OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective:To investigate the role of RNA helicase DDX5 in renal interstitial fibrosis and its potential mechanism, and provide possible molecular target for the diagnosis and treatment of renal interstitial fibrosis.Methods:The animal and cell models of unilateral ureteral obstruction (UUO) and DDX5-pharmacological and genetic blocking were established. Twenty-four male mice aged 6-8 weeks and weighting about 18-22 g were divided into sham operation group, UUO group, sham operation+RX5902 group and UUO+RX5902 group by random number table method, with 6 mice in each group. Supinoxin (RX5902, a phosphorylated DDX5 inhibitor, 75 mg/kg) was administered by gavage in mice in the sham operation+RX5902 group and UUO+RX5902 group on day 0 and day 3 after the operation, respectively. The mice were sacrificed to collect kidney specimens one week after the surgery. The human renal tubular epithelial cell line (HK-2 cells) was routinely cultured and divided into control group, scramble siRNA group, DDX5 siRNA group, TGF-β1 group, scramble siRNA+TGF-β1 group and DDX5 siRNA +TGF-β1 group. The dosage of RX5902 was 20 nmol/L, and the dosage of transforming growth factor-β1 (TGF-β1) was 10 ng/ml. HE staining and Masson staining were used to evaluate renal tubule injury and collagen fiber deposition. Western blotting, immunofluorescence and immunohistochemistry were used to detect the protein expression levels of DDX5 and fibrosis-related indexes such as fibronectin and α-smooth muscle actin (α-SMA). The flow cytometry was used to detect the cell cycle. Results:In comparison to sham operation group, UUO group exhibited significantly elevated protein expression levels of fibronectin, α-SMA and DDX5 in kidney tissues (all P<0.05), accompanied by notable nuclear translocation of DDX5. TGF-β1 stimulation facilitated the upregulation of fibronectin, α-SMA, and DDX5 expression, as well as DDX5 nuclear translocation in HK-2 cells (all P<0.05). Pharmacological and genetic inhibition of DDX5 attenuated UUO or TGF-β1-induced elevated protein levels of fibronectin and α-SMA. Compared with scramble siRNA+TGF-β1 group, DDX5 siRNA+TGF-β1 group exhibited reduced protein expression levels of fibronectin, α-SMA and DDX5 in HK-2 cells (all P<0.05). Compared with UUO group, UUO+RX5902 group showed alleviation of renal epithelial cell exfoliation, renal tubule atrophy or lumen dilation and decreased scores of both tubular injury and interstitial collagen deposition, along with reduced protein expression levels of fibronectin, α-SMA and DDX5 (all P<0.05). Similarly, RX5902 inhibited TGF-β1-induced fibrotic responses in HK-2 cells (all P<0.05). Flow cytometry analysis results revealed that TGF-β1 stimulation resulted in a significant increase in the proportion of HK-2 cells in the G2/M phase. Conversely, silencing of DDX5 led to a significant reduction in the proportion of HK-2 cells in the G2/M phase (all P<0.05). Conclusions:DDX5 is significantly elevated in the renal tissues of UUO mice and TGF-β1-induced HK-2 cells. The pharmacological and genetic blockade of DDX5 can delay renal fibrosis by reducing cell cycle arrest and alleviating cell damage.

Objective:To investigate the prognostic value and safety of thoracic radiotherapy in patients with synchronous oligometastatic, driver gene-negative non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) as first-line treatment.Methods:Data were retrospectively collected from 55 patients diagnosed with synchronous oligometastatic, driver gene-negative NSCLC who received first-line ICIs from January 2017 to March 2022. These patients were categorized into two groups based on the administration of thoracic radiotherapy: the thoracic radiotherapy group ( n = 27) and the non-thoracic radiotherapy group ( n = 28). Comparative analyses were conducted to evaluate survival outcomes and safety profiles between the two groups. Results:Among the 55 patients, 27 (49.1%) received thoracic radiotherapy. The median follow-up time was 37.0 months (2.2-76.7 months). Patients in the thoracic radiotherapy group exhibited significantly improved median overall survival (OS: 53.4 vs. 21.3 months, P = 0.049) and median progression-free survival (PFS: 13.6 vs. 8.3 months, χ2=4.11, P = 0.043) compared to those in the non-thoracic radiotherapy group. Multivariate Cox regression analysis identified thoracic radiotherapy as an independent prognostic factor for OS ( HR = 0.39, 95% CI: 0.17-0.90, P = 0.027) and PFS ( HR = 0.53, 95% CI: 0.28-0.99, P = 0.046). The most common grade 3 or higher toxicity was bone marrow suppression, occurring in seven patients (12.7%). There was no significant difference between both groups in the incidence of grade 3 or higher treatment-related adverse events, including pneumonitis. Conclusion:In patients with driver gene-negative, synchronous oligometastatic NSCLC, first-line immunotherapy combined with thoracic radiotherapy may improve survival outcomes without increasing the incidence of severe treatment-related adverse events. Further large-scale, randomized prospective trials are needed to verify the findings of this study.

