Volume 103 ·  Issue 24 ·  2023

Heart valve disease (HVD) is one of the most common cardiovascular diseases, and its incidence increases gradually with the aging of population. Surgery has long been the main solution to treat HVD. In recent years, the transcatheter interventional therapy of HVD has made great progress with the continuous technology innovation and improvement of devices. This article mainly describes the applications and challenges of transcatheter interventional therapy in aortic valve, mitral valve, tricuspid valve and pulmonary valve.

The Asian Pacific Society of Cardiology proposed an expert consensus on the treatment of mitral regurgitation (MR) using transcatheter edge-to-edge repair technique (the representative product: MitraClip) in 2021. The expert panel reviewed the latest literature to develop consensus recommendations on the use of MitraClip for treating MR. The current article combines the current situation of MR treatment in China and provides a comprehensive interpretation and reflection on the consensus in terms of the concept and classification of MR, and the use of MitraClip for the treatment of degenerative and functional MR, thereby providing valuable reference for the clinical practice of MR treatment in China.

Patients with intrahepatic cholangiocarcinoma have a poor overall prognosis and a low long-term survival rate. Currently, multimodal treatment is the mainstay of treatment, and surgical resection is the most important treatment for patients with intrahepatic cholangiocarcinoma for a long-term survival. Although the treatment strategies have been constantly updated in recent years to improve survival rates, there are still many controversial issues in the existing treatment strategies. Based on our center′s clinical practice and recent research progress, analyzes several issues affecting long-term survival were analyzed based on three aspects: accurate clinical assessment methods, the related decisions making for surgical resection, and the strategies of precision medicine.

To investigate the risk and influencing factors of long-term mortality of valvular heart disease (VHD) adults aged 35 years and over in Chinese communities.

A cohort study was carried out. The data of the subjects who underwent echocardiography were collected from the Chinese Hypertension Survey between 2012 and 2015 and survival outcomes were followed up between 2018 and 2019. Kaplan-Meier survival curves were plotted and compared using log-rank test. Cox proportional hazards models were used to analyze the influence of VHD on mortality.

During an average follow-up time of (4.6±0.9) years, a total of 23 237 participants (10 881 males and 12 356 females) were pooled into the final analysis from 5 eastern, 5 central, and 4 western provinces, cities and autonomous regions in China, with a mean age of (56.9±13.2) years. Among the included participants, 1 004 had VHD (467 males and 537 females), with a mean age was of (68.1±12.6) years. In the Kaplan-Meier analysis, participants with VHD had a significantly increased risk of all-cause mortality (log-rank χ²=351.82, P<0.001) and cardiovascular mortality (log-rank χ²=284.14, P<0.001) compared with those without VHD. Multivariate Cox regression analysis showed that compared with those without VHD, the participants with rheumatic VHD had a 45% increased risk of all-cause mortality (HR=1.45, 95%CI: 1.12-1.89) and degenerative VHD increased the risk of cardiovascular mortality by 69% (HR=1.69, 95%CI: 1.19-2.38). The risk factors of cardiovascular mortality for VHD were age 55 years and over (55-<75 years: HR=4.93, 95%CI: 1.17-20.85;≥75 years: HR=11.92, 95%CI: 2.85-49.80) and diabetes mellitus (HR=1.71, 95%CI: 1.00-2.93).

VHD is a risk factor of all-cause mortality and cardiovascular mortality among adults aged 35 years and over. Age 55 years and over and diabetes mellitus are adverse prognostic factors for patients with VHD.

To analyze the incidence and risk factors of ventricular septal defect (VSD) in Qingdao.

A prospective cohort study design was used to include pregnant women who underwent prenatal screening in Qingdao between August 2018 and June 2020 (the whole population coverage). VSD was diagnosed according to the pulse oxygen saturation and heart auscultation, and the final diagnosis was made according to the echocardiography of VSD positive newborns within postnatal day 7.

