ABSTRACT
Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.
Subject(s)
Airway Remodeling , Asthma , Clarithromycin , Epithelial-Mesenchymal Transition , Kv1.3 Potassium Channel , Mice, Inbred BALB C , Ovalbumin , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Epithelial-Mesenchymal Transition/drug effects , Asthma/drug therapy , Asthma/metabolism , Asthma/chemically induced , Asthma/pathology , Ovalbumin/immunology , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Mice , Kv1.3 Potassium Channel/metabolism , Kv1.3 Potassium Channel/antagonists & inhibitors , Airway Remodeling/drug effects , Humans , Disease Models, Animal , Female , Ficusin/pharmacology , Ficusin/therapeutic use , Epithelial Cells/drug effectsABSTRACT
Severe asthma is a complex and heterogeneous chronic airway inflammatory disease. Current treatment strategies are increasingly focused on disease classification, facilitating the transition towards personalized medicine by integrating biomarkers and monoclonal antibodies for tailored therapeutic approaches. Several approved biological agents, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-4, anti-IL-5, and anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, have demonstrated significant efficacy in reducing asthma exacerbations, eosinophil counts, improving lung function, minimizing oral corticosteroid usage, and enhancing patients' quality of life. The utilization of these biological agents has brought about profound transformations in the management of severe asthma. This article provides a comprehensive review on biomarkers and biological agents for severe asthma while emphasizing the increasing importance of further research into its pathogenesis and novel treatment modalities.
Subject(s)
Asthma , Precision Medicine , Humans , Asthma/drug therapy , Asthma/immunology , Anti-Asthmatic Agents/therapeutic use , Biomarkers , Animals , Molecular Targeted Therapy , Antibodies, Monoclonal/therapeutic use , Cytokines/metabolism , Biological Therapy/methodsABSTRACT
Context: The early symptoms of embryo development arrest are not typical. There is currently no model tool available to predict embryo development arrest. Objective: To explore the influencing factors of embryo development arrest in early pregnancy and build a risk prediction model. Methods: From May 2019 to March 2023, 277 patients suspected of embryonic development arrest during the first ultrasound examination in the Department of Obstetrics and Gynecology of the Ninth Affiliated Hospital of Soochow University were retrospectively selected as the study subjects. They were divided into diapause group and non-diapause group according to the second ultrasound (review after 1-2 weeks) to diagnose whether embryo development arrest. Collect two sets of data for analysis, Screen out the influencing factors of early pregnancy embryo development arrest. The logistic regression model and random forest model were constructed respectively. Evaluate the predictive performance of two statistical models. Results: Out of 277 suspected cases of embryonic developmental arrest, 88 were ultimately confirmed. Older age (OR: 2.259, P = .017), higher ultrasonic blood flow resistance index (RI) (OR: 1.728, P = .038), higher ultrasonic gestational sac diameter/embryo head hip length ratio (MSD/CRL) (OR:1.919, P = .007), lower progesterone (OR: 0.562, P = .011), and lower pregnancy-associated protein A (PAPP-A) (OR: 0.495, P = .023). The low expression of vascular endothelial growth factor (VEGF) (OR: 0.618, P = .005) was the influencing factor of embryo development arrest in early pregnancy. Building a prediction model based on the above indicators, it was found through testing that the random forest model is superior to the logistic regression model in predicting the risk of embryo development arrest. Conclusion: A random forest model based on age, ultrasound RI, progesterone, PAPP-A, ultrasound MSD/CRL ratio, and VEGF index can help clinicians identify the risk of embryonic developmental arrest.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.
