OBJECTIVE: To explore the effectiveness of the combined anteversion angle technique in total hip arthroplasty (THA) for treating ankylosing spondylitis (AS) affecting the hip joint. METHODS: A retrospective analysis was conducted on the clinical data of 73 patients with AS affecting the hip joint who underwent THA between August 2018 and August 2021. According to whether the combined anteversion angle technique was used in THA, the patients were divided into study group (37 cases, combined anteversion angle technique was used in THA) and control group (36 cases, traditional THA). There was no significant difference in baseline data such as gender, age, body mass index, disease duration, preoperative Harris score, range of motion (ROM), acetabular anteversion angle, acetabular abduction angle, femoral anteversion angle, and combined anteversion angle between the two groups ( P>0.05). The operation time, hospital stay, and complications of the two groups were recorded and compared. The Harris score and hip ROM were compared between the two groups before operation, at 1, 3, 6, 12 months after operation, and at last follow-up. The acetabular component anteversion angle, femoral component anteversion angle, acetabular component abduction angle, and component combined anteversion angle were measured postoperatively. RESULTS: The operation time in the study group was significantly shorter than that in the control group ( P<0.05), and there was no significant difference in hospital stay between the two groups ( P>0.05). There was no intraoperative complication such as acetabular and proximal femoral fractures, neurovascular injuries in both groups, and the incisions healed by first intention. All patients were followed up 2-3 years, with an average of 2.4 years; there was no significant difference in the follow-up time between the two groups ( P>0.05). During the follow-up period, there was no complication such as hip dislocation, wound infection, delayed wound healing, deep venous thrombosis, and hip dislocation in both groups. The hip Harris score and ROM of the two groups gradually increased with time after operation, and the differences were significant when compared with those before operation ( P<0.05); the above two indicators of the study group were significantly better than those of the control group at each time point after operation ( P<0.05). Extensive bone ingrowth on the surface of the components could be observed in the anteroposterior X-ray films of the hip joint of the two groups at 12 months after operation, and the acetabular components was stable without femoral stem subsidence, osteolysis around the components, and heterotopic ossification. At last follow-up, the acetabular component anteversion angle, femoral component anteversion angle, and component combined anteversion angle in the study group were significantly superior to those in the control group ( P<0.05), except that there was no significant difference in the acetabular component abduction angle between the two groups ( P>0.05). CONCLUSION For patients with AS affecting the hip joint, the use of the combined anteversion angle technique during THA effectively promotes the recovery of hip joint function and enhances the postoperative quality of life of patients when compared to traditional THA.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Hip Dislocation/surgery* ; Spondylitis, Ankylosing/surgery* ; Retrospective Studies ; Quality of Life ; Treatment Outcome ; Hip Joint/surgery* ; Hip Prosthesis

Objective:To explore the prognostic value of epidermal growth factor receptor (EGFR) co-mutation status in patients with advanced lung adenocarcinoma.Methods:Clinical data of patients with stage ⅢB-Ⅳ lung adenocarcinoma who were first diagnosed in the Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Hebei North University from January 2019 to December 2022 were collected prospectively. Patients were divided into EGFR mutation group ( n=82) and EGFR co-mutation group ( n=74) according to whether EGFR was combined with other gene mutations. The level of circulating tumor DNA (ctDNA) in peripheral blood was measured by real time fluorescence quantitative PCR. Objective response rate (ORR), disease control rate (DCR), the levels of ctDNA in peripheral blood, and progression-free survival (PFS) were compared between two groups of patients before and after 1 month of treatment. The univariate and multivariate analyses were conducted by Cox proportional hazards regression model. Results:In the EGFR mutation group, there were 45 cases of EGFR19 deletion mutation and 37 cases of EGFR21 mutation. In the EGFR co-mutation group, there were 41 cases of EGFR19 deletion mutation, 33 cases of EGFR21 mutation, 46 cases of TP53 mutation, 16 cases of RB1 mutation, 6 cases of PTEN mutation, 2 cases of MET amplification, 1 case of ERBB2 mutation, 1 case of KRAS mutation, 1 case of RET rearrangement, and 1 case of ALK rearrangement. There were statistically significant differences between the EGFR mutation group and the EGFR co-mutation group in the maximum tumor diameter ( χ2=5.04, P=0.025) and stage ( χ2=3.92, P=0.048). The ORRs of the two groups were 64.63% (53/82) and 37.84% (28/74), respectively, with a statistically significant difference ( χ2=11.19, P<0.001). The DCRs were 96.34% (79/82) and 86.49% (64/74), respectively, with a statistically significant difference ( χ2=4.95, P=0.026). The ctDNA levels in the EGFR mutation group and EGFR co-mutation group after one month of treatment decreased compared to before treatment[2.63 (1.83, 3.30) ng/μl vs. 4.73 (3.92, 5.49) ng/μl, Z=-7.06, P<0.001; 4.26 (2.26, 6.07) ng/μl vs. 5.28 (4.37, 6.09) ng/μl, Z=-5.15, P<0.001], the ctDNA levels in the EGFR co-mutation group were higher than those in the EGFR mutation group before treatment and after 1 month of treatment ( Z=-2.47, P=0.013; Z=-4.29, P<0.001). In the EGFR co-mutation group, the ctDNA levels in peripheral blood of patients who were effectively treated with targeted therapy decreased after 1 month of treatment compared to before treatment [(2.03±0.63) ng/μl vs. (3.92±0.82) ng/μl, t=42.94, P<0.001], the levels of ctDNA in peripheral blood of ineffectively treated patients before and after 1 month of treatment were higher than those of effectively treated patients [(5.84±0.57) ng/μl vs. (3.92±0.82) ng/μl, t=-11.91, P<0.001; (5.87±1.64) ng/μl vs. (2.03±0.63) ng/μl, t=-14.43, P<0.001]. The median PFS of the EGFR mutation group and the EGFR co-mutation group of patients were 10.4 and 8.3 months, respectively, with a statistically significant difference ( χ2=22.28, P<0.001). Univariate analysis suggested that the maximum tumor diameter ( HR=0.10, 95% CI: 0.06-0.16, P<0.001), performance status (PS) score ( HR=0.09, 95% CI: 0.06-0.15, P<0.001), stage ( HR=0.09, 95% CI: 0.05-0.14, P<0.001), pre-treatment ctDNA level ( HR=12.04, 95% CI: 8.21-17.65, P<0.001), ctDNA level after 1 month of treatment ( HR=3.75, 95% CI: 3.10-4.54, P<0.001) and EGFR co-mutations ( HR=2.21, 95% CI: 1.57-3.12, P<0.001) were found to be significant factors affecting the PFS of stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy; Multivariate analysis demonstrated that PS score ( HR=0.25, 95% CI: 0.14-0.47, P<0.001), stage ( HR=0.49, 95% CI: 0.24-0.98, P=0.044), pre-treatment ctDNA level ( HR=4.73, 95% CI: 3.08-7.28, P<0.001), ctDNA level after 1 month of treatment ( HR=2.15, 95% CI: 1.65-2.80, P<0.001), and EGFR gene co-mutation ( HR=2.26, 95% CI: 1.40-3.64, P<0.001) were independent risk factors for PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy. Conclusion:Both the EGFR mutation group and EGFR co-mutation group show a decrease in ctDNA levels after targeted therapy for one month compared to before treatment. The median PFS of EGFR co-mutation patients is shorter than that of patients with a single EGFR mutation. PS score, stage, ctDNA levels before and after treatment, and EGFR gene co-mutation are all independent factors affecting PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients after targeted therapy.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals ; Mice ; Ferroptosis ; Network Pharmacology ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; Influenza A virus ; Iron ; Hypoxia

Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on as-trocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.

ObjectiveTo observe the effect of the enhanced external counterpulsation （EECP） combined with drug on social function and efficacy in patients with depressive episodes， so as to provide references for the treatment of depressive episodes. MethodsA total of 66 hospitalized patients who was in hospital at department of psychiatry of the Second Xiangya Hospital of Central South University， met the criteria of Diagnostic and Statistical Manual of Mental Disorders，fifth edition（DSM-5） diagnosis of depressive episode or bipolar disorder depressive episode from May 2019 to March 2020 were included by simple random sampling. The participants were divided into study group （n=36） and control group （n=30） according to the random number table method. Both groups received conventional drug treatment， and the study group recieved the EECP intervention at same time. The Depression symptoms and social function were assessed before and after treatment by using Hamilton Depression Scale-24 item （HAMD-24） and Sheehan Disability Scale （SDS）. Treatment efficacy of the two groups was compared. ResultsAfter the intervention， the HAMD-24 and SDS scores in both groups were lower than those before treatment， the differences were statistically significant （t=8.149， 5.791， 8.016， 3.488， P˂0.01）. And the SDS score of the study group was siginficantly lower than that of the control group （t=-3.008， P<0.05）. The total effective rate of treatment in the study group was higher than that of the control group， and the difference was statistically significant （90.63% vs. 63.33%， χ²=8.725， P˂0.05）. ConclusionEECP therapy combined with drug has better efficacy on the patients with depressive episodes， and it can improve social function effectively.

Objective:To apply the multi-modal deep learning model to automatically classify the ultra-widefield fluorescein angiography (UWFA) images of diabetic retinopathy (DR).Methods:A retrospective study. From 2015 to 2020, 798 images of 297 DR patients with 399 eyes who were admitted to Eye Center of Renmin Hospital of Wuhan University and were examined by UWFA were used as the training set and test set of the model. Among them, 119, 171, and 109 eyes had no retinopathy, non-proliferative DR (NPDR), and proliferative DR (PDR), respectively. Localization and assessment of fluorescein leakage and non-perfusion regions in early and late orthotopic images of UWFA in DR-affected eyes by jointly optimizing CycleGAN and a convolutional neural network (CNN) classifier, an image-level supervised deep learning model. The abnormal images with lesions were converted into normal images with lesions removed using the improved CycleGAN, and the difference images containing the lesion areas were obtained; the difference images were classified by the CNN classifier to obtain the prediction results. A five-fold cross-test was used to evaluate the classification accuracy of the model. Quantitative analysis of the marker area displayed by the differential images was performed to observe the correlation between the ischemia index and leakage index and the severity of DR.Results:The generated fake normal image basically removed all the lesion areas while retaining the normal vascular structure; the difference images intuitively revealed the distribution of biomarkers; the heat icon showed the leakage area, and the location was basically the same as the lesion area in the original image. The results of the five-fold cross-check showed that the average classification accuracy of the model was 0.983. Further quantitative analysis of the marker area showed that the ischemia index and leakage index were significantly positively correlated with the severity of DR ( β=6.088, 10.850; P<0.001). Conclusion:The constructed multimodal joint optimization model can accurately classify NPDR and PDR and precisely locate potential biomarkers.

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.

Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m² vs. (26.6±3.5) kg/m², all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO₂) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO₂ was significant (β=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO₂, and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration clinicalTrials.gov, NCT03362385.

Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m² vs. (25.55±3.44) kg/m², t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ²=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ²=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ²=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration Clinical Trial.gov, NCT03362385.