The study included 115 238 live births, among which 388 were diagnosed as VSD, with an incidence of 3.37‰. The results of multivariate logistic regression analysis showed that mother with postgraduate level (OR=1.61, 95%CI: 1.00-2.58, P=0.049) (compared with junior high school and below), preterm birth history (OR=2.90, 95%CI: 1.47-5.70, P=0.002), and pregnancy history of congenital heart disease (OR=5.98, 95%CI: 2.63-14.73, P<0.001) were risk factors for VSD. Compared with female infants, the overall risk of VSD in male infants was relatively low (OR=0.74, 95%CI: 0.60-0.91, P=0.005).

The incidence of VSD in Qingdao is 3.37‰. The risk factors of VSD include higher maternal education level, pregnancy history of congenital heart disease and preterm birth history. Moreover, the overall risk of VSD in male infants is low.

To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis.

The clinical data of patients with severe aortic stenosis who underwent TAVR at the People′s Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded.

A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm² vs (0.65±0.21) cm², P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly.

TAVR is effective and safe for patients with severe aortic stenosis.

To analyze the recurrence pattern of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy.

The clinicopathological characteristics and follow-up information of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy in the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2004 to December 2017 were retrospectively collected. The recurrence pattern including the time and site was investigated.

The age of 537 patients was (55.5±11.7) years, of whom 361 were male (67.2%). The median follow-up time [M(Q₁,Q₃)] was 77.9 (64.5, 95.6) months. Moreover, 30.7% (165/537) of patients had distant metastasis or local recurrence; 26.8% (144/537) of patients had distant metastasis; 5.6% (30/537) of patients had local recurrence; 1.7% (9/537) of patients had both distant metastasis and local recurrence. In all the recurrent patients, 23.6% (39/165) were in the first year after surgery, followed by 27.3% (45/165) in the second year, 17.0% (28/165) in the third year, and 15.8% (26/165) after five years. According to the risk curve drawn by the life table, the highest metastasis risk of patients occurred in the second year after surgery, and the metastasis risk peak occurred again after more than five years. The lung was the most common metastatic organ, accounting for 47.9% (69/144), followed by the liver (18.8%, 27/144). The ratios of the recurrent patients in each ypTNM stage were 9.5% (8/84), 12.0% (12/100), 26.5% (41/155), 52.5% (104/198), respectively. The proportion of recurrent patients in tumor regression grade (TRG) 1-2 and TRG 3-5 patients were 19.2% (38/198) and 37.5% (127/339), respectively.

The recurrence pattern of patients undergoing radical surgery after neoadjuvant chemoradiotherapy is mainly distant metastasis. The lung is the primary metastatic organ. The risk of distant metastasis and local recurrence is high in the first three years after surgery, and there is still high risk of recurrence after five years. For patients with ypTNM stage 2, 3 and TRG3-5, the postoperative adjuvant chemotherapy and long-term follow-up should be strengthened.

To establish a hysteroscopic chronic endometritis (hCE) scoring system for patients with chronic endometritis, and observe the correlation of hCE score with in vitro fertilization-embryo transfer (IVF-ET) pregnancy outcomes in infertile women.

The study retrospectively investigated the correlation of morphologic features and hCE score with pregnancy outcomes during IVF-ET in infertile women with CE (n=429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The clinical pregnancy rate and live birth rate with different score levels (1-3,4-7 and 8-14) after IVF-ET treatment were analyzed. Multivariate regression analysis was performed to adjust for confounding factors. The correlation and regression between hCE score and pregnancy outcomes was analyzed by curve fitting.

The age of 429 patients [M(Q₁, Q₃)] was 31 (29, 35) years. There were 50.6% (217 cases), 35.4% (152 cases), and 14.0% (60 cases) of patients with hCE score of 1-3, 4-7, and 8-14, respectively. The pregnancy rates of the three groups were 60.8% (132 cases), 44.7% (68 cases) and 16.7% (10 cases), P<0.001; The live birth rates were 51.2% (111 cases), 36.8% (56 cases) and 13.3% (8 cases), respectively (P<0.001). Compared with patients with hCE of 1-3, pregnancy rates in those with hCE of 4-7 and 8-14 were lower, and the OR values were 0.521 (0.342-0.793) and 0.129 (0.062-0.268). The live birth rates in patients with hCE of 4-7 and 8-14 were lower than that in patients with hCE of 1-3, and the OR values were 0.570 (0.372-0.873) and 0.162 (0.073-0.360), all P<0.05. Quadratic curve fitting results showed that clinical pregnancy rate and live birth rate decreased with the increase of hCE score.

