Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

Objectives: To compare the pregnancy outcomes of luteal phase and follicular phase progestin-primed ovarian stimulation protocol with clomiphene citrate supplementation (LPPOS+CC and FPPOS+CC) in young women with diminished ovarian reserve (DOR).

Methods: A total of 483 women aged ≤35 years with DOR, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (n=257) or FPPOS+CC (n=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, superovulation results, laboratory related indicators between the two groups, and the pregnancy outcomes of women who achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst were compared between the two groups.

Results: No statistically significant differences were identified between the groups with respect to age, duration of infertility, proportion of secondary infertility, previous failed cycles, body mass index, anti-Müllerian hormone, antral follicle count, basal luteinizing hormone level, basal progesterone level, number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, live birth rate and preterm birth rate (all P>0.05). The LH levels on the day of trigger [4.0 (2.7, 5.3) vs. 5.1 (3.2, 7.2) IU/L], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% vs. 10.67%), and the two pronucleus (2PN) rate of ICSI oocytes (72.16% vs. 79.56%) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group (P<0.05 or P<0.01). The duration of stimulation [11 (9, 12) vs. 9 (8, 11) d], the consumption of total gonadotropin [2213 (1650, 2700) vs. 2000 (1575, 2325) IU], the progesterone levels on the day of trigger [1.3 (0.8, 2.9) vs. 0.9 (0.6, 1.2) ng/mL], the clinical pregnancy rate [61.88% vs. 46.84%], and implantation rate [42.20% vs. 31.07%] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group (all P<0.01).

Conclusions: Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF/ICSI-ET.

Objectives: To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET).

Methods: A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center, Sir Run Run Shaw Hospital were included in the study. The participants were randomly divided into study group and control group. The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer, while the control group received routine medication only. The general condition, embryo implantation rate, clinical pregnancy rate, live birth rate, and the blood routine and liver and kidney function were evaluated and compared between two groups.

Results: There were 277 cases who completed the study, including 134 in the study group and 143 in the control group. The embryo implantation rate (68.7% vs. 55.9%), the clinical pregnancy rate (56.7% vs. 44.8%) and the live birth rate (50.7% vs. 37.8%) in the study group were all higher than those in the control group (all P<0.05). Subgroup analysis revealed that in patients of advanced age (≥35 years) and those with decreased ovarian reserve function (anti-Müllerian hormone <1.68 ng/mL), the embryo implantation rate, clinical pregnancy rate, and live birth rate in the study group were all higher than those in the control group (all P<0.05). During the follow-up period, there were no abnormalities in the basic vital signs of both groups, and no adverse events were reported.

Conclusions: Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET, reduce the embryo miscarriage rate, increase the live birth rate as well as improve the clinical outcomes.

Chemotherapy is a main treatment option for malignant tumors, but it may cause various adverse effects, including dysfunction of female endocrine system and fertility. Chemotherapy-induced ovarian damage has been concerned with ovarian preservation but also the prevention and treatment of ovarian dysfunction. In this article, the mechanisms of ovarian injury caused by chemotherapy, including apoptosis of the follicle and supporting cells, follicle "burn out", ovarian stromal and microvascular damage; and influencing factors, including age at diagnosis, initial low pre-treatment anti-Müllerian hormone levels, toxicity, dose and regimen of chemotherapy drugs are reviewed based on the latest research results and clinical practice. The article also discusses measures and frontier therapies for the prevention and treatment of ovarian injury, including the application of gonadotropin releasing hormone agonists or antagonists, tyrosine kinase inhibitors, antioxidants, sphingosine-1-phosphate, ceramide-1-phosphate, mammalian target of rapamycin inhibitors, granulocyte-colony stimulating factor, stem cell therapy and artificial ovaries.

Objectives: To explore the influence factors for futile recanalization following endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO).

Methods: Clinical data of patients with acute BAO, who underwent endovascular treatment within 24 h of onset from January 2017 to November 2022, were retrospectively analyzed. The futile recanalization was defined as modified thrombolysis in cerebral infarction (mTICI) grade ≥2b or 3 after successful reperfusion, but the modified Rankin Scale score >2 at 3 months after EVT. Binary logistic regression model was used to analyze the influencing factors of futile recanalization.

