Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/ß-endorphin Signaling in the Spinal Cord of Rats.

The underlying pathogenesis of chronic inflammatory pain is greatly complex, but the relevant therapies are still unavailable. Development of effective candidates for chronic inflammatory pain is highly urgent. We previously identified that trifluoro-icaritin (ICTF) exhibited a significant therapeutic activity against complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, however, the precise mechanisms remain elusive. Here, the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis were used to determine the pain-related behaviors. The expression and co-localization of pain-related signaling molecules were detected by Western blot and immunofluorescence staining. Our results demonstrated that ICTF (3.0 mg/kg, i.p.) effectively attenuated mechanical allodynia, thermal hyperalgesia and improved motor dysfunction induced by CFA, and the molecular docking displayed that CB2 receptor may be the therapeutic target of ICTF. Furthermore, ICTF not only up-regulated the levels of CB2 receptor, IL-10, ß-endorphin and CD206, but also reduced the expression of P2Y12 receptor, NLRP3, ASC, Caspase-1, IL-1ß, CD11b, and iNOS in the spinal cord of CFA rats. Additionally, the immunofluorescence staining from the spinal cord showed that ICTF significantly increased the co-expression between the microglial marker Iba-1 and CB2 receptor, IL-10, ß-endorphin, respectively, but markedly decreased the co-localization between Iba-1 and P2Y12 receptor. Conversely, intrathecal administration of CB2 receptor antagonist AM630 dramatically reversed the inhibitory effects of ICTF on CFA-induced chronic inflammatory pain, leading to a promotion of pain hypersensitivity, abnormal gait parameters, microglial activation, and up-regulation of P2Y12 receptor and NLRP3 inflammasome, as well as the inhibition of CB2 receptor and IL-10/ß-endorphin cascade. Taken together, these findings highlighted that ICTF alleviated CFA-induced neuroinflammation by enhancing CB2 receptor-mediated IL-10/ß-endorphin signaling and suppressing microglial activation in the spinal cord, and uncovered that CB2 receptor may be exploited as a novel and promising target for ICTF treatment of chronic inflammatory pain.

Exercise Alleviates Cardiovascular Diseases by Improving Mitochondrial Homeostasis.

Engaging in regular exercise and physical activity contributes to delaying the onset of cardiovascular diseases (CVDs). However, the physiological mechanisms underlying the benefits of regular exercise or physical activity in CVDs remain unclear. The disruption of mitochondrial homeostasis is implicated in the pathological process of CVDs. Exercise training effectively delays the onset and progression of CVDs by significantly ameliorating the disruption of mitochondrial homeostasis. This includes improving mitochondrial biogenesis, increasing mitochondrial fusion, decreasing mitochondrial fission, promoting mitophagy, and mitigating mitochondrial morphology and function. This review provides a comprehensive overview of the benefits of physical exercise in the context of CVDs, establishing a connection between the disruption of mitochondrial homeostasis and the onset of these conditions. Through a detailed examination of the underlying molecular mechanisms within mitochondria, the study illuminates how exercise can provide innovative perspectives for future therapies for CVDs.

Investigating optimal compression approach following radial artery puncture: a retrospective study.

BACKGROUND: The method for compressing hemorrhagic sites after transradial access has been a topic of interest, yet definitive guidelines remain elusive. This study aims to address this gap by optimizing the mechanical compression hemostasis protocol after transradial access. METHODS: This retrospective analysis included 300 patients from the Department of Cerebrovascular Diseases, Shanghai Fourth People's Hospital affiliated to Tongji University, who underwent transradial access for cerebrovascular angiography. Following the procedure, patients received radial artery compression hemostasis using a balloon compressor. They were divided into group A (n=100, continuous deflation) and group B (n=200, intermittent deflation) according to different hemostasis methods. The incidence of bleeding at the puncture site and complications were compared between the two groups. RESULTS: The rate of bleeding at the puncture site was significantly lower in group B (20 out of 200 patients) compared to group A (20 out of 100 patients) (P=0.032). Similarly, the incidence of puncture site complications, such as edema, congestion, and wound infection was lower in group B (5 out of 200 patients) compared to group A (10 out of 100 patients) (P=0.006). CONCLUSION: Four hours of compression with intermittent deflation (group B) emerged as the optimal compression method after transradial access, demonstrating fewer complications at the patient's puncture site.

Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.