Objective:Committee of Minimally Invasive Cardiovascular Surgery(CMICS) conducts an annual summary of minimally invasive cardiovascular surgery procedures performed throughout the country, which includes a comprehensive survey of the total number of minimally invasive procedures by region and the distribution of minimally invasive procedures by hospital. Since CMICS first published the 2018-2019 China Minimally Invasive Cardiovascular Surgery Data White Paper in 2020, the report has received great attention from peers within and outside the industry. In this statistical report, CMICS will focus on publishing the data related to minimally invasive cardiovascular surgery in China from 2021 to 2023 for reference and use by industry peers.

OBJECTIVES: To analyze the early clinical outcomes of the Xcor^TM transcatheter aortic valve replacement (TAVR) system in treating severe aortic stenosis. This study has been registered at Chinese Clinical Trial Registry (ChiCTR2200065593). METHODS: This single-arm, prospective clinical trial enrolled patients with severe aortic stenosis treated with the Xcor^TM TAVR system at the Section of Heart Valve & Coronary Artery Surgery, Guangdong Provincial People's Hospital. Perioperative and follow-up parameters were compared to evaluate differences in hemodynamic outcomes. All-cause mortality, aortic regurgitation, paravalvular leakage, cerebrovascular events, and reoperation were analyzed. RESULTS: Thirty-two patients with severe aortic stenosis were included (20 males, 12 females), with (70.9±4.3) years old and a Society of Thoracic Surgeons (STS) score of 6.45% (6.07%, 7.28%). Notably, 87.5% of patients had New York Heart Association (NYHA) class≥Ⅲ. All patients underwent successful Xcor^TM bioprosthesis implantation, achieving an immediate technical success rate of 100.0% and device success rate of 96.9%. Mean aortic valve gradient decreased from (55.21±23.17) mmHg (1 mmHg=0.133 kPa) to (8.45±5.30) mmHg, peak aortic jet velocity decreased from (4.66±0.85) m/s to (1.99±0.48) m/s, aortic valve area increased from (0.66±0.21) cm² to (2.09±0.67) cm² (all P<0.01). Intraoperative ventricular fibrillation occurred in one patient, while one case exhibited moderate prosthetic valve regurgitation and paravalvular leakage post-procedure. At 12-month follow-up, sustained improvements were observed in cardiac function, left ventricular ejection fraction, hemodynamic parameters, and SF-12 quality-of-life scores (all P<0.01). All-cause mortality was 12.5% (4/32), with 13.8% (4/29) developing moderate paravalvular leakage. CONCLUSIONS The Xcor^TM TAVR system demonstrated favorable early outcomes in severe aortic stenosis patients, significantly improving symptoms and hemodynamics while exhibiting excellent performance in preventing malignant arrhythmias and coronary obstruction.
Humans ; Male ; Female ; Aortic Valve Stenosis/surgery* ; Transcatheter Aortic Valve Replacement/methods* ; Aged ; Follow-Up Studies ; Prospective Studies ; Treatment Outcome ; Aged, 80 and over ; Heart Valve Prosthesis ; Middle Aged

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

Objective To analyze the current application status,research hotspots and develop-ment trends of sedation strategies from both domestic and international perspectives in mechanically ventilated patients in the intensive care unit(ICU).Methods Relevant literature on the application of sedation strategies in mechanically ventilated patients from 2014 to 2024 was retrieved from data-bases including China National Knowledge Infrastructure(CNKI),Wanfang and Web of Science.Visual analysis of publication volume and keywords was conducted using CiteSpace 6.2.R3 software.Results A total of 475 Chinese-language articles and 405 English-language articles were included.Significant differences were observed in publication volume between domestic and international re-search,with early domestic activity followed by a decline,while international research had demonstra-ted robust and sustained growth over the past five years.International studies primarily emphasized protocol-driven sedation processes and standardized strategies,whereas domestic research focused on optimizing the concept of comfort-oriented sedation management and exploring postoperative sedation strategies.Analysis of research hotspots revealed that precise pharmacological regulation,the development of disease-specific sedation strategies,and the establishment of multidisciplinary collaborative protocols were key areas of focus in sedation strategies for ICU mechanically ventilated patients.Conclusion Future research should prioritize shortening the update cycle of clinical guidelines,enhancing the transla-tion of evidence-based practices into clinical settings,establishing clear application standards for disease-specific sedation strategies,improving multicenter collaborative research capabilities,and developing artificial intelligence-based sedation monitoring technologies.