[Clinical characteristics analysis of patients with severe immune checkpoint inhibitors related myocarditis].

Objective: To analyze the clinical characteristics of patients with severe immune checkpoint inhibitors (ICIs) related myocarditis. Methods: A retrospective study was conducted on the 50 patients with ICIs-related myocarditis in the multidisciplinary cardio-oncology clinic of Zhongshan Hospital affiliated to Fudan University from April 2020 to April 2022. The age of patients was (63.7±10.8) years old, including 37 males and 13 females. The patients were divided into the mild group (n=37) and the severe group (n=13) according to severity. The differences of basic characteristics, clinical manifestations, laboratory tests, auxiliary examination, combined irAEs, treatment and outcomes between the two groups of patients were analyzed. Results: The immunotherapy time [M(Q1,Q3)] of patients in the mild group and severe group were 81 (49, 134) and 24 (20, 116) days, respectively (P<0.05). In the severe group, the levels of cTnT [0.605 (0.317, 1.072) µg/L], NT-proBNP [1 126 (386, 1 744) ng/L], CK-MB [78 (48, 238) U/L], and CK-MM [240 (45, 6 543) U/L] were higher than those in the mild group [0.104 (0.045, 0.189) µg/L, 237 (39, 785) ng/L, 24 (20, 33) U/L, 108 (72, 168) U/L, respectively] (all P<0.05). The left ventricular ejection fraction of the severe group [64% (57%, 65%)] was lower than that of the mild group [66% (63%, 69%)] (P<0.05), and the incidence of conduction block (n=4, 4/13) and abnormal ventricular wall motion (n=4, 4/13), the incidence of ICIs-related myositis (n=10, 10/13), ICIs-related hepatitis (n=4, 4/13) and ICIs-related neurotoxicity (n=4, 4/13) were higher than those in the mild group (n=1, 2.7%; n=2, 5.4%; n=16, 43.2%; n=2, 5.4%; n=1, 2.7%, respectively) (all P<0.05). The proportion of patients receiving intensified immunosuppressive therapy and mortality rate in the severe group were 12/13 (n=12) and 4/13 (n=4), which were both higher than those in the mild group [10.8% (n=4) and 0] (both P<0.05). Conclusions: The incidence of ICIs-related myocarditis is not high, but the severe rate and mortality are high. The differential diagnosis of severe ICIs related myocarditis should be combined with myocardial markers, electrocardiogram and echocardiogram, and early diagnosis and treatment can improve the prognosis of patients.

[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

[Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center].

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

[Effect analysis of treating intracranial wide-neck bifurcation aneurysms through Woven EndoBridge].

Objective: To explore the clinical effect of Woven EndoBridge (WEB) in the treatment of wide-neck bifurcation aneurysms. Methods: The clinical and imaging data of 11 patients with intracranial wide-neck bifurcation aneurysms treated by WEB alone at Department of Neurosurgery of the Northern Theater General Hospital from September 2017 to May 2018, were retrospectively analyzed. The patients were 7 males and 4 females, aged (54±11) years (ranged from 31 to 66 years). The aneurysms of 5 patients were located in the anterior communicating artery, 3 in the top of the basilar artery, and 3 in the bifurcation of the middle cerebral artery. The intraoperative and postoperative conditions of the patients were recorded, and the degree of aneurysm embolization was evaluated by WEB embolization aneurysm occlusion scale (WOS). Results: The intraoperative WEB release of all the 11 patients was good, with 3 cases of WOS grade A, 1 of grade B and 7 of grade C, with no intraoperative acute complications occurring. The imaging follow-up was not carried out in 1 patient due to economic reason, and the clinical follow-up was good until 3 years after the operation; 10 patients were followed up by imaging for 6 months to 3 years, and no postoperative complications occurred in the target treatment area. Among the 2 patients with WOS grade A and 1 patient with grade B during operation, according to the postoperative follow-up, all were WOS grade A; among the 7 patients with WOS grade C during operation, 4 were still of grade C and 3 were of grade D according to the follow-up. Among the 3 patients with WOS grade D, 1 patient received secondary embolization due to poor recurrence morphology, unstable hemodynamics and high possibility of rupture of aneurysm, stent assisted coil embolization was adopted, with good immediate effect; the other 2 cases had recurrent aneurysms, but the aneurysms had good morphology and stable hemodynamics, therefore, clinical follow-up was continued and no secondary surgery was performed. No complications occurred in all these 11 patients. Conclusions: The operation of treating unruptured intracranial wide-neck bifurcation aneurysms with WEB device alone is simple, and there is no need for anticoagulation and antiplatelet treatment before and after the operation, the clinical effect is being good. WEB device provides a new treatment option for intracranial wide-neck bifurcation aneurysms.

