[Mining of Differentially Expressed Genes in Diabetic Cardiomyopathy Based on GEO Database].

Objective To screen out the key genes leading to diabetic cardiomyopathy by analyzing the mRNA array associated with diabetic cardiomyopathy in the GEO database. Methods The online tool GEO2R of GEO was used to mine the differentially expressed genes (DEG) in the datasets GSE4745 and GSE5606.R was used to draw the volcano map of the DEG,and the Venn diagram was established online to identify the common DEG shared by the two datasets.The clusterProfile package in R was used for gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment of the DEG.GSEA was used for gene set enrichment analysis,and STRING for the construction of a protein-protein interaction network.The maximal clique centrality algorithm in the plug-in Cytohubba of Cytoscape was used to determine the top 10 key genes. The expression of key genes was studied in the primary cardiomyocytes of rats and compared between the normal control group and high glucose group. Results The expression of Pdk4,Ucp3,Hmgcs2,Asl6,and Slc2a4 was consistent with the array analysis results.The expression of Pdk4,Ucp3,and Hmgcs2 was up-regulated while that of Acsl6 and Slc2a4 was down-regulated in the cardiomyocytes stimulated by high glucose (25 mmol/L) for 72 h. Conclusion Pdk4,Ucp3,Hmgcs2,Asl6,and Slc2a4 may be associated with the occurrence and development of diabetic cardiomyopathy,and may serve as the potential biomarkers of diabetic cardiomyopathy.

Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFß1/MAPK signaling pathway.

BACKGROUND: Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis. METHODS: Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFß1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected. RESULTS: After Ang II stimulation, TGFß1, TGFß1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFß1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFß1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFß1/MAPK signaling pathway. CONCLUSIONS: This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFß1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.

Asymmetric Synthesis of Spiropyrazolones via Chiral Pd(0)/Ligand Complex-Catalyzed Formal [4+2] Cycloaddition of Vinyl Benzoxazinanones with Alkylidene Pyrazolones.

In the presence of the chiral Pd(0)/ligand complex, vinyl benzoxazinanones underwent the [4+2] cycloaddition with alkylidene pyrazolones smoothly and delivered spiropyrazolones in reasonable yields, diastereoselectivities, and eneantioselectivities (up to >99% yield, >99:1 dr and 99% ee). The absolute configuration of the obtained spiropyrazolones was unambiguously characterized with the use of X-ray single-crystal structure analysis. Moreover, the reaction mechanism was assumed to interpret the formation of the target compounds.

Isolated metastasis of mediastinal carcinoid to the left ventricle: A case report.

Carcinoid tumors are uncommon neuroendocrine tumors that produce high levels of serotonin and are mainly located in the gastrointestinal tract and bronchopulmonary system but very rarely in the mediastinum. These are slow-growing tumors that most commonly present metastatic lesions in the liver, followed by the bones, lungs, and peritoneum. Solid cardiac metastases from carcinoid tumors have seldom been reported. In this case report, we present a patient with a rare localized metastasis in the left ventricle with an antecedent history of resected carcinoid tumor of the anterior mediastinum.

Recurrent Talaromyces marneffei Infection Presenting with Intestinal Obstruction in a Patient with Systemic Lupus Erythematosus.

Talaromyces marneffei is an important opportunistic pathogen mainly afflicting the HIV-infected patients, in rare instance, it could cause infection in non-HIV-infected individuals. We report a 51-year-old Chinese woman who, with histories of SLE for 14 years and disseminated talaromycosis for 4 years, occurred partial intestinal obstruction that was demonstrated to be caused by Talaromyces marneffei infection. The randomly amplified polymorphic DNA results of paraffin-embedded tissues from both the present episode and the previous infection suggested that the present infection was a recurrent. The patient was performed excision of involved intestine and treated with oral itraconazole at a daily dose of 400 mg for 3 months, leading to an excellent response. However, she died with unknown reason more than a year later. We also reviewed the literature on Talaromyces marneffei infection associated with SLE as well as intestinal talaromycosis alone.

