Publications by authors named "Lian Fang"

87 Publications

The effect of mildly stimulated cycle versus artificial cycle on pregnancy outcomes in overweight/obese women with PCOS prior to frozen embryo transfer: a retrospective cohort study.

BMC Pregnancy Childbirth 2022 May 7;22(1):394. Epub 2022 May 7.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

Background: Previous studies have shown that frozen embryo transfer (FET) resulted in increased live birth rates (LBR) and reduced the risk of ovarian hyperstimulation syndrome (OHSS) than did fresh embryo transfer in women with polycystic ovary syndrome (PCOS). In addition, overweight/obese women with PCOS are at increased risk of subfertility and complications of pregnancy, compared with normal-weight women. The ovarian stimulation and artificial hormone regimes are the two more commonly used endometrial preparation protocols in PCOS patients.This retrospective study aims to compare the pregnancy outcomes of mildly stimulated cycles (mSTC) and artificial cycles (AC) prior to FET in overweight/obese women with PCOS.

Methods: A retrospective analysis was conducted in overweight/obese women with PCOS who underwent their first FET cycles from January 2018 to December 2020. Two endometrial preparation protocols were used: the mildly stimulated cycles (N = 173) and the artificial cycles (N = 507). All pregnancy outcomes were analyzed by Student's t-test, Chi-square (χ) statistics and multivariable logistic regression analyses.

Results: This study enrolled 680 cases of FET cycles. The mSTC group exhibited significantly higher LBR compared with the AC group (49.7% vs. 41.0%; P = 0.046), while the rate of miscarriage was significantly lower (6.4% vs. 23.0%; P < 0.001). No statistically significant differences were observed in positive pregnancy rate (57.8% vs. 60.0%, P = 0.618), clinical pregnancy rate (54.3% vs. 55.6%, P = 0.769), and ectopic pregnancy rate (2.1% vs. 3.2%, P = 0.860) between two groups. After adjusting for possible confounding factors, multivariate logistic regression analysis also yielded similar results.

Conclusions: For overweight/obese women with PCOS, mSTC-FET demonstrated a higher LBR and a lower pregnancy loss rate than that in the AC-FET. When considering the most cost-effective treatment with the least adverse effects on patients, the mSTC for FET endometrial preparation may be considered. To corroborate our findings, additional prospective randomized clinical trials with larger sample sizes are required.
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http://dx.doi.org/10.1186/s12884-022-04728-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080216PMC
May 2022

Overexpression of PD-L1 causes germ cells to slough from mouse seminiferous tubules via the PD-L1/PD-L1 interaction.

J Cell Mol Med 2022 May 5;26(10):2908-2920. Epub 2022 Apr 5.

Department of Neurobiology, School of Medicine, South China University of Technology, Guangzhou, China.

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.
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http://dx.doi.org/10.1111/jcmm.17305DOI Listing
May 2022

Age-related differential gene expression in granulosa cells and its effects on fertility using high-throughput transcriptomics.

Syst Biol Reprod Med 2022 Mar 24:1-13. Epub 2022 Mar 24.

Reproductive and Genetic Center of Integrated Traditional and Western Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

More couples worldwide, delay their childbearing years. The increase in age causes a gradual decrease in female ovarian function and fertility, leading to an exponential decrease in women over 35 years of age having children. Although promising for some, assisted reproductive technology (ART) is not promising for older women. Decreased fertility in advanced age has become a growing concern in the field of reproduction. In this study, high-throughput transcriptome sequencing was used to identify the differentially expressed genes (DEGs) in the ovarian granulosa cells (GCs) of older women (aged 35-44) with infertility and younger women (aged 25-34). The enriched functions and signaling pathways of DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The function of DEGs were analyzed and predicted combined with clinical ART data. Sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Retrospective clinical data and bioinformatics analyses revealed marked reductions in the retrieved oocyte, metaphase II oocyte, 2PN fertilization, and effective embryo numbers in older women. Although the clinical pregnancy and live birth rates did not differ notably between the groups, the miscarriage rate increased significantly in older women. In total, 620 DEGs were identified, of which 246 were upregulated, and 374 were downregulated in the older group. GO, and KEGG analyses indicated that the mechanism of fertility decline in older women was probably related to chronic inflammation, cytokine receptor interaction, and oxidative stress. In conclusion, combined with basic clinical ART data and pregnancy outcomes, we tried to provide a more intuitive and in-depth understanding of age-related reduction in ovarian function and pathogenesis of infertility with regard to chronic inflammation and oxidative stress.
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http://dx.doi.org/10.1080/19396368.2022.2028320DOI Listing
March 2022