[Comparison of single incision robot-assisted laparoscopic radical prostatectomy with and without extraperitoneal special channel device].

Objective: To compare the clinical effects of single-incision robot-assisted laparoscopic radical prostatectomy (RARP) with and without extraperitoneal special channel device. Methods: The clinical data of 70 patients who had undergone RARP in the Robotic Minimally Invasive Surgery Center of Sichuan Provincial People's Hospital from September 2020 to February 2021 were analyzed retrospectively, including 29 cases who were operated on without special channel device (group A) and 41 cases with special channel device (group B). All operations were performed by robot-assisted single-incision retrograde bladder neck exfoliation via extraperitoneal approach in patients by the same operator. The operation time, intraoperative blood loss, the bladder neck urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, positive rate of incisal margin, indwelling time of urinary catheter, retention rate of postoperative erectile function, satisfaction rate of immediate postoperative urine control, positive rate of postoperative lymph node pathology, incision length, treatment cost and the rate of prostate specific antigen (PSA)lower than 0.2 µg/L at 6 weeks after operation were compared between the two groups. Results: All 70 cases were operated successfully. The difference of age[ (68.9±3.9) vs (69.4±5.4) years], preoperative PSA level[14.1(6.3, 19.8)vs13.7(5.8, 18.1)µg/L], prostate volume[44.8(30.7,172.6)vs 56.3(40.9,163.4)ml ] of the two groups was not statistically significant(all P>0.05). The difference of operation time [ (59.1±18.5) vs (59.6±18.0) min ], intraoperative blood loss [93(66,198)vs 95(68,203) ml ], bladder neck urethral anastomosis time [ (12.6±1.3) vs (13.7±2.8) min ], postoperative hospital stay [ (8.1±2.3) vs (9.1±1.3) d], postoperative exhaust time [ (1.4±0.6) vs (1.3±0.6) d], positive rate of incisal margin (20.7% vs 19.5%), indwelling time of the urinary catheter after operation [ (6.8±1.5) vs (7.1±2.0) d ], the retention rate of postoperative erectile function (31.0% vs 27.0%), the satisfaction rate of immediate postoperative urine control (79.3% vs 75.6%), the positive rate of postoperative lymph node pathology (17.2% vs 14.6%), the length of incision [ (5.1±0.5) vs (6.1±0.4) cm ], the rate of PSA lower than 0.2 µg/L at 6 weeks after operation (86.2% vs 83.0%) of the two groups was not statistically significant(all P>0.05). The operation cost of group A[(62 000±4 000) yuan]was lower than group B[(68 000±4 000) yuan] (P<0.05). Conclusion: Extraperitoneal non-special channel device single-incision RARP is safe and feasible.

[Practice guideline for patients with ankylosing spondylitis/spondyloarthritis].

In recent years, the clinical experts consensuses or guidelines of ankylosing spondylitis (AS)/spondyloarthritis (SpA) have been constantly updated, but to better understand and practice, patient self-participation management is one of the key points to improve the level of diagnosis and treatment. Through questionnaire survey of these patients, we screened out the most concerned issues, and established the AS/SpA patient practice guideline working group with multidisciplinary physicians and patients. Fifteen opinions, as the AS/SpA patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process.

