ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

Objective To summarize the aortographic features of child patients with Kawasaki disease(KD)complicated by coronary artery lesion(CAL)who were treated at the Wuhan Children's Hospital of China.Methods The clinical data of 30 child patients with early recovery stage KD complicated by CAL,who received aortic angiography examination at Wuhan Children's Hospital of China between June 2016 and June 2023,were retrospectively analyzed.Preoperative echocardiography was adopted to evaluate the severity of CAL,and aortic angiography under laryngeal mask general anesthesia was performed.Results Successful aortic angiography examination was accomplished in all the 30 child patients with KD complicated by CAL.After angiography,the CAL risk classification results showed that grade I was seen in 5,grade Ⅱ in 7,grade Ⅲ in 12,grade Ⅲ in 4,and grade V in 2 child patients.Of all child patients,old coronary thrombosis was found in one(grade Ⅲb),and coronary artery stenosis with collateral circulation formation in one(grade Ⅴ).The CAL was located at the proximal segment(n=15),middle segment(n=3)and distal segment(n=2)of the right coronary artery,at the left main coronary artery(n=12),and at the proximal segment of left coronary artery anterior descending branch(n=9).Electrocardiography showed sinus rhythm(n=17),sinus arrhythmia(n=4),right bundle branch block(n=4),atrial premature beat(n=1),ventricular premature beat(n=2),T-wave change(n=1),and Q-wave change(n=1,coronary lesion grade V,echocardiography suggested left heart enlargement).No cardiac enlargement,cardiac functional insufficiency,or valvular regurgitation signs were observed in the remaining child patients.Conclusion It is clinically safe and feasible to perform aortic angiography examination in child patients with early recovery stage KD complicated by CAL.In this series of child patients with KD,CAL mainly occurs at the proximal segment of coronary artery,especially at the proximal segment of right coronary artery as well as at the left main artery and left anterior descending branch.

Objective To investigate the relationship between expression levels of epidermal growth factor receptor(EGFR),proliferation marker protein Ki-67(Ki-67),P53 and circulating tumor cell(CTC)and the prognosis of triple negative breast cancer.Methods A total of 95 patients with triple negative breast cancer were selected.The expression levels of EGFR,Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry.All patients underwent 8 cycles of chemotherapy,and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells(ISET).The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed.The correlation between CTC and expression levels of EGFR,Ki-67 and P53 was analyzed.Patients were followed up for progression free survival(PFS).Risk factors of progression for triple negative breast cancer were analyzed by COX regression.Results The positive detection rates of EGFR,Ki-67 and P53 were 44.21%(42/95),63.16%(60/95)and 56.84%(54/95).The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy(14.74%vs.61.05%,P＜0.05).The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy(P＜0.001).COX regression analysis found that clinical stage Ⅲ,positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer(P＜0.05).PFS of patients at clinical stage Ⅰ,stage Ⅱ,and stage Ⅲ decreased in order(P＜0.05).PFS of EGFR positive patients was shorter than that of EGFR negative patients(P＜0.05).PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy(P＜0.05).Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer.The lower the positive detection rate of CTC after chemotherapy,the better the efficacy of chemotherapy.

Objective:To analyze the clinical characteristics and risk factors of asparaginase-associated pancreatitis(AAP)in children with acute lymphoblastic leukemia(ALL),and to investigate the impact of AAP on their prognosis following re-exposure to asparaginase(ASP).Methods:Clinical children data with ALL at Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology between January 2015 and June 2020 were collected to analyze the clinical features of AAP.Logistic regression was used to identify risk factors for AAP.Prognostic analysis was performed using the Log-rank test and Kaplan-Meier survival curves.Results:Overall,252 children with ALL were included,among whom 23(9.1%)developed AAP.Most AAP cases(82.6%)occurred during remission induction,with a medi-an time from the last ASP to AAP of 12 d.Elevated total cholesterol(≥3.5 mmol/L)at initial diagnosis was identified as an independent risk factor.Six children(26.1%)were re-exposed to ASP,leading to recurrent pancreatitis in 3 cases.The 5-year overall survival(OS)was signific-antly lower in the AAP group(78.3%±8.6%)compared to the non-AAP group(90.3%±2.2%)(P<0.05).Similarly,children who discontinued ASP due to AAP had a 5-year OS of 77.8%±9.8%,significantly lower than the control group(90.1%±2.1%).Conclusions:AAP typically oc-curred within 12 d of the last ASP administration and was associated with poorer 5-year OS.Re-exposure to ASP posed a risk of recurrent AAP;however,completing the ASP chemotherapy regimen may be crucial for improving prognosis.