The metabolic network's primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body's metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

The Role of Exerkines in Obesity-Induced Disruption of Mitochondrial Homeostasis in Thermogenic Fat.

There is a notable correlation between mitochondrial homeostasis and metabolic disruption. In this review, we report that obesity-induced disruption of mitochondrial homeostasis adversely affects lipid metabolism, adipocyte differentiation, oxidative capacity, inflammation, insulin sensitivity, and thermogenesis in thermogenic fat. Elevating mitochondrial homeostasis in thermogenic fat emerges as a promising avenue for developing treatments for metabolic diseases, including enhanced mitochondrial function, mitophagy, mitochondrial uncoupling, and mitochondrial biogenesis. The exerkines (e.g., myokines, adipokines, batokines) released during exercise have the potential to ameliorate mitochondrial homeostasis, improve glucose and lipid metabolism, and stimulate fat browning and thermogenesis as a defense against obesity-associated metabolic diseases. This comprehensive review focuses on the manifold benefits of exercise-induced exerkines, particularly emphasizing their influence on mitochondrial homeostasis and fat thermogenesis in the context of metabolic disorders associated with obesity.

Synergistic effects of the bimetallic Ni-Fe systems and their application in the reductive amination of polyether polyols.

We report the synthesis of xNi-yFe/γ-Al2O3 catalysts which were applied to the reductive amination of polypropylene glycol (PPG) for the preparation of polyether amine (PEA). The catalysts were characterized by N2-sorption, X-ray diffraction, H2-temperature programmed reduction, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy to reveal the synergistic effect of the bimetallic Ni-Fe-loaded catalysts. It was found that in the reductive amination of PPG to PEA, the conversion and product selectivity of the reaction were closely related to the types of active centers of the catalyst. In particular, the surface Ni0 content increased by adding Fe as a promoter, with a maximum Ni0 content on the 15Ni-7.5Fe/Al2O3 catalyst, which also led to the highest conversion rate (>99%). In addition, no deactivation was observed after three cycles of reaction carried out by the catalyst.

Exercise Alleviates Aging of Adipose Tissue through Adipokine Regulation.

Adipose tissue undergoes changes with aging, leading to increased adiposity, inflammatory cell infiltration, reduced angiogenesis, heightened oxidative stress, and alterations in its metabolic function. Regular exercise has been recognized as a powerful intervention that can positively influence adipose tissue health and mitigate the effects of aging. However, the molecular mechanisms underlying the benefits of regular exercise on aging adipose tissue function remain poorly understood. Adipokines released through regular exercise play a potential role in mitigating adipose tissue aging, enhancing the metabolism of glucose and lipids, reducing inflammation and fibrosis, and promoting fat browning and thermogenesis. This review comprehensively summarizes the benefits of regular exercise in addressing the age-related decline in adipose tissue function. Utilizing relevant examples of this approach, we address the possibility of designing therapeutic interventions based on these molecular mechanisms.

Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction.

The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy, neurodegenerative diseases, cancer, obesity, diabetes, and fatty liver diseases. However, the molecular mechanisms of the benefits of exercise or physical activity on ageing and age-related disorders remain poorly understood. Mitochondrial dysfunction is implicated in the pathogenesis of ageing and age-related metabolic diseases. Mitochondrial health is an important mediator of cellular function. Therefore, exercise alleviates metabolic diseases in individuals with advancing ageing and age-related diseases by the remarkable promotion of mitochondrial biogenesis and function. Exerkines are identified as signaling moieties released in response to exercise. Exerkines released by exercise have potential roles in improving mitochondrial dysfunction in response to age-related disorders. This review comprehensive summarizes the benefits of exercise in metabolic diseases, linking mitochondrial dysfunction to the onset of age-related diseases. Using relevant examples utilizing this approach, the possibility of designing therapeutic interventions based on these molecular mechanisms is addressed.

Phosphorus-Doped directly interconnected networks of amorphous Metal-Organic framework nanowires for efficient methanol oxidation.