[Impact of discontinuation of aspirin and clopidogrel before off-pump coronary artery bypass grafting on postoperative bleeding and transfusion requirement].

Objective: To investigate the influence of different discontinuation time of aspirin and clopidogrel before off-pump coronary artery bypass grafting (OPCABG) on postoperative bleeding and blood products transfusion requirement. Methods: Three hundred and fifty-three coronary artery disease patients who underwent OPCABG from January 2017 to January 2018 at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University were retrospectively analysed. There were 268 males and 85 females, aged (66.0±9.1)years. All patients were divided into three groups: (1) guideline-recommended group: patients who discontinued clopidogrel for >5 days without discontinuing aspirin before surgery; (2) without discontinuing group: patients who discontinued clopidogrel for ≤5 days without discontinuing aspirin before surgery; (3) discontinuing group: patients who discontinued clopidogrel for >5 days with discontinuing aspirin before surgery. Postoperative bleeding recorded as chest tube drainage (CTD) volume and blood products transfusion requirement and perioperative complications were recorded. CTD volumes within 12 hours after surgery between groups were compared by Mann-Whitney U tests, CTD volumes after 12 hours postoperatively were compared by repeated measures analysis of variance and blood products transfusion and complications incidence were compared by χ(2) test or Fisher's precise test. Results: The 12 hours CTD volumes of guideline-recommended group, without discontinuing group, discontinuing group after surgery were 280(153) ml (M(Q(R))), 291(229) ml, 225(161) ml, respectively. There were no significant differences in postoperative 12 hours CTD volumes (P=0.865), red blood cells transfusion incidence (χ(2)=2.626, P=0.149) and fresh frozen plasma (FFP) transfusion incidence (χ(2)=1.258, P=0.324) between guideline-recommended group and without discontinuing group. However, the 12 hours CTD volumes were significantly higher in guideline-recommended group patients compared with disconutinuing group patients (U=5 247, P=0.002). No significant differences were observed in red blood cells (χ(2)=0.182, P=0.757) and FFP (χ(2)=0.083, P=0.839) transfusion rate between these two groups. Repeated measures analysis of variance indicated that when patients began to take antiplatelet drugs (aspirin and clopidogrel) after 12 hours postoperatively, the change of CTD volumes beyond 12 hours after surgery didn't differ either between guideline-recommended group and without discontinuing group (F=0.019, P=0.941) or between guideline-recommended group and discontinuing group (F=2.447,P=0.113). Besides, the incidence of perioperative arrhythmia was significantly higher in guideline-recommended group patients compared with without discontinuing group patients (4.8% vs. 0, χ(2)=5.073, P=0.038). Conclusions: OPCABG patients who discontinued aspirin before surgery had lower postoperative 12 hours CTD volumes but similar blood products transfusion rate and CTD volumes beyond 12 hours postoperatively compared with patients adhering to the current guideline-recommended protocol. And for patients who discontinued clopidogrel for ≤5 days, postoperative CTD volumes and blood products transfusion requirement were similar but the incidence of perioperative arrhythmia was significantly lower compared with guideline-treated patients.

[Meta-analysis on safety and efficacy of dual antiplatelet therapy combining with proton pump inhibitors for patients after percutaneous coronary intervention].

Objective: To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI). Methods: The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI. Results: MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01). Conclusions: The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

[Association of CYP19A1 gene rs7176005 single nucleotide polymorphism with breast cancer risk and clinicopathologic features of tumor].

