[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

[Analysis of efficacy and safety of daratumumab-containing regimen in relapsed and refractory multiple myeloma patients].

Objective: To investigate the efficacy and safety in relapsed and refractory multiple myeloma (RRMM) patients with combination regimen of daratumumab. Methods: The clinical data of 42 RRMM patients admitted to Qingdao Municipal Hospital from December 2020 to November 2023 were retrospectively analyzed, which included 26 males and 16 females, with a median age of 59 (47, 82) years old. According to the number of courses of treatment with Daratumumab, patients were divided into three groups: long course group (≥9 courses, n=21), medium course group (7-8 courses, n=12), and short course group (≤6 courses, n=9). The deadline for follow-up was November 10, 2023, and the follow-up period was 15.6 (6.0, 34.0) months. After completing at least 2 courses of treatment, patients were evaluated for efficacy, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), and progressive disease (PD). Basic clinical characteristics of patients, overall response rate of treatment, and adverse reactions were statistically analyzed. Kaplan-Meier method was used to compare the differences of progression-free survival (PFS) in patients with different courses of treatment. Results: Among the 42 patients, 15 (35.7%) had extramedullary disease or plasmacytic leukemia, 7 (16.6%) had amyloidosis, and 18 (42.9%) had renal insufficiency. In Mayo stage, 25 patients (59.5%) were at high risk of myeloma cytogenetic stratification, 8 patients (19%) were standard risk, 9 patients (21.4%) had no cytogenetic data. There were 16 patients with second-line treatment (38.0%), 13 patients with third-line treatment (31%), and 13 patients with more than fourth-line treatment (31%). All patients received at least 2 courses of treatment, achieving the best degree of disease response in 4 cases of sCR (9.5%), 3 cases of CR (7.1%), 10 cases of VGPR (23.8%), 11 cases of PR (26.2%), and 6 cases of MR (14.2%). The overall response rate (ORR) was 80.9% (34/42). The overall response rate was 100% (21/21) in the long course group, 91.6% (11/12) in the medium course group and 22.2% (2/9) in the short course group. Kaplan-Meier survival analysis showed that the duration of PFS was 5.0 (95%CI: 3.1-6.9) months in the short course group,>8.0 months in the medium course group, and>38.0 months in the long course group, the difference was statistically significant (P<0.05). Grade≥3 adverse reactions were mainly neutropenia (3 cases) and thrombocytopenia (1 case). None of the patients discontinued treatment due to adverse reactions. Conclusion: Treatment of RRMM with a regimen containing Daratumumab requires a longer course of treatment to achieve maximum efficacy and the adverse reactions can be controlled.

MRI-based radiomics model to preoperatively predict mesenchymal transition subtype in high-grade serous ovarian cancer.

AIM: To develop a magnetic resonance imaging (MRI)-based radiomics model for the preoperative identification of mesenchymal transition (MT) subtype in high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and eighty-nine patients with histopathologically confirmed HGSOC were enrolled retrospectively. Among the included patients, 55 patients were determined as the MT subtype and the remaining 134 were non-MT subtype. After extracting a total of 204 features from T2-weighted imaging (T2WI) and contrast-enhanced (CE)-T1WI images, the Mann-Whitney U-test, Spearman correlation test, and Boruta algorithm were adopted to select the optimal feature set. Three classifiers, including logistic regression (LR), support vector machine (SVM), and random forest (RF), were trained to develop radiomics models. The performance of established models was evaluated from three aspects: discrimination, calibration, and clinical utility. RESULTS: Seven radiomics features relevant to MT subtypes were selected to build the radiomics models. The model based on the RF algorithm showed the best performance in predicting MT subtype, with areas under the curves (AUCs) of 0.866 (95 % confidence interval [CI]: 0.797-0.936) and 0.852 (95 % CI: 0.736-0.967) in the training and testing cohorts, respectively. The calibration curves, supported with Brier scores, indicated very good consistency between observation and prediction. Decision curve analysis (DCA) showed that the RF-based model could provide more net benefit, which suggested favorable utility in clinical application. CONCLUSION: The RF-based radiomics model provided accurate identification of MT from the non-MT subtype and may help facilitate personalised management of HGSOC.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.

