ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

BACKGROUND: Lung cancer has the highest mortality rate among all malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancers. Lobectomy and lymph node dissection are one of the most important treatment methods, and lymph node dissection, as an important part, has attracted much attention. And its mode and scope of dissection may affect postoperative complications, particularly the occurrence of chronic cough. The aim of this study is to investigate the effect of lymph node dissection on postoperative chronic cough in patients with NSCLC undergoing lobectomy, and to provide clinical evidence for optimizing surgical strategy and reducing postoperative chronic cough. METHODS: A retrospective analysis was conducted on the clinical data of 365 NSCLC patients who underwent lobectomy at the First Affiliated Hospital of University of Science and Technology of China from December 2020 to December 2023. The relationship between clinical characteristics and postoperative chronic cough was analyzed. The Chinese version of the Leicester Cough Questionnaire (LCQ-MC) scores were collected from the patients at 2 time points: 1 day before surgery and 8 weeks after surgery. Patients were divided according to lymph node dissection methods, to explore the relationship between lymph node dissection and chronic cough after lobectomy. Additionally, patients were divided into chronic cough and non-chronic cough groups based on the presence of postoperative chronic cough, to investigate whether perioperative data, lymph node dissection methods, and lymph node dissection regions were influencing factors. RESULTS: Patients undergoing lobectomy were more likely to have chronic cough after surgery in the systematic lymph node dissection group than in the lymph node sampling group (P<0.05). LCQ-MC scale evaluation showed that the psychological, physiological, social and total score of the patients in systematic lymph node dissection group were significantly lower than those in lymph node sampling group (P<0.05). Multivariate analysis showed that anesthesia time, operation site, lymph node dissection method, whether to perform upper mediastinal lymph node dissection, number of upper mediastinal lymph node dissection, whether to perform lower mediastinal lymph node dissection and total number of lymph node dissection were independent risk factors for postoperative chronic cough in NSCLC patients (P<0.05). CONCLUSIONS When NSCLC patients underwent lobectomy, lymph node sampling was associated with a significantly lower risk of chronic cough than systematic lymph node dissection. Dissecting lymph nodes in the upper and lower mediastinal regions and the number of lymph nodes dissected may increase the risk of postoperative cough and reduce the quality of life of patients after surgery.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Female ; Lung Neoplasms/surgery* ; Middle Aged ; Cough/etiology* ; Retrospective Studies ; Lymph Node Excision/methods* ; Aged ; Chronic Disease ; Postoperative Complications/etiology* ; Adult ; Lymph Nodes/surgery* ; Pneumonectomy/adverse effects* ; Chronic Cough

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

Background and objective Cough is one of the main complications after pulmonary surgery,which seriously affects the postoperative quality of life.Preserving the pulmonary branch of vagus nerve may reduce the incidence of postoperative cough.Therefore,the aim of this study was to investigate whether preserving the pulmonary branch of the vagus nerve could reduce the incidence of postoperative chronic cough in patients with stage I peripheral lung adenocarcinoma.Methods A total of 125 patients who underwent single-port thoracoscopic radical resection for lung cancer in the Depart-ment of Thoracic Surgery,The First Affiliated Hospital of University of Science and Technology of China from June 2022 to June 2023 were retrospectively selected,and divided into two groups according to whether the vagopulmonary branch was preserved during the operation,namely,the vagopulmonary branch group(n=61)and the traditional group(n=64).The general clinical data,perioperative conditions,lymph node dissection,Mandarin Chinese version of The Leicester Cough Questionnaire(LCQ-MC)scores before and 8 weeks after operation were recorded in the two groups.Both the two groups were divided into tamponade group and non-tamponade group according to whether autologous fat or gelatin sponge was tamponade after lymph node dissection.LCQ-MC scores and postoperative chronic cough of both groups were calculated.Results The LCQ-MC score of the traditional group was significantly lower than that of the vagopulmonary branch group in physiological,psychological,social and total scores at 8 weeks after surgery,and the difference was statistically significant(P<0.05).There were more cough patients in the traditional group than the vagopulmonary branch group at 8 weeks after surgery,with significant difference(P=0.006).Subgroup analysis was conducted separately for the vagopulmonary branch group and the traditional group.Among the patients in the vagopulmonary branch group and the traditional group,the LCQ-MC scores of the non-tamponade group 8 weeks after surgery were lower than those of the tamponade group(P<0.05).There were more patients with cough in the group 8 weeks after surgery than in the tamponade group(P=0.001,P=0.024).Conclusion For patients with stage I peripheral lung adenocarcinoma,the preservation of the pulmonary branch of vagus nerve is safe and effective,which can reduce the incidence of postoperative chronic cough and improve the postoperative quality of life of the patients.