Objective: The aim of this study was to investigate the association of the CYP19A1 rs7176005 single nucleotide polymorphism (SNP) with breast cancer risk and with clinicopathologic features of tumors. Methods: This study was conducted by including 138 patients with breast cancer (cancer group), those who diagnosed as primary breast cancer after operation by pathology. There were 293 cases in the group of benign breast disease which was presented as a solid mass by the color ultrasound and pathologically diagnosed as "fibroadenoma or adenosis" (benign breast disease group), the cases were paired with breast cancer patients by age±5 in the same period, and there were 259 cases in the group of healthy control who received routine physical examination during the same period and were paired with breast cancer patients by age±5 without any detection of breast related diseases (healthy control group) at West China hospital between September 2012 and November 2016. The CYP19A1 rs7176005 SNP was detected by a direct sequencing method. Hardy-Weinberg test was used to analyze the genetic balance of the 3 groups. Chi square test was used to compare the distribution of rs7176005 genotypes between the 3 groups, and the differences of clinicopathological features in breast cancer patients carrying different genotypes. Results: The ages of the breast cancer cases, the benign breast disease group and the healthy control group were (44.69±8.09), (42.33±11.44) and (41.92±9.61) years old, respectively. Hardy-Weinberg equilibrium test identified that the composition ratios of alleles C and T in breast cancer group, benign breast disease group and healthy group were not statistically significant (χ(2) values were 0.83, 0.34 and 0.04, respectively, P values were 0.363, 0.561, and 0.852, respectively). All the three groups met the genetic balance, had consistency and could represent the population. Among the 138 cases of breast cancer, the CYP19A1 rs7176005 SNP was significantly associated with the diameter of the tumor (P=0.031). The majority of tumor size was <2 cm in patients who carrying TT and CT genotypes, and the proportion was 75% (12/16) and 58% (40/69), respectively. While those patients with TT genotype were mainly >2 cm and ≤5 cm, and the proportion was 51% (27/53). The distribution of TNM stage among patients with different genotypes was also statistically significant (χ(2)=11.19, P=0.025). The most common stage was Ⅱ in Patients who carrying CC and CT genotypes, and the proportion was 45.3% (24/53) and 52.2% (36/69), respectively. While those patients with TT genotype was mainly in stage Ⅰ and the proportion was 56.3% (9/16). Conclusion: Though the CYP19A1 rs7176005 SNP is not associated with breast cancer development, breast cancer patients with the C allele exhibit a high tumor growth rate and large diameters.

The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial.

OBJECTIVE: To investigate the clinical outcome and endocrinological characteristics of progestin-primed ovarian stimulation (PPOS) using 4 versus 10 mg of medroxyprogesterone acetate (MPA) per day in infertile women with normal ovary reserve. DESIGN: A randomised parallel controlled trial. SETTING: Tertiary-care academic medical centre. PARTICIPANTS: A cohort of 300 infertile women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. METHODS: Human menopausal gonadotropin (hMG; 225 iu per day) and MPA (group A, 10 mg per day; group B, 4 mg per day) were started simultaneously from cycle day 3 onwards. Ovulation was co-triggered by human chorionic gonadotropin (hCG; 1000 iu) and gonadotropin-releasing hormone agonist (GnRH agonist; 0.1 mg) when dominant follicles matured. Viable embryos were cryopreserved for later frozen embryo transfer (FET) in both groups. MAIN OUTCOME MEASURES: The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the incidence of a premature surge in luteinising hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. RESULTS: The number of oocytes retrieved and viable embryos were similar between two groups (9.8 ± 6.3 versus 9.6 ± 5.9; 4.2 ± 2.6 versus 3.7 ± 3.0; P > 0.05). No significant difference was found in clinical pregnancy rate (58.0 versus 48.7%) and live birth rate per participant (48.7 versus 42.0%; P > 0.05). No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred in either group. CONCLUSIONS: Progestin-primed ovarian stimulation (PPOS) using 4 or 10 mg of MPA per day was comparable in terms of the number of oocytes retrieved and pregnancy outcome after FET. The administration of 4 mg of MPA per day was sufficient to prevent an untimely LH rise in women undergoing IVF/ICSI treatment. TWEETABLE ABSTRACT: An RCT confirmed similar pregnancy outcome in P-primed ovarian stimulation with a daily dose of 4 or 10 mg MPA.