Objective To report two cases of dyskeratosis congenita(DC)and provide a comprehensive literature review to improve the understanding of the disease.Methods Clinical characteristics of two DC cases were retrospectively collected and analyzed in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.Gene mutations were assessed by high-throughput sequencing analysis and telomere length was assessed by Terminal Restriction Fragment(TRF)analysis.A literature search was carried out using the National Knowledge Infrastructure(CNKI),Wanfang database,PubMed,and Web of Science,updated to June 2024,with"Dyskeratosis congenita"and"telomere biology disorders"as the keywords.Results Case 1 was a boy admitted with"nail dystrophy of fingers and toes for more than 8 years and pancytopenia for 1 week".Physical examination revealed fingernails and toenails dysplasia,reticular skin pigmentation over the neck,and restricted mouth opening.Genetic testing identified a mutation in the DKC1 gene and shorter telomeres.Case 2 was a girl admitted with"confirmed aplastic anemia over 3 years".Physical examination showed no specific abnormalities.A blood routine test showed pancytopenia,with missense mutations found in the RTEL1 and TERT genes.Case 1 received blood transfusion support,while Case 2 was treated with subcutaneous injections of PEGylated recombinant human granulocytes,cyclosporine,and eltrombopag olamine,but the outcomes were not satisfactory.Both cases developed bone marrow failure,prompting hematopoietic stem cell transplantation.However,both cases were lost to follow-up after discharge.Conclusions Dyskeratosis congenita is a rare disease with various clinical manifestations.It may present with skin manifestations or hematological abnormalities.A precise diagnosis is made through a genetic testing.Currently,efficacious medical treatment for DC is lacking,and hematopoietic stem cell transplantation is necessary for patients with bone marrow failure.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H₂O₂) to disintegrate into CO and Mn²⁺. The comprehensive effect of CO/Mn²⁺ and CBD can induce ROS-mediated cell apoptosis. In addition, HMPOC@M-mediated excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that HMPOC@M+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.

OBJECTIVE: To evaluate the feasibility and safety of one- stage bilateral video-assisted thoracic surgery (VATS) for resection of bilateral multiple pulmonary nodules (BMPNs). METHODS: We analyzed the clinical characteristics, pathological features, perioperative outcomes and follow-up data of 41 patients with BMPNs undergoing one-stage bilateral VATS from July, 2011 to August, 2021. RESULTS: One-stage bilateral VATS was performed uneventfully in 40 of the patients, and conversion to open surgery occurred in 1 case. The surgical approaches included bilateral lobectomy (4.9%), lobar-sublobar resection (36.6%) and sublobar-sublobar resection (58.5%) with a mean operative time of 196.3±54.5 min, a mean blood loss of 224.6±139.5 mL, a mean thoracic drainage duration of 4.7±1.1 days and a mean hospital stay of 14±3.8 days. Pathological examination revealed bilateral primary lung cancer in 15 cases, unilateral primary lung cancer in 21 cases and bilateral benign lesions in 5 cases. A total of 112 pulmonary nodules were resected, including 67 malignant and 45 benign lesions. Postoperative complications included pulmonary infection (5 cases), respiratory failure (2 cases), asthma attack (2 cases), atrial fibrillation (2 cases), and drug-induced liver injury (1 case). No perioperative death occurred in these patients, who had a 1-year survival rate of 97.6%. CONCLUSION With appropriate preoperative screening and perioperative management, one-stage bilateral VATS is feasible and safe for resection of BMPNs.
Humans ; Multiple Pulmonary Nodules ; Thoracic Surgery, Video-Assisted ; Feasibility Studies ; Postoperative Complications ; Drainage

