliferation of RSC-364 cells mediated by IL-6 through inducing apoptosis. CGA was also able to suppress the expression levels of key molecules in the JAK/STAT and NF-κB signaling pathways, and inhibit the activation of these signaling pathways in the inflammatory response through IL-6-mediated signaling, thereby resulting in the inhibition of the inflammatory proliferation of synoviocytes. The present results indicated that CGA may have potential as a novel therapeutic agent for inhibiting inflammatory hyperplasia of the synovium through inducing synoviocyte apoptosis in patients with RA.

Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model.

In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.