[The value of (18)F-FDG PET-CT imaging in predicting the malignant potential of GIST].

Objective: To evaluate the value of (18)F-FDG PET-CT in predicting the malignant potential of Gastrointestinal Stromal Tumors (GIST). Methods: The clinical and pathological features of 31 patients with GIST confirmed by surgery or biopsy were retrospectively analyzed. The malignant potential of GIST before treatment was assessed by (18)F-FDG PET-CT. The GIST risk classification was graded according to the Standard revised by the National Institutes of Health (NIH) in 2008. The relationship between the maximal standard uptake value (SUVmax) and GIST risk classification, tumor diameter, Ki-67 index, and mitotic count were analyzed respectively. The cut-off level of SUVmax for the diagnosis of malignant GIST was calculated from the Receiver Operating Characteristic (ROC) curve. Results: Among the 31 cases of GIST patients, 14 cases were gastric primary (stomach group) and 17 cases were nongastric primary (outside stomach group). The SUVmax, tumor diameter, Ki-67 index and mitotic count of the 31 patients were 8.21±4.68, (7.82±5.12)cm, (10.03±11.07)% and (12.29±10.55)/50 HPF, respectively. SUVmax was significantly correlated with GIST risk classification (r=0.727, P<0.01), but not with tumor diameter, Ki-67 index and mitotic count (r=0.348, r=0.284, r=0.290, P=0.055, P=0.121, P=0.114). The SUVmax, tumor diameter, Ki-67 index and mitotic count in the stomach group were 4.36±2.36, (6.08±4.31)cm, (3.43±3.03)% and (5.71±2.20)/50 HPF, respectively. SUVmax was significantly correlated with tumor diameter, GIST risk classification and Ki-67 index (r=0.682, r=0.868, r=0.732, P<0.01) but not with mitotic count (r=0.510, P=0.063). The SUVmax of the GIST in the gastric group and the outside gastric group were 4.36±2.36 and 10.68±5.50, respectively. The difference was statistically significant (P=0.001). The SUVmax in the malignant group of GIST (middle or high risk grade) was 8.90±4.89, which was significantly higher than 2.22±0.86 in the benign group (low or very low risk grade). The difference was statistically significant between the two group (P<0.01). ROC curve analysis showed that a SUVmax cut-off of 3.75 was the most sensitive for predicting malignant GIST. When the area under the curve of 0.969, the sensitivity was 84.6% and the specificity was 100%. Conclusions: The SUVmax was strongly correlated with the GIST risk category and also with the tumor diameter and Ki-67 index in the gastric primary GIST, so it can be used as an effective indicator in predicting malignant potential of GIST before treatment.

[Inhibitory effect of migration-inducing gene-7-shRNA recombinant retrovirus combined with endostatin on growth and metastasis of hepatoma xenograft].