Objective:To investigate the expression of WT1 gene in children with acute lymphoblastic leukemia (ALL), and explore its clinical characteristics and correlation with the prognosis of ALL.Methods:The clinical data of 183 children with newly diagnosed ALL in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2015 to May 2019 were retrospectively analyzed. The expression level of WT1 gene in bone marrow samples was detected by real-time fluorescence quantitative polymerase chain reaction. The children were followed up to June 2021 with a median follow-up time of 46 months (0 to 63 months).Results:Among 183 children with ALL, the WT1 gene positive was in 130 cases (71.04%), and the expression level was 1.41% (0.26%, 6.73%); WT1 gene negative was in 53 cases (28.96%). The expression levels of WT1 gene in children with T-cell lymphoblastic leukemia (T-ALL), non-hyperdiploid and middle/high-risk were significantly increased, and there were statistical differences ( P<0.05 or <0.01); however, there were no statistical differences in the expression levels of WT1 gene between children with different gender, chromosome karyotype, hepatosplenomegaly and the first diagnosis white blood cell count ( P>0.05). There were no statistical differences in complete remission rate and recurrence rate after induction chemotherapy between WT1 gene positive children and WT1 gene negative children: 87.69% (114/130) vs. 86.79% (46/53) and 16.15% (21/130) vs. 18.87% (10/53), P>0.05. By the end of follow-up, 179 children were followed up, and there was no statistical difference in survival rate between WT1 gene positive children and WT1 gene negative children: 89.68% (113/126) vs. 86.79% (46/53), P>0.05. Among the children with WT1 gene positive, relapse was in 21 cases, and there was no statistical difference in the expression level of WT1 gene after complete remission or after relapse, compared with that while the first diagnosis ( P>0.05); among non-relapse children, 96 completed the detection, the expression level of WT1 gene after complete remission was significantly lower than the first diagnosis: 0.17% (0.04%, 0.49%) vs. 2.01% (0.41%, 8.82%), and there was statistical difference ( P<0.01). Kaplan-Meier survival curve analysis result showed there was no statistical difference in survival time between WT1 gene positive children and WT1 gene negative children ( P>0.05). According to the median expression level of WT1 gene (1.41%), the children with WT1 gene positive were divided into high expression (66 cases) and low expression (64 cases), there was no statistical difference in survival time between high expression children and low expression children ( P>0.05). Conclusions:WT1 gene is commonly expressed in children with ALL and is associated with some clinical features and prognosis of the children. Decreased WT1 gene expression may result in better prognosis.

Object:To explore the clinical effect of periacetabular osteotomy (PAO) in the treatment of developmental dysplasia of hip (DDH).Methods:The clinical data of 305 patients with DDH admitted to Tangshan Second Hospital from January 2012 to June 2018 were analyzed retrospectively. All patients were treated with PAO alone. There were 123 cases of left hip dysplasia, 131 cases of right hip dysplasia and 51 cases of double hip dysplasia (356 hips in total). The patients underwent X-ray examination before and on the second day after operation to compare the acetabular index and the lateral center edge angle (LCEA) and the anterior center edge angle (ACEA) of the acetabulum before and after operation. The ability of daily living and hip joint function were evaluated before and 6 months after operation, and Barthel index and Harris score of hip joint were compared before and after treatment. The measurement data with normal distribution are expressed in xˉ± s, and the paired t test was used for comparison before and after operation. The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison before and after surgery is performed by the rank sum test. Results:On the second day after operation, the LCEA and ACEA of 356 hip joints in 305 patients were greater than those before operation (32.5(20.0,47.5)° vs 8.5(-18.5 23.0)°, 29.0(18.5,52.3)° vs 2.5(-20.8, 24.5)°), while the acetabulum index was lower than that before operation (6.7(-8.4,12.5)° vs 26.8(10.0, 62.3)°), and the differences were statistically significant ( Z values were 51.50, 45.37, 32.22, all P<0.001). After 6 months of follow-up, the Barthel score and Harris score of the hip joint were higher than those before the operation (92.5±1.3) scores vs (65.6±1.5) scores, (96.4±2.5) scores vs (85.1±1.3) scores, and the difference was statistically significant ( t values were 335.56 and 89.70, both P<0.001). Conclusions:PAO can make the acetabulum cover the femoral head well through acetabular transposition, improve the ability of daily living and hip joint function of DDH patients, reduce pain, increase joint range of motion, and correct limb deformities. It is an effective means to treat DDH.