[Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve].

Objective: To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR). Methods: This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ² test. Results: No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time (M(IQR)) was 109 (34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76 (26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was complete in all patients, with a follow-up of 5.5 (9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion: For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

[Application of PRAME immunohistochemistry in the differential diagnosis of primary endometrial and endocervical adenocarcinomas].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.

[Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases].

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.

[Short-term efficacy of anti-IgE monoclonal antibody in patients with recurrent chronic rhinosinusitis with nasal polyps combined with asthma].

Objective: To investigate the short-term efficacy of anti-IgE monoclonal antibody (Omalizumab) in the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) complicated with asthma. Methods: Patients with recurrent CRSwNP and comorbid asthma in Beijing TongRen Hospital from May to December of 2020 were continuously recruited and received a 4-month therapy of stable background treatment plus Omalizumab. Results of visual analog scales (VAS) of nasal symptoms, sino-nasal outcome test-22 (SNOT 22) and nasal polyp scores were collected at baseline and post-treatment (1, 2, 3 and 4 months after treatment). Blood routine tests, total nasal resistances (TNR), minimum cross-sectional areas (MCA), total nasal cavity volumes (NCV), forced expiratory volumes in one second (FEV1)/forced vital capacity (FVC) and adverse events were collected at baseline and 4 months after treatment. All results were evaluated for short-term efficacy of Omalizumab. GraphPad Prism 8.2.1 was used for statistic analysis. Results: Ten patients were collected, including 3 males and 7 females, aged (41.13±12.64) years old (x¯±s). Compared to results at baseline, the VAS scores of nasal obstruction, rhinorrhea, hyposmia and headache after 4 months treatment were significantly decreased (1.80±1.48 vs 6.70±2.83, 2.40±1.27 vs 6.40±3.44, 2.70±2.91 vs 8.20±2.25, 0.60±1.08 vs 3.60±2.72, t value was 5.045, 4.243, 5.312, 3.402, respectively, all P<0.01). The scores of SNOT-22 (25.6±20 vs 61.3±33.32, t=4.127, P=0.002 6), nasal polyp scores (2.20±0.92 vs 4.60±0.84, t=9.000, P<0.01) and the count and percentage of eosinophils in peripheral blood were significantly decreased ((94.10±97.78)×109/L vs (360.00±210.80)×109/L, (32.90±27.06)% vs (64.40±20.73)%, t value was 3.678, 2.957, respectively, all P<0.05). NCV (0-5 cm and 0-7 cm) of patients were improved from baseline ((12.62±2.84) cm3 vs (10.40±2.09) cm3, (27.50±14.15) cm3 vs (16.81±6.40) cm3, t value was 2.371, 2.445, respectively, all P<0.05). Conclusions: The 4-month treatment of Omalizumab can significantly improve the nasal symptoms and quality of life of patients with recurrent CRSwNP complicated with asthma, shrink nasal polyps size and reduce the number of peripheral blood eosinophils. Omalizumab can be used as an alternative therapy for refractory CRSwNP patients in the future.

[Comparison of myotomy and coronary artery bypass grafting in surgical treatment of symptomatic left anterior descending myocardial bridges].

Objective: To compare the effect of myotomy and coronary artery bypass grafting (CABG) to treat symptomatic myocardial bridges (MBs) of the left anterior descending artery (LAD). Methods: From January 2009 to December 2017, a total of 54 eligible patients [34 males, 20 females, with a median age of 60 (51, 64) years old] with symptomatic MBs of LAD who underwent myotomy (31 patients) or CABG (23 patients) at the Department of Cardiovascular Surgery of Zhongshan Hospital, Fudan University were included in the study. Surgical effect of the two groups were compared and multivariate logistic regression models were used to analyze the risk factors of major adverse cardiac events (MACE). Results: No significant differences between the two groups were observed with respect to age, gender, risk factors of coronary artery disease (CAD), symptoms, angiographic findings of MBs and preoperative cardiac status, and 0 surgery-associated death was observed. Among the 31 myotomy patients, 4 patients underwent off-pump myotomy (including one patient who underwent urgent conversion from off-pump to on-pump surgery due to massive hemorrhaging secondary to the right ventricular perforation), and the remaining 27 cases received myotomy under cardiopulmonary bypass with cardiac arrest. All 23 bypass surgery patients underwent off-pump CABG surgery with in situ left internal mammary artery (LIMA) grafting to the distal LAD. After LIMA grafting, the median graft flow was 14 (11, 20) ml/min. During a median follow-up of 26 months, 11 patients developed MACEs (7.4% for myotomy vs 40.9% for bypass surgery, P=0.007). Surgical strategy (CABG surgery vs myotomy) was an independent risk factor for MACE (OR=3.681, 95% CI: 1.812-8.685, P=0.011). Compared with myotomy, CABG surgery had a significantly higher incidence of adverse angiographic results (3.7% of residual compression vs 40.9% of LIMA graft failure, P=0.003). Among 10 CABG surgery patients with LAD-MBs and proximal coronary obstruction, all LIMA grafts were patent, though one case reported recurrent angina pectoris 2 years after the surgery which was relieved after drug therapy. Conclusions: For patients with symtomatic LAD-MBs, myotomy may be associated with favorable mid-term outcomes and angiographic results. However, CABG surgery should be recommended for those with concomitant proximal obstruction of LAD.