Subject(s)
Antitussive Agents , Communicable Diseases , Humans , Guinea Pigs , Animals , Swine , Antitussive Agents/pharmacology , Antitussive Agents/therapeutic use , Cough/drug therapy , Tryptases , RNA, Ribosomal, 16S , Inflammation Mediators , TRPV Cation ChannelsABSTRACT
BACKGROUND: The degree of psychological stress and the difficulty and efficacy of laparoscopic surgery differ in patients with pelvic abscesses after different durations of anti-infection treatment. AIM: To compare and analyse the effects of different durations of anti-infective therapy on patients' preoperative psychological stress level and the clinical efficacy of laparoscopic surgery in patients with pelvic abscesses to offer a reference for the selection of therapy plans. METHODS: A total of 100 patients with pelvic abscesses who were admitted to the Department of Gynecology of Suzhou Ninth Hospital affiliated to Soochow University (Suzhou Ninth People's Hospital) from January 2018 to December 2022 were retrospectively enrolled. According to the different durations of anti-infective therapy, they were divided into Group S (50 patients, received anti-infective therapy for 24-48 h) and Group L (50 patients, received anti-infective therapy for 48-96 h). Baseline data, state-trait anxiety score at admission and before surgery, self-rating anxiety scale (SAS) + self-rating depression scale (SDS) score, surgery time, adhesion grading score, intraoperative blood loss, presence or absence of intraoperative intestinal injury, ureteral injury or bladder injury, postoperative body temperature, length of hospital stay, and presence or absence of recurrence within 3 mo after surgery, chronic pelvic pain, incision infection, dysmenorrhea, menstrual disorder or intestinal obstruction were compared between the S group and the L group. RESULTS: There was no significant difference in the background data between the S group and the L group (P < 0.05). There was no significant difference in the state-trait anxiety score or SAS + SDS score between the S group and the L group on admission (P < 0.05). The state-trait anxiety score and SAS + SDS score of the S group were lower than those of Group L after receiving different durations of anti-infective therapy (P < 0.05). There was no significant difference in the incidence of intestinal, ureteral or bladder injury between the S group and the L group (P < 0.05). The surgery time of Group S was shorter than that of Group L, and the adhesion score and intraoperative blood loss volume were lower than those of Group L (P < 0.05). There was no significant difference in the incidence of incision infection, dysmenorrhea, menstrual disorder or intestinal obstruction between the S group and the L group (P < 0.05). The postoperative body temperature of Group S was lower than that of Group L (P < 0.05), and the hospital stay was shorter than that of Group L (P < 0.05). The incidences of recurrence and chronic pelvic pain within 3 mo after surgery were lower than that of Group L (P < 0.05). CONCLUSION: Twenty-four to forty-eight hours of anti-infective therapy is better than 48-96 h of anti-infective therapy for patients with pelvic abscesses because the degree of psychological stress is lower, which is more conducive to achieving better outcomes after laparoscopic surgery.
ABSTRACT
Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.
Subject(s)
Asthma , Extracellular Traps , Humans , Asthma/therapy , Histones , Health Care Costs , EosinophilsABSTRACT
BACKGROUND: Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery. METHODS: We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking. RESULT: Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate. CONCLUSION: For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Subject(s)
Endometriosis , Female , Humans , Endometriosis/drug therapy , Endometriosis/surgery , Danazol/therapeutic use , Gestrinone/therapeutic use , Leuprolide/therapeutic use , Mifepristone/therapeutic use , Network Meta-Analysis , Levonorgestrel/therapeutic useABSTRACT
RATIONALE: Ectopic twin gestation involving a complete hydatidiform mole (CHM) and coexisting embryo is an exceedingly rare occurrence. PATIENT CONCERNS: In this report, we present the case of a 22-year-old female (gravida2, para 1) who was in her 8th week of gestation and presented with abdominal pain. Due to the detection of active bleeding and a ruptured right fallopian tube, the patient underwent a salpingectomy on the right side. DIAGNOSIS: The patient was diagnosed with an ectopic twin gestation involving a CHM and coexisting embryo. INTERVENTIONS: The patient was treated with right-side salpingectomy. OUTCOMES: The operation was successful and her recuperation was satisfactory. LESSONS: In the management of ectopic pregnancy involving CHM, it is crucial to enhance the accuracy of preoperative diagnosis. Additionally, histopathological examination of the salpingectomy specimen and conceptus is definitely essential for accurate diagnosis and appropriate follow-up management of tubal pregnancies.
