Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.

Purpose To investigate the clinical value of artificial intelligence(AI)quantitative parameters in predicting the invasion degree of lung adenocarcinoma with diameter≤2 cm of ground-glass density.Materials and Methods A total of 80 patients with lung adenocarcinoma with diameter≤2 cm ground-glass density confirmed by pathology from March 2019 to April 2022 were retrospectively analyzed.A total of 90 nodules were rerolled,including 8 adenocarcinomas in situ(AIS),34 minimally invasive adenocarcinomas(MIA)and 48 invasive adenocarcinomas(IAC).They were divided into the experimental group(IAC)and the control group(AIS and MIA).The differences of the AI quantitative parameters such as volume,three-dimensional length diameter,maximum area,maximum CT value,minimum CT value and average CT value were compared between two groups,and the predictive values of AI quantitative parameters for the invasion degree of lung adenocarcinoma was evaluated.Results There were statistically significant differences with age,volume,three-dimensional length diameter,maximum area,maximum CT value and average CT value between the two groups(all P<0.05),but no statistically significant differences in gender and minimum CT value(both P>0.05).Binary Logistic regression analysis showed that the three-dimensional length diameter(odd ratio=2.020,P=0.034)and the maximum CT value(odd ratio=1.008,P=0.013)were independent predictors for lung adenocarcinoma with diameter≤2 cm of ground-glass density.The regression model based on the three-dimensional length diameter and the maximum CT value had the best predictive performance,and its AUC was 0.901.When the critical value was 2.432,its sensitivity and specificity were 93.75%and 71.43%,respectively.Conclusion AI quantitative parameters have a high value in predicting the degree of invasion of lung adenocarcinoma with diameter≤2 cm of ground-glass density,and the combined model with three dimensional long diameter and maximum CT value has the highest diagnostic efficiency.

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablativeradiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor;irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grewto the touchable size, mice were randomly divided into eight treatment groups. These groupsreceived normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not tothe primary tumor. The further tumor growth/regression of mice were followed andobserved. Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primarytumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primaryand secondary tumor growth could be observed, indicated an abscopal effect wasinduced. Mechanism analysis suggested that programmed death-ligand 1 expressionincreased with SABR was counteract by additional apatinib therapy. Furthermore, whenapatinib was combined with SABR, the composition of immune cells could be changed.More importantly, this two-pronged approach evoked tumor antigen–specific immune responsesand the mice were resistant to another tumor rechallenge, finally, long-term survivalwas improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib,which was effective in eliciting an abscopal effect induced by SABR.

Objective To evaluate the influence of menopause status on breast fibrograndular tissue (FGT),background parenchymal enhancement volume ratio (BPEv) and intensity ratio (BPEI) by breast MR image automatic quantitative analysis.Methods From 14 033 consecutive patients who underwent breast MR in our center from 2009 to 2012,we randomly selected 101 normal cases (47cases of premenopausal and 54 cases of postmenopausal).Premenopausal status was subclassified into four groups (8 cases in the 1st week and 13 cases in the 2nd,3rd and 4th week,respectively) based on the menstrual cycle.We evaluated FGT,BPEv and BPEI at early (2 minutes),medium (4 minutes) and late (6 minutes) enhanced time phases of breast MRI for quantitative assessment.The FGT,BPEv and BPEI in premenopausal and postmenopausal women were compared using the Mann-Whitney U test.Comparison of each menstrual cycle was made using the Kruskal-Wallis test.Results The FGT,BPEv and middle-late BPEI of postmenopausal women were significantly lower than that of premenopausal women (P＜0.05).The maximum BPEI was in the 1st week,the minimum in the 2nd week in premenopausal women (P＜0.05).The FGT and BPEv in the 1st week were the highest among the 4 weeks,but there was no significant difference.Conclusions The FGT,BPEv and BPEI were significantly decreased after menopause.The optimal time of breast MR examination is in the 2nd week of menstrual cycle.

