Humans ; Blood Pressure/physiology* ; Cohort Studies ; Patient Discharge ; Ischemic Stroke ; Stroke ; Brain Ischemia ; Diabetes Mellitus ; Hypertension

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To investigate the mechanism of methyltetrahydrofolate reductase ( MTHFR) C677T polymorphism in the pathogenesis of lower extremity deep vein thrombosis (DVT). Methods:Used retrospective controlled study method, a total of 64 DVT patients (DVT group) and 96 healthy people (control group) were enrolled in the Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University from August 2019 to August 2021. Clinical manifestations and related detection, including D-dimer, fibrinogen, prothrombin time, prothrombin activity and prothrombin time-international normalized ratio of the subjects were recorded, and plasma homocysteine (Hcy) and soluble endothelial cell protein C receptor (sEPCR) were detected by enzyme linked immunosorbent assay (ELISA). The polymorphism of C677T locus of MTHFR gene was detected by polymerase chain reaction-restricted fragment length polymor-phism (PCR-RFLP), and the differences of blood indexes and MTHFR genotypes between the two groups were compared. Measurement data with normal distribution were represented as mean ± standard deviation ( ± s), and comprison between groups was conducted using the t-test; the skewness data were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. comprison between groups of count data was conducted using the chi-square test or Fisher exact probability. Results:Compared with the control group, DVT group showed more symptoms of limb skin redness, limb swelling, skin temperature rise, local tenderness, skin rupture, skin tension, pigmentation, limb movement and sensory disturbance, the difference were statistically significant ( P<0.05); the prothrombin time-international normalized ratio [0.98(0.95, 1.04) vs 1.05(1.00, 1.13)], fibrinogen [2.76(2.31, 3.30) mg/L vs 3.36(2.74, 4.35) mg/L], D-dimer [0.52(0.38, 0.62) mg/L vs 4.73(2.44, 12.05) mg/L], Hcy[(1 639.03±390.29)ng/mL vs (2 423.03±631.95) ng/mL] and sEPCR [(108.62±25.07) ng/mL vs (137.79±26.23) ng/mL] in DVT group were significantly higher than those in control group, the difference were statistically significant ( P<0.05); the prothrombin activity [90.70% (75.80%, 100.00%) vs 103.00%(93.00%, 112.50%)] was significantly lower than that of the control group, the difference was statistically significant ( P<0.05). Compared with the control group, CC, CT, TT genotype frequency and allele frequency of MTHFR C677T site in DVT group showed a trend of change, but the difference were not statistically significant ( P>0.05). Conclusion:TT mutation at MTHFR C677T site in patients with DVT has an increasing trend, which may promote the expression level of Hcy, and high expression of Hcy and sEPCR can induce the occurrence and development of DVT.

Objective:To understand the status of psychological capital and disaster preparedness of clinical nurses and analyze the relationship between them.Methods:From August to October 2020, 508 clinical nurses were selected from 8 Class Ⅲ hospitals in Zhejiang province by convenience sampling method. General information questionnaire, nurses' psychological capital questionnaire and disaster preparedness questionnaire were used. A total of 508 questionnaires were sent out and 503 valid questionnaires were collected with an effective rate of 99.01%.Results:The total score of disaster preparedness score of 503 clinical nurses was (179.53±41.11) points, mean items score was (3.99±0.91) points, psychological capital was (91.86±14.68) points, mean items score was (4.49±0.73) points. Correlation analysis showed that nurses' psychological capital was positively correlated with disaster preparedness ( r value was 0.610, P<0.05). Regression analysis showed that psychological capital, department, working years, whether participated in disaster training and disaster event rescue had significant impact on disaster preparedness of clinical nurses ( t values were 2.002-16.770, P<0.01 or 0.05). Conclusions:The knowledge, skills and post disaster management of clinical nurses are still deficient. Psychological capital affects the level of disaster preparedness of nurses to a certain extent. Nursing managers should formulate targeted intervention measures to enhance the level of psychological capital of nurses, so as to better improve the disaster preparedness of clinical nurses.