Simple and rapid UPLC-MS/MS method for quantification of entecavir in human plasma: Application to a bioequivalence study
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A simple and fast ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated to determine entecavir in human plasma with the stable isotopically labeled internal standard entecavir-13C215N. Samples (100 µL each) were pretreated by protein precipitation with methanol, and then separated on an ACQUITY UPLC BEH C18 analytical column (2.1 × 50 mm, 1.7 µm) with a simple isocratic elution. The detection was operated by a positive ionization electrospray mass spectrometry in multiple reaction monitoring mode. The method had a short chromatographic run time of 2 minutes, and obtained sharp peaks of entecavir and the internal standard. Good linearity was found within 0.1 - 20 ng/mL. The intra- and inter-day precision and accuracy met the acceptance criteria, and no matrix effect was observed. This method was successfully applied in a bioequivalence study of two kinds of entecavir tablets in healthy Chinese volunteers. And the results showed that no significant differences were found between the test and reference preparations in pharmacokinetic parameters (p > 0.05) by ANOVA. The 90% confidence intervals for the geometric mean ratios (test/reference) of Cmax, AUC0-tlast, and AUC0-∞ fell within the bioequivalence acceptance criteria (80 - 125%). No significant difference was found in tmax between the two preparations. The two one-sided t-tests showed that these two products were bioequivalent.
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Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors.

Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 µM, respectively). The structure-activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 µM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi-Sigma interaction and three Pi-Alkyl interactions.

Research progress in spasmodic torticollis rehabilitation treatment.

Spasmodic torticollis (ST) is a focal dystonia that affects adults, causing limited muscle control and impacting daily activities and quality of life. The etiology and curative methods for ST remain unclear. Botulinum toxin is widely used as a first-line treatment, but long-term usage can result in reduced tolerance and adverse effects. Rehabilitation therapy, with its minimal side effects and low potential for harm, holds significant clinical value. This article explores the effectiveness of adjunctive therapies, including exercise therapy, transcranial magnetic stimulation, shockwave therapy, neuromuscular electrical stimulation, vibration therapy, electromyographic biofeedback, and acupuncture, in the treatment of ST. The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.

Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation.

BACKGROUND: The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations. AIMS: We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation. PATIENTS/METHODS: This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events. RESULTS: The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months. CONCLUSIONS: Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

LDHA contributes to nicotine induced cardiac fibrosis through autophagy flux impairment.

Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.

Localized secondary erythromelalgia in an 11-year-old boy.

We report an 11-year-old boy with localized secondary erythromelalgia on his left medial thigh. The episodes responded well to indomethacin and prednisone but recurred after the medications were stopped. The disease was stable after being treated for 5 months.

Recalcitrant nodular scabies showing excellent response to tofacitinib: five case reports.

Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.

[Sulfur oxidation-reduction process and its coupling effects with other elements in marsh soil: A review]. / 湿地土壤硫氧化-è¿˜åŽŸè¿‡ç¨‹åŠå ¶ä¸Žå ¶ä»–å ƒç´ çš„è€¦åˆä½œç”¨ç ”ç©¶è¿›å±•.

Sulfur oxidation-reduction process (SORP) in marsh soil is an important link in sulfur cycle, which plays an important role in maintaining the stability and health of marsh. We summarized the SORP in marsh soil and its influencing factors, and analyzed the research progress of its coupling effects with other elements. The influencing factors of SORP in marsh soil mainly involved biotic (plants, microorganisms, zoobenthos, human activities, etc.) and abiotic factors (physical factors such as temperature, moisture and particle size, and chemical factors such as pH, salinity, organic matter, etc.). Related research on the coupling effects of SORP and other elements in marsh soil mainly involved in biogenic elements such as carbon (C), nitrogen (N) and phosphorus (P), and metal elements such as iron (Fe) and manganese (Mn). Currently, the underlying mechanism of SORP was not deeply explored, the research on coupling effects was unbalance, and the ecological effects were insufficient. In the future, key functional microorganisms involved in SORP should be strengthened, the coupling mechanism between SORP and micro-elements should be enhanced, and the ecological effects produced by the coupling effects of SORP with other elements should be emphasized.

Auricular erythermalgia showing excellent response to itraconazole: a case report.

Erythermalgia, a rare painful disorder, is characterized by recurrent pain attacking, warmth, and erythema that mainly involves the distal extremities. Red ear syndrome shares similar clinical features of erythermalgia afflicting the external ear with unilateral/bilateral distribution. The treatments of both diseases are still difficult without controlled therapeutics available up to date. A 12-year-old boy was referred because of 3 years of recurrent attacking of painful erythema and warmth that involved the ears alone, the episodes occurred several times daily with duration of dozens of minutes to hours for each flare. The symptoms could be relieved by cold water and triggered by heat stimuli as well as exciting and movement, and showed mild response to gabapentin, celecoxib, and topical lidocaine compounds in combination, but moderate to blocking injection of botulinum toxin to nervus auricularis magnus. However, systemic itraconazole 200 mg daily resulted in an excellent response after 5-week treatment, leading to milder erythema, warmth and burning sensation, shorter duration, and fewer relapses. The treatment continued for 6 months and then itraconazole was decreased to 100 mg daily for another 6 months until it was stopped, with maintenance of good conditions. In 3 months of follow-up after the treatment ceased, the patient had only 7 to 8 attacks over 10 days presenting as tolerable erythema that lasted for less than 10 min and relieved spontaneously, with absence of warmth and no need of treatment. We considered the patient to be a variant of erythermalgia rather than a red ear syndrome. The results showed that erythermalgia might involve the ears alone and itraconazole might be a potential agent for its treatment.

