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

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.
Humans ; NF-kappa B/metabolism* ; Microglia ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To conduct a preliminary study on joint injuries of anterior and calcaneal fibular ligaments of the lateral ankle joint, and to analyze mechanism of action of shaking and poking in treating ankle joint and biomechanical properties of ankle during the recovery of joint injuries. METHODS: CT scan was performed on a male volunteer with right ankle sprain. Mimics 10.0, Solidworks 2016, Hypermesh 12.0 and Abaqus 6.13 software were used to establish 3D nonlinear finite element analysis model of foot and ankle, and the validity of model was verified. Combined with clinical study, the finite element simulation analysis was carried out on the toe flexion, dorsiflexion, varus and valgus of ankle joint under different treatment periods by adjusting elastic modulus of ligament to simulate ligament injury. RESULTS: With the treatment of shake and prick and recovery of ligament injury, the maximum stress and area with large stress on tibial pitch and fibular joint surface gradually increased under the four working conditions, and the stress value of the maximum stress ligament gradually increased, and the stress of the anterior and calcaneal fibular ligament dispersed and transferred, and the axial force gradually decreased. CONCLUSION The finite element method was used to simulate the mechanical condition of the shaking and stamping technique, and the changes of the forces of the ligament and articular surface before and after treatment of anterior and calcaneal ligament combined injury of ankle talus were intuitively observed. The treatment effect was quantified, and could provid objective and scientific basis for clinical promotion and application of this technique.
Male ; Humans ; Ankle Joint ; Finite Element Analysis ; Ligaments, Articular ; Sprains and Strains/therapy* ; Ankle Injuries/therapy*

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.
Male ; Female ; Humans ; Middle Aged ; Aged ; Tibia/surgery* ; Osteoarthritis, Knee/surgery* ; Knee Joint/surgery* ; Treatment Outcome ; Osteotomy/methods* ; Pain, Postoperative ; Retrospective Studies