With the increase of hCE score, the clinical pregnancy rate and live birth rate of patients gradually decrease. hCE 4 is an important cut-off threshold significantly affecting the pregnancy outcome.

A prospective, single-center, single-arm, and open-design study was performed to evaluate the feasibility and safety of transseptal transcatheter mitral valve replacement in the treatment of severe mitral regurgitation. Patients with symptomatic moderate-severe or severe mitral regurgitation at high-surgical risk and anatomically appropriate for the HighLife transseptal mitral valve replacement (TSMVR) system in West China Hospital, Sichuan University from December 2021 to August 2022 were enrolled. Four patients (1 male and 3 females) with severe mitral regurgitation were included, with a median age of 68.5 (64.0-77.0) years and a median Society of Thoracic Surgeons (STS) score of 8.1% (6.4%-8.9%). Technical success was achieved in all the patients. There was no residual mitral regurgitation, paravalvular leakage, or left ventricular outflow tract obstruction. Three major cardiovascular and cerebrovascular adverse events occurred within 30 days after the procedure, including ventricular tachycardia, iatrogenic atrial septal defect closure, and heart failure readmission. The current study preliminarily demonstrates that transcatheter mitral valve replacement using the HighLife system via the transseptal approach for severe mitral regurgitation is feasible and relatively safe.

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years. The Eastern Cooperative Oncology Group(ECOG) score was 0 in 6 cases and 1 in 2 cases. There were 5 cases of high-grade urothelial carcinoma (1 case of T3b; 2 cases were T2; 2 cases of T1 stage, with multiple tumors and repeated recurrence), 1 case of high-grade urothelial carcinoma with carcinoma in situ (T1/Tis stage), 1 case of high-grade urothelial carcinoma with squamous differentiation (T3b stage), and 1 case of high-grade urothelial carcinoma with glandular differentiation (T2). All patients underwent "quadri-combination" therapy.The patient′s tolerance, success rate of bladder preservation and prognosis were evaluated.The median follow-up time was 22.5 (12-35) months. One patient with high-grade muscle-invasive bladder cancer (T2) received mTURBT, albumin-bound paclitaxel and durvalumab combined therapy for 3 cycles, concurrent radiotherapy, and immune maintenance therapy for 18 months, and the tumor recurrence was found. The pathology was high-grade urothelial carcinoma. Salvage radical cystectomy combined with pelvic lymph node dissection is recommended. The remaining 7 patients were regularly reexamined, and no recurrence or metastasis was found.The 2-year progression-free survival rate was 80%, and the success rate of bladder preservation was 87.5%(7/8). Treatment-related adverse reactions were resolved by symptomatic treatment, and patients′ compliance and tolerance were acceptable.The "quadri-combination" bladder-preserving therapy is feasible and well tolerated, but further studies are needed.

The current study aimed to evaluate the early efficacy in infants with isolated non-syndromic sagittal synostosis who underwent minimally invasive endoscopic-assisted surgery. The clinical data of infants with isolated non-syndromic sagittal synostosis who were admitted to the Department of Neurosurgery of the Children′s Hospital of Nanjing Medical University and underwent endoscopic-assisted surgery from October 2018 to December 2021 were retrospectively analyzed. All the infants underwent minimally invasive endoscopic-assisted surgery, and were treated with supine sleeping position after surgery. Computer-aided reconstruction technique was used to reconstruct and measure the thin-slice CT scan images of the head before and 3 months after surgery, and the differences in cranial index (CI), cranial cavity volume and angle drawn between the cranial vertex, nasion, and opisthocranion (VNO angle) of preoperative and postoperative groups were analyzed. A total of 103 infants were included in the final analysis, including 85 males and 18 females. The age at surgery was (2.1±0.8) months, and the weight was (6.1±0.9) kg. The postoperative CI was (84±6)%, which increased obviously compared with the pre-operation [(70±5)%] (P<0.001). The cranial volume of post-operation was (947±130) cm³, which was larger than that of the pre-operation [(748±104) cm³] (P<0.001). The VNO angle after surgery was (45±4)°, which showed a significant reduction compared with the pre-operation [(55±4)°] (P<0.001). The correction of head shape was satisfactory. For the treatment of sagittal synostosis in infants, minimally invasive endoscopic-assisted surgery is safe and effective, and in the case of switching from an auxiliary helmet to a supine position, the postoperative correction efficacy of head shape is better.

