Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

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 completed 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.

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 completed 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.

Objective:To investigate the accuracy and reproducibility of diaphragmatic excursion (DE) measurements through hepato-renal/spleno-renal section as a novel method for assessing diaphragmatic function.Methods:Twelve healthy participants were recruited. Each participant underwent DE measurements performed by four operators with varying levels of experience using traditional methods (liver/spleen section) and novel methods (hepato-renal/spleno-renal section), respectively. Among them, two experienced operators were critical care clinicians, and diaphragmatic ultrasound was performed in more than 50 cases. The other two inexperienced operators were respiratory therapists, with less than 10 cases of diaphragmatic ultrasound operations, who received a 2-hour theoretical and operational training before the study. Operators initially used the conventional method with a 1.5-6.0 MHz convex probe in M-mode, placing the sampling line perpendicular to the diaphragm at the point of maximum excursion, and the liver/spleen section DE was determined during normal breathing of participant. Then, they used the novel method with a 1.6-4.5 MHz phased array probe to observe diaphragmatic movement cranio-caudally along the mid-axillary line, employing anatomic M-mode with the sampling line placed perpendicular to the diaphragm at the level of the renal midpoint, and the DE of the hepato-renal/spleno-renal section was measured during normal breathing. The liver and hepato-renal sections were used to assess the right diaphragm, and spleen and spleno-renal sections were used to assess the left diaphragm. Correlation analysis of DE measurements from different sections was conducted using the Deming method, while consistency was assessed using the Bland-Altman method. The consistency of clinical acceptability was defined as the absence of fixed and proportional bias, with a difference of two standard deviations less than 40% of the mean measurement value. Percentage consistency limit = two standard deviations of the differences between measurements/mean measurement value×100%.Results:Four operators performed image scans of DE in all four sections for each of the twelve subjects, with a high DE acquisition rate of 100% (48/48) for hepato-renal and spleno-renal sections, followed by the liver section [91.7% (44/48)] and the spleen section [66.7% (32/48)], particularly for the left diaphragm assessment, where the DE acquisition rate of spleno-renal section was significantly higher than that of traditional spleen section ( P < 0.01). The overall measurement results showed that no significant difference was found in DE determined via the hepato-renal and spleno-renal sections using the novel method (cm: 1.64±0.10 vs. 1.55±0.14, P > 0.05), and they were significantly higher than those determined via the conventional liver and spleen sections (cm: hepato-renal section vs. liver section was 1.64±0.10 vs. 1.44±0.09, spleno-renal section vs. spleen section was 1.55±0.14 vs. 1.09±0.14, both P < 0.01). Correlation analysis revealed good correlations of DE between hepato-renal section and spleno-renal section, between liver section and hepato-renal section, between liver section and spleno-renal section ( r values were 0.62, 0.59, and 0.42, all P < 0.01). Consistency analysis showed that the consistency in DE between hepato-renal section and spleno-renal section, as well as between liver section and hepato-renal section was good (both % consistency limits < 40%). However, the DE measured in the spleen section were not correlated with the other three sections, and there was no inconsistency (all % consistency limits > 40%). There was no statistically significant difference in DE measured by the four operators in the liver, spleen, hepato-renal, and spleno-renal sections (cm: 1.49±0.34, 1.44±0.37, 1.43±0.30, and 1.40±0.27 in liver section; 1.10±0.36, 1.05±0.18, 1.09±0.22, and 1.06±0.26 in spleen section; 1.67±0.43, 1.57±0.34, 1.63±0.32, and 1.66±0.36 in hepato-renal section; 1.45±0.33, 1.48±0.34, 1.50±0.24, and 1.65±0.26 in spleno-renal section; all P > 0.05). According to the clinically acceptable range of consistency limits, the DE measured by the four operators in all four sections showed good consistency (all % consistency limits < 40%). Conclusion:The novel method of measuring DE through hepato-renal/spleno-renal sections is accurate, highly reproducible, and has a high acquisition rate, serving as a viable alternative to the conventional method involving the liver/spleen section.

A large spontaneous mass on the dorsal abdomen near the hip joint was found in an aged female Tupaia belangeri subsp. yaoshanensis after 5 years of routine feeding. The tumor in the diseased tree shrew was huge, with an intact surface and no ulceration; however, it caused inconvenience in movement while maintaining a good mental state. After inhalation anesthesia with isoflurane (2%-4%), the tree shrew was euthanized after the tree shrew entered deep anesthesia. Anatomical dissection of the tumor, the tumor boundary was unclear and infiltrated into surrounding tissues. HE staining showed that small focal pleomorphism and large areas of adipocytes were seen in the tumor tissue. The pleomorphic sarcoma area was mainly composed of atypical epithelioid cells with easily visible nuclear divisions. The size of the adipocytes was significantly different, and more pleomorphic adipocytes were seen. The cell volume was large, the nucleus was deeply stained and deformed, the edge was impressed, and the cytoplasm was seen with multiple vesicular lipid droplets. Immunohistochemical results showed that the tumor cells were positive for Vimentin, the small focal polymorphic adipocyte nucleus was positive for S-100, and Ki-67 exhibited a higher proportion of positivity. Combined with HE staining and immunohistochemical results, the spontaneous tumor in this tree shrew was comprehensively diagnosed as pleomorphic liposarcoma.

ObjectiveTo observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma. MethodsA tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months. ResultsHE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells. ConclusionCombined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.

Objective:To investigate the short term outcomes and postoperative respiratory complications of patients with chronic thromboembolic pulmonary hypertension(CTEPH) treated by pulmonary endarterectomy(PEA).Methods:45 consecutive CTEPH patients underwent PEA between December 2017 and January 2020 in our institution were enrolled, including 25 females and 20 males. The mean age of operation was 51.2(25-70) years old. 24(53.5%) patients were in New York Heart Association(NYHA) functional class Ⅲ-Ⅳ. The mean PVR before operation was 923(461-2 711) dyn·s·cm -5. All patients’ data were entered in a prospective database, divieded into patients with respiratory complications group(WRC)and without respiratory complications group(WORC). To assess risk factors for postoperative respiratory complications and its effect on short term outcomes. Results:There was a significant reduction in mPAP(from 37 mmHg to 20 mmHg) and PVR(from 923 dyn·s·cm -5 to 293 dyn·s·cm -5) in the entire group. The in-hospital mortality rate was 4.4%(2 cases), died due to postoperative cardiogenic circulatory failure, even with VA-ECMO treatment and mediastinal infection, respectively. Postoperative respiratory complications occurred in 32 patients(71.1%). The most common complications were reperfusion pulmonary edema 44.4%(20 cases) and residual pulmonary hypertension 11.1%(5 cases). The WRC group showed a tendency to have longer periods of mechanical ventilation, longer ICU stays and more ICU costs. Independent predictors of postoperative respiratory complications were time from symptom onset to PEA>36 months( OR=12.2, 95% CI: 2.1-70.7, P=0.005)and six-minute walking distance<300 m( OR=12.6, 95% CI: 1.1-138.0, P=0.0038). Conclusion:Pulmonary endarterectomy is an effective and safe treatment for CTEPH. Postoperative respiratory complications were mainly determined by symptom onset time and pre-operative status. Patients with CTEPH should consider PEA surgery early.