Subject(s)
Hydatidiform Mole , Pregnancy, Ectopic , Pregnancy, Tubal , Humans , Pregnancy , Female , Young Adult , Adult , Pregnancy, Twin , Pregnancy, Tubal/diagnosis , Pregnancy, Tubal/surgery , Pregnancy, Ectopic/surgery , Hydatidiform Mole/diagnosis , Hydatidiform Mole/surgery , Hydatidiform Mole/pathology , Fallopian Tubes/pathologyABSTRACT
Background: Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant Artemisia annua, which is often used to treating malaria. In vivo and in vitro studies suggested it may help decrease inflammation and attenuate airway remodeling in asthma. However, its underlying mechanism of action is not elucidated yet. Herein, an attempt is made to investigate the ART molecular mechanism in treating asthma. Methods: The BALB/c female mice sensitized via ovalbumin (OVA) have been utilized to establish the asthma model, followed by carrying out ART interventions. Lung inflammation scores by Haematoxylin and Eosin (H&E), goblet cell hyperplasia grade by Periodic Acid-Schiff (PAS), and collagen fibers deposition by Masson trichrome staining have been utilized for evaluating how ART affected asthma. RNA-sequencing (RNA-seq) analyses were performed to identify differentially expressed genes (DEGs). The DEGs were analyzed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Protein-Protein interaction (PPI) function analyses. Hub clusters were found by Cytoscape MCODE. Subsequently, Real-Time quantitative PCR (RT-qPCR) verified the mRNA expression profiles of DEGs. Finally, immunohistochemistry (IHC) and western blots have validated the relevant genes and potential pathways. Results: ART considerably attenuated inflammatory cell infiltration, mucus secretion, and collagen fibers deposition. KEGG pathway analysis revealed that the ART played a protective role via various pathways including the mitogen-activated protein kinase (MAPK) pathway as one of them. Moreover, ART could alleviate the overexpression of found in inflammatory zone 1(FIZZ1) as revealed by IHC and Western blot analyses. ART attenuated OVA-induced asthma by downregulating phosphorylated p38 MAPK. Conclusion: ART exerted a protective function in a multitarget and multi-pathway on asthma. FIZZ1 was a possible target for asthma airway remodeling. The MARK pathway was one of the key pathways by which ART protected against asthma.
ABSTRACT
This report describes a 17-year-old patient with ovarian granulosa cell tumor torsion, which is rare. The patient presented with lower abdominal pain for 1 day after defecation, accompanied by nausea and vomiting. Gynecological examination revealed a palpable mass of about 150 mm × 130 mm in the uterus. The mass had high surface tension, tight cysts, well-defined borders, and marked tenderness at its pedicle. Gynecological B-ultrasonography showed that the uterus was not compressed, and a mixed echo of about 152 mm × 112 mm was seen in the pelvic cavity. The initial diagnosis was ovarian tumor torsion. After explaining the condition to the patient's family, an emergent open resection of left ovarian tumor was performed. The postoperative pathology report indicated juvenile granulosa cell tumor. The patient's body temperature was normal, and there was no infection or thrombosis after operation.