Objective: To investigate the inhibitory effect of migration-inducing gene-7(Mig-7)interfered with retrovirus-mediated RNA(shRNA)combined with recombinant human endostatin(ES)on the growth and metastasis of subcutaneous xenograft of human hepatoma cells in nude mice. Methods: Two Mig-7-mRNA oligonucleotide sequences(Mig-7-shRNA-1 and Mig-7-shRNA-2)and one sequence as a negative control(Mig-7-shRNA-N)were designed. The specific Mig-7-shRNA recombinant retrovirus expression vector plasmid was constructed and used for the transfection of human hepatoma MHCC-97H cells with high expression of Mig-7. The subcutaneous xenograft tumor model of human hepatocellular carcinoma(HCC)in nude mice was established, and according to the condition of transfection and administration, the nude mice were divided into pSIREN-M1 group, pSIREN-MN group, ES group, and pSIREN-M1+ES group. The xenograft tumor volume, mass, and metastasis were compared between groups. Immunohistochemistry was used to observe the formation of vasculogenic mimicry(VM)in xenograft tumor and the difference in tumor microvascular density(MVD), and Western blot was used to measure the expression of Mig-7 and vascular endothelial growth factor(VEGF)in each group. A one-way analysis of variance was used for comparison between groups, and the Fisher's exact test was used for comparison of continuous data between groups. Results: Compared with the pSIREN-MN group, the pSIREN-M1 group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, and formation of VM(P < 0.05), as well as significantly higher VEGF expression and MVD(P < 0.05). Compared with the pSIREN-MN group, the ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, VEGF expression, and MVD(P < 0.05), as well as significantly higher Mig-7 expression and formation of VM(P < 0.05). Compared with the pSIREN-M1 group and the ES group, the pSIREN-M1+ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, formation of VM, VEGF expression, and MVD(P < 0.05). Conclusion: Mig-7-shRNA recombinant retrovirus combined with ES has a better inhibitory effect on the growth and metastasis of HCC xenograft tumor than Mig-7-shRNA recombinant retrovirus or ES alone. The anti-tumor angiogenesis therapy alone, which targets vascular endothelial cells in vivo, has a limited effect, since it may promote the formation of VM.

[Echocardiographic features of sinus of Valsalva aneurysm extending into left ventricle].

OBJECTIVE: To observe image features of sinus of Valsalva aneurysm (SVA) extending into left ventricle by echocardiography. METHODS: Echocardiographic features of 5 cases of SVA extending into left ventricle and underwent surgery at Union Hospital from July 1995 to September 2015 were reviewed retrospectively and image and surgical findings were compared. A total of 4 patients were diagnosed by conventional and 3D echocardiography before surgery, and 1 patient was diagnosed by conventional echocardiography. RESULTS: The origin, extending position, rupture status, complications of the SVA and associated cardiovascular lesions determined by echocardiography were entirely consistent with surgical findings in all cases, with the exception of one failed diagnosis of hypoplasty of an adjacent aortic cusp. Besides the common features of SVA, echocardiographic features of SVA extending into left ventricle included a thin-walled saccular lesion arising from the aortic root in continuation with the aortic annulus, with significant morphological changes and movement. Moreover, following features were observed: very low origin of the saccular lesion arising between the sinus base and the aortic annulus; the aneurysm going back and forth between the aortic root and the left ventricular outflow tract in 4 cases with an intact interventricular septum, and between the left ventricle and the right ventricle through the septal defect in another case complicated by a huge ventricular septal defect; diastolic shunt into the left ventricle when ruptured; displacement of the adjacent aortic annulus due to compression of aneurismal origin and prolapse of both aortic valve and annulus observed in all cases, resulting in a severe aortic regurgitation; obstructions of the left ventricular outflow tract due to the space-occupying effect were also found in 2 cases. CONCLUSION: The SVA extending into left ventricle has distinguished echocardiographic characteristics, which could be accurately diagnosed either by conventional or real-time 3D echocardiography.

[Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen].

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

[The preliminary application of vonoprazan fumarate on laryngopharyngeal reflux disease].