The crosstalk between IGF-1R and ER-α in the proliferation and anti-inflammation of nucleus pulposus cells.

OBJECTIVE: Insulin-like growth factors-1 receptor (IGF-1R) and estrogen receptor (ER) are reported to co-express and engage in crosstalk involving in the synergistic effect of various aspects. It is unknown whether this crosstalk exists in the nucleus pulposus (NP) cells. We aimed to investigate the interaction between IGF-1R and ER-α in regulating NP cell proliferation and inflammation response under IGF-1 stimulation. PATIENTS AND METHODS: We analyzed the IGF-1, IGF-1R, and ER-α in different degenerated degree human NP tissues. NP cells were cultured with IGF-1 protein with or without the inhibitor of IGF-1R or ER-α to investigate their effects on the proliferation and inflammation response. In addition, we also upregulated the IFG-1R and ER-α expression by plasmid transfection to investigate the impact on each other. The content of IGF-1, IFG-1R, and ER-α was analyzed by enzyme-linked immunosorbent assay (ELISA). The proliferative cell rate was determined by flow cytometry. Additionally, intracellular collagen-II, p16, PCNA, IL-1ß, IL-6, TNF-α, and MMP-13 expression were also detected. RESULTS: We found IGF-1, IFG-1R, and ER-α content were decreased in higher degenerated NP tissues. IGF-1 protein treatment upregulated the IFG-1R and ER-α expression and promoted NP cell proliferation, collagen-II, and PCNA expression. However, the suppression of IGF-1R (or ER-α) weakened the IGF-1 induced collagen-II expression, proliferation, and anti-inflammation effects on NP cells, decreased ER-α (or IGF-1R) expression, and partly reversed the protective effect of NP cells caused by IGF-1 Similarly, the upregulation of one of IGF-1R and ER-α may increase the other as well. CONCLUSIONS: There is an interaction between IGF-1R and ER-α acts synergistically to promote the proliferation and suppress inflammation in NP cells.

[Current status and prospect of surgical strategy for isolated tricuspid regurgitation following left-sided valve surgery].

Severe isolated tricuspid regurgitation following left-sided heart valve surgery appears a growing clinical concern. Due to elevated operational risk of redo-sternotomy operation, it brings upon poor prognosis and decreased quality of life for these patients, and technical challenges for cardiac surgeons as well. With the advancing of minimally invasive surgical theory and skills, Chinese cardiac surgeons are building up their own surgical experience with this patient population. However, there remains controversy about the optimal surgical timing and strategy for these high-risk patients. With the lack of recommendation from evidence-based medicine, it is necessary to learn from the pioneers' experience and contemplate on gains and losses in clinical practice, which would help to improve the safety and outcome of the procedure and to benefit these patients.

[Short-term outcomes of minimally invasive reoperation for tricuspid regurgitation after left-sided valve surgery].