To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of uterine carcinosarcoma (UCS), and to explore the gene mutation characteristics and tumor mutation burden (TMB) of UCS. The clinical imaging, pathomorphological data and immunohistochemical expression of 4 cases of UCS, which were archived in the Department of Pathology of the Second Affiliated Hospital of Soochow University from January 2021 to May 2022 were retrospectively analyzed. All exon groups of 4 cases of UCS were sequenced. All the 4 patients were female, aged 47-81 years. The maximum diameter of the tumor was 4.0-13.0 cm, and the boundary was unclear. Microscopically, the tumor was composed of malignant epithelium and sarcoma. Immunohistochemistry showed that the epithelial components of 4 patients expressed broad-spectrum cytokeratin (AE1/E3), the sarcoma components expressed Vimentin, PAX8, ER, PR were expressed to varying degrees, and Ki-67 positive index was high (60%-90%). There were 3 p53 missense mutations, 1 nonsense mutation, 4 MLH1, PMS2, MSH2, MSH6 were positive and PD-L1 was negative. The sequencing results of the whole exon group of 4 UCS patients showed that TP53, BCL9L, BRD4, CLTCLI, PSMD1I, PLEC genes showed a high mutation ratio, which was 3/4, 2/4, 2/4, 2/4, 2/4, 2/4, respectively. TMB analysis showed that the TMB of 4 cases of UCS was<5 mut/Mb. UCS is a rare and highly malignant endometrial tumor. The sequencing results of the whole exon group suggested that TP53, BCL9L, BRD4 and other genes had high mutation rates, suggesting that the occurrence and development of UCS may be closely related to Wnt signaling pathway. Molecular typing indicated that 3 cases of UCS were of high copy number type/p53 mutation type, and 1 case had POLD1 mutation. Microsatellite stability, low PD-L1 expression and TMB results suggested that UCS patients have no obvious advantage in immunotherapy.

A case of type I neurofibromatosis with family history was reported. He was admitted to hospital because of "left retroperitoneal occupation found on physical examination". After admission, blood neuronal enolase, abdominal MRI and CT examination considered the possibility of neurogenic tumor. The tumor was surgically explored and removed, and the postoperative pathology showed: ganglioneuroblastoma (nodular type). According to the Chinese Children's Cancer Committee (CCCG) -Neuroblastoma (NB) -2021 protocol, the stage was L2, and it was entered into the low-risk group.

Transcatheter aortic valve replacement (TAVR) has become a reliable treatment for patients with aortic valve disease, and accurate preoperative evaluation is crucial for the operator. Cardiovascular 3D printing technology can provide more rich information that is difficult to display in traditional imaging examinations, thus greatly simplifying and standardizing the above complex processes and making TAVR surgery more accurate and safe. The purpose of this review is to discuss the current research status of this field at home and abroad from the aspects of model printing, preoperative simulation and protocol formulation, major complication prediction, postoperative verification and teaching training, and to prospect the future development direction of this technology in guiding TAVR surgery.