[Structure and diversity of nirK-type denitrifying microbial community in marsh soils at different invasion stages of Spartina alterniflora in the Minjiang River estuary, China.] / é—½æ±Ÿæ²³å£äº’èŠ±ç±³è‰ä¸åŒå ¥ä¾µé˜¶æ®µæ¹¿åœ°åœŸå£¤nirKåž‹åç¡åŒ–å¾®ç”Ÿç‰©ç¾¤è½ç»“æž„åŠå¤šæ ·æ€§.

To explore the differences in structure and diversity of nirK-type denitrifying microbial community in marsh soils at different invasion stages of Spartina alterniflora, the mudflat (MF, before invasion) and the S. alterniflora marsh after seaward invasion for 1-2 years (SAN) and 6-7 years (SA) in Shanyutan of the Minjiang River estuary were investigated by high-through put sequencing method. Results showed that the seaward invasion of S. alterniflora reduced the richness and diversity of nirK-type denitrifying microbial community in marsh soils. The nirK-type denitrifying microbial community in soils at different invasion stages included Proteobacteria and Actinobacteria, with Proteobacteria as the dominant one. The seaward invasion of S. alterniflora greatly altered the composition of nirK-type denitrifying microbial community in marsh soils. The highest relative abundance of genus in soils from different invasion stages were Bradyrhizobium, Mesorhizobium and Alcaligenes, respectively. The seaward invasion of S. alterniflora increased the spatial heterogeneity of nirK-type denitrifying microbial community composition in marsh soils. In SAN plot, the enhancement of spatial heterogeneity was primarily due to higher environmental disturbances in plots and the increased spatial heterogeneity of environmental variables caused by the seaward invasion of S. alterniflora. The seaward invasion of S. alterniflora altered the physico-chemical properties (e.g., grain composition, pH and moisture) and N nutrient conditions (total N, NH4+-N and NO3--N) in marsh soils, which greatly altered the structure and diversity of nirK-type denitrifying microbial community. Our findings reveal the microbial mechanism of denitrification process in marsh soils during the seaward invasion of S. alterniflora.

[Analysis on rules of acupoint compatibility and application characteristics in acupuncture treatment of migraine based on complex network technique].

OBJECTIVE: To analyze the compatible rules of acupoints in the treatment of migraine with acupuncture and moxibustion based on complex network technique so as to provide a reference for composing best acupoint recipes. METHODS: Clinical papers about acupuncture treatment of migraine published from January of 2010 to October of 2020 were searched from Chinese and English databases including CNKI, Wanfang, VIP and Pubmed by using keywords of acupuncture, moxibustion and migraine. According to our inclusive and exclusive criteria, the collected papers were screened out to set up a database. The SPSS Modeler 18.0 software was used to analyze the association rules of acupoints, and the Gephi 0.9.2 software was used to conduct a complex network analysis about the compatibility rules of acupoints and their application characteristics of moxibustion and needling methods in the treatment of migraine. RESULTS: In the end, 572 articles meeting the conclusive criteria were selected, and a total of 1 091 acupoint prescriptions for the treatment of migraine were extracted, including 230 acupoints with a total appea-rance frequency of 7 902. Those acupoints most frequently used were mainly attributed to the Gallbladder Meridian, with Fengchi (GB20) being the highest in the cumulative frequency. The association rule analysis showed that the highest supporting degree acupoints was GB20-Taiyang(EX-HN5). The highest levels of confidence were EX-HN5-Touwei(ST8), GB20-Baihui(GV20), and GB20-ST8. The analysis of complex network topology showed that a total of 17 acupoints including GB20, EX-HN5, Shuaigu(GB8), Taichong(LR3), GV20, Ashi point, etc. were the core node acupoints for acupuncture treatment of migraine. CONCLUSION: In the treatment of migraine, the acupoints selected are mainly distributed in the head region. When the specific acupoints chosen, the five Shu acupoints, Yuan (source) acupoints and the confluent acupoints of eight meridians are frequently used. In terms of composing acupoint recipes, the acupoints in the local and distant part of the body are often used in combination. These outcomes may have a certain guiding significance for clinical treatment of migraine.