Objective: To evaluate the clinical effect of vonoprazan fumarate on laryngopharyngeal reflux disease (LPRD). Methods: The clinical data of 89 patients from June 2020 to January 2022, including 45 males and 44 females, aged 18-77 (45.54±13.53) years old, were retrospectively analyzed. All the patients were diagnosed as suspected LPRD according to reflux symptom index (RSI) and reflux finding score (RFS). Patients of the Vonoprazan Fumarate group were prescribed Vonoprazan Fumarate orally (20 mg, qd) for 8 weeks.Patients of the Esomeprazole group were prescribed Esomeprazole orally (20 mg, bid) for 8 weeks. RSI and RFS of all the patients before and after treatment were compared. SPSS 18.0 was used for statistics analysis. Results: Before treatment, gender, age, RSI and RFS of the two groups had no obvious differences. After treatment, RSI and RFS in both groups were alleviated significantly. In the vonorazan fumarate group, the RSI before treatment was 12.62±7.18, and after treatment was 4.74±3.87(t=6.91, P<0.001), the RFS was 10.78±2.29 before treatment and 8.24±2.45 after treatment (t=7.06, P<0.001). While in the esomeprazole group, the RSI was 13.27±6.95 before treatment and 6.02±4.28 after treatment (t=7.50, P<0.001), the RFS was 10.59±3.14 before treatment and 8.14±3.30 after treatment (t=5.41, P<0.001). There was no significant difference in the effective rate between the two groups (86.7% in the vonoprazan fumarate group and 77.3% in the esomeprazole group, χ2=1.443, P=0.486). Conclusion: Vonoprazan fumarate could effectively alleviate the symptoms and signs of LPRD patients. The effect of vonoprazan fumarate on LPRD is not inferior to Esomeprazole. It can be used as a supplement to PPI.

[Evaluation of reliability and validity of the Chinese version of a new symptom score of laryngopharyngeal reflux disease].

Objective: To produce the Chinese version of a new reflux symptom score (RSS) of laryngopharyngeal reflux disease (LPRD) and to evaluate its reliability, validity and clinical value. Methods: This was a retrospective study which contained 42 healthy volunteers and 135 possible LPRD patients. RSI,RFS,oropharyngeal pH monitoring (Dx-pH monitoring) and RSS of each patient were performed. RSS was performed again after 1 week. Confirmed LPRD patients were treated with proton pump inhibitor for 8 week. And RSS was performed again after treatment. Reliability and validity of RSS were evaluated. Results: The Cronbach's α coefficient of RSS was 0.77, which indicated good internal reliability of the new score. The results of test-retest found all P values were less than 0.05, which supported good external reliability. Comparing RSS with laryngopharyngeal reflux test results, the diagnostic coincidence rate was 84.44% (114/135), and the positive predictive value was 85.71% (114/133), which showed good criterion validity. After 8 weeks treatment of PPI, RSS decreased significantly (pretreatment 84.79±42.50,posttreatment 20.11±22.82,t=-10.54, P<0.001), indicating good reactivity of RSS. The score of quality of life impact (Qol) in possible LPRD patients was obviously higher than that of healthy volunteers (t=7.15,P<0.001). All patients and volunteers believed that RSS was a good way to evaluate their symptoms. Conclusions: The new score RSS have good internal and external reliability, criterion validity and reactivity. RSS can be one of the important reference indexes to evaluate LPRD.

[Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis].

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

New technique for mouse oocyte injection via a modified holding pipette.

To improve mouse oocyte survival from intracytoplasmic sperm injection, the sharp tip of the injection pipette has been modified to have a flat end. Here, for the same goal but for a more convenient manipulation, a sharp injection pipette was kept whereas the holding pipette was modified to have a trumpet-shaped opening, which allows deeper injection into the oocyte as it is held. Mouse oocyte injection with mouse and human spermatozoa was performed at 37°C. For the injection of mouse oocyte with mouse sperm head, a significantly higher survival rate (83%) was achieved by utilizing the modified holding pipette than the conventional one (21%; P<0.001) and the fertilization rates were normal and comparable for both methods (82% versus 81%). A superior survival rate (82%) and acceptable normal fertilization rate (71%) were also achieved by utilizing the modified holding pipette for interspecies ICSI (injecting mouse oocyte with human spermatozoon). Taken together, by utilizing a holding pipette with a trumpet-shaped opening, acceptable rates of mouse oocyte survival and fertilization can be achieved using a sharp injection pipette under conditions usual for human oocyte injection.

[Analysis of clinical effects of artificial dermis in functional reconstruction in the late stage of extremely severe burn].