The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear. Here, we show that KIF18A inhibition drives a modest and widespread increase in spindle assembly checkpoint (SAC) signaling from kinetochores which can result in lethal mitotic delays. Whether cells arrest in mitosis depends on the robustness of the metaphase-to-anaphase transition, and cells predisposed with weak basal anaphase-promoting complex/cyclosome (APC/C) activity and/or persistent SAC signaling through metaphase are uniquely sensitive to KIF18A inhibition. KIF18A-dependent cancer cells exhibit hallmarks of this SAC:APC/C imbalance, including a long metaphase-to-anaphase transition, and slow mitosis overall. Together, our data reveal vulnerabilities in the cell division apparatus of cancer cells that can be exploited for therapeutic benefit.

[Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study].

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

[Progress in the application of laparoscopic and endoscopic cooperative surgery in gastrointestinal stromal tumors].

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor among gastrointestinal tumors, with an inherent potential for malignancy. The primary approach to addressing GIST remains surgical intervention. Laparoscopic and endoscopic cooperative surgery (LECS) has emerged as an innovative treatment approach for GIST. LECS includes various techniques, such as classic LECS, inverted LECS, and laparoscopic-assisted endoscopic full-thickness resection, all of which aim to combine the advantages of laparoscopy and endoscopy. This treatment offers benefits such as accurate localization, complete lesion removal, and a good prognosis. Generally, LECS can be used for GIST with a tumor diameter less than 50 mm, which cannot be completely removed through traditional endoscopic surgery. The clinical application of LECS deserves further exploration and expansion in the future, ultimately benefiting patients.

[Analysis of disease composition and primary surgical procedures in pediatric secondary glaucoma inpatients: a single-center study].

Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

[Opportunities and challenges in the diagnosis and treatment of optic chiasm lesions: a clinical and research perspective].

The optic chiasm is a critical component of the visual pathway, and lesions in the pituitary and sellar regions can cause irreversible damage to a patient's visual function, resulting in a significant decrease in their quality of life. As a result, neuro-ophthalmology evaluation is a crucial part of the multidisciplinary treatment of pituitary diseases. However, due to the significant variation in the anatomical structure of the optic chiasm and the sellar region, as well as the complexity of the injury mechanism, chiasm injury can result in diverse manifestations and severity levels, which can make it difficult to correlate with anatomical parameters. In recent years, research has increasingly focused on the early recognition of optic chiasm compression, the prediction of visual function after intervention, and the long-term neurodegenerative effects, while optical coherence tomography (OCT), electrophysiological examinations, and functional magnetic resonance imaging are currently the most commonly used methods for evaluating sellar region lesions. However, the role of these methods, represented by OCT, in clinical diagnosis and treatment, still lacks high-level clinical evidence support, and the evaluation and prediction of optic chiasm function remain key areas for further study. In addition to compression lesions, lesions such as inflammation, infiltration, and demyelination in the sellar region, caused by systemic multi-system diseases, can also lead to visual function damage and require recognition in clinical practice.

[Pathologic features of paraspinal muscle biopsies in patients with adolescent idiopathic scoliosis].

OBJECTIVE: To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology. METHODS: Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically. RESULTS: Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers. CONCLUSION: The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.

Predictive value of endometrial receptivity evaluated by three-dimensional ultrasound in ectopic pregnancy after in vitro fertilization-embryo transfer.

