OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

Purpose To analyze the precursor lesions,clinicopathological features and prognosis of mucinous carcinoma(MC).Methods A total of 303 MC cases diagnosed by surgi-cal specimens were included,including 193 pure mucinous car-cinomas(PMC)and 110 mixed mucinous carcinomas(MMC).PMC included 163 cases of type A(hypocellular type)and 30 cases of type B(hypercellular type).The histomorphological characteristics,surrounding breast tissue morphology,and im-mune markers were evaluated to analyze the clinicopathological features related to MC precursor lesions and prognosis.Results The median age at diagnosis of MC was 50 years,and the me-dian tumor size was 2.5 cm.Compared to PMC,MMC had more lymph node(LN)involvement,more grade Ⅲ-Ⅳ and Ki67＞20％tumors(P＜0.05).There were no significant differences in tumor size,LN involvement and clinical stage between type A and type B PMC.55 cases of MC(49 PMC and 6 MMC)with precursor lesions of mucocoele-like lesions(MLL)were all grade 1 to 2,most of them(54/55,98.2％)were T1-T2,and the proportions of MC component in all 6 MMCs were all ≥ 50％.There were 119 cases of MC whose precursor lesions were ductal carcinoma in situ(DCIS),of which 28.6％of cases(34/119)had LN involvement,and 16.8％(20/119)of cases showed high proliferative activity(Ki67＞20％).The precursor lesions of MC in 16 cases were solid papillary carcinoma(SPC)in situ,inclu-ding 7 cases of type BPMC and 9 cases of MMC.The median age of these patients was 67 years and no recurrence or metastasis was observed during follow-up.The disease-free survival(DFS)and overall survival(OS)of the 303 cases of MC was 93.5％and 98.6％,respectively.PMC had a better prognosis than MMC(DFS:95.2％vs.90.6％;OS:99.5％vs.97.2％),but there was no significant difference between type A and type B PMC.The prognosis of patients with LN involvement and clinical stage Ⅲ-Ⅳ was worse(P＜0.05).Conclusion MC of the breast is a kind of heterogeneous malignant tumors.Our findings support that MC with specific precursor lesions have different ev-olutionary pathways,that MC with precursor lesions of MLL and SPC have a good prognosis,and MC associated with high-grade DCIS are more aggressive.LN involvement,higher clinical grade,and younger age are associated with poor prognosis.Focu-sing on precursor lesions and high risk clinicopathological fea-tures can contribute to providing more effective treatments for these patients.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.

Purpose To analyze the precursor lesions,clinicopathological features and prognosis of mucinous carcinoma(MC).Methods A total of 303 MC cases diagnosed by surgi-cal specimens were included,including 193 pure mucinous car-cinomas(PMC)and 110 mixed mucinous carcinomas(MMC).PMC included 163 cases of type A(hypocellular type)and 30 cases of type B(hypercellular type).The histomorphological characteristics,surrounding breast tissue morphology,and im-mune markers were evaluated to analyze the clinicopathological features related to MC precursor lesions and prognosis.Results The median age at diagnosis of MC was 50 years,and the me-dian tumor size was 2.5 cm.Compared to PMC,MMC had more lymph node(LN)involvement,more grade Ⅲ-Ⅳ and Ki67＞20％tumors(P＜0.05).There were no significant differences in tumor size,LN involvement and clinical stage between type A and type B PMC.55 cases of MC(49 PMC and 6 MMC)with precursor lesions of mucocoele-like lesions(MLL)were all grade 1 to 2,most of them(54/55,98.2％)were T1-T2,and the proportions of MC component in all 6 MMCs were all ≥ 50％.There were 119 cases of MC whose precursor lesions were ductal carcinoma in situ(DCIS),of which 28.6％of cases(34/119)had LN involvement,and 16.8％(20/119)of cases showed high proliferative activity(Ki67＞20％).The precursor lesions of MC in 16 cases were solid papillary carcinoma(SPC)in situ,inclu-ding 7 cases of type BPMC and 9 cases of MMC.The median age of these patients was 67 years and no recurrence or metastasis was observed during follow-up.The disease-free survival(DFS)and overall survival(OS)of the 303 cases of MC was 93.5％and 98.6％,respectively.PMC had a better prognosis than MMC(DFS:95.2％vs.90.6％;OS:99.5％vs.97.2％),but there was no significant difference between type A and type B PMC.The prognosis of patients with LN involvement and clinical stage Ⅲ-Ⅳ was worse(P＜0.05).Conclusion MC of the breast is a kind of heterogeneous malignant tumors.Our findings support that MC with specific precursor lesions have different ev-olutionary pathways,that MC with precursor lesions of MLL and SPC have a good prognosis,and MC associated with high-grade DCIS are more aggressive.LN involvement,higher clinical grade,and younger age are associated with poor prognosis.Focu-sing on precursor lesions and high risk clinicopathological fea-tures can contribute to providing more effective treatments for these patients.

