Objective To compare the outcomes of in-vitro maturation (IVM) and in-vitro fertilization (IVF) after early follicular phase gonadotropin-releasing hormone agonist (GnRH-a)down-regulation in infertile patients with polycystic ovary syndrome (PCOS).Methods From July 2010 to December 2012,72 infertile patients with PCOS undergoing assisted reproductive technology treatment in the Affiliated First Hospital of Wenzhou Medical University were enrolled in this study.The patients were divided into 2 groups,which were patients with early follieular phase down-regulation IVM (36 cases) at IVM group and early follicular phase down-regulation long protocol IVF (36 cases) at IVF group.The laboratory parameters and clinical outcomes were compared between two groups.Results (1) Lab parameters:a total of 442 oocytes were retrieved in group IVM,and 560 were in group IVF.The rate of mature oocytes of 83.8％ (469/560) and high-quality embryos of 70.9％ (212/299) at group IVF were significantly higher than that of group IVM [54.1％ (239/442) and 50.7％ (73/144),retrospectively,P ＜0.01].In group IVM,the average duration of gonadotropin (Gn) was (2.8 ± 1.5) days and the average dosage of Gn was (285 ± 169) U,which were significantly lower than (11.0 ± 1.0) days and (1499 ±165) U in group IVF (P ＜0.01).The mean number of oocytes retrieved 12.8 ± 2.5,fertilization rate of 64.8％ (155/239),and implantation rate of 31％ (23/74) in group IVM and 15.6 ±3.1,65.5％ (307/469),31％ (23/74) in group IVF,which did not reach statistical difference (P ＞0.05).(2) Clinical outcomes:the clinical pregnancy rate (17/31,55％) of IVF group was not significantly higher than that 44％ (14/32) at IVM group (P ＞ 0.05).The abortion rate was 1/17 at Group IVF and 1/14 in group IVM,which did not show statistical difference.Women at IVM group has no ovarian hyper-stimulation syndrome (OHSS) cycle,group IVF has 31％ (11/36) cycles presented moderate and severe OHSS.Conclusions Infertile patients with PCOS undergoing IVM and IVF treatment after early follicular phase GnRH-a down-regulation can get satisfactory laboratory and clinical outcome.In addition to short treatment cycle,IVM can also avoid the occurrence of OHSS completely,but it has a rising trend in the abortion rate.IVF has a high incidence of OHSS,meanwhile,it increases the dosage of gonadotropins.

Objective To analysis the incidence and management of monozygotic twin (MZT) conceived by assisted reproductive techniques (ART). Methods A retrospective analysis of clinical pregnancies and MZT that resulted from ART was performed in Reproductive Medical Center,the First Affiliated Hospital,Wenzhou Medical University between January 2011 and January 2014. Results A total of 5 908 pregnancies were diagnosed: 2 012 twins, 157 high-order multiple pregnancy (HOMP), including 4 quadruplets. Overall, 51 MZT pregnancies were identified of them including 32 cases HOMP and 19 cases MZT. The incidence of MZT resulting from cleavage-stage embryo transfer was similar to blastocyst transfer (P=0.960). The percent of MZT resulting from in vitro fertilization [0.93% (28/3 022)], frozen-thawed embryo transfer [0.87% (13/1 502)] and intracytoplamic sperm injection [0.72% (10/1 384)] did not show statistical significance (P=0.794). The expectantly managed MZT was associated with a significantly greater likelihood of miscarriage [6/19 vs 5.11% (101/1 976)], and low birth weight infant [73.91% (17/23) vs 42.89% (1 453/3 388), P<0.01], when compared with dizygotic twin (DZT) did not undergo selective embryo reduction(SER). In monozygotic (MZ)-triplets with SER to 2 fetuses or to 1 fetus, there was no cases of preterm birth or low birth weight infant observed in MZ-triplets with SER to 1 fetus;when compared with MZ-triplets with SER to 2 fetuses, the low birth weight infant [56.00% (14/25), P=0.021] has statistical significance. The likelihood of the survival of two babies was lower in MZ-triplets with SER to 2 fetuses when compared with non-MZ triplets with SER to 2 fetuses [42.86%(9/21)vs 75.21%(91/121), P=0.003]. Conclusions The incidence of MZT pregnancies following ART is high. It plays a significant role in the occurrence of HOMP. MZT pregnancies are at an increased risk of adverse outcomes , it should transform to a single embryo thansfer (SET) program to reduce them incideuce. Reduction of MZT contained in multiple pregnancies appears to be a safe option.

