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PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.
Sujets)
Rats , Animaux , Lésion pulmonaire/génétique , Capra/génétique , Kératine-4 , Analyse de profil d'expression de gènes , Expression des gènesRésumé
Objective To explore the international hotspots and frontiers of sports training in cardiovascular disease research and provide a reference for future research in China.Methods On September 5,2023,we retrieved the Web of Science Core Collection(WosCC)database,including studies on exercise training in cardiovascular disease between 2010 and 2022.Microsoft Excel 2019 was used to analyze the annual changes in the number of publications,and Cite Space was used to analyze the literature journals,authors,references,and keywords,etc.Results A total of 1 274 articles were included,and the number of publications gradually increased between 2010 and 2022.The research on exercise training in cardiovascular disease is receiving increasing attention from the international academic community,mainly focusing on the United States.However,there is a lack of cooperation among countries,institutions,and authors in this research field.Conclusions The research on exercise training in cardiovascular disease spans across other disciplines such as medicine,molecular biology,physical chemistry,and has a wide range of research fields.The hot keywords in this research field are exercise training,cardiac rehabilitation,and coronary heart disease,while future research directions are intervention,inflammatory response,resistance,and adults.
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Objective To observe the therapeutic effect and mechanism of Modified Banxia Shumi Decoction on p-chlorophenylalanine(PCPA)-induced insomnia model rats.Methods Forty-eight male SD rats were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Chinese medicine and the Diazepam group,with 8 rats in each group.For 7 consecutive days before modeling,rats in the Chinese medicine low-,medium-and high-dose groups were treated with Modified Banxia Shumi Decoction for prophylactic treatment.Except for the normal group,PCPA-induced insomnia rat model was established in all groups.After modeling on day 1,each group continued to be administered the corresponding drug for 7 days.Body mass was monitored,open-field behavioral tests were performed,serum levels of orexin A(OXA)and orexin B(OXB)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of hypothalamic orexin receptor 1(OX1R)was determined by immunohistochemistry,and hematoxylin-eosin(HE)staining was used to observe the pathologic changes in the hypothalamus of rats.Results(1)Before modeling,the growth trend of body mass of rats in each group was smooth,with no significant difference between groups;after modeling,except for the normal group,the growth rate of body mass of rats in each group slowed down or even declined;after 14 days of administration of Modified Banxia Shumi Decoction,the body mass of the Chinese medicine medium-dose group was significantly increased compared with that of the model group(P<0.01).(2)Compared with the normal group,the model group showed an increase in the total distance of activity in the open field,the distance of activity in the central region and the number of times of entering the central region(P<0.01),a significant increase in serum OXA and OXB contents(P<0.01),a significant increase in the expression of hypothalamic OX1R(P<0.01),and HE staining showed mild hyperplasia of the hypothalamic glial cells;compared with the model group,the total distance of activity in the open field,the distance of activity in the central region and the number of times entering the central region were reduced in the rats in the Chinese medicine medium-dose group and the Diazepam group(P<0.01),the levels of serum OXA and OXB were significantly reduced(P<0.01),the expression of hypothalamic OX1R was significantly reduced(P<0.01),and the HE staining showed that a large number of neurons with perineurial interspace enlarged and the local glial cell hyperplasia.Conclusion Modified Banxia Shumi Decoction can improve insomnia and reduce anxiety in rats by down-regulating the levels of OXA and OXB in serum and the expression of OX1R in the hypothalamus.