Objective:To explore how to make transplantation strategy for patients of different ages in frozen-thawed embryo (FET) cycle.Methods:A retrospective cohort analysis of the first FET cycles during the period from January 2018 to April 2020 in Reproductive Center of Ningbo Women & Children Hospital was performed. Based on the age of the patients, they were divided into three groups: ≤30 years old group (1150 cycles), 30-35 years old group (932 cycles) and >35 years old group (405 cycles). In each age group, according to the grade and number of transferred embryos, they were divided into the single cleavage stage embryo transplant (SET3) subgroup, the single 5th day blastocyst transplant (SET5) subgroup, the single 6th day blastocyst transplant (SET6) subgroup, the double cleavage stage embryos transplant (DET3) subgroup, the double 5th day blastocyst transplant (DET5) subgroup and the double 6th day blastocyst transplant (DET6) subgroup. All patients were followed up until June 30, 2020. The clinical outcomes of each subgroups within the same age group were compared.Results:1) In ≤30 years old group: the clinical pregnancy rate, the persistent pregnancy rate and the live birth rate in SET5 subgroup were 66.17% (221/334), 60.48% (202/334), 35.93% (120/334), respectively, which were higher than those in SET3 subgroup [41.18% (28/68), 36.76% (25/68), 25.00% (17/68); P<0.001, P=0.001, P=0.045] and that in SET6 subgroup [54.42% (80/147), 43.54% (64/147), 27.21% (40/147); P<0.001, P=0.001, P<0.001]. The multiple rate in DET5 subgroup was 47.80% (76/159), which was higher than that in DET6 subgroup [29.49% (23/78), P=0.007]. 2) In 30-35 years old group: the clinical pregnancy rate, the persistent pregnancy rate and the live birth rate in SET5 subgroup were 63.59% (138/217), 55.30% (120/217) and 29.95% (65/217), which were higher than those in SET3 subgroup [30.65% (19/62), 27.42% (17/62),14.52% (9/62); P<0.001, P<0.001, P=0.015]. The multiple rate in DET5 subgroup was 56.86% (58/102), which was higher than that in DET3 subgroup [32.54% (41/126)] and DET6 subgroup [28.57% (16/56)], and the differences were statistically significant ( P<0.001, P=0.001). 3) In >35 years old group: the clinical pregnancy rate, the sustained pregnancy rate and the live birth rate in DET5 subgroup were 53.45% (31/58), 39.66% (23/58), 20.69% (12/58), compared with those in SET6 subgroup [43.75% (21/48), 35.42% (17/48), 16.76% (8/48)], the differences were not statistically significant ( P=0.320, P=0.655, P=0.583), while compared with SET3 subgroup [16.98% (9/53), 15.09% (8/53), 7.55% (4/53)], the differences were statistically significant ( P<0.010, P=0.004, P=0.049). The clinical pregnancy rate and the sustained pregnancy rate in DET5 subgroup were 66.67% (26/39), 53.85% (21/39), which were higher than those in DET3 subgroup [33.89% (61/180), 27.22% (49/180)], and the differences were statistically significant ( P<0.001 , P=0.001). The clinical pregnancy rate in DET5 subgroup was higher than that in DET6 subgroup [51.85% (14/27)], and the difference was statistically significant ( P=0.001) .Conclusion:For patients of all ages, single embryo transfer should be selected, and avoid the transfer of two 5th day blastocysts as far as possible. The 5th day single blastocyst is preferred for embryo transfer.