Developing high-performance and low-cost electrocatalysts toward methanol oxidation reaction (MOR) is essential for fuel cell applications. Herein, we report a defect engineering strategy integrating amorphization and phosphorization to construct directly interconnected networks of amorphous NiCo-based metal-organic framework nanowires (a-NiCo-MOFNWs) with phosphorus (P) doping. The resulting P-doped a-NiCo-MOFNWs (a-NiCo-MOFNWs-P) network displays superior MOR efficiency and long-term durability over 1000 cyclic voltammetry (CV) measurements. The special structure of directly interconnected networks and the synergistic effect between the amorphous MOFs and dispersed phosphorus species give rise to abundant exposed active sites, accelerated electron transport, and increased porosity for mass transfer, thus boosting the reaction kinetics of MOR. This work provides additional insights into the network assembly and structural evolution of one-dimensional (1D) MOFs, and also opens up new avenues for the design of highly reactive and robust non-precious metal-based electrocatalysts.

Multifunctional Mesoporous Carbonaceous Materials Enable the High Performance of Lithium-Sulfur Batteries.

Focusing on multifunctional mesoporous carbonaceous materials (MCMs) is one of the hot research topics due to increasing demand in the high-energy-density devices of lithium-sulfur (Li-S) batteries (2600 Wh kg-1). On the premise of applying MCMs as a porous framework to load elemental sulfur, to improve the electronic conductivity of the cathode, and to trap the in situ-formed electrolyte-soluble intermediates of lithium polysulfides (LiPSs), the commercialization of MCMs-based energy storage devices still needs to solve solid/solid and solid/liquid interfacial issues such as the chemical anchoring of the electrically insulating active substances, the sluggish redox kinetics of intermediate LiPSs, and so on. Through the permutation of multifunctional MCMs serving as the primary sulfur-loading carrier of the cathode, as the secondary surface-coating layers of the separator, the cathode, and the anode separately, this Perspective highlights research challenges to clarify a comprehensive high-performance mechanism of MCM-based Li-S batteries and provides new chemical insight for potential application purposes.

Trifluoro-icaritin ameliorates spared nerve injury-induced neuropathic pain by inhibiting microglial activation through α7nAChR-mediated blockade of BDNF/TrkB/KCC2 signaling in the spinal cord of rats.

Neuropathic pain is still a serious and unsolved health problem. Activation of α7 nicotinic acetylcholine receptor (α7nAChR) is known to modulate neuropathic pain by inhibiting microglial activation and BDNF/TrkB/KCC2 signaling. We previously identified that trifluoro-icaritin (ICTF) has an attenuated effect on spared nerve injury (SNI)-induced neuropathic pain, but its potential mechanisms remain unknown. Here, the pain-related behaviors were determined by paw withdrawal threshold (PWT), CatWalk gait analysis, rotarod test, open field test and elevated plus maze test. The expression of pain-related signal molecules was evaluated by Western blot and immunofluorescence staining. The results showed that ICTF (5.0 mg/kg, i.p.) successfully relieved SNI-induced mechanical allodynia and anxiety-like behavior, we subsequently found there existed either positive or negative correlation between mechanical allodynia and gait parameters or rotating speed following ICTF treatment. Moreover, ICTF not only enhanced the expression of spinal α7nAChR, KCC2, CD206 and IL-10, but also decreased the levels of spinal BDNF, TrkB, CD11b, Iba-1, CD40 and IL-1ß in SNI rats. Conversely, α7nAChR antagonist α-Bgtx (I.T.) effectively reversed the inhibitory effects of ICTF on SNI rats, resulting in a remarkable improvement of mechanical allodynia, activation of microglia. and suppression of α7nAChR-mediated BDNF/TrkB/KCC2 signaling. Additionally, exogenous BDNF (I.T.) dramatically abrogated both blockade of BDNF/TrkB/KCC2 cascade and alleviation of mechanical allodynia by ICTF treatment. Altogether, the study highlighted that ICTF could relieve SNI-induced neuropathic pain by suppressing microglial activation via α7nAChR-mediated inhibition of BDNF/TrkB/KCC2 signaling in the spinal cord, suggesting that ICTF may be served as a possible painkiller against neuropathic pain.

Clinical analysis of neuromyelitis optica spectrum disease with area postrema syndrome as the initial symptom.

