ObjectiveTo investigate the effects of Chaihu Jia Longgu Mulitang（CJLM） on depression-like behaviors and neuroinflammation in rats subjected to social isolation combined with chronic unpredictable mild stress（CUMS）， and to explore the potential underlying mechanisms. MethodsSixty male SD rats were randomly divided into a normal group， a model group， and low-， medium-， and high-dose CJLM groups（2.89， 5.78， 11.56 g·kg^-1）， as well as a fluoxetine group（10 mg·kg^-1）. Except for the normal group， all other groups were subjected to social isolation combined with CUMS for 63 d. During the first 35 d， depression models were established only， and from day 36 onward， modeling and drug administration were conducted simultaneously for a total intervention period of 28 d. Depression-like behaviors were evaluated using the sucrose preference test， open-field test， and forced swimming test. Hematoxylin-eosin（HE） staining was performed to observe hippocampal histomorphology. Immunohistochemistry（IHC） was used to detect the expression levels of ionized calcium-binding adapter molecule 1（Iba1） and gasdermin D（GSDMD） proteins in the hippocampus. Western blot analysis was employed to determine the protein expression levels of adenosine 5′-monophosphate（AMP）-activated protein kinase（AMPK） and phosphorylated（p）-AMPK， silent information regulator 1（SIRT1）， nuclear factor-κB（NF-κB） and p-NF-κB， NOD-like receptor protein 3（NLRP3）， and Caspase-1 in the hippocampus. Real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-6， and IL-1β in the hippocampus. ResultsCompared with the normal group， the model group showed a decreased sucrose preference rate（P<0.01）， reduced total movement distance（P<0.01）， prolonged immobility time（P<0.01）， and decreased central zone residence time（P<0.01） in the open-field test， and increased immobility time in the forced swimming test（P<0.01）. Hippocampal neuronal structure was damaged. The contents of Iba1 and GSDMD in the hippocampus were significantly increased（P<0.01）. The protein expression levels of p-AMPK and SIRT1 in the hippocampus were significantly decreased（P<0.01）， whereas the protein expression levels of p-NF-κB， NLRP3， and Caspase-1 were significantly increased（P<0.01）. The mRNA expression levels of IL-1β， IL-6， and TNF-α in the hippocampus were significantly upregulated（P<0.01）. Compared with the model group， the low-， medium-， and high-dose CJLM groups and the fluoxetine group all were able to reverse depression-like behavioral changes， as evidenced by increased sucrose preference rate， increased total movement distance with shortened immobility time in the open-field test， prolonged central zone residence time， and reduced immobility time in the forced swimming test（P<0.05， P<0.01）. Meanwhile， hippocampal neuronal structural damage was alleviated. In the hippocampus， the expression levels of Iba1 and GSDMD were downregulated， the expression levels of p-AMPK and SIRT1 were upregulated， and the abnormal elevations of p-NF-κB， NLRP3， Caspase-1， as well as IL-1β， IL-6， and TNF-α mRNA were suppressed（P<0.05， P<0.01）. ConclusionCJLM can ameliorate depression-like behaviors in rats subjected to social isolation combined with CUMS and attenuate hippocampal neuroinflammation and pyroptosis， suggesting that its effects may be associated with the regulation of AMPK/SIRT1/NF-κB/NLRP3 signaling pathway.