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Objective To compare the clinical efficacy of three different therapies,including transjugular intrahepatic portosystemic shunt(TIPS)treatment,endoscopic treatment and medication treatment,combined with transhepatic arterial chemoembolization(TACE)in treating primary liver cancer complicated by portal hypertension and upper gastrointestinal bleeding.Methods A total of 105 patients with primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,who were admitted to the No.980 Hospital of PLA Joint Logistics Support Forces of China to receive treatment between January 2014 and June 2020,were enrolled in this study.According to the therapeutic scheme,the patients were divided into TIPS+TACE group(TIPS group,n=25),endoscopy+TACE group(endoscopy group,n=30),and medication+TACE group(medication group,n=50).The clinical efficacy,recurrence rate of bleeding,incidence of hepatic encephalopathy,and survival rate were compared between each other among the three groups.Results The differences in the postoperative 6-month,12-month and 24-month recurrence rates of bleeding between each other among the three groups were statistically significant(all P<0.05).In TIPS group,the portal vein pressure decreased from preoperative(38.47±9.35)mmHg(1 mmHg=0.133 kPa)to postoperative(25.24±5.68)mmHg,the difference was statistically significant(P<0.05).After treatment,the hemoglobin level in the three groups showed varying degrees of elevation,which in the TIPS group and endoscopy group were better than that in the medication group,the differences were statistically significant(P<0.05).In all three groups,the differences in the recurrence rate of bleeding between postoperative 6-month value,12-month value and 24-month value were statistically significant(all P<0.05).The postoperative 6-month,12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P<0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group,and the differences were statistically significant(P<0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the endoscopy group were lower than those in the medication group(P<0.05),and the difference in the postoperative 6-month recurrence rate of bleeding between the two groups was not statistically significant(P>0.05).The postoperative 6-month and 12-month incidences of hepatic encephalopathy in the TIPS group were higher than those in the endoscopy group and the medication group,the differences were statistically significant(P<0.05),while the differences in the postoperative 6-month and 12-month incidences of hepatic encephalopathy between the endoscopy group and the medication group were not statistically significant(P>0.05),and the differences in the postoperative 24-month incidence of hepatic encephalopathy between each other among the three groups were not statistically significant(P>0.05).No statistically significant difference in the 6-month mortality existed between TIPS group and endoscopy group(P>0.05),and the 6-month mortality of both TIPS group and endoscopy group was remarkably lower than that of the medication group(P<0.05).The postoperative 12-month mortality and 24-month mortality in TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P<0.05),but the differences in the postoperative 12-month mortality and 24-month mortality between the endoscopy group and the medication group were not statistically significant(P>0.05).Conclusion For primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,TIPS combined with TACE can effectively control tumor progression and prolong survival.(J Intervent Radiol,2024,32:33-37)
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BACKGROUND:The type of graft selected during anterior cruciate ligament revision is considered one of the main factors affecting the postoperative outcome,but there are few reports on the comparison between different graft materials. OBJECTIVE:To explore the medium-to-long-term clinical efficacy after anterior cruciate ligament revision with autologous ligament,allogeneic ligament,and LARS artificial ligament. METHODS:A total of 67 patients with the first anterior cruciate ligament revision admitted to the Department of Joint and Sports Medicine,The Second Hospital of Tangshan from May 2011 to May 2020 were selected,including 41 males and 26 females,with a mean age of(45.83±7.39)years.They were divided into three groups according to different grafts used:autologous ligament group(n=24),allogeneic ligament group(n=22),and LARS artificial ligament group(n=21).Follow-up for more than 36 months after revision was performed to evaluate the effect of revision. RESULTS AND CONCLUSION:(1)International Knee Documentation Committee(IKDC)score,Lysholm knee score,and Tegner motor score 1 year after surgery and at the last follow-up in the three groups were higher than those before surgery(P<0.05).There were no significant differences in IKDC score,Lysholm knee score,and Tegner motor score among the three groups 1 year after surgery and the last follow-up(P>0.05).(2)The lateral differences of KT-1000 at 1 year after surgery and the last follow-up among the three groups were lower than those before surgery(P<0.05).The lateral difference of KT-1000 and the positive rate of the axial shift test in the last follow-up of the LARS artificial ligament group were higher than those in the autologous ligament group and allogeneic ligament group(P<0.05).(3)At the last follow-up,X-ray films showed no obvious enlargement of the reconstructed bone tunnel and no obvious failure of the graft fixation device.There was no obvious aggravation of osteoarthritis,but bone density decreased significantly in some elderly patients.(4)These findings suggest that anterior cruciate ligament revision with LARS artificial ligaments can obtain good initial stability,but with the extension of time,the stability of partial cases tends to decrease,even with reconstructed ligament failure.Both allogeneic and autogenous ligaments can obtain good clinical efficacy in anterior cruciate ligament revision.