Hybrid Hydrogel Composed of Hyaluronic Acid, Gelatin, and Extracellular Cartilage Matrix for Perforated TM Repair.

Front Bioeng Biotechnol 2021 24;9:811652. Epub 2021 Dec 24.

ENT Department, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., biocompatibility was assessed by the CCK-8 and live-dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.
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http://dx.doi.org/10.3389/fbioe.2021.811652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741272PMC
December 2021

Propofol alleviates postoperative cognitive dysfunction by inhibiting inflammation via up-regulating miR-223-3p in aged rats.

Cytokine 2022 02 31;150:155783. Epub 2021 Dec 31.

Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China. Electronic address:

Objective: Postoperative cognitive dysfunction (POCD) affects 15-25% of surgical patients and causes significant morbidity and mortality. This study aims to investigate the mechanism of propofol reducing POCD in aged rats.

Method: Rats in Operate group and Propofol group were anesthetized with isoflurane and propofol, respectively, and then underwent cardiac surgery. Rats in Antagomir group were anesthetized with propofol and underwent cardiac surgery with preoperative injection of miR-223-3p antagomir. Barnes maze and Morris water maze (MWM) were used to test spatial learning and memory of rats. Immunofluorescence was used to detect the level of microglial cell marker IBA1. In addition, qRT-PCR was performed to measure the expression of miR-223-3p and inflammatory factors TNF-α, IL-1β and IL-6. Western blotting was conducted to detect the protein expression of Foxo1, TNF-α, IL-1β and IL-6.

Result: Isoflurane-anesthetized rats undergoing cardiac surgery showed significantly reduced spatial learning and memory, promoted microglia activation, decreased miR-223-3p expression and increased inflammatory response in the hippocampus, while isoflurane-anesthetized rats without surgery showed insignificant changes in these indices. Compared to isoflurane anesthesia, propofol anesthesia exhibited less effect on spatial learning and memory of rats with cardiac surgery and contributed to a relative reduction in activated microglia in the hippocampus, a notable increase in miR-223-3p expression, and a decrease in inflammation. The results were reversed after miR-223-3p antagomir was injected into propofol-anesthetized surgical rats. miR-223-3p negatively regulated Foxo1 to suppress the expression of inflammatory factors.

Conclusion: Propofol reduced inflammation by up-regulating miR-223-3p, thereby reducing POCD in aged rats.
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http://dx.doi.org/10.1016/j.cyto.2021.155783DOI Listing
February 2022

Sulfide with Oxygen-Rich Carbon Network for Good Lithium-Storage Kinetics.

ACS Nano 2022 Feb 30;16(2):2651-2660. Epub 2021 Dec 30.

School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.