Acute respiratory distress syndrome (ARDS) is a common severe syndrome. Although it has been studied for more than 50 years, its pathophysiological mechanism and effective treatment are still being explored. As important immune cells in lung, macrophages exhibit functions such as recruitment, migration, polarization, pyroptosis and phagocytosis according to different microenvironments, and play a pro-inflammatory or anti-inflammatory role in different stages of ARDS. Extracellular vesicles, as a kind of nanoscale membrane vesicle structure, realize information exchange between different cells through surface receptor interaction or transfer of substances. In recent years, more and more studies have shown that other lung cells (including alveolar epithelial cells, pulmonary capillary endothelial cells, neutrophils), extrapulmonary tissues and pathogenic microorganisms secrete a large number of pro-inflammatory, anti-inflammatory and pro-fibrotic extracellular vesicles, which act on macrophages, thereby mediating the occurrence, development and regression of ARDS. Extracellular vesicles of mesenchymal stem cells can also regulate the phenotype of alveolar macrophages through different mechanisms, and play a role in alleviating lung injury in ARDS. This paper reviews the research progress of extracellular vesicles from different sources mediating ARDS through the regulation of macrophage function, in order to provide new ideas and references in the study of the pathogenesis, diagnosis and treatment of ARDS.

In children undergoing cardiac surgery, injection of nitric oxide into the airflow of an extracorporeal circulation oxygenator reduces the occurrence of postoperative low cardiac output syndrome, thereby promoting recovery and shortening invasive mechanical ventilation time. It is not clear whether injection of nitric oxide into an extracorporeal bypass oxygenator improves ventilator-free days (survival and no mechanical ventilation days). To clarify the effect of nitric oxide applied to an extracorporeal oxygenator and standard therapy on the number of days without mechanical ventilation in children undergoing congenital heart disease surgery, the study group conducted a double-blind, multicenter, randomized clinical trial in six pediatric cardiac surgery centers in Australia, New Zealand and the Netherlands. Between July 2017 and April 2021, a total of 1 371 children under 2 years of age who underwent surgery for congenital heart disease (7 children did not undergo cardiopulmonary bypass) were enrolled, and the last participant completed a 28-day follow-up on 24 May 2021. Children were randomly assigned to receive a concentration of 20×10^-6Nitric oxide injection into an extracorporeal bypass oxygenator therapy (n=679) or standard cardiopulmonary bypass therapy without nitric oxide (n=685）。 The primary outcome was the number of days without mechanical ventilation from the start of cardiopulmonary bypass to Day 28. The four secondary outcomes were low cardiac output syndrome, extracorporeal life support or death, length of stay in intensive care unit, total length of stay, and postoperative troponin levels. A total of 1 371 children, aged (21.2±23.5) weeks, 587 (42.8%) were female and 1 364 (99.5%) completed the trial. The results showed no statistically significant difference in the number of days without mechanical ventilation between the nitric oxide group and the standard treatment group, with a median of 26.6 d (IQR: 24.4 to 27.4) and 26.4 d (IQR: 24.0 to 27.2), with an absolute difference of-0.01 d (95%CI：-0.25~0.22，P=0.92）。 22.5% and 20.9% of patients in the nitric oxide and standard treatment groups, respectively, developed low cardiac output syndrome or required extracorporeal life support within 48 h, or died within 28 d (adjustedOR=1.12，95%CI：0.85~1.47）。 There were no significant differences in other secondary outcomes between the two groups. The results of this study indicate that in children under 2 years of age who underwent cardiopulmonary bypass for congenital heart disease surgery, the use of cardiopulmonary nitric oxide has no significant effect on the number of days without mechanical ventilation. This finding does not support the application of nitric oxide to an extracorporeal circulation oxygenator in cardiac surgery.