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BACKGROUND:Dendritic cells exhibit extremely strong antigen phagocytic function in the immature stage,and they can demonstrate great advantages in immune tolerance,cancer immunotherapy,and other aspects.However,due to the extremely low content of immature dendritic cells in living organisms,its clinical and scientific applications are severely limited. OBJECTIVE:To study the extraction and identification of mature and immature dendritic cells from Lewis rat bone marrow. METHODS:Bone marrow precursor cells were isolated from the bone marrow of Lewis rats,and immature dendritic cells were induced by 20 ng/mL of granulocyte colony-stimulating factor and 10 ng/mL of interleukin-4 for 7 days,and then mature dendritic cells were induced by adding 1 μg/mL of lipopolysaccharide to immature dendritic cells for 2 days.The morphology of dendritic cells was observed using inverted fluorescence microscopy.The surface-specific molecules of mature and immature dendritic cells were identified by flow cytometry,and the secretion levels of supernatant interleukin-10,interleukin-12,and interleukin-17A in mature and immature dendritic cells were detected by ELISA.The response of mature and immature dendritic cells to T lymphocyte stimulation was measured by mixed lymphocyte reaction. RESULTS AND CONCLUSION:(1)The dendritic cells showed an obvious protrusion structure under an ordinary inverted fluorescence microscope.(2)Flow cytometry showed low expression of CD40,CD86,and other co-stimulatory molecules in immature dendritic cells.On the contrary,mature dendritic cells highly expressed the above co-stimulatory molecules.(3)The secretion of interleukin-10 and interleukin-17A in immature dendritic cells was much higher than that in mature dendritic cells(P<0.01).Interleukin-12 secretion in immature dendritic cells was much lower than that in mature dendritic cells(P<0.05).(4)Mature dendritic cells stimulated T cells significantly better than immature dendritic cells,and the stimulation ability was stronger when the ratio of mature dendritic cells to T lymphocytes reached 1:10.(5)The results indicate that Lewis rat bone marrow precursor cells can differentiate into dendritic cells and distinguish between mature and immature dendritic cells by flow cytometry identification,related factor detection,and mixed lymphocyte reaction.
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Interventional therapy for hepatic malignant tumours primarily includes cardiovascular system surgery,diges-tive system surgery,and various diagnostic and therapeutic procedures.Referring to the"International Classification of Diseases,Ninth Edition,Clinical Modification,ICD-9-CM-3"(2011 revision),the relevant surgical procedure codes on the front page of the case are contained mainly in the 9th chapter for cardiovascular system surgery,the 11th chapter for digestive system surgery,and the 18th chapter for various diagnostic and therapeutic procedures and other related chapters on diagnostic and therapeutic procedures.It has become a challenge for the history coders to complete the first page of interventional surgery cases by reviewing the surgery records,extracting the surgical steps,and then identifying the appropriate surgery codes and their sequencing.Accord-ing to the current classification of interventional therapy for hepatic malignant tumors,it is suggested to conduct the search and re-trieval using the keywords like"arteriography""embolization""perfusion""implantation""destruction"and"ablation".
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Cognitive dysfunction caused by blast traumatic brain injury (bTBI) is a serious neurological disease with high incidence, serious condition and poor prognosis. bTBI can lead to a series of symptoms such as short-term memory loss, inattention or multi-tasking difficulties. In severe cases, bTBI can develop into Alzheimer′s disease, which has a great impact on patients′ normal work and life. At present, researches on cognitive dysfunction caused by bTBI mainly involve model construction, pathogenesis, pathophysiological changes, diagnosis and treatment, etc., and the molecular mechanism of its occurrence remains to be further studied. Under normal physiological conditions, the release of excitatory and inhibitory neurotransmitters, the release and uptake of Ca 2+, oxidation and antioxidant systems, and the promotion and inhibition of apoptosis are in a dynamic balance. bTBI disturbs the balance, which will lead to the damage of nerve cells at the molecular level, thus resulting in the occurrence of cognitive dysfunction. To this end, the authors summarized the aspects of excitatory toxicity and Ca 2+homeostasis disorder, oxidative stress, inflammation and edema, apoptosis, etc., and reviewed the research progress on the molecular mechanism of cognitive dysfunction caused by bTBI, so as to provide a reference for the treatment and rehabilitation of cognitive dysfunction in patients with bTBI.
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Purpose@#This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. @*Materials and Methods@#This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. @*Results@#A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). @*Conclusion@#Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.
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Objective@#To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability.@*Methods@#From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated.@*Results@#The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2.@*Conclusions@#Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.
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Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.