ABSTRACT
This study aims to evaluate the effectiveness and safety of Suhuang Zhike Capsules in treating chronic obstructive pulmonary disease. The Chinese and English databases were searched(from the establishment to July 2021) for randomized controlled trials(RCTs) on the treatment of chronic obstructive pulmonary disease with Suhuang Zhike Capsules, yielding 130 articles and finally 12 eligible RCTs. The 12 RCTs enrolled a total of 1 159 patients(579 in experimental group, 580 in control group), with 728 males(62.8%) and 431 females(37.2%). Meta-analysis showed that the conventional western medicine combined with Suhuang Zhike Capsules increased clinical efficacy(OR=4.31, 95%CI[2.88, 6.46], Z=7.08, P<0.000 01), forced expiratory volume in one second(FEV1)(SMD=0.88, 95%CI[0.60, 1.16], Z=6.24, P<0.000 01), forced vital capacity(FVC)(SMD=0.96, 95%CI[0.38, 1.55], Z=3.22, P=0.001), forced vital capacity rate of one second(FEV1/FVC%)(SMD=0.85, 95%CI[0.51, 1.19], Z=4.92, P<0.000 01), and maximum voluntary ventilation(MVV)(SMD=0.61, 95%CI[0.39, 0.83], Z=5.40, P<0.000 01) compared with the conventional western medicine alone. The differences in residual volume/total lung capacity(RV/TLC)(SMD=-0.93, 95%CI[-3.38, 1.53], Z=0.74, P=0.46) and adverse reactions(OR=1.39, 95%CI[0.76, 2.56], Z=1.07, P=0.28) are insignificant. The study showed that the conventional western medicine combined with Suhuang Zhike Capsules could improve clinical efficacy and lung functions in the treatment of chronic obstructive pulmonary disease. In addition, the combination had been verified to be safe. However, in view of the uneven method quality, small sample size, and inconsistent outcome indicators of the included studies, higher-quality, multi-center, and large-sample RCTs are needed for further verification.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Capsules , Female , Forced Expiratory Volume , Humans , Lung , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory Function TestsABSTRACT
Background: There is currently no agreement on the optimal management of caesarean scar pregnancy. Caesarean scar pregnancy is currently categorised into two subtypes according to the site of implantation. This may consequently result in the difference in treatment options. However, the comparison of the success rate of each treatment option according to the subtypes has not been fully investigated. Methods: 71 patients who were treated by uterine curettage (D and C), or uterine artery embolization with curettage (UAE) or hysteroscopy in conjunction with laparoscopy between January 2016 and March 2020 were included. Data on maternal age, gestational sac age, the sac diameter, the interval between two pregnancies, the number of previous caesarean sections, amount of bleeding and ß-hCG levels were collected and analysed dependent on the subtypes. Results: There was no difference in the clinical parameters of the cases who received different options of treatment, as well as no difference in the clinical parameters between type 1 and type 2 caesarean scar pregnancy. The primary success rate for type 1 caesarean scar pregnancy by D and C, or UAE, or hysteroscopy in conjunction with laparoscopy was 95, or 100 or 100%, respectively. The primary success rate for type 2 caesarean scar pregnancy by D and C, or UAE, or hysteroscopy in conjunction with laparoscopy was 27, or 67, or 95% respectively. Conclusion: Our data demonstrates that hysteroscopy in conjunction with laparoscopy for type 2 caesarean scar pregnancy was the most successful compared to other options, but for type 1 caesarean scar pregnancy, D and C could be the cost-effective option.
ABSTRACT
AIM: To compare the effect of pituitrin local injection (PIT) and uterine artery embolization (UAE) as pretreatment before surgery during the management of cesarean scar pregnancy (CSP). METHODS: Forty-nine CSP patients diagnosed in our department of Suzhou Ninth People's Hospital from October 2017 to October 2019. All patients underwent hysteroscopy and negative pressure aspiration (for type I CSP) or laparoscopic wedge-resection (for type II and III CSP) following one of the preoperative treatments: PIT group (n = 26) and UAE group (n = 23). The baseline clinical data, intraoperative blood loss, blood transfusion rate, postoperative hospital stay, hospitalization expenses, postoperative pain, postoperative fever, postoperative serum ß-human chorionic gonadotropin (ß-hCG) level, and pregnancy outcome were reviewed and analyzed. RESULTS: There was no significant difference (p ≥ 0.05) between two groups in baseline characteristics including age, gravidity, previous cesarean section times, interval since last cesarean delivery, menolipsis time, maximum diameter of gestational sac or mass under ultrasound, fetal cardiac activity and preoperative ß-hCG level. There was no significant difference in blood loss, transfusion rate, and postoperative ß-hCG reduction percentage (p ≥ 0.05) either. The postoperative hospital stay, hospitalization expenses, postoperative pain, and postoperative fever rate in PIT group were significantly lower than those in UAE group (p < 0.05). Moreover, ß-hCG level of all patients turned negative 1 month after surgery successfully. CONCLUSIONS: PIT pretreatment seems to be a same effective, more economical, and with fewer side effects pretreatment method compared to traditional UAE pretreatment in the management of CSP.