Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 （PbK173）-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free （SPF） male C57BL/6 mice were randomly divided into three groups， with 30 mice each in the control group and PbK173-resistant （PbK173-R） group， and 42 mice in the PbK173-sensitive （PbK173-S） group. Except for the control group， the rest groups were vaccinated with 1×10⁷ PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods （control group， PbK173-R/PbK173-S）， dihydroartemisinin （DHA， 40 mg·kg^-1） and malaridine （MD， 6 mg·kg^-1） were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration （dosing period） and on the fifth day at the end of administration （recovery period）， and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods， there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period， there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However， during the recovery period， the red blood cell count， hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group （P<0.05） in the MD group. Compared with that of the control group， the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced （P<0.01）， and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group （P<0.01）. The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period （P<0.01）. The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period （P<0.05）. Compared with those in the control group， the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced （P<0.01）. Compared with those in the PbK173-R group， the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane， and the erythrocyte flexibility exhibited a decreasing trend in the following order： normal group， PbK173-R group， and PbK173-S group.

Objective To evaluate the predictors of biochemical recurrence after laparoscopic radical prostatectomy.Methods The study cohort consisted of 416 consecutive prostatecancer patients who underwent radical prostatectomy in Zhongshan Hospital,Fudan University between Jan 2016 and Jun 2018.No patient received adjuvant therapy until documented biochemical recurrence.Biochemical recurrence-free survival(BCRFS)was estimated using the Kaplan-Meier method.Univariable and multivariable Cox proportional hazards regression models were utilized to determine variables predictive of biochemical recurrence.Results The median follow-up period was 174 weeks(inter quartile range 133-209 weeks).The overall biochemical recurrence rate was 21.39%(88/416).The time to biochemical recurrence was(51.11±47.71)weeks.Until the end of follow-up,the biochemical recurrence rates were 10%(1/10),6.12%(3/49),16.41%(43/262)and 43.16%(41/95)for low-risk,medium-risk,high-risk and locally advanced prostate cancer,respectively.On multivariable analysis,tumor invasion of the seminal vesicles(HR:2.119,95%CI:1.154-3.891,P=0.016);Seminal vesicle invasion(HR:1.824,95%CI:1.034-3.220,P=0.038),Gleason score≥8(HR:2.746,95%CI:1.268-5.943,P=0.010),prostate-specific antigen(PSA)=10-20 ng/mL(HR:4.240,95%CI:2.550-7.050,P<0.001);PSA>20 ng/mL(HR:6.341,95%CI:3.296-12.202,P<0.001)were the main predictors of biochemical recurrence.Conclusion Laparoscopic radical prostatectomy provides effective control of biochemical recurrence during the mid-term follow-up period.Tumor invasion of the seminal vesicles,seminal vesicle invasion,GS≥8,PSA=10-20 ng/mL,PSA>20 ng/mL were important predictors of biochemical recurrence after radical prostatectomy.

Objective To investigate the diagnostic value of CT radiomics features in pulmonary alveolar proteinosis(PAP).Methods The general data and clinical characteristics of 24 patients with PAP in the Chinese PLA General Hospital from November 2008 to August 2022 were retrospectively collected and analyzed.Another 53 patients with other diffuse lung diseases except for PAP during the same period served as control group.The differences in the 10 conventional CT signs(semantic features)and 107 radiomics features between the two groups were compared.All patients were randomly divided into the training group(n=53)and the validation group(n=24)at a ratio of 7:3.CT semantic feature model,radiomics model and combined model to diagnose PAP were constructed in training group,and the diagnostic efficacy of models was compared using the receiver operating characteristic(ROC)curve in validation group.Decision curve analysis(DCA)was used to assess the value of models for practical clinical application.Radscore was calculated for the model with the highest diagnostic efficacy.Results A total of 24 patients with pathologically confirmed PAP were enrolled,with a male to female ratio of 3:1 and an average age of(44.6±15.2)years.The main clinical symptoms of patients with PAP included shortness of breath,cough,sputum and chest tightness.Compared with control group,the incidence of pleural effusion in PAP group was significantly lower(P＜0.05),while no significant differences were observed in other CT features(P＞0.05).The areas under the curve(AUC)of the semantic feature model for diagnosing PAP in training and validation group were 0.590 and 0.594,respectively,and in validation group,the accuracy,sensitivity,and specificity for diagnosis of PAP were 0.188,1.000,and 0.188,respectively.The AUCs of the radiomics model in training group and validation group were 0.845 and 0.867,respectively,and in validation group,the accuracy,sensitivity,and specificity were 0.641,0.938,and 0.703,respectively.The AUCs of the combined model in training group and validation group were 0.850 and 0.883,respectively,and in validation group,the accuracy,sensitivity,and specificity were 0.688,0.750,and 0.938,respectively.The AUCs of the radiomics model and the combined model were significantly greater than that of the semantic feature model,but there was no significant difference in the AUCs between the first two models.The decision curve analysis showed that both the radiomics model and the combined model had high application value for predicting PAP.Conclusion CT radiomics shows higher clinical value in the diagnosis of PAP compared with conventional CT features.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Electrochemiluminescence(ECL)refers to the process of luminescence triggered by high-energy electron transfer between intermediate products during the oxidation-reduction reaction on the electrode surface.In the co-reactants involved ECL process,the presence of co-reaction accelerators can effectively catalyze the decomposition of co-reactants,leading to the generation of abundant free radical intermediates,thereby significantly enhancing the ECL signals.This plays a critical role in constructing simple,sensitive,and efficient ECL sensing platforms.This review focused on the novel co-reaction accelerators developed in recent years.Based on different types of co-reaction accelerator materials,including single atom catalysts,metal-based nanomaterials,polymers and other materials,the ECL reaction process and signal enhancement mechanisms,as well as their relevant applications in constructing ECL sensing platforms,were elucidated.Furthermore,the current research challenges and development prospect of co-reaction accelerators were also discussed.