Objective Using female mice to investigate the reparative effects of human umbilical cord mesenchymal stem cells on radiation-induced ovarian injury. Methods Mice were randomly divided into three groups: a blank control group, a radiation model group, and a cell therapy group. Mice in the radiation model group and the cell therapy group received a single whole-body irradiation of 5 Gy X-rays. Within 2 hours post-irradiation, mice in the cell therapy group underwent ovarian transplantation of UC-MSCs. On days 1, 7, and 14 post-irradiation, body weight was measured, ovarian index was calculated, histopathological changes in ovarian tissue were examined, serum levels of reproductive hormones (follicle-stimulating hormone, anti-Müllerian hormone, and estradiol) were determined, and the colonization of implanted UC-MSCs in the mice was observed. Results On days 1, 7, and 14 post-irradiation, both the cell therapy group and the radiation model group showed decreased body weight compared to the blank control group (P < 0.05). On day 1 post-irradiation compared to day 1 pre-irradiation within the same group, the radiation model group exhibited a greater decrease in body weight than the cell therapy group (P < 0.05). On days 1, 7, and 14 post-irradiation, the ovarian index decreased in both the radiation model group and the cell therapy group compared to the blank control group (P < 0.05). On days 7 and 14 post-irradiation, the ovarian index in the cell therapy group was significantly higher than that in the radiation model group (P < 0.05). Ovarian tissue in the radiation model group exhibited atrophy and a reduction in the number of follicles at all stages. In contrast, follicles in the cell therapy group were large and abundant. On days 1, 7, and 14 post-irradiation, serum follicle-stimulating hormone levels in the cell therapy group were lower than those in the radiation model group, while anti-Müllerian hormone and estradiol levels were higher than those in the radiation model group (P < 0.01). In vivo fluorescence imaging demonstrated that UC-MSCs successfully colonized the ovarian tissue on days 1, 7, and 14 after transplantation. Conclusion UC-MSCs exert a repair effect on radiation-induced ovarian injury in mice.

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective To determine the median effective dose(ED50)of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method.Methods This is a prospective clinical study.Pediatric patients scheduled for elective short surgery(surgery time≤1 h)under general anesthesia from January to July 2023 were selected.Inclusion criteria were age 1-6 years,an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale(PSAS)score≥3 points.Remimazolam was administered intravenously preoperatively,and its sedative effect was assessed.The modified Dixon sequential method was used to determine the ED50 of remimazolam,with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg.Sedation was considered successful(positive,included in positive group)if the child with sedation score≥2 points,preoperative PSAS score<3 points,and the mask acceptance score of 4 points during anesthesia induction.If any criterion was not met,sedation was considered failure(negative,included in negative group),and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage.The test was completed after 7 consecutive positive and negative turning points appeared alternately.Probabilistic unit regression analysis was used to determine the ED50,ED95 and the corresponding 95%confidence interval(CI)of remimazolam for preoperative sedation.Postoperative recovery time and adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting during anesthesia were recorded.Results A total of 23 pediatric patients were included,with 13 in positive group and 10 in negative group.There were no statistically significant differences in mean arterial pressure,pulse oxygen saturation or heart rate before and after sedation(P>0.05).Compared with negative group,positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia(P<0.05).There was no significant difference in sedation score and anesthesia awakening time between two groups(P>0.05).The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg(95%CI 0.033-0.065 mg/kg),and the ED95 was 0.077 mg/kg(95%CI 0.064-0.161 mg/kg).No adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting occurred during anesthesia in any of pediatric patients.Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg(95%CI 0.033-0.065 mg/kg).

Background::Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods::We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients’ survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3).Results::A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P <0.001) when compared with low circPRKCI expression in diverse human cancers. However, elevated circPRKCI expression was not associated with DFS (HR = 1.34, 95% CI: 0.93, 1.95, P = 0.121). Furthermore, the patient with a higher circPRKCI expression was prone to have a larger tumor size, advanced clinical stage, and lymph node metastasis, but it was not significantly correlated with age, gender, and distant metastasis. Conclusion::Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features, suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

By introducing the connotation of deductive teaching and analyzing the significance of early contact clinical course of "doctor-patient communication", the author reinterpreted the educational concept of deductive teaching combined with the characteristics of medical humanities, and reformed the early contact clinical course of "doctor-patient communication" by introducing deductive teaching method. Taking the early contact clinical course of "doctor-patient communication" of a medical university as an example, the teaching framework was designed to share experience from three aspects: teaching content, teaching process and teaching effect evaluation. At the same time, combined with the characteristics of the course and the needs of students, found out the problems encountered in the teaching process, and put forward constructive opinions and strategies, in order to provide theoretical and practical reference for the teaching of medical humanities course.

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.