Objective To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients.Methods We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan.2008 to Dec.2013 into 4 groups:group A1B1,PCOS patients underwent unstimulated IVM protocol,240 cycles; group A1B2,PCOS patients underwent IVM converted from conventional stimulated IVF protocol,153 cycles; group A2B1,non-PCOS patients underwent unstimutlated IVM protocol,103 cycles; group A2B2,non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol,95 cycles.Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes.Results The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B)=3.37,P＜0.01].The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B=0.05,P=0.010).High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B=0.08,P=0.010; B=0.09,P=0.001),as well as implantation rate related with them (B=0.07,P=0.010; B=0.10,P＜0.01).PCOS and IVM converted from IVF improved hCG positive (hCG＞10 U/L) rate (OR=1.636,95％CI:1.113-2.204,P＜0.05; OR=1.861,95％CI:1.307-2.649,P＜0.05) and the clinical pregnancy rate (OR=1.507,95％CI:1.041-2.240,P＜0.05; OR=1.881,95％CI:1.312-2.696,P＜0.05).IVM converted from IVF protocol decreased the spontaneous abortion rate (OR=0.490,95％CI:0.245-0.978,P＜0.05).Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P＞0.05).Conclusions PCOS and IVM converted from IVF protocol improved the high-quality embryo rate,implantation rate,hCG positive rate and clinical pregnancy rate.IVM converted from IVF protocol reduced the spontaneous abortion rate.PCOS patients may be more suitable for the IVM treatment.No matter PCOS or non-PCOS patients,IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.

Objective To evaluate the efficacy of lateral femoral approach to continuous sciatic nerve block for patient-controlled analgesia after foot and ankle surgery.Methods One hundred American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes,aged 18-60 yr,weighing 50-100 kg,with body height of 145-190 cm,scheduled for elective foot and ankle surgery,were divided into 2 groups (u =50 each) using a random number table:patient-controlled nerve block analgesia (PCNA) group and patient-controlled intravenous analgesia (PCIA) group.In group PCNA,the lateral femoral approach to sciatic nerve block was performed under the guidance of ultrasound and a neurostimulator,0.2％ ropivacaine 20 ml was injected after successful location,the catheter was inserted,and 0.2％ ropivacaine 10 ml was injected again.In group PCIA,0.2％ ropivacaine 30 ml was injected after successful location of the sciatic nerve.General anesthesia was performed using laryngeal mask airway in both groups.In group PCNA,PCNA was performed with 0.2％ ropivacaine (diluted to 200 ml in normal saline) at the end of surgery,and the PCNA pump was set up with a 0.5 ml bolus dose,a 15-min lockout interval and background infusion at a rate of 5 ml/h.In group PCIA,PCIA was performed with sufentanil 100 μg,tramadol 500 mg and tropisetron 10 mg (diluted to 200 ml in normal saline) at the end of surgery,and the PCIA pump was set up with a 0.5 ml bolus dose,a 15-min lockout interval and background infusion at a rate of 2 ml/h.The visual analog scale score was maintained≤ 3,and postoperative analgesia lasted until postopera-tive 72 h.When visual analog scale scores ≥ 4,tramadol 100 mg was intramuscularly injected as rescue analgesic.The requirement for rescue analgesia and development of adverse effects such as nausea and vomiting,insomnia,puncture site infection and bleeding were recorded within 72 h after surgery.Results The requirement for rescue analgesia and incidence of nausea and vomiting were significantly lower in group PCNA than in group PCIA (P＜ 0.05).Conclusion The lateral femoral approach to continuous sciatic nerve block can be safely and effectively used for patient-controlled analgesia after foot and ankle surgery.

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD^-) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD^- rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD^- status. ②The 2-year PFS rate of patients with MRD^- status was significantly higher than that of MRD⁺ status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD⁺) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD^- status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD^-status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD^- status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD^- duration (median MRD^- duratio: 25 months vs 10 months, P=0.034) . Conclusion Our findings supported MRD⁺ status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD^- status also played a significant role in evaluation of prognosis, while loss of MRD^-status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.

Objective:To explore the relationship between integrin ɑ3(ITGA3)expression and immune cell infiltration in colorectal cancer(CRC).Methods:Bioinformatic methods were used to analyze ITGA3 mRNA expression in pan-cancer and CRC tissues,as well as its associ-ation with CRC prognosis.The correlation between ITGA3 and tumor-infiltrating immune cells was also investigated.In total,233 cases of CRC diagnosed at Shanxi Provincial Cancer Hospital between January and December 2021 were included,and ITGA3,CD8,CD163,FOXP3,PD-L1,CTLA-4,and PD-1 expression in CRC tissues were determined by immunohistochemistry(IHC)to analyze the relationship between ITGA3 and infiltrating immune cells and immune checkpoints.Results:Bioinformatics analysis showed elevated ITGA3 mRNA levels in CRC.High ITGA3 expression was associated with PFS(P＜0.05).Univariate and multifactorial analyses showed that age and stage were significantly cor-related with prognosis(P＜0.05).In addition,ITGA3 upregulation was closely correlated with multiple immune cell infiltration levels in CRC.Furthermore,IHC results showed that ITGA3 expression in CRC tissues was significantly higher than that in adjacent normal tissues(P＜0.05).ITGA3 expression was associated with lymph node metastasis(P＜0.05)and correlated with the expression of immune markers,such as CD8+T-cells,PD-L1,and CTLA-4(P＜0.05).Conclusions:ITGA3 is highly expressed in CRC,which is closely related to immune cell infiltration and may regulate the tumor immune microenvironment,which provides a new idea for clinical treatment and a potential new independent predictive marker.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.