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ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate (MSU) crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups (n=10): a normal group, a model group, a dexamethasone (DXMS, 0.07 mg·kg-1) group, and low- (DH50-D, 9 mg·kg-1) and high-dose (DH50-G, 18 mg·kg-1) DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5, the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4, 8, 24, and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 (NLRP3), cysteine-aspartic protease-1 (Caspase-1), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), IL-1β, and cyclooxygenase-2 (COX-2) in the synovial tissue. Furthermore, the cell inflammation model was established with RAW264.7 cells stimulated with MSU (75 mg·L-1). The cell experiments were carried out with 6 groups: a normal group, a model group, a positive drug (DXMS, 100 μmol·L-1) group, and low- (DH50-D, 25 mg·L-1), medium- (DH50-Z, 50 mg·L-1), and high-dose (DH50-G, 100 mg·L-1) DH50 groups. Methyl thiazolyl tetrazolium (MTT) assay was employed to determine the cell viability, ELISA to determine the content of TNF-α in the supernatant of cell culture, and Western blot to determine the protein levels of NLRP3, cleaved Caspase-1, IL-1β, TNF-α, and COX-2. ResultCompared with the normal group, the rat model group showed increased toe swelling degree and joint inflammatory index (P<0.01), serious infiltration of the synovium, elevated levels of inflammatory cytokines in the tissue homogenate (P<0.01), and up-regulated protein levels of NLRP3, Caspase-1, ASC, IL-1β, and COX-2 (P<0.05, P<0.01). Compared with the rat model group, low- and high-dose DH50 mitigated the toe swelling degree, decreased the joint inflammatory index, alleviated the inflammatory infiltration, lowered the levels of inflammatory cytokines in the tissue homogenate (P<0.01), and down-regulated the expression of related proteins (P<0.05, P<0.01). Compared with the normal group, the cell model group showed elevated level of TNF-α in the supernatant (P<0.01) and up-regulated protein levels of NLRP3, cleaved Caspase-1, IL-1β, TNF-α, and COX-2 (P<0.05). Compared with the model group, low, medium, and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins (P<0.05, P<0.01). ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.
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Abstract@#Myopia has become a major global public health problem. Exposure to outdoor light may explain the protective effect of outdoor activities on myopia. Currently, a growing number of studies focus on the effects of the spectrum on eye health. Recent studies have found that violet light may have a protective effect on myopia, but the mechanism of action between violet light and myopia is not yet fully understood. The paper reviews the association between violet light and myopia prevention and control, and the possible mechanisms of violet light and myopia to provide a reference value for further exploration of the role of violet light on myo pia .
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ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum (MHD-80) on reducing uric acid (UA) and protecting the kidney in the hyperuricemia (HUA) model in vivo. MethodPotassium oxazine (350 mg·kg-1) and adenine (80 mg·kg-1) were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups, including the normal group, model group, allopurinol group (5 mg·kg-1), febusotan group (5 mg·kg-1), and MHD-80 low-, medium-, and high-dose groups (3, 6, 12 mg·kg-1), with 10 in each group. Except for the normal group, the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8th to 14th day after modeling, each group was given corresponding drugs by intragastric administration, once a day. 1 h after the last administration, blood was collected from the eyeballs, and kidney and liver tissues of mice were collected. Serum levels of UA, urea nitrogen (BUN), and creatinine (Cr) and liver activity of xanthine oxidase (XOD) were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxilin-eosin (HE) staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 (ABCG2) and glucose-facilitating transporter 9 (GLUT9) in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group, the serum levels of UA, Cr, BUN, inflammatory factors TNF-α, IL-1β, and liver XOD activity in the serum of mice in the model group were significantly increased (P<0.05, P<0.01), and the expression of GLUT9 in kidney tissues was significantly up-regulated (P<0.05). ABCG2 protein expression was significantly down-regulated (P<0.05), and renal injury was obvious. Compared with the model group, the levels of UA, BUN, Cr, TNF-α, IL-1β, and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees (P<0.05, P<0.01), GLUT9 protein expression was significantly down-regulated (P<0.01), ABCG2 protein expression was significantly up-regulated (P<0.05) in the high-dose group of MHD-80, and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction, anti-inflammatory, and anti-renal injury effects, which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.