The rapid development of virtual healthcare leads to a surge in the amount of information received by patients, accompanied by more workload and burnout of medical professionals. Artificial intelligence (AI) assistants may assist in drafting responses to patient questions, which are reviewed by clinicians. The study evaluated the ability of the AI Chatbot Assistant (ChatGPT), released in November 2022, to provide high-quality and empathetic answers to patients' questions. The study randomly selected 195 sessions in October 2022 from a database of questions from a public social media forum (Reddit'r/AskDocs) where an already certified physician answered patients'questions. While the chatbot answers were generated by entering the original question into the new conversation box on December 22 and 23, 2022. The original questions and anonymous and randomly sorted physician and chatbot responses were evaluated 3 times by a team of licensed medical professionals. Evaluators choose "whose response is better" and judge "quality of information provided" (very poor, poor, acceptable, good, or very good) and "empathy provided or attitude towards the patient" (no empathy, slightly empathy, moderately empathy, empathy, and very empathy) and compare the responses of the chatbot and the physician. 78.6% of 585 assessments (95%CI: 75.0% ~81.8%) of evaluators preferred the responses of chatbots. Average of physician responses (IQR) is significantly less than that of the chatbot [52 (17-62) than 211 (168-245) words,t=25.4，P<0.001]。 The quality of answers from chatbots was significantly higher than that of physicians (t=13.3，P<0.001）。 For example, the proportion of chatbots rated as good or very good in response quality was higher than that of physicians (chatbots: 78.5%, 95%CI：72.3%~84.1%； Physicians: 22.1%, 95%CI：16.4%~28.2%）。 This is equivalent to 3.6 times the proportion of chatbot answers that are good or very good than physicians. The chatbot's response was more empathetic than the physician's (t=18.9，P<0.001）。 The proportion of responses rated as empathetic or very empathetic was higher for chatbots than for physicians (chatbots: 45.1%, 95%CI：38.5%~51.8%； Physicians: 4.6%, 95%CI：2.1%~7.7%）。 This equates to 9.8 times the proportion of chatbots responding empathetically or very empathetically compared to physicians. In the study, the chatbots were high-quality and empathetic in response to questions about patients in online forums. It is necessary to further explore this technique in clinical work, such as using chatbots to draft drafts of responses, which are then edited and revised by physicians. Randomized trials can further evaluate whether the use of AI assistants can improve response, reduce clinician burnout for occupation, and improve patient prognosis.

Patent ductus arteriosus (PDA) in infants and young children is commonly treated with cyclooxygenase (COX) inhibitors, but the efficacy of such drugs is not clear. In this multicenter, non-inferiority trial, very premature infants (gestational age) with echocardiographic diagnosis of PDA (>1.5 mm diameter, left-to-right shunt<28 weeks) were randomly assigned to either expectant treatment or early ibuprofen treatment. Primary outcomes included necrotizing enterocolitis (Bell grade IIA and above), moderate to severe bronchopulmonary dysplasia, or death within 36 weeks of modified gestational age. Non-inferiority of expected treatment compared to early ibuprofen treatment was defined as unilateral 95%CIThe upper limit of<Absolute hazard margin of 10 percentage points. A total of 273 children were randomized with a median gestational age of 26 weeks and a median birth weight of 845 g. The primary outcome event occurred in 63 (46.3%) of 136 children in the expected treatment group and in 87 (63.5%) of 137 children in the early ibuprofen treatment group (difference in absolute risk = -17.2%, unilateral 95%CIUpper limit = -7.4%, non-inferiorityP<0.001）。 Necrotizing enterocolitis occurred in 24 of 136 children (17.6%) in the expected treatment group and in 21 of 137 children (15.3%) in the early ibuprofen treatment group (absolute risk difference =2.3%, bilateral 95%CI：-6.5%~11.1%）。 In the expectant treatment group, 117 patients were evaluated for bronchopulmonary dysplasia, and 39 patients (33.3%) were moderate to severe bronchopulmonary dysplasia; 112 children in the early ibuprofen treatment group were evaluated, and 57 (50.9%) were diagnosed with moderate to severe bronchopulmonary dysplasia (absolute risk difference = -17.6%, bilateral 95%CI：-30.2%~-5.0%）。 There were 19 (14.0%) deaths in the expected treatment group and 25 (18.2%) deaths in the early ibuprofen treatment group (absolute risk difference = -4.3%, bilateral 95%CI：-13.0%~4.4%）。 The incidence of other adverse events was similar in both groups. It is therefore concluded that expectant treatment of PDA in very premature infants shows no inferior effect to early ibuprofen treatment in reducing the incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, or death within 36 weeks of corrected gestational age.