Objective To retrospectively investigate the characteristics of background parenchymal enhancement(BPE)in the contralateral breast following neoadjuvant chemotherapy(NAC)and whether BPE could help predict tumor response in early stage of advanced breast cancer. Methods Data from 161 patients who were diagnosed with unilateral breast cancer and then underwent NAC before surgery were analyzed retrospectively from August 2014 to December 2016.All the patients underwent both bilateral breast MRI scan with contrast enhancement. Two experienced radiologists independently categorized the patients' levels of BPE into four categories (1=minimal, 2=mild, 3=moderate, 4=marked) at baseline and after the 2nd cycle of NAC. All the patients were divided in to pathologic complete response (pCR) group and non-pCR group according to the histopathologic tumour response.The status of estrogen receptor(ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were recorded before underwent NAC.The t test and Pearson chi-squared test were used to compare the baseline characteristics of the pCR and Non-pCR groups.The kappa test was used to test the inter-observer agreement.The Wilcoxon test was used to test for changes of BPE categories after NAC.The Mann-Whitney U test was used to test the difference of BPE between pre-and post-menopausal status. Associations were evaluated using Binary logistic regression models. Results Fifty nine patients achieved pCR, and 102 patients had residual disease (non-pCR). Age, tumor size, distribution of size, menopausal status and lymph node showed no significance between pCR and non-pCR groups(all P>0.05),while only ER/PR status and HER2 status had a significant difference (P>0.05 in both). Inter-observer agreement regarding BPE categorization was moderate and substantial before and after NAC(Kappa value 0.644 and 0.708).The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the 2nd cycle of NAC(P<0.01). Decreased BPE was observed in 106 cases(premenopausal 60 cases and postmenopausal 46 cases),and no change in BPE were observed in 55 cases (premenopausal 27 cases and postmenopausal 28 cases). A significant reduction in BPE was observed after the 2nd NAC cycle in the overall cases, pre-and post-menopausal cases (all P<0.01). Logistic model showed that hormonal receptor (HR) negative and HER-2 receptor at baseline and the change of BPE after NAC were the independent factors for predicting pCR. Conclusions Regardless of the menopausal status, BPE showed a reduction after NAC, and it can serve as an additional imaging biomarker of tumour response at an early stage of NAC.

OBJECTIVEWe investigate the magnitudes of waveform changes of arterial blood gas (ABG) in patients with heart failure.

METHODSFive patients with heart failure were selected, continuous collecting radial artery blood and measured PaO2, PaCO2, pHa and Sao2. We selected two typical breaths cycles of waveform changes of ABG from each patient for data analysis. Comparison of the adjacent highest and lowest values to verify the presence of a periodic waveform changes of ABG, and in addition, we used t test to analysis the range of waveform changes of ABG in patients with heart failure and patients with normal cardiac function and compared whether the difference between them.

RESULTSThe 5 patients (2 surgical and 3 ICU) with heart failure, were 4 male and 1 female, (69 ± 7)year, (169 ± 10) cm, (75 ± 19)kg, LVEF = (38 ± 3)%. The heart beat numbers for full blood into the blood sampling pipe were 17 ± 2, and all covered more than 2 breath cycles. There were significant changes of PaO2, PaCO2, [H+]a and SaO2 (P < 0.05). The magnitudes of changing PaO2, PaCO2, [H+]a and Sao2 were (7.94 ± 2.02)mmHg, (1.18 ± 0.56)mmHg, (0.54 ± 0.17)nmol/L and (0.21 ± 0.07)%, and they were (6.1 ± 1.5)%, (3.2 ± 1.5)%, (1.5 ± 0.5)% and (0.2 ± 0.1)% from their mean respectively. Even these magnitudes fo all ABG parameters were trendily lower than those of patients with normal cardiac function, but only PaO2 and [H+]a were significant (P < 0.05).

CONCLUSIONUsing this simple continuous beat-by-beat arterial blood sampling method, we obtained a clear evidence of periodic waveform of ABG parameters following by breath cycle in patients with heart failure, but the magnitude trendily be decreased.

Aged ; Blood Gas Analysis ; Cardiovascular Diseases ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; methods

OBJECTIVESince 2011 EB-APS conference, we hypotheses that phase switching of inspiration-expiration is dominantly initiated by oscillatory information PaO2, PaCO2 and [H+] via fast peripheral chemical receptors. However, the evidence of the waveform of ABG is lack.

METHODSSix surgery patients with normal heart function and negative Allen test, had been placed the arterial catheterization directly connected to 3 x 1 000 mm pre-heparin plastic pipe for continuous collecting arterial blood. We counted the number of heart beat for the blood collecting time, and separated the blood pipe into the heart beat numbers' short pieces using haemostatic forceps, then put pipe into iced water at once fir analyzing PaO2, PaCO2, pH and SaO2 as soon as possible. We selected two breaths cycles of waveform from each patient for data calculations of magnitudes and time interval.

RESULTSThe heart beat numbers for filling blood into pipe were 16 ± 2, and all covered more than 2 breathing cycles. Each breathing cycle is cover 5 ± 0.6 heart beat. There were significant changes of PaO2, PaCO2, [H+] a and SaO2 (i.e. the highest high values compare to the next lowest values, P < 0.05). The time interval of changing PaO2, PaCO2, [H+]a and SaO2 magnitudes were 11.28 ± 1.13 mmHg, 1.77 ± 0.89 mmHg, 1.14 ± 0.35 nmol/L and 0.52% ± 0.44% respectively.

CONCLUSIONThis simple continuous beat-by-beat arterial blood sampling and ABG analyzing method is new and practicable. We obtain a clear evidence of periodic parameters ABG waveform, which following breathing cycle.

Arteries ; physiology ; Blood Gas Analysis ; Heart Rate ; Humans ; Monitoring, Physiologic ; methods ; Respiration