OBJECTIVE: The objective of this study was to report and discuss clinical analysis, including the diagnosis and treatment of 4 cases of neuromyelitis optica spectrum disease (NMOSD) with area postrema syndrome (APS) as the first symptom. METHODS: Four patients with intractable nausea, vomiting, and confirmed NMOSD were included in the final analysis. All of these patients were initially misdiagnosed and mismanaged. RESULTS: Among the 4 patients, 3 were admitted to the department of gastroenterology at the onset of the disease, and 2 were not correctly diagnosed and treated promptly due to misdiagnosis. Therefore, their symptoms worsened, and they were transferred to Intensive Care Unit (ICU) for life support. No obvious early medulla lesions were found in one patient. One patient was treated with intravenous immunoglobulin, methylprednisolone, and plasma exchange, but there was no significant clinical improvement, after which the disease relapsed during the treatment with low-dose rituximab. CONCLUSION: The clinical manifestations of NMOSD are complex and diverse, and the initial symptoms, onset age of the patient, and magnetic resonance imaging (MRI) findings can influence the final diagnosis. Early identification of the APS and timely therapy can prevent visual and physical disabilities, even respiratory failure, coma, and cardiac arrest. Therefore, it is necessary to identify specific and sensitive serum and imaging markers for predicting the prognosis and recurrence of the disease.

RNA-Seq and Iso-Seq Reveal the Important Role of COMT and CCoAOMT Genes in Accumulation of Scopoletin in Noni (Morinda citrifolia).

Scopoletin, the main component of clinical drugs and the functional component of health products, is highly abundant in noni fruit (Morinda citrifolia). Multiple enzyme genes regulate scopoletin accumulation. In the present study, differentially expressed genes of noni were analyzed by RNA sequencing (RNA-Seq) and the full-length genes by isoform-sequencing (Iso-Seq) to find the critical genes in the scopoletin accumulation mechanism pathway. A total of 32,682 full-length nonchimeric reads (FLNC) were obtained, out of which 16,620 non-redundant transcripts were validated. Based on KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation and differential expression analysis, two differentially expressed genes, caffeic acid 3-O-methyltransferase (COMT) and caffeoyl-CoA O-methyltransferase (CCoAOMT), were found in the scopoletin accumulation pathway of noni. Real-time quantitative polymerase chain reaction (q-PCR), phylogenetic tree analysis, gene expression analysis, and the change in scopoletin content confirmed that these two proteins are important in this pathway. Based on these results, the current study supposed that COMT and CCoAOMT play a significant role in the accumulation of scopoletin in noni fruit, and COMT (gene number: gene 7446, gene 8422, and gene 6794) and CCoAOMT (gene number: gene 12,084) were more significant. These results provide the importance of COMT and CCoAOMT and a basis for further understanding the accumulation mechanism of scopoletin in noni.

3BDO Alleviates Seizures and Improves Cognitive Function by Regulating Autophagy in Pentylenetetrazol (PTZ)-Kindled Epileptic Mice Model.

3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO) is a mTOR agonist that inhibits autophagy. The main purpose of this study is to investigate the effects of 3BDO on seizure and cognitive function by autophagy regulation in pentylenetetrazol (PTZ)-kindled epileptic mice model. The PTZ-kindled epileptic mice model was used in study. The behavioral changes and electroencephalogram (EEG) of the mice in each group were observed. The cognitive functions were tested by Morris water maze test. The loss of hippocampal neurons was detected by hematoxylin-eosin (HE) staining and immunofluorescence analysis. Immunohistochemistry, western blot and q-PCR were employed to detect the expression of autophagy-related proteins and mTOR in the hippocampus and cortex. Less seizures, increased hippocampal neurons and reduced astrocytes of hippocampus were observed in the 3BDO-treated epileptic mice than in the PTZ-kindled epileptic mice. Morris water maze test results showed that 3BDO significantly improved the cognitive function of the PTZ-kindled epileptic mice. Western blot analyses and q-PCR revealed that 3BDO inhibited the expression of LC3, Beclin-1, Atg5, Atg7 and p-ULK1/ULK1, but increased that of p-mTOR/mTOR, p-P70S6K/P70S6K in the hippocampus and temporal lobe cortex of epileptic mice. Immunohistochemistry and immunofluorescence also showed 3BDO inhibited the LC3 expression and increased the mTOR expression in the hippocampus of epileptic mice. In addition, the autophagy activator EN6 reversed the decrease in the 3BDO-induced autophagy and aggravated the seizures and cognitive dysfunction in the epileptic mice. 3BDO regulates autophagy by activating the mTOR signaling pathway in PTZ-kindled epileptic mice model, thereby alleviating hippocampus neuronal loss and astrocytes proliferation, reducing seizures and effectively improving cognitive function. Therefore, 3BDO may have potential value in the treatment of epilepsy.