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ObjectiveTo investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis (CNP) and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 (NLRP3) pathway. MethodNormal human prostatic stromal cells, namely WPMY-1 were induced by lipopolysaccharide (LPS) of 5 mg·L-1, and the effects of Lycopi Herba extract of 3.125, 6.25, 12.5, 25, 50, and 100 mg·L-1 on interleukin-6 (IL-6) level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay (ELISA). The half-maximal inhibitory concentration (IC50) was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba extract of 50, 75, and 100 mg·L-1 was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5α-dihydrotestosterone (5α-DHT) in serum, as well as the levels of IL-6, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) in prostate tissue were detected by ELISA. The key protein expressions of COX-2, TGF-β1, and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expressions of COX-2, IL-1β, TGF-β1, and TNF-α mRNA in prostate tissue. ResultCompared with the normal group, the level of IL-6 and the protein expression levels of NLRP3, ASC, Caspase-1, and IL-1β of WPMY-1 cells in the model group were increased (P<0.05, P<0.01). Compared with the model group, Lycopi Herba extract could inhibit the levels of IL-6 (P<0.01) released by LPS-induced WPMY-1 cells, with IC50 of 38.26 mg·L-1. The protein expression levels of NLRP3, ASC, and IL-1β in the low-, medium-, and high-dose groups of Lycopi Herba extract were significantly down-regulated (P<0.05, P<0.01). The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba extract were significantly down-regulated (P<0.05, P<0.01). Compared with the sham operation group, the prostate organ index of rats in the model group was significantly increased (P<0.01), a large number of inflammatory cells were infiltrated in the prostate tissue, and the histopathological score was significantly increased (P<0.05); the levels of 5α-DHT in serum, the levels of TNF-α, PGE2, IL-6, TGF-β1, NOS2/iNOS, and COX-2 in prostate tissue, and expression levels of COX-2, IL-1β, and TGF-β1 were significantly increased (P<0.05, P<0.01). The mRNA expression levels of COX-2, TGF-β1, NLRP3, Caspase-1, ASC, and IL-1β in prostate tissue were significantly up-regulated (P<0.05, P<0.01). Compared with model group, the low and high doses of Lycopi Herba extract could alleviate the pathological changes in prostate tissue induced by carrageenan, significantly reduce the level of 5α-DHT in serum, levels of TNF-α, PGE2, TGF-β1, and iNOS in prostate tissue (P<0.05, P<0.01), and mRNA expression levels of COX-2, IL-1β, and TGF-β1 (P<0.05, P<0.01). The protein expression levels of COX-2, Caspase-1, ASC, and NLRP3 in prostate tissue were significantly down-regulated (P<0.05, P<0.01). The prostate organ index of the low-dose group of Lycopi Herba extract was significantly decreased (P<0.01). The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba extract was significantly decreased, and the protein expression levels of TGF-β1 and IL-1β were significantly down-regulated (P<0.05). ConclusionLycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.
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Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.
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OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).
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Humains , Femelle , Tumeurs du sein/thérapie , Points d'acupuncture , Études rétrospectives , Lymphoedème/complications , Thérapie par acupuncture/effets indésirables , Membre supérieur , Résultat thérapeutiqueRésumé
Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Sujets)
Parvalbumines/métabolisme , Corps strié/métabolisme , Interneurones/physiologie , Neurones/métabolisme , NéostriatumRésumé
OBJECTIVE@#To compare and analyze the effect of unplanned versus planned admission to the intensive care unit (ICU) on the prognosis of high-risk patients after surgery, so as to provide a clinical evidence for clinical medical staff to evaluate whether the postoperative patients should be transferred to ICU or not after surgery.@*METHODS@#The clinical data of patients who were transferred to ICU after surgery admitted to the Affiliated Hospital of Guizhou Medical University from January to December in 2021 were retrospectively analyzed, including gender, age, body mass index, past history (whether combined with hypertension, diabetes, pulmonary disease, cardiac disease, renal failure, liver failure, hematologic disorders, tumor, etc.), acute physiology and chronic health evaluation II (APACHE II), elective surgery, pre-operative hospital consultation, length of surgery, worst value of laboratory parameters within 24 hours of ICU admission, need for invasive mechanical ventilation (IMV), duration of IMV, length of ICU stay, total length of hospital stay, ICU mortality, in-hospital mortality, and survival status at 30th day postoperative. The unplanned patients were further divided into the immediate transfer group and delayed transfer group according to the timing of their ICU entrance after surgery, and the prognosis was compared between the two groups. Cox regression analysis was used to find the independent risk factors of 30-day mortality in patients transferred to ICU after surgery.