Objective:To explore how to make transplantation strategy for patients of different ages in frozen-thawed embryo (FET) cycle.Methods:A retrospective cohort analysis of the first FET cycles during the period from January 2018 to April 2020 in Reproductive Center of Ningbo Women & Children Hospital was performed. Based on the age of the patients, they were divided into three groups: ≤30 years old group (1150 cycles), 30-35 years old group (932 cycles) and >35 years old group (405 cycles). In each age group, according to the grade and number of transferred embryos, they were divided into the single cleavage stage embryo transplant (SET3) subgroup, the single 5th day blastocyst transplant (SET5) subgroup, the single 6th day blastocyst transplant (SET6) subgroup, the double cleavage stage embryos transplant (DET3) subgroup, the double 5th day blastocyst transplant (DET5) subgroup and the double 6th day blastocyst transplant (DET6) subgroup. All patients were followed up until June 30, 2020. The clinical outcomes of each subgroups within the same age group were compared.Results:1) In ≤30 years old group: the clinical pregnancy rate, the persistent pregnancy rate and the live birth rate in SET5 subgroup were 66.17% (221/334), 60.48% (202/334), 35.93% (120/334), respectively, which were higher than those in SET3 subgroup [41.18% (28/68), 36.76% (25/68), 25.00% (17/68); P<0.001, P=0.001, P=0.045] and that in SET6 subgroup [54.42% (80/147), 43.54% (64/147), 27.21% (40/147); P<0.001, P=0.001, P<0.001]. The multiple rate in DET5 subgroup was 47.80% (76/159), which was higher than that in DET6 subgroup [29.49% (23/78), P=0.007]. 2) In 30-35 years old group: the clinical pregnancy rate, the persistent pregnancy rate and the live birth rate in SET5 subgroup were 63.59% (138/217), 55.30% (120/217) and 29.95% (65/217), which were higher than those in SET3 subgroup [30.65% (19/62), 27.42% (17/62),14.52% (9/62); P<0.001, P<0.001, P=0.015]. The multiple rate in DET5 subgroup was 56.86% (58/102), which was higher than that in DET3 subgroup [32.54% (41/126)] and DET6 subgroup [28.57% (16/56)], and the differences were statistically significant ( P<0.001, P=0.001). 3) In >35 years old group: the clinical pregnancy rate, the sustained pregnancy rate and the live birth rate in DET5 subgroup were 53.45% (31/58), 39.66% (23/58), 20.69% (12/58), compared with those in SET6 subgroup [43.75% (21/48), 35.42% (17/48), 16.76% (8/48)], the differences were not statistically significant ( P=0.320, P=0.655, P=0.583), while compared with SET3 subgroup [16.98% (9/53), 15.09% (8/53), 7.55% (4/53)], the differences were statistically significant ( P<0.010, P=0.004, P=0.049). The clinical pregnancy rate and the sustained pregnancy rate in DET5 subgroup were 66.67% (26/39), 53.85% (21/39), which were higher than those in DET3 subgroup [33.89% (61/180), 27.22% (49/180)], and the differences were statistically significant ( P<0.001 , P=0.001). The clinical pregnancy rate in DET5 subgroup was higher than that in DET6 subgroup [51.85% (14/27)], and the difference was statistically significant ( P=0.001) .Conclusion:For patients of all ages, single embryo transfer should be selected, and avoid the transfer of two 5th day blastocysts as far as possible. The 5th day single blastocyst is preferred for embryo transfer.

Objective:To analyze the clinical outcomes and cost-effectiveness ratio of the patients with ovarian reserve dysfunction in three different ovulation induction protocols during in vitro fertilization-embryo transfer (IVF-ET), and to explore a cost-effective ovulation induction protocol. Methods:A retrospective analysis was made on the low prognosis in IVF-ET of elderly patients with low ovarian reserve function (according to POSEIDON criteria, group 4) in Reproductive Center of Ningbo Women & Children Hospital during January 2017 to October 2018. According to the different ovarian stimulation protocols used, they were divided into three groups: antagonist group (group A, 169 cycles), micro-stimulation group (group B, 57 cycles), and progestin-primed ovarian stimulation (PPOS) group (group C, 59 cycles). The clinical outcome and cost-effectiveness of three ovulation-promoting protocols were analyzed.Results:In group A, compared with group B and group C, both the number of obtained eggs [4.46±1.45, 2.42±1.12, 3.28±1.62, respectively in the three groups ( P=0.013, P=0.021)] and the cumulative clinical pregnancy rate were higher (35.50%, 21.43%, 23.73%, respectively in the three groups)( P=0.012, 0.021). In group A, the rate of cycle cancellation was the lowest in the three groups (0.95%, 21.05%, 15.24%, respectively). In group A, the average cost of each egg acquisition was the lowest [(3817±1450) yuan, (5868±1820) yuan, (4484±1678) yuan, respectively in the three groups)]( P=0.001, P=0.012, P=0.017), and the cost of each available embryo was the lowest too [(7276±2329) yuan, (7978±2560) yuan, (7466±2175) yuan, respectively in the three groups)]( P=0.001, P=0.021, P=0.033).The cost per clinical pregnancy was lower in group A than in group B and group C [(47 957±22 388) yuan, (67 450±35 210) yuan, (61 984±33 463) yuan, respectively in the three groups)]( P=0.012, P=0.021). Conclusion:For patients aged over 35 years with poor ovarian reserve before stimulation, antagonist protocol was superior to micro-stimulation and PPOS, considering the clinical outcome and cost-effectiveness ratio, and it was an ideal ovary stimulation protocol.