Objective:To investigate the perinatal outcome of selective fetal reduction of dizygotic twins pregnancies after double embryo transferred assisted by in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Methods:The clinical data of patients with single birth who underwent IVF/ICSI after double embryo transferred from September 1, 2005 to July 31, 2020 in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The patients were divided into three groups according to the occurrence of fetal reduction: 80 cases of dizygotic twins to singleton by selective fetal reduction (group A), 832 cases of dizygotic twins to singleton by spontaneous fetal reduction (group B), and 6 178 cases of singleton (group C). Using group A as the reference, after approximately propensity score matching (PSM) with 1∶4 ratio, 289 cases in group B and 271 cases in group C were obtained. The differences in baseline data and perinatal outcomes between group A and group B or group C were analyzed.Results:1) Before PSM, there were statistically significant differences in patients' age, previous fertility history, type of infertility, and stage of embryo transferred between group A and group B or group C (all P<0.05); after PSM, there were no statistically significant differences in baseline data between group A and group B or group C (all P>0.05). 2) After PSM, the premature birth rate was higher in group A than in group B [17.5% (14/80) vs. 8.7% (25/289), P=0.023] and the gestational weeks [(38.18±1.98) weeks vs. (38.64±1.83) weeks, P=0.034] were lower; group A had higher incidence rates of premature birth [17.5% (14/80) vs. 7.7% (21/271), P=0.011] and premature rupture of membranes [5.0% (4/80) vs. 0.4% (1/271), P=0.002] than those in group C, but gestational weeks [(38.18±1.98) weeks vs. (38.85±1.47) weeks, P=0.002] and birth weight [(3 253.07±475.73) g vs. (3 384.89±479.54) g, P=0.029] were lower. Conclusion:Perinatal outcomes of selective fetal reduction of dizygotic twins pregnancies after assisted by IVF/ICSI were poor. Selective fetal reduction in multiple pregnancies is not the best remedy. The strategy of selective single embryo transfer should be adopted to effectively reduce the rate of multiple pregnancies and improve maternal and infant outcomes.

Objective:To investigate the perinatal outcome of selective fetal reduction of dizygotic twins pregnancies after double embryo transferred assisted by in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Methods:The clinical data of patients with single birth who underwent IVF/ICSI after double embryo transferred from September 1, 2005 to July 31, 2020 in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The patients were divided into three groups according to the occurrence of fetal reduction: 80 cases of dizygotic twins to singleton by selective fetal reduction (group A), 832 cases of dizygotic twins to singleton by spontaneous fetal reduction (group B), and 6 178 cases of singleton (group C). Using group A as the reference, after approximately propensity score matching (PSM) with 1∶4 ratio, 289 cases in group B and 271 cases in group C were obtained. The differences in baseline data and perinatal outcomes between group A and group B or group C were analyzed.Results:1) Before PSM, there were statistically significant differences in patients' age, previous fertility history, type of infertility, and stage of embryo transferred between group A and group B or group C (all P<0.05); after PSM, there were no statistically significant differences in baseline data between group A and group B or group C (all P>0.05). 2) After PSM, the premature birth rate was higher in group A than in group B [17.5% (14/80) vs. 8.7% (25/289), P=0.023] and the gestational weeks [(38.18±1.98) weeks vs. (38.64±1.83) weeks, P=0.034] were lower; group A had higher incidence rates of premature birth [17.5% (14/80) vs. 7.7% (21/271), P=0.011] and premature rupture of membranes [5.0% (4/80) vs. 0.4% (1/271), P=0.002] than those in group C, but gestational weeks [(38.18±1.98) weeks vs. (38.85±1.47) weeks, P=0.002] and birth weight [(3 253.07±475.73) g vs. (3 384.89±479.54) g, P=0.029] were lower. Conclusion:Perinatal outcomes of selective fetal reduction of dizygotic twins pregnancies after assisted by IVF/ICSI were poor. Selective fetal reduction in multiple pregnancies is not the best remedy. The strategy of selective single embryo transfer should be adopted to effectively reduce the rate of multiple pregnancies and improve maternal and infant outcomes.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective:To compare the acceptance of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening.Methods:Questionnaire surveys were conducted in women attending cervical cancer screening in Xiangyuan County and Yangcheng County in Shanxi Province from July to November 2015 and from October to December 2018. Both surveys included the following three parts: feelings and acceptance of women in urine self-sampling, vaginal self-sampling and physician sampling, and the ease evaluation of two self-samplings.Results:There were 3 485 questionnaires were collected finally. The proportions of women felt embarrassed in urine self-sampling, vaginal self-sampling and physician sampling were 2.3% (81/3 472), 7.1% (247/3 472) and 8.6% (299/3 472), and 1.3% (46/3 472), 9.7%(3 37/3 472) and 14.9% (518/3 472) of women felt uncomfortable, and 1.0% (35/3 469), 8.5% (295/3 469) and 15.3% (531/3 469) felt pain, and 98.3% (3 334/3 393), 96.3% (3 267/3 393) and 99.0% (3 360/3 393) thought that the sampling were conducted properly ( P<0.05). Based on the feeling during sample collection, 61.2% (1 876/3 064), 39.1% (1 199/3 064) and 66.5% (2 037/3 064) women were willing to use the corresponded sampling methods in cervical cancer screening, respectively ( P<0.05). If the accuracy was the same, there were 31.8% (1 109/3 485) women preferred self-sampling and 68.2% (2 376/3 485) preferred physician sampling for cervical cancer screening. Meanwhile, 23.5% (820/3 482) preferred vaginal self-sampling in comparison with 76.5% (2 662/3 482) for urine self-sampling in cervical cancer screening. 86.5% (3 007/3 478) of the women thought urine self-sampling was very easy, comparing 40.9% (1 423/3 478) for vaginal self-sampling. Conclusions:The bad feeling of women during urine self-sampling is less common and less serious than those during physician sampling and vaginal self-sampling, and the acceptance for physician sampling is highest, following by urine self-sampling and vaginal self-sampling. Urine self-sampling is much easier than vaginal self-sampling.