Transition metal sulfides are of great interest as electrode material for alkali metal-ion batteries due to their high theoretical capacity. However, sluggish ion migration and electron transfer kinetics lead to poor cycling stability and rate performance, which hinders their practical applications. Herein, we develop a two-step localized carbonization and sulfurization method to construct a CoS composite material ([email protected]@C) from an integrated zeolitic imidazolate framework (ZIF-67) and multiwalled carbon nanotube precursor ([email protected]). The as-prepared [email protected]@C composites with a nanoscale carbon skeleton inherit a large specific surface area and suitable nanopore size distribution from ZIF-67 and incredibly abundant oxygenated functional groups from CNTs. The theoretical calculation and material characterization demonstrate that the oxygenated functional groups on the porous carbon networks accelerate lithium-ion diffusion and electron transfer and especially electrocatalyze the progressive conversion of LiS to the final product LiS. Meanwhile, the three-dimensional conductive network guarantees the conductive and structural stability of [email protected]@C during the repeated lithium-storage process. Therefore, the [email protected]@C electrode material can deliver an initial discharge capacity of 1282.3 mA h g at 200 mA g with a high Coulombic efficiency of 93.5% and a reversible capacity of 558.8 mA h g at 2000 mA g in 600 cycles with a high capacity retention of 96.1%.
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http://dx.doi.org/10.1021/acsnano.1c09446DOI Listing
February 2022

Septicemic Melioidosis Detection Using Support Vector Machine with Five Immune Cell Types.

Dis Markers 2021 6;2021:8668978. Epub 2021 Dec 6.

Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan, China.

Melioidosis, caused by (), predominantly occurs in the tropical regions. Of various types of melioidosis, septicemic melioidosis is the most lethal one with a mortality rate of 40%. Early detection of the disease is paramount for the better chances of cure. In this study, we developed a novel approach for septicemic melioidosis detection, using a machine learning technique-support vector machine (SVM). Several SVM models were built, and 19 features characterized by the corresponding immune cell types were generated by Cell type Identification Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Using these features, we trained a binomial SVM model on the training set and evaluated it on the independent testing set. Our findings indicated that this model performed well with means of sensitivity and specificity up to 0.962 and 0.979, respectively. Meanwhile, the receiver operating characteristic (ROC) curve analysis gave area under curves (AUCs) ranging from 0.952 to 1.000. Furthermore, we found that a concise SVM model, built upon a combination of CD8+ T cells, resting CD4+ memory T cells, monocytes, M2 macrophages, and activated mast cells, worked perfectly on the detection of septicemic melioidosis. Our data showed that its mean of sensitivity was up to 0.976 while that of specificity up to 0.993. In addition, the ROC curve analysis gave AUC close to 1.000. Taken together, this SVM model is a robust classification tool and may serve as a complementary diagnostic technique to septicemic melioidosis.
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http://dx.doi.org/10.1155/2021/8668978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668356PMC
March 2022

Rational Design of β-NiOOH Nanosheet-Sheathed CNTs as a Highly Efficient Electrocatalyst for Practical Li-S Batteries.

ACS Appl Mater Interfaces 2021 Dec 4;13(49):58789-58798. Epub 2021 Dec 4.

Beijing Key Laboratory of Advanced Chemical Energy Storage Technology and Materials, Research Institute of Chemical Defense, Beijing 100191, P. R. China.

The shuttle effects of polysulfide intermediates (LiPSs) and sluggish kinetics during sulfur reduction reaction (SRR) process severely exacerbate the electrochemical performances of Li-S batteries. Herein, a unique nanocatalyst comprising β-NiOOH nanosheets uniformly implanted on the surface of carbon nanotubes ([email protected]) was designed and synthesized for sulfur cathodes. The β-NiOOH nanosheets have great capability of adsorbing LiPSs as well as superior catalytic activity for accelerating LiPS conversion, providing a more efficient method to restrain shuttle effects and improve the kinetics of SRR. Moreover, the nanometer-scale epitaxial growth and uniform distribution of β-NiOOH on CNTs provide a multidimensional catalytic skeleton with sufficient accessible active surfaces, unimpeded LiPS diffusion pathways, and resultant high utilization of active sites. Simultaneously, stable electron transportation pathways are also obtained by being synthesized on CNTs to avoid the faultiness of poor electron conductivity of β-NiOOH. These conspicuous advantages contribute to fully exert the catalytic and LiPS anchoring potential of [email protected], bringing about the ultralong cycle performance and excellent capacity reversibility at a high discharge rate. Reticular [email protected] frameworks are assembled with the sulfur composite materials (SCMs) by a self-assembly method, and a super-high capacity of 813.3 mA h g after 400 cycles at 0.5 C with a small capacity degradation of 0.07% per cycle is achieved. Furthermore, the 3 A h pouch-type cell with the SCM/[email protected] cathode attains a super-high energy density of about 320 W h kg and shows a superior capacity retention as high as 75.9% after 50 cycles at 0.2 C. This work provides a promising method to accelerate the SRR process and restrain the shuttle effects for practical long-life and high-capacity Li-sulfur batteries.
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http://dx.doi.org/10.1021/acsami.1c19915DOI Listing
December 2021