Objective: To explore the clinical effects of artificial dermis combined with autologous split-thickness skin transplantation in the treatment of functional reconstruction in the late stage of extremely severe burn. Methods: From May 2015 to May 2017, medical records of 40 patients with limited activity after scar hyperplasia and conforming to the study criteria, injured in August 2nd Kunshan factory aluminum dust explosion accident in 2014, and had surgeries in our hospital and rehabilitation treatment in our hospital's alliance rehabilitation hospital, Rehabilitation Hospital of Kunshan Zhou City, were retrospectively analyzed. According to the treatment methods, 20 patients (12 males and 8 females, aged 20 to 45 years) were enrolled in artificial dermis group. They were conducted with stage Ⅰ functional site scar loosening and artificial dermis (PELNAC) implanting+ stage Ⅱ transplantation of autologous split-thickness skin. Another 20 patients (14 males and 6 females, aged 20 to 45 years) were enrolled in conventional skin grafting group. They were conducted with stage Ⅰ functional site scar loosening and transplantation of autologous thin medium-thickness skin. After 5 days of autologous skin transplantation, the survival rates of autologous skin in patients of 2 groups were calculated. The autologous skin infection and complete healing time of skin grafting area in patients of 2 groups were recorded. In 3, 6, and 10 months after autologous skin transplantation, the Vancouver Scar Scale (VSS) was used to assess the scar condition of recipient site in patients of 2 groups. The complete healing time of donor site in patients of 2 groups was recorded. In 10 months after autologous skin transplantation, VSS was used to assess the scar condition of donor site in patients of 2 groups. In 12 months after autologous skin transplantation, the functional recovery of surgical function reconstruction site in patients of 2 groups was evaluated and rated. Data were processed with t test, analysis of variance for repeated measurement, Wilcoxon rank-sum test, chi-square test, Fisher's exact probability test, and Bonferroni correction. Results: (1) After 5 days of autologous skin transplantation, the survival rate of autologous skin in patients of artificial dermis group was (95±3)%, similar to (93±3)% in conventional skin grafting group (t=1.262, P>0.05). The results of autologous skin infection of patients in the 2 groups were similar (P>0.05). (2) After autologous skin grafting, the complete healing time of skin grafting area in patients of artificial dermis group was (12.3±2.5) d, similar to (12.7±2.0) d of conventional skin grafting group (t=-0.139, P>0.05). In 3, 6, and 10 months after autologous skin transplantation, the VSS scores of scars in recipient site of patients in artificial dermis group were significantly lower than those of conventional skin grafting group (t=-4.428, -5.655, -6.839, P<0.01). (3) After autologous skin grafting, the complete healing time of donor site in patients of artificial dermis group was obviously shorter than that in conventional skin grafting group (t=-12.435, P<0.01). In 10 months after autologous skin transplantation, the VSS score in donor site of patients in artificial dermis group was significantly lower than that of conventional skin grafting group (t=-16.971, P<0.01). (4) After 12 months of autologous skin transplantation, the functional improvement levels of the functional site of patients in artificial dermis group were good in 4 patients, fair in 15 patients, and bad in 1 patient, while the functional improvement levels of the functional site of patients in conventional skin grafting group were good in 5 patients, fair in 8 patients, and bad in 7 patients. The functional improvement levels of the functional site of patients between the two groups were similar (Z=371.5, P>0.05). Conclusions: Compared with conventional stage Ⅰ functional site scar loosening and transplantation of autologous thin medium-thickness skin, stage Ⅰ functional site scar loosening and artificial dermis implanting+ stage Ⅱ transplantation of autologous split-thickness skin does not affect the survival of skin in the early stage and can effectively improve functional site function, reduce VSS scores of donor site and recipient site, and shorten complete healing time of donor site.

[Efficacy and associated factors of olfactory training in the treatment of olfactory dysfunction].

Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin' Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ(2)=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion: Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.