Multichalcogen-Integrated Cathodes for Novel Lithium-Chalcogenide Batteries in Ether and Ester Electrolytes.

Lithium-sulfur (Li-S) batteries and lithium-selenium (Li-Se) batteries that contain only one single active element have unique advantages and disadvantages. Inspired by ternary lithium batteries, multielement chalcogenide compounds with integrated advantages may improve upon the performance of lithium-chalcogenide batteries at the source. In this work, activated carbon (AC) with an Al2O3@SiO2 heterojunction is used as the carrier, and the performances and mechanisms of elemental substances (X/AC, X = S, Se, and Te) are studied in ether and ester electrolytes as the basis for preparing multielement chalcogenide composites (SST/AC, SST: S-Se-Te compound). In the ester electrolyte system, SST811/AC (where S/Se/Te = 8:1:1, molar ratio) exhibited the best cycling performance, and the capacity remained at 1024.9 mA h g-1 after 300 cycles. The characterization results revealed the mechanisms and sequences of the gradual liquid-phase reactions of SST/AC in ether electrolytes and the direct solid-phase reactions in ester electrolytes. The active elements in SST/AC fully demonstrated their own functions, enabling the effective construction of new lithium-chalcogenide battery systems. This work provides inspiration for the subsequent research of multielement lithium-chalcogenide batteries and paves the way for their application.

Ni nanocatalysts supported on MIL-53(Al) for DCPD hydrogenation.

Metal organic frameworks (MOFs) with many unique advantages have drawn wide attention in the field of catalysis. However, the poor structural stability of MOFs limits its application. Heat treatment for MOFs can enhance its electrical conductivity and structural stability, which helps to improve the catalytic performance. Ni nanoparticles supported on MIL-53(Al) were synthesized through different heat treatment temperature. Catalysts with uniform distribution of active nickel and rich mesoporous structure were obtained by adjusting the heat treatment temperature to 500 °C. The results show this catalyst has the best hydrogenation activity and stability. Under the reaction conditions of 60 °C and 2 h, the conversion rate of DCPD is 100%, and the selectivity of endo-THDCPD is higher than 95%. After five cycles, the catalyst also show excellent stability and high activity, the conversion rate of DCPD is still 100%.

Trifluoro-icaritin alleviates chronic inflammatory pain through α7nAChR-mediated suppression of HMGB1/NF-κB signaling in the spinal cord of rats.

Inflammatory pain is a chronic, persistent and serious disease that greatly impacts public health, which is often accompanied by allodynia, hyperalgesia, and spontaneous pain. It is evident that α7 nicotinic acetylcholine receptor (α7nAChR) plays a key role in cholinergic anti-inflammatory pathway and exhibits the inhibition of neuroinflammation in chronic pain. Trifluoro-icaritin (ICTF), a derivative of icaritin from the extract of a genus of Epimedium plant, is identified to possess profound anti-inflammatory activity. However, whether ICTF has anti-nociceptive effect on inflammatory pain and its potential mechanisms remain poorly elucidated. Intraperitoneal injection (i.p.) of ICTF to complete Freund's adjuvant (CFA)-induced inflammatory pain rats once daily for 21 consecutive days. Pain-related behaviors were evaluated with paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis. Expression of pain-related signaling molecules in the spinal cord were detected using qRT-PCR, western blot assay, and immunofluorescence staining. This results showed that ICTF (3.0 mg/kg, i.p.) effectively alleviated mechanical allodynia and thermal hyperalgesia not 0.3 and 1.0 mg/kg in CFA rats. Subsequently, we further observed that ICTF (3.0 mg/kg) dramatically decreased the mRNA and protein levels of HMGB1, NF-κB p65, and IL-1ß but markedly enhanced α7nAChR and IL-10 expression in the spinal cord of CFA rats, and Immunofluorescence staining also showed that ICTF (3.0 mg/kg) significantly increased the expression of α7nAChR and reduced IBA1 in the spinal cord of CFA rats, along with suppressing the alterations of gait parameters induced by CFA. Moreover, Intrathecal injection (i.t.) of α7nAChR antagonist alpha-bungarotoxin (α-Bgtx, 1.0 µg/kg) not only reversed the anti-nociceptive effect of ICTF on pain hypersensitivity, but also inhibited the down-regulation of HMGB1, NF-κB p65, and IL-1ß as well as the up-regulation of α7nAChR and IL-10 protein expression induced by ICTF treatment. Altogether, our results illustrate that ICTF enables to ameliorate CFA-induced inflammatory pain through α7nAChR-mediated inhibition of HMGB1/NF-κB signaling pathway in the spinal cord of rats, suggesting that ICTF may be exploited as a potential painkiller against chronic inflammatory pain.