Objective To investigate the feasibility, safety, and short-term efficacy of minimally invasive McKeown esophagectomy (MIME) in patients with locally advanced thoracic esophageal squamous cell carcinoma (TESCC) after neoadjuvant immunotherapy. Methods The clinical data of the patients with locally advanced TESCC in the First Affiliated Hospital of University of Science and Technology of China from July 2022 to March 2023 were restrospectively analyzed. They were divided into a neoadjuvant immunotherapy (NI) group and a non-neoadjuvant immunotherapy (NNI) group according to different preoperative neoadjuvant therapy. The perioperative clinical data and 3-month follow-up data were compared between the two groups. Results A total of 47 patients were collected, including 31 males and 16 females with a mean age of (67.57±7.64) years. There were 29 patients in the NI group and 18 patients in the NNI group. There were no statistical differences in baseline data, perioperative complications, short-term complications, surgical time, intraoperative bleeding, postoperative adjuvant therapy, metastasis/recurrence within 3 months, R0 resection rate, postoperative pathological staging decline, or College of American Pathologists (CAP) tumor regression grade between the two groups (P＞0.05). Conclusion Neoadjuvant immunotherapy combined with minimally invasive McKeown esophagectomy can be safely and effectively performed for patients with locally advanced TESCC without increasing operation time, intraoperative blood loss and perioperative complications.

Objective:To investigate the protective mechanism of TRPV4 channel inhibitor on blood-brain barrier(BBB)damage after traumatic brain injury(TBI).Methods:The TBI rat model was established.TRPV4 channel inhibitor HC067047 or PKC-δ inhibitor Rottlerin was used to detect changes in BBB permeability,neurological function score,and the expression of microvascular endothelial tight junction proteins ZO-1 and ZO-2 in brain injury areas after TBI.Results:Compared with the Sham group,BBB permeability significantly increased,brain neurological function score significantly decreased,and the expression of ZO-1 and ZO-2 significantly decreased in TBI group(P＜0.05).Compared with the TBI group,after administration of HC067047 or Rottlerin,changes in BBB permeability,brain neurological function score,the expression of ZO-1 and ZO-2 were partially reversed(P＜0.05).Conclusions:TBI-induced BBB injury may be mediated by TRPV4 channel regulating PKC-δ signaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δ signal molecule can partially alleviate BBB damage induced by TBI.This study may provide new ideas for the treatment of clinical TBI.

Objective The imaging findings of X-ray defecography(XRD)and magnetic resonance defecog-raphy(MRD)of patients with Solitary Rectal Ulcer syndrome(SRUS)were retrospectively analyzed to provide important information for clinical diagnosis and treatment.Methods 19 patients with SRUS confirmed by clinical,pathological and colonoscopy were included in this study.Among them,15 patients underwent XRD and 7 patients underwent MRD,and 3 patients underwent both XRD and MRD.Data of all enrolled patients were collected and pelvic floor function was measured.Results In the results of XRD,3 patients(20%)showed rectal intussusception.8 patients(53.3%)showed external rectal prolapse and 2 patients(13.3%)showed moderate rectocele.In addition,there were 2 patients of puborectal muscle hypertrophy,and 1 patient of bladder prolapse and uterine prolapse,respectively.For MRD,3 patients(42.9%)showed rectal mucosal prolapse(partial prolapse).At 4 patients(57.1%)with rectocele,3 patients(all female)had moderate rectocele,1 patient had mild rectocele.3 patients were also observed related anterior and middle compartment organ descent.2 patients of pubulorectal muscle hypertrophy,no sigmoidocoele.Conclusion Defecography can evaluate the structural and functional abnormalities of pelvic floor in SRUS patients,such as external rectal prolapse,rectal protrusion,rectal mucosal prolapse,and rectal intussusception,which has guiding significance for the treatment of SRUS patients.