OBJECTIVE: The aim of this study was to use three-dimensional (3D) ultrasound to detect ultrasound parameters related to the uterine artery and endometrium, evaluate endometrial receptivity, and investigate the predictive value of each parameter for ectopic pregnancy (EP) after in vitro fertilization-embryo transfer (IVF-ET). PATIENTS AND METHODS: Fifty-seven cases of pregnancy following IVF-ET in our institution were collected and split into EP and intrauterine pregnancy (IP) groups based on the location of pregnancy, with 27 cases in EP and 30 cases in IP. Endometrial thickness, type, volume, endometrial blood flow parameters, and uterine artery blood flow parameters were all measured one day before transplantation in both groups, and the differences between the two groups were examined. RESULTS: There were differences in endometrial blood flow typing between the two groups, with type III endometrium accounting for the highest proportion in both; the uterine spiral artery pulsatility index PI was significantly higher in the EP group than in the IP group; there were no statistical differences in uterine volume, uterine artery resistance index mRI, or uterine artery resistance index S/D between the two groups; there were no statistical differences in uterine volume, or uterine artery. CONCLUSIONS: Intracavitary 3D ultrasound can assess endometrial tolerance and may predict pregnancy outcome after IVF-ET.

[A lightweight multiscale target object detection network for melanoma based on attention mechanism manipulation].

OBJECTIVE: To propose a deep learning target detection model AM- YOLO that integrates coordinate attention and efficient attention mechanism. METHODS: Mosaic image enhancement and MixUp mixed-class enhancement were used for image preprocessing. In the target detection model YOLOv5s with One-Stage structure and modified backbone network and neck network, the maximum pooling layer of the spatial pyramid of the backbone network was replaced with a two-dimensional maximum pooling layer, and the coordinate attention mechanism and the efficient channel attention mechanism were integrated into the C3 module and the backbone network of the model, respectively. The improved model was compared with the unmodified YOLOv5s model, YOLOv3 model, YOLOv3-SPP model, and YOLOv3-tiny model for relevant algorithmic indicators in comparative experiments. RESULTS: The AM-YOLO model incorporating coordinate attention and efficient channel attention mechanism effectively improved the accuracy of melanoma recognition with also a reduced size of the model weight. This model showed significantly better performance than other models in terms of precision, recall rate and mean average precision, and its mean average precision for benign and malignant melanoma reached 92.8% and 87.1%, respectively. CONCLUSION: The deep learning-based target object detection algorithm model can be applied in recognition of melanoma targets.

[Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection].

Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.

[Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles].

Objective: To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China. Methods: Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use. Results: Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol (OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol (OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased (OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased (OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant (P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient (P<0.01). Conclusion: For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Emerging Issues Questioning the Current Treatment Strategies for Lumbar Disc Herniation.

Lumbar disc herniation is among the common phenotypes of degenerative lumbar spine diseases, significantly affecting patients' quality of life. The practice pattern is diverse. Choosing conservative measures or surgical treatments is still controversial in some areas. For those who have failed conservative treatment, surgery with or without instrumentation is recommended, causing significant expenditures and frustrating complications, that should not be ignored. In the article, we performed a literature review and summarized the evidence by subheadings to unravel the cons of surgical intervention for lumbar disc herniation. There are tetrad critical issues about surgical treatment of lumbar disc herniation, i.e., favorable natural history, insufficient evidence in a recommendation of fusion surgery for patients, metallosis, and implant removal. Firstly, accumulating evidence reveals immune privilege and auto-immunity hallmarks of human lumbar discs within the closed niche. Progenitor cells within human discs further expand the capacity with the endogenous repair. Clinical watchful follow-up studies with repeated diagnostic imaging reveal spontaneous resolution for lumbar disc herniation, even calcified tissues. Secondly, emerging evidence indicates long-term complications of lumbar fusion, such as adjacent segment disease, pseudarthrosis, implant failure, and sagittal spinal imbalance, which get increasing attention. Thirdly, systemic and local reactions (metallosis) for metal instrumentation have been noted with long-term health concerns and toxicity. Fourthly, the indications and timing for spinal implant removal have not reached a consensus. Other challenging issues include postoperative lumbar stiffness. The review provided evidence from a negative perspective for surgeons and patients who attempt to choose surgical treatment. Collectively, the emerging underlying evidence questions the benefits of traditional surgery for patients with lumbar disc herniation. Therefore, the long-term effects of surgery should be closely observed. Surgical decisions should be made prudently for each patient.

[MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance].

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.