Effects of half-dose and full-dose GnRH antagonists on IVF-ET outcomes: a retrospective study.

BMC Pregnancy Childbirth 2021 Oct 27;21(1):727. Epub 2021 Oct 27.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

Background: Gonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant during controlled ovarian stimulation (COS) may improve endometrial receptivity and clinical pregnancy rate. However, the GnRH-ant dose is relatively flexible and there is no fixed requirement for guidance. In this retrospective study, we determined the effects of half-dose and full-dose GnRH-ant on IVF-ET outcomes.

Methods: Of the 316 cycles in the 314 patients analyzed in this study, 149 received GnRH-ant half-dose (Group1), while 167 received GnRH-ant full-dose (Group2). The groups were further classified based on age and BMI. Age subgroups, were divided as age ≤ 35(subgroup A) and age > 35(subgroup B): 180 cycles in subgroup A (107 cycles in subgroup A1,73 cycles in subgroup A2), 136 cycles in subgroup B (42 cycles in subgroup B1,94 cycles in subgroupB2). The subgroups based on BMI were divided as BMI < 25 (subgroup C)and BMI ≥ 25 (subgroup D):208 cycles in subgroup C (94 cycles in subgroup C1,114 cycles in subgroup C2), 108 cycles in subgroup D (55 cycles in subgroup D1,53 cycles in subgroup D2).

Results: The number of fertilized oocytes, superior-quality embryos, clinical pregnancy rate, and live birth rate differed significantly between the two groups. However, the number of retrieved oocytes and available embryos were significantly higher in Group 1 than Group 2 (8.17 ± 4.10 vs. 7.07 ± 4.05, 2.96 ± 2.03 vs. 2.52 ± 1.62, respectively,p<0.05). Differences between the age subgroups were not statistically significant. However, in the subgroups based on BMI, the fertilized oocytes, available embryos, the number of superior-quality embryos, and the live birth rate differed significantly between the four subgroups. The number of retrieved oocytes was higher in subgroup C1 than in subgroup C2 (8.24 ± 4.04 vs. 6.83 ± 3.92,p < 0.05), In addition, the clinical pregnancy rate was slightly higher in subgroup D1 than in subgroup D2(45.45 vs. 24.53%, P < 0.05).

Conclusions: The results showed that half-dose GnRH-ant was as effective as full-dose GnRH-ant for most patients. Moreover, half-dose GnRH-ant may be more suitable in patients with BMI greater than or equal to 25. The findings of this study need to be validated in a large sample RCT.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12884-021-04176-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549158PMC
October 2021

Current Review of Leptomeningeal Amyloidosis Associated With Transthyretin Mutations.

Neurologist 2021 Sep 7;26(5):189-195. Epub 2021 Sep 7.

Department of Neurology, Innovation Center for Neurological Disorders.

Introduction: Leptomeningeal amyloidosis (LA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges. Of >120 TTR mutations identified, few have been associated with LA.