HDAC9 in the Injury of Vascular Endothelial Cell Mediated by P38 MAPK Pathway.

Ischemic stroke caused by atherosclerosis (AS) poses a serious threat to human life expectancy and quality. With the development of genome-wide association studies, the association of histone deacetylase 9 (HDAC9) expression of atheromatous plaques with ischemic stroke in large arteries has been revealed, but the molecular mechanisms behind this phenomenon have not been elucidated. In this study, we explored the effect of HDAC9 on the P38 mitogen activated protein kinase (P38 MAPK), a classic cellular inflammation-related pathway, by knocking down HDAC9 in vascular endothelial cells with short hairpin RNA (shRNA) and found that HDAC9 may mediate oxidized low density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells by regulating the phosphorylation level of P38 MAPK to lead to AS. It can be seen that HDAC9 may be a target to control the formation of atherosclerotic plaques. In follow-up experiments, it was verified that sodium valproate (SVA), as a HDAC9 inhibitor, can indeed antagonize the inflammatory damage of vascular endothelial cells, as well as SB203580, which is a P38 MAPK inhibitor. It proves that SVA may be a potential drug for the prevention and treatment of ischemic stroke.

Severe Pneumonia Caused by Infection With Tropheryma whipplei Complicated With Acinetobacter baumannii Infection: A Case Report Involving a Young Woman.

Whipple's disease is a very rare systemic infectious disease, and very few cases have been reported. However, it can be fatal if not diagnosed and treated appropriately. The major clinical manifestations of this disease are usually digestive and nervous system symptoms. The majority of patients are male and between 40 and 50 years old. Although respiratory symptoms of this disease have rarely been reported, they pose a serious threat to the lives of the patients, especially when they progress to severe pneumonia. During admission to the hospital, Acinetobacter baumannii infection makes treatment more difficult. While most patients are middle-aged men, more attention should be given to the diagnosis and treatment of affected young women. To our knowledge, the case presented in the study is the first case of Tropheryma whipplei infection that resulted in severe pneumonia and was complicated by A. baumannii infection during treatment. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.

The Effect of Shaoyao Gancao Decoction on Sphincter of Oddi Dysfunction in Hypercholesterolemic Rabbits via Protecting the Enteric Nervous System-Interstitial Cells of Cajal-Smooth Muscle Cells Network.

OBJECTIVE: This study observes the morphological changes in the enteric nervous system (ENS) - interstitial cells of Cajal (ICC) - smooth muscle cells (SMC) network in sphincter of Oddi dysfunction (SOD) in hypercholesterolemic rabbits following treatment with Shaoyao Gancao decoction (SGD), as well as the apoptosis of the ICC. METHODS: In this study, 48 healthy adult New Zealand rabbits are randomly divided into three groups (n = 16 in each group): the control, the model, and the SGD treatment groups. The hypercholesterolemic rabbit model is established. Hematoxylin and eosin staining, transmission electron microscopy, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction are used to detect the morphological changes in the ENS-ICC-SMC network, the expression of apoptosis-related proteins in the ICC, and to observe the curative effect of SGD after treatment. RESULTS: Compared with the control group, the morphology and the ultrastructure of the SO are destroyed in the model group. In addition, the protein gene product 9.5 (PGP9.5), nitric oxide (NO), the SMCs, and the ICC all significantly decreased while substance P (SP) significantly increased. Compared with the model group, the SO morphology and ultrastructure are repaired in the SGD group. In addition, the PGP9.5, NO, the SMCs, and the ICC significantly increased while SP decreased. In addition, SGD may activate the stem cell factor (SCF)/c-Kit signaling pathway to treat SO dysfunction by up-regulating the expression of c-Kit and SCF. Similarly, this pathway restores SO by up-regulating the expression of Bcl2 and inhibiting cleaved caspase-3, Bax, and the tumor necrosis factor. CONCLUSION: Shaoyao Gancao decoction can promote the recovery of sphincter of Oddi dysfunction in hypercholesterolemic rabbits by protecting the ENS-ICC-SMC network.