Objective: To examine the short-term outcomes of minimally invasive reoperation for severe tricuspid regurgitation after left-sided valve surgery. Methods: From January 2015 to December 2018, a total of 89 patients with severe tricuspid regurgitation after left-sided valve surgery received reoperation in Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University were included in this study. There were 21 males and 68 females, aging of (56.4±7.9) years (range: 41 to 74 years). The interval between previous left-sided valve surgery and tricuspid reoperation was (14.1±6.1) years (range: 4 to 33 years). A combination of multiple minimally invasive techniques were adopted, including endoscopy-assist right minithoracotomy approach, peripheral cannulation strategy with the vacuum-assist single venous drainage technique, heart beating technique, and temporary percutaneous pacemaker implantation, with a concomitant enhancement in preoperative right cardiac function optimization. Results: All patients received minimally invasive isolated tricuspid valve replacement (n=81) or tricuspid valve repair (n=8). After the application of multiple minimally invasive techniques, the operative mortality rate was only 3.4% (3/89). The causes of death were progressive right heart failure with multiorgan failure (n=1) and low cardiac output associated with postoperative bleeding (n=2). Regarding to the perioperative complications, renal replacement therapy rate was 5.6% (5/89), permanent pacemaker implantation rate was 1.1% (1/89), and the incidence of stroke was 0. Mechanical ventilation time was 24(24) hours, ICU stay time was 2.5 (3.0) days (M(Q(R))). During the short-term follow-up, there were no case of severe tricuspid regurgitation, 2 cases of moderate regurgitation, 4 cases of mild-to-moderate regurgitation. Conclusions: For severe tricuspid regurgitation after left-sided valve surgery, the advanced minimally invasive techniques can significantly reduce the operative mortality and morbidity. Minimally invasive bioprosthetic tricuspid valve replacement is a reliable alternative for severe tricuspid regurgitation after left-sided valve surgery.

[Surgical treatment for tricuspid regurgitation after left-sided valve surgery].

Late tricuspid regurgitation after left-sided valve surgery can negatively affect long-term prognosis. The surgical timing and strategy of tricuspid valve reoperation will have important impact on the surgical outcomes. However, there is no clear recommendations of the surgical timing for this condition in the current guidelines. Generally, tricuspid valve reoperation should be performed before irreversible right heart failure occurs. Although tricuspid valve repair is the first choice for tricuspid regurgitation, bioprosthetic tricuspid valve replacement might be a reliable alternative when tricuspid leaflets have severe rheumatic damage or right ventricle and tricuspid annulus significantly dilate. Combined minimally invasive surgical techniques, including right minithoracotomy approach, accessing the right atrium directly through the pericardium with limited dissection, peripheral cannulation strategy with the vacuum-assist single venous drainage technique and heart beating technique, can significantly decrease the operative mortality and postoperative bleeding. With development of interventional therapy, transcatheter tricuspid valve repair or replacement may become alternatives for tricuspid regurgitation after left-sided valve surgery in the future.

LncRNA Bmncr alleviates the progression of osteoporosis by inhibiting RANML-induced osteoclast differentiation.

OBJECTIVE: To elucidate whether long non-coding RNA (lncRNA) Bmncr could inhibit RANML-induced osteoclast differentiation, thus alleviating the progression of osteoporosis. MATERIALS AND METHODS: Expression level of lncRNA Bmncr at different stages of osteoclast differentiation was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After Bmncr overexpression or knockdown in RAW 264.7 cells, expression levels of osteoclast-related genes were detected. Bone marrow mesenchymal stem cells (BMMs) isolated from rats undergoing ovariectomy (OVX) were induced with RANKL (50 ng/mL) and M-CSF (50 ng/mL) for 120 h. TRAP staining was conducted to count the number of TRAP-positive osteoclasts containing more than three nuclei. Bone resorption area of bone fragments was quantitatively analyzed. Osteoporosis model in mice was established. Mice were subjected to MicroCT analyses for recording BMD and BV/TV. The expression level of lncRNA Bmncr in the marrow and spleen of osteoporosis mice was examined. RESULTS: LncRNA Bmncr was lowly expressed in the marrow and spleen of osteoporosis mice. Besides, Bmncr expression gradually downregulated during RANKL-induced in vitro osteoclast differentiation, reaching the lowest level at 72 h. The overexpression of Bmncr reduced the amount of osteoclasts, inhibited bone resorption capacity, and downregulated expression levels of Atp6v0d2, Acp5, Ctr, and Mmp9. Conversely, Bmncr knockdown obtained the opposite trends. CONCLUSIONS: LncRNA Bmncr inhibits RANKL-induced osteoclast differentiation, thus alleviating the progression of osteoporosis.

[Problems and thoughts of preserving femoral head treatment of osteonecrosis of femoral head].

By literature review and experience summary, some problems are found in conservative treatment of osteonecrosis of femoral head(ONFH): lacking in researches of natural history of ONFH, disunion in classfication and the standard of outcome evaluation, lacking in high-level-evidence study and standard of treatment methods. It is necessary to improve the study on natural history of ONFH, unify the classfications and the standard of outcome evaluations, normalize the treatment methods, and design impeccable multi-centre study for improving the effect of conservative treatment of ONFH.