Objective:To analyze the clinical outcomes and cost-effectiveness ratio of the patients with ovarian reserve dysfunction in three different ovulation induction protocols during in vitro fertilization-embryo transfer (IVF-ET), and to explore a cost-effective ovulation induction protocol. Methods:A retrospective analysis was made on the low prognosis in IVF-ET of elderly patients with low ovarian reserve function (according to POSEIDON criteria, group 4) in Reproductive Center of Ningbo Women & Children Hospital during January 2017 to October 2018. According to the different ovarian stimulation protocols used, they were divided into three groups: antagonist group (group A, 169 cycles), micro-stimulation group (group B, 57 cycles), and progestin-primed ovarian stimulation (PPOS) group (group C, 59 cycles). The clinical outcome and cost-effectiveness of three ovulation-promoting protocols were analyzed.Results:In group A, compared with group B and group C, both the number of obtained eggs [4.46±1.45, 2.42±1.12, 3.28±1.62, respectively in the three groups ( P=0.013, P=0.021)] and the cumulative clinical pregnancy rate were higher (35.50%, 21.43%, 23.73%, respectively in the three groups)( P=0.012, 0.021). In group A, the rate of cycle cancellation was the lowest in the three groups (0.95%, 21.05%, 15.24%, respectively). In group A, the average cost of each egg acquisition was the lowest [(3817±1450) yuan, (5868±1820) yuan, (4484±1678) yuan, respectively in the three groups)]( P=0.001, P=0.012, P=0.017), and the cost of each available embryo was the lowest too [(7276±2329) yuan, (7978±2560) yuan, (7466±2175) yuan, respectively in the three groups)]( P=0.001, P=0.021, P=0.033).The cost per clinical pregnancy was lower in group A than in group B and group C [(47 957±22 388) yuan, (67 450±35 210) yuan, (61 984±33 463) yuan, respectively in the three groups)]( P=0.012, P=0.021). Conclusion:For patients aged over 35 years with poor ovarian reserve before stimulation, antagonist protocol was superior to micro-stimulation and PPOS, considering the clinical outcome and cost-effectiveness ratio, and it was an ideal ovary stimulation protocol.

A total of 296 patients were randomly divided into short message group (n =153) and non short message group (n =143).The former group received short message service (SMS) for follow-ups while the latter group had routine oral follow-ups.The return visit rate,recall rate of glycosylated hemoglobin (HbA1c),HbAlc level and glucose control rate for diabetics were assessed after one-year follow-up.The return visit rate (96％) and recall rate of HbAlc (78％) in the short message group were significantly higher than those in the non-short message group (59％,25％,P ＜0.01 for both).The HbAlc level after one-year follow-up (6.51 ± 0.74) ％ was lower than that one year before (6.85 ± 1.26) ％ in the short message group.The glucose control rate after one year (82％) were significantly higher than that one year before in the short message group (65％) and that after one year in the non-short message group(59％,P ＜ 0.01).Use of SMS platform system for follow-ups and health education can effectively improve the return visit rate and glucose control rate,lower the HbA1c level.in diabetics.

Objective To study clinical efficacy of leuprorelin acetate in treatment of uterine adenomyosis with infertility.Methods From January 1,2011 to March 31,2012,166 cycles in 166 infertile patients combined with uterine adenomyosis undergoing in vitro fertilization embryo transplant (IVF-ET) with long protocol ovum induction by leuprorelin acetate in centre of medical reproduction,ningbo women and children's hospital were studied retrospectively.In the mean time,200 cycles in 200 infertile patients with tubal factors were enrolled as control group.The volume of uterus and outcome of IVF-ET were compared and studied between two groups.Results (1) Volume of uterus:in adenomyosis group,after 2-6 cycles of injecting leuprorelin acetate (3.75 mg/28 days),the mean uterine volume was shrinked from (180 ±73) cm3 to (86 ± 67) cm3 (P ＜ 0.05).(2) Outcome of IVF-ET:the rate of embryo implantation was 39.1％ in adenomyosis group and 35.8％ in control group.The rate of clinical pregnancy was 54.2％ in adenomyosis group and 53.7％ in control group.The rate of abortion was 4.7％ in adenomyosis group and 4.2％ in control group.They all did not show statistical differences (P ＞0.05).(3) In adenomyosis group,the rate of fertilization,two pronuclear (2PN) and superior embryo were 67.2％ (319/475),60.8％(289/475) and 52.9％ (162/306) in patients with failed pregnancy and 74.2％ (423/570),67.7％(386/570) and 62.1％ (256/412) in patients with successful pregnancy after IVF-ET,which reached significant difference (P ＜ 0.05).Conclusion Leuprorelin acetate could improve volume of uterine adenomyosis and outcome of pregnancy in patients undergoing IVF-ET.