[Analysis on clinical application characteristics of acupuncture and moxibustion in the treatment of Meniere's disease based on topology model by complex network].

OBJECTIVE: To analyze the application characteristics of acupuncture and moxibustion in clinical treatment of Meniere's disease by using complex network technology, so as to provide evidence for selecting acupoints, needling and moxibustion methods and treatment ideas. METHODS: Articles both in English and Chinese published from the inception of databases of CNKI, Wanfang VIP, Chinese biomedical literature database (SinoMed), PubMed, Embase, EBSCO (Academic Search Pre-mier), Web of Science and Ovid to April of 2021 were retrieved by using key words "acupuncture" or "moxibustion" or "acupuncture and moxibustion" and "Meniere disease" or "Meniere's syndrome" or "Ménières vertigo" or "otogenic vertigo" or "auditory vertigo", followed by screening the literature according to the inclusion and exclusion criteria and establishing a database of clinical li-terature about acupuncture treatment of Meniere's Disease with software Epidata 3.1. Then, the descriptive analysis was conducted first, followed by association rule analysis using SPSS Modeler 18.0, and complex network analysis using Gephi 0.9.2 software. RESULTS: A total of 232 articles were included, containing 152 acupoints [97 body acupoints as Baihui (GV20), Fengchi (GB20), Neiguan (PC6), etc., 28 otopoints as Ershenmen (MA-TF1), Shen (MA-SC), etc., 20 scalp points as Yunting Area, 7 extra-points as Sishencong (EX-HN1), Taiyang (EX-HN5), etc.] which were used to be a total frequency of 1 569. Descriptive analysis showed that the main meridians were the Governor Vessel, Stomach Meridian of Foot Yangming, Trienergizer Meridian of Hand Shaoyang, and Gallbladder Meridian of Foot Shaoyang. Acupuncture was the most commonly used therapy for Meniere's disease. The association analysis showed that the most relevant combination of acupoints was GV20 and GB20, GV20 and PC6, reflecting the principles of local acupoint selection and combination of local and distant acupoints. Finally, "K-core Analytic Hierarchy Process" and "Community Analysis" revealed that 3 core acupoint groups were most frequently used in clinical treatment of Meniere's disease, including 1) auricular acupoints, as MA-TF1, MA-SC, Neier(MA-L), Zhen(MA-AT) and Pizhixia(MA-AT1), 2) acupoints of the 14 meridians and extra-points, as Tinggong(SI19), Yifeng(TE17), GB20, 3) acupoints of the Shaoyang meri-dians of hand and foot, as Shuaigu (GB8), Tinghui (GB2), Zhongzhu (TE3), Ermen (TE21), etc. CONCLUSION: The principle of acupoint selection is mainly based on the combination of acupoints along the meridians and local areas, while paying attention to the coordination among the auricular points, scalp acupoints and extra-points, which may provide a reference for the clinical treatment and scientific research on acupuncture treatment of Meniere's disease.

Mycorrhizal response strategies of trifoliate orange under well-watered, salt stress, and waterlogging stress by regulating leaf aquaporin expression.

Aquaporins (AQPs) involved in water and small molecule transport respond to environmental stress, while it is not clear how arbuscular mycorrhizal fungi (AMF) regulate AQP expression. Here, we investigated the change in leaf water potential and expression level of four tonoplast intrinsic proteins (TIPs), six plasma membrane intrinsic proteins (PIPs), and four nodin-26 like intrinsic proteins (NIPs) genes in trifoliate orange (Poncirus trifoliata) inoculated with Funneliformis mosseae under well-watered (WW), salt stress (SS), and waterlogging stress (WS). Root AMF colonization and soil hyphal length collectively were reduced by SS and WS. Under WW, inoculation with AMF gave diverse responses of AQPs: six AQPs up-regulated, three AQPs down-regulated, and five AQPs did not change. Such up-regulation of more AQPs under mycorrhization and WW partly accelerated water absorption, thereby, maintaining higher leaf water potential. However, under SS, all the fourteen AQPs were dramatically induced by AMF inoculation, which improved water permeability of membranes and stimulated water transport of the host. Under WS, AMF colonization almost did not induce or even down-regulated these AQPs expressions with three exceptions (PtTIP2;2, PtPIP1;1, and PtNIP1;2), thus, no change in leaf water potential. As a result, mycorrhizal plants under flooding may have an escape mechanism to reduce water absorption. It is concluded that AMF had different strategies in response to environmental stresses (e.g. SS and WS) by regulating leaf AQP expression in the host (e.g. trifoliate orange).