Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

Objective To observe the effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism(MDRO)infection.Methods Patients who were detected MDRO in a hospital from January to December 2022 were selected as the research subjects.MDRO monitoring data and implementation status of prevention and control measures were collected.Fluorescence labeling assay was adopted to monitor the cleaning and disinfection effectiveness of the surrounding object surface of the bed units.Based on the bundled prevention and control measures as well as management mode of the pre-intervention group,the post-intervention group implemented enhanced rectification measures for the problems found by the pre-interven-tion group.Changes in relevant indicators between January-June 2022(before intervention)and July-December 2022(after intervention)were compared.Results There were 136 MDRO-infected patients in the pre-intervention group,208 MDRO strains were detected and 10 healthcare-associated infection(HAI)occurred.There were 128 MDRO-infected patients in the post-intervention group,198 MDRO strains were detected and 9 HAI occurred.Af-ter intervention,the total detection rates of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-re-sistant Acinetobacter baumannii(CRAB),and total MDRO from patients decreased significantly compared to before intervention(all P＜0.05).After intervention,the detection rates of MRSA,carbapenem-resistant Pseudomonas aeruginosa(CRPA),CRAB,and total MDRO from the surrounding object surface were all lower than those before intervention(all P＜0.05).The detection rate of MDRO from surrounding object surface before intervention was 34.52％,which showed a decreased trend after intervention(P＜0.05).The clearance rate of fluorescent labeled markers before intervention was 41.84％,which showed an upward trend after implementing intervention measures(from July to December),and increased to 85.00％at the end of intervention(November-December).The comp-liance rates of issuing isolation medical orders,placing isolation labels,using medical supplies exclusively,and cor-rectly handling medical waste after intervention have all increased compared to before intervention(all P＜0.05).Conclusion Adopting fluorescence labeling-based assay bundle intervention can effectively improve the effectiveness of MDRO infection prevention and control.

Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

OBJECTIVE: To explore clinical effect of arthroscopic modification of triangular fibrocartilage complex (TFCC) combined with oblique osteotomy shortening of distal ulna in treating ulna impact syndrome. METHODS: A retrospective analysis was performed on 49 patients with ulnar impingement syndrome admitted from 2017 to 2021, 3 patients were lost to follow-up, and 46 patients were finally included in study, including 23 males and 23 females, aged from 21 to 53 years old with an average of (36.5±3.3) years old. The patients were divided into TFCC group and control group according to different operation methods. Twenty-four patients in TFCC group, including 13 males and 11 females, aged from 21 to 53 years old with an average of (36.5±3.2) years old;10 patients on the left side and 14 patients on the right side;arthroscopic TFCC trimming combined with oblique osteotomy shortening of distal ulna was performed. Twenty-two patients in control group, including 10 males, 12 females, aged from 21 to 53 years old with an average of (36.5±3.3) years old;13 patients on the left side, 9 patients on the right side; oblique osteotomy of distal ulna was performed. Operative time, hospital stay, intraoperative bleeding and osteotomy healing time between two groups were observed and compared. Cooney wrist function score and visual analogue scale (VAS) were used to evaluate improvement of wrist function and pain before and 12 months after operation, respectively. The variation values of ulna and grip strength were compared. RESULTS: The follow-up time of TFCC group ranged from 12 to 21 months with an average of (15.10±2.67) months, and that of control group ranged from 12 to 20 months with an average of (15.06±2.81) months, there was no statistical significance between two groups (P>0.05). Operative time, osteotomy healing time, intraoperative bleeding and hospital stay in TFCC group were (68.51±13.50) min, (16.21±1.16) weeks, (25.13±4.22) ml and (7.35±1.20) d, respectively;while control group were (45.65±5.64) min, (17.46±2.06) weeks, (24.61±5.10) ml and (7.51±1.13) d, respectively; there were statistically significant differences in operative time and osteotomy healing time between two groups (P<0.05). There were no significant differences in intraoperative bleeding and hospital stay between two groups(P>0.05). There were no significant differences in total score and scores of Cooney wrist joint function between two groups before operation(P>0.05). Pain, functional status, range of motion, grip strength and Cooney wrist function score in TFCC group were higher than those in control group at 12 months after operation (P<0.05). According to Cooney wrist joint function score at 12 months after operation, 16 patients got excellent results, 6 good, and 2 fair in TFCC group; while 7 excellent, 11 good and 4 fair in control group;there was no significant difference between two groups (P>0.05). However, the proportion of wrist function recovery in TFCC group was higher than that in control group (P>0.05). At 12 months after operation, VAS of TFCC group (3.41±0.16) was lower than that of control group(3.52±0.13), P<0.005. There was no significant difference in ulnar variation between TFCC group and control group(P>0.05). The grip strength of TFCC group (93.6±10.1) % was better than that of control group (83.5±10.3) % (P<0.005). CONCLUSION Compared with oblique osteotomy shortening of distal ulna, TFCC trimming combined with oblique osteotomy shortening of distal ulna took longer to treat ulna collision syndrome, but the osteotomy healing time was shortened and wrist joint function was improved, especially pain, ulna variation, grip strength and motion were significantly improved.
Humans ; Male ; Female ; Adult ; Triangular Fibrocartilage/surgery* ; Osteotomy/methods* ; Ulna/surgery* ; Middle Aged ; Arthroscopy/methods* ; Retrospective Studies ; Young Adult

