ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

OBJECTIVES: With the accelerating aging of the population and the rising prevalence of chronic diseases, the number of patients with pressure injuries (PIs) has increased markedly, prolonging the period of disease-related care. Informal caregivers play a critical role in the daily care of patients with pressure injuries, and their care burden has become increasingly prominent. This study aims to investigate the current status and influencing factors of care burden among informal caregivers of patients with PIs, providing evidence for targeted intervention strategies. METHODS: A total of 170 informal caregivers of patients with PIs were selected by convenience sampling from the Third Xiangya Hospital of Central South University. General demographic and clinical data of both patients and caregivers were collected. The Zarit Caregiver Burden Inventory (ZBI), Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, General Self-Efficacy Scale (GSES), and Family Caregiver Task Inventory (FCTI) were used to assess caregiving burden, knowledge-attitude-practice level, self-efficacy, and caregiving ability, respectively. Pearson correlation analysis was conducted to evaluate relationships among ZBI, Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, GSES, and FCTI scores. Stepwise multiple linear regression analysis was used to identify factors influencing caregiving. RESULTS: Among the 170 patients with pressure injuries, the age was (65.52±15.88) years; 118 (69.41%) were male and 52 (30.59%) were female. The duration of PIs was less than 1 month in 108 (63.53%) cases and 1 to 6 months in 40 cases (23.53%). Stage II injuries were predominant (135 cases, 79.41%). A total of 193 pressure injury sites were recorded, most commonly located at the sacrococcygeal region (127 sites, 65.80%), followed by the head (3 sites, 1.55%), shoulder and back (9 sites, 4.66%), feet (24 sites, 12.44%), and other regions (30 sites, 15.55%). Informal caregivers were 48.82% aged 46 to 59 years, 54.71% female, 41.77% primarily spouses and 47.06% children of the patients, and 77.06% lived with the patients. Caregivers who received assistance from others or had higher family per-capita monthly income reported significantly lower caregiver burden scores than those without assistance or with lower income (all P<0.001). The total ZBI score was 50.89±14.95, indicating a moderate burden. The total scores of the Knowledge-Attitude-Practice Scale for Informal Caregivers, GSES, and FCTI were 50.61±7.22, 26.03±7.11, and 14.76±8.70, respectively. Pearson correlation analysis revealed that ZBI scores were correlated with scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs (r=-0.543, P<0.001), GSES scores (r=-0.545, P<0.001), and FCTI scores (r=0.800, P<0.001). The scores on Knowledge-Attitude-Practice Scale for Informal Caregivers of patients with PIs were correlated with GSES scores (r=0.500, P<0.001) and FCTI scores (r=-0.461, P<0.001); GSES scores was negatively correlated with FCTI scores (r=-0.415, P<0.001). Stepwise multiple linear regression analysis showed that assistance availability, family per-capita monthly income, total scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, total GSES score, and total FCTI score were the main influencing factors of caregiver burden, jointly explaining 79.38% of its variance. CONCLUSIONS The main factors influencing the caregiving burden of informal caregivers of patients with PIs include the availability of assistance, family per-capita monthly income, total score on the Knowledge-Attitude-Practice Scale for Informal Caregivers of PI patients, total score on the GSES, and total score on the FCTI. Developing targeted intervention strategies addressing these factors may help alleviate the caregiving burden among informal caregivers of patients with PIs.
Humans ; Caregivers/psychology* ; Pressure Ulcer/nursing* ; Female ; Male ; Middle Aged ; Cost of Illness ; Adult ; Aged ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; Self Efficacy ; Caregiver Burden ; China

Objective To explore the effect of mangiferin(MF)on pyroptosis in an amyotrophic lateral sclerosis(ALS)cell model by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Methods(1)Mouse NSC-34 cell lines transfected with hSOD1WT and hSOD1G93A plasmids were randomly divided into blank group,model group,MF(100 μmol/L)group,MF(200 μmol/L)group.MF was added into the culture plate for 24 hours.Cell viability was assessed using CCK-8 kit.Lactate dehydrogenase(LDH)release was measured using LDH cytotoxicity detection kit.Levels of inflammatory factors interleukin(IL)-1β and IL-18 in cell supernatant were determined by enzyme-linked immunosorbent assay(ELISA).The expression of Nrf2,HO-1,NADPH quinone oxidoreductase-1(NQO-1),NOD-like receptor protein 3(NLRP3),gasdermin D(GSDMD)-N and caspase-1 was detected by Western blotting.(2)Mouse hSOD1G93A NSC-34 cells were randomly divided into model group,MF(200 μmol/L)group,Nrf2-siRNA group and Nrf2-siRNA+MF(200 μmol/L)group.The cells were transiently transfected with Nrf2-siRNA using LipofectamineTM 3000.Western blotting was used to detect the protein expression levels of Nrf2,HO-1,NQO-1,NLRP3,caspase-1 and GSDMD-N.Results(1)The results of the CCK-8 assay showed that after the hSOD1G93A NSC-34 cells were treated with MF at concentrations of 300 μmol/L and below for 24 hours,the changes in cell viability were not significant(P>0.05).Compared with blank group,the release of LDH,the contents of IL-1β and IL-18 in the cell culture supernatant of model group were increased(P<0.001);the protein expression levels of Nrf2,HO-1,and NQO-1 were decreased(P<0.05 or P<0.01);the protein expression levels of NLRP3,caspase-1,and GSDMD-N were increased(P<0.05 or P<0.01 or P<0.001).Compared with model group,the release of LDH,the contents of IL-18 and IL-1β in the culture supernatant in MF(100 μmol/L)and MF(200 μmol/L)groups were decreased(P<0.001);the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.05 or P<0.001),and the expression levels of Nrf2,HO-1 and NQO-1 were increased(P<0.05 or P<0.01).(2)Compared with model group,the protein expession levels of Nrf2,NO-1 and NQO-1 were increased(P<0.05 or P<0.001)in MF(200 μmol/L)group,while the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.001);the protein expression levels of Nrf2 and HO-1 were decreased in Nrf2-siRNA group(P<0.01 or P<0.001),while the protein expression levels of NLRP3,caspase-1 and GSDMD-N were increased(P<0.001).Compared with Nrf2-siRNA group,the protein expression levels of Nrf2,HO-1 and NQO-1 in Nrf2-siRNA+MF(200 μmol/L)group were increased(P<0.01 or P<0.001),and the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.001).Conclusion MF can inhibit pyroptosis in the ALS cell model through Nrf2/HO-1 signaling pathway,playing a protective role.

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.