@*RESULTS@#Finally, 377 patients were included in the post-operative admission to the ICU, including 232 in the planned transfer group and 145 in the unplanned transfer group (42 immediate transfers and 103 delayed transfers). Compared to the planned transfer group, patients in the unplanned transfer group had higher peripheral blood white blood cell count (WBC) at the time of transfer to the ICU [×109/L: 10.86 (7.09, 16.68) vs. 10.11 (6.56, 13.27)], longer total length of hospital stay [days: 23.00 (14.00, 34.00) vs. 19.00 (12.00, 29.00)], and 30-day post-operative mortality was higher [29.66% (43/145) vs. 17.24% (40/232)], but haemoglobin (Hb), arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), and IMV requirement rate were lower [Hb (g/L): 95.00 (78.00, 113.50) vs. 98.00 (85.00, 123.00), PaCO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 36.00 (29.00, 41.50) vs. 39.00 (33.00, 43.00), PaO2/FiO2 (mmHg): 197.00 (137.50, 283.50) vs. 238.00 (178.00, 350.25), IMV requirement rate: 82.76% (120/145) vs. 93.97% (218/232)], all differences were statistically significant (all P < 0.05). Kaplan-Meier survival curve showed that the 30-day cumulative survival rate after surgery was significantly lower in the unplanned transfer group than in the planned transfer group (Log-Rank test: χ2 = 7.659, P = 0.006). Univariate Cox regression analysis showed that unplanned transfer, APACHE II score, whether deeded IMV at transfer, total length of hospital stay, WBC, blood K+, and blood lactic acid (Lac) were associated with 30-day mortality after operation (all P < 0.05). Multifactorial Cox analysis showed that unplanned transfer [hazard ratio (HR) = 2.45, 95% confidence interval (95%CI) was 1.54-3.89, P < 0.001], APACHE II score (HR = 1.03, 95%CI was 1.00-1.07, P = 0.031), the total length of hospital stay (HR = 0.86, 95%CI was 0.83-0.89, P < 0.001), the need for IMV on admission (HR = 4.31, 95%CI was 1.27-14.63, P = 0.019), highest Lac value within 24 hours of transfer to the ICU (HR = 1.17, 95%CI was 1.10-1.24, P < 0.001), and tumor history (HR = 3.12, 95%CI was 1.36-7.13, P = 0.007) were independent risk factors for patient death at 30 days post-operative, and the risk of death was 2.45 times higher in patients unplanned transferred than in those planned transferred. Subgroup analysis showed that patients in the delayed transfer group had significantly longer IMV times than those in the immediate transfer group [hours: 43.00 (11.00, 121.00) vs. 17.50 (2.75, 73.00), P < 0.05].@*CONCLUSIONS@#The 30-day mortality, WBC and total length of hospital stay were higher in patients who were transferred to ICU after surgery, and PaO2/FiO2 was lower. Unplanned transfer, oncology history, use of IMV, APACHE II score, total length of hospital stay, and Lac were independent risk factors for patient death at 30 days postoperatively, and patients with delayed transfer to ICU had longer IMV time.
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Humains , Études rétrospectives , Ventilation artificielle , Hospitalisation , Pronostic , Unités de soins intensifsRésumé
OBJECTIVES@#Firefighters are prone to suffer from psychological trauma and post-traumatic stress disorder (PTSD) in the workplace, and have a poor prognosis after PTSD. Reliable models for predicting PTSD allow for effective identification and intervention for patients with early PTSD. By collecting the psychological traits, psychological states and work situations of firefighters, this study aims to develop a machine learning algorithm with the aim of effectively and accurately identifying the onset of PTSD in firefighters, as well as detecting some important predictors of PTSD onset.@*METHODS@#This study conducted a cross-sectional survey through convenient sampling of firefighters from 20 fire brigades in Changsha, which were evenly distributed across 6 districts and Changsha County, with a total of 628 firefighters. We used the synthetic minority oversampling technique (SMOTE) to process data sets and used grid search to finish the parameter tuning. The predictive capability of several commonly used machine learning models was compared by 5-fold cross-validation and using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, precision, recall, and F1 score.@*RESULTS@#The random forest model achieved good performance in predicting PTSD with an average AUC score at 0.790. The mean accuracy of the model was 90.1%, with an F1 score of 0.945. The three most important predictors were perseverance, forced thinking, and reflective deep thinking, with weights of 0.165, 0.158, and 0.152, respectively. The next most important predictors were employment time, psychological power, and optimism.@*CONCLUSIONS@#PTSD onset prediction model for Changsha firefighters constructed by random forest has strong predictive ability, and both psychological characteristics and work situation can be used as predictors of PTSD onset risk for firefighters. In the next step of the study, validation using other large datasets is needed to ensure that the predictive models can be used in clinical setting.