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

Objective: To investigate the role of platelet derived growth factor receptor alpha (PDGFRα) on bidirectional differentiation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells (Gli1+-MSC). Methods: Breeding double reporter transgenic mice ROSAmT/mG/Gli1-Cre^ERt2/PDGFRα^fl (Experimental group) and ROSA^mT/mG/Gli1-Cre^ERt2 (Control group), 20 mice in each of the two groups at four weeks of age were selected, MSC were isolated from the mouse aortic epithelium. After tamoxifen inducement, the two groups of Gli1⁺-MSC were screened by green fluorescent protein (GFP) labeling and flow cytometry sorting. PDGFRα was conditionally knocked out in the experimental group, and the control group Gli1⁺-MSC expressed PDGFRα normally. The two groups of Gli1⁺-MSC were subjected to adipogenic induction and fibrogenic induction, the Western blotting was performed to detect PDGFRα, adipocyte markers [perilipin and CCAAT/enhancer binding protein alpha (C/EBPα)] and fibrogenic markers [alpha smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1)] and semi-quantitative analysis was performed. The degree of cellular adipose differentiation after bidirectional induction of Gli1+-MSC in both groups was observed by oil red O staining and analyzed semi-quantitatively. Results: After tamoxifen induction, Gli1⁺-MSC could be accurately isolated from flow cytometry by GFP labeling. Via adipogenic differentiation, the expression of PDGFRα in the experimental group (0.017±0.002) was significantly lower than that in the control group (0.184±0.012) (t=25.48，P=0.002). The protein expressions of perilipin (3.138±0.414) and C/EBPα (3.565±0.289) were significantly higher than those in the control group (2.312±0.218 and 2.179±0.103, respectively) (t=6.21，P=0.025；t=6.69，P=0.022). Thus, the knock-out of PDGFRα enhanced the adipogenic differentiation ability of Gli1⁺-MSC. After fibrogenesis induction, the protein expressions of PDGFRα, α-SMA and FSP-1 in the experimental group (0.030±0.001, 0.932±0.177 and 0.276±0.020, respectively) were significantly lower than those in the control group (0.439±0.006, 1.352±0.170 and 0.835±0.097, respectively) (t=149.40, P<0.001; t=66.38,P<0.001; t=11.41,P<0.08). This suggested that the knock-out of PDGFRα significantly inhibited Gli1⁺-MSC differentiation toward fibroblasts. After bidirectional induction, significantly less adipocyte formation was seen in the control group and more in the experimental group. Quantitative analysis showed that the amount of oil red O staining in the experimental group (0.461±0.042) was significantly higher than that in the control group (0.017±0.007) after bidirectional induction (t=23.20, P<0.01). Conclusions: PDGFRα plays an important role in the regulation of bidirectional differentiation of vascular adventitial Gli1+-MSC.

Humans ; Anemia, Aplastic ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Immunophenotyping