Case Report: A 27-year-old male presented with a 2-year history of progressive symptoms including cognitive decline and right-sided weakness and numbness. Cerebrospinal fluid (CSF) analyses demonstrated high protein level. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed extensive leptomeningeal enhancement over the surface of the brain and spinal cord. Pathologic analyses revealed a TTR mutation c.113A>G (p.D38G).

Review Summary: Fifteen mutations and genotype-phenotype correlation of 72 LA patients have been summarized to provide an overview of LA associated with transthyretin mutations. The mean age of clinical onset was 44.9 years and the neurological symptoms primarily included cognitive impairment, headache, ataxia seizures and hearing, visual loss. CSF analysis showed elevated high CSF protein level and MRI revealed extensive leptomeningeal enhancement.

Conclusion: Clinicians should be aware of this rare form of familial transthyretin amyloidosis as well as its typical MRI enhancement and high CSF protein. The important role of biopsy, genetic testing and the potential early diagnosis value of contrast MRI were suggested. Early recognition of these characteristics is important to provide misdiagnosis and shorten the time before correct diagnosis. These findings expand the phenotypic spectrum of TTR gene and have implications for the diagnosis, treatment, and systematic study of LA.
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http://dx.doi.org/10.1097/NRL.0000000000000337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423141PMC
September 2021

miR-221-3p regulates apoptosis of ovarian granulosa cells via targeting FOXO1 in older women with diminished ovarian reserve (DOR).

Mol Reprod Dev 2021 04 10;88(4):251-260. Epub 2021 Mar 10.

Integrative Medicine Research Centre of Reproduction and Heredity, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

In our earlier study, we showed that the expression of microRNA-221-3p (miR-221-3p) was significantly lower in women of advanced age with diminished ovarian reserve (DOR) compared with young women with normal ovarian reserve (NOR). Therefore, in this study, we aimed to explore how miR-221-3p regulates apoptosis of granulosa cells and the pathogenesis of DOR. Bioinformatics prediction and dual-luciferase reporter assay were conducted to identify the target gene of miR-221-3p. miR-221-3p expression was manipulated by transfecting KGN cells with miR-221-3p mimics, inhibitor, and negative control. Following transfection, apoptosis of granulosa cells was determined by flow cytometry, and the expression of the target gene was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis (WB). In addition, the expression of the target gene in granulosa cells of DOR patients and NOR patients was measured. miR-221-3p were found to directly bind the 3' untranslated region of Forkhead box O1 (FOXO1). Transfection with miR-221-3p mimics significantly decreased the apoptosis rate of KGN cells compared with transfection with miR-221-3p inhibitors. The expression level of miR-221-3p was negatively correlated with the messenger RNA and protein levels of the FOXO1 gene. Besides, FOXO1 expression was upregulated in DOR patients. In conclusion, these results provide evidence that downregulation of miR-221-3p expression promotes apoptosis of granulosa cells by upregulating FOXO1 expression, thus serving an important role in DOR pathogenesis.
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http://dx.doi.org/10.1002/mrd.23457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251591PMC
April 2021

Hydrogel composite scaffolds with an attenuated immunogenicity component for bone tissue engineering applications.

J Mater Chem B 2021 03;9(8):2033-2041

Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, P. R. China.

Xenogeneic bones are potential templates for bone regeneration. In this study, decellularized porcine bone powder with attenuated immunogenicity was incorporated into a photocurable hydrogel, gelatin methacryloyl (GelMA), to obtain scaffolds with good mechanical properties for bone tissue engineering. The decellularized bone powder (DCB)-GelMA hybrid scaffolds had higher compressive strength and stiffness values when the DCB content was increased. In vitro evaluations revealed the biocompatibility of these scaffolds. The scaffolds could induce human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation even in the absence of an induction medium. The efficiency of the scaffolds for bone regeneration applications was further evaluated using an in vivo cranial bone defect model in rats. Micro-CT images showed that the hybrid scaffolds with 20% DCB content had the best effect in promoting new bone regeneration. Thus, it was concluded that the DCB-GelMA hybrid