Results: A total of 471 patients with a median age of 68 (57, 74) years were included and 68.9% were males, among whom 298 (63.27%) experienced futile recanalization. Multivariate analysis revealed that concomitant atrial fibrillation (OR=0.456, 95%CI: 0.282-0.737, P<0.01), bridging thrombolysis (OR=0.640, 95%CI: 0.416-0.985, P<0.05), achieving mTICI grade 3 (OR=0.554, 95%CI: 0.334-0.918, P<0.05), arterial occlusive lesion (AOL) grade 3 (OR=0.521, 95%CI: 0.326-0.834, P<0.01), and early postoperative statin therapy (OR=0.509, 95%CI: 0.273-0.948, P<0.05) were protective factors for futile recanalization after EVT in acute BAO patients. High baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=1.068, 95%CI: 1.049-1.087, P<0.01), coexisting hypertension (OR=1.571, 95%CI: 1.017-2.427, P<0.05), multiple retrieval attempts (OR=1.237, 95%CI: 1.029-1.488, P<0.05) and postoperative hemorrhagic transformation (OR=8.497, 95%CI: 2.879-25.076, P<0.01) were risk factors. For trial of ORG 10172 in acute stroke treatment (TOAST) classification, cardiogenic embolism (OR=0.321, 95%CI: 0.193-0.534, P<0.01) and other types (OR=0.499, 95%CI: 0.260-0.961, P<0.05) were related to lower incidence of futile recanalization.

Conclusions: The incidence of futile recanalization after EVT in patients with acute BAO is high. Bridging venous thrombolysis before operation and an early postoperative statin therapy may reduce the incidence of futile recanalization.

Ligand-gated ion channels are a large category of essential ion channels, modulating their state by binding to specific ligands to allow ions to pass through the cell membrane. Purinergic ligand-gated ion channel receptors (P2XRs) and acid-sensitive ion channels (ASICs) are representative members of trimeric ligand-gated ion channel. Recent studies have shown that structural differences in the intracellular domain of P2XRs may determine the desensitization process. The lateral fenestrations of P2XRs potentially serve as a pathway for ion conductance and play a decisive role in ion selectivity. Phosphorylation of numerous amino acid residues in the P2XRs are involved in regulating the activity of ion channels. Additionally, the P2XRs interact with other ligand-gated ion channels including N-methyl-D-aspartate receptors, γ-aminobutyric acid receptors, 5-hydroxytryptamin receptors and nicotinic acetylcholine receptors, mediating physiological processes such as synaptic plasticity. Conformational changes in the intracellular domain of the ASICs expose binding sites of intracellular signal partners, facilitating metabolic signal transduction. Amino acids such as Val16, Ser17, Ile18, Gln19 and Ala20 in the ASICs participate in channel opening and membrane expression. ASICs can also bind to intracellular proteins, such as CIPP and p11, to regulate channel function. Many phosphorylation sites at the C-terminus and N-terminus of ASICs are involved in the regulation of receptors. Furthermore, ASICs are involved in various physiological and pathophysiological processes, which include pain, ischemic stroke, psychiatric disorders, and neurodegenerative disease. In this article, we review the roles of the intracellular domains of these trimeric ligand-gated ion channels in channel gating as well as their physiological and pathological functions, in order to provide new insights into the discovery of related drugs.

Objectives: To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.

Methods: Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3 and a platelet count <100×10⁹/L were obtained from a multicenter register. Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was a 1-year all-cause death. The short-term neurological outcomes were evaluated by modified Rankin scale (mRS) score at discharge.

Results: A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled. Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge (OR=1.657, 95%CI: 1.253-2.192, P<0.01) and did not increase the risk of intracranial hemorrhage (OR=2.359, 95%CI: 0.301-18.503, P>0.05), compared with those without antiplatelet therapy. However, dual-antiplatelet therapy did not bring more neurological benefits (OR=0.923, 95%CI: 0.690-1.234, P>0.05), but increased the risk of gastrointestinal bleeding (OR=2.837, 95%CI: 1.311-6.136, P<0.01) compared with those with mono-antiplatelet therapy. For patients with platelet counts ≤75×10⁹/L and >90×10⁹/L, antiplatelet therapy significantly improved neurological functional outcomes (both P<0.05). For those with platelet counts (>75-90)×10⁹/L, antiplatelet therapy resulted in a significant improvement of 1-year survival (P<0.05). For patients even with concurrent coagulation abnormalities, mono-antiplatelet therapy did not increase the risk of various types of bleeding (all P>0.05) but improved neurological functional outcomes (all P<0.01). There was no significant difference in the occurrence of bleeding events, 1-year all-cause mortality risk, and neurological functional outcomes between aspirin and clopidogrel (all P>0.05).

Conclusions: For non-cardioembolic mild stroke patients with thrombocytopenia, antiplatelet therapy remains a reasonable choice. Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objectives: To investigate the role of m.4435A>G and YARS2 c.572G>T (p.G191V) mutations in the development of essential hypertension.

Methods: A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data. Clinical data were collected, and a molecular genetic study was conducted in the proband and his family members. Peripheral venous blood was collected, and immortalized lymphocyte lines constructed. The mitochondrial transfer RNA (tRNA), mitochondrial protein, adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) in the constructed lymphocyte cell lines were measured.

Results: Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation. The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability, which may influence the anticodon ring structure. Compared with the control group, the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis, mitochondrial protein expression, ATP production and MMP levels, as well as increased ROS levels (all P<0.05).

Conclusions: The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction, indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

Objectives: To investigate the association between baseline hemoglobin level and early neurologic deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).

Methods: Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation (CASE-Ⅱ, NCT04487340). Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy, and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis.

Results: A total of 8162 patients were included. Patients with END had lower baseline hemoglobin levels (136 and 140 g/L, P<0.01) and higher rates of anemia (24.2% and 16.9%, P<0.01) compared with non-END patients. Binary logistic regression analysis showed that baseline hemoglobin level (OR=0.995, 95%CI: 0.991-0.999, P<0.05) and anemia (OR=1.238, 95%CI: 1.055-1.454, P<0.01) were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients. Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients (P<0.01), although this relationship was only significant in male patients (P<0.05) and not in female patients (P>0.05).

Conclusions: There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis, especially in male patients, in whom both lower and higher hemoglobin level may increase the risk of END.

Objectives: To compare the effect of anesthesia mode on the neurological functional outcomes in patients undergoing endovascular treatment for acute posterior circulation ischemic stroke.

Methods: Clinical data of 656 patients undergoing intravascular therapy for acute posterior circulation ischemic stroke registered in online Acute Stroke Patients for Stroke Management Quality Evaluation Database from January 2017 to December 2022 were retrospectively analyzed. The data included 163 cases with conscious sedation and 493 cases with general anesthesia during the procedure. After propensity score matching, 428 patients were included in the analysis, including 155 cases in the conscious sedation group and 273 cases in the general anesthesia group. The differences of operation mode, etiology type, vascular recanalization, hemorrhagic transformation at 24 h, modified Rankin Scale (mRS) score at 3 months and mortality within 3 months were compared between the two groups. Binary logistic regression was used to explore the effect of different anesthesia mode on neurological functional outcomes.

Results: There was a significant difference in operation mode between the two groups (P<0.01), while there were no significant differences in etiology type, vascular recanalization, hemorrhagic transformation at 24 h, mRS score at 3 months or mortality within 3 months (all P>0.05). Binary logistic regression analysis revealed that anesthesia modes were not significantly associated with functional outcomes of patients (OR=1.151, 95%CI: 0.751-1.765, P>0.05).

Conclusions: Anesthesia mode (conscious sedation or general anesthesia) will not affect the neurological functional outcomes in patients with acute posterior circulation ischemic stroke undergoing endovascular treatment.

Objectives: To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom, and to determine its sequence and structure.

Methods: Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom, and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording. The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry; its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry; its structure was established based on iterative thread assembly refinement online analysis.

Results: A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8, and its primary sequence consists of 53 amino acid residues NH₂-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSGDSRLKD-OH. Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell, with 1.0 μmol/L SsTx-P2 suppressing 95% current of Kv4.1 channel. Its structure showed that SsTx-P2 shared a conserved helical structure.

Conclusions: The study has isolated a novel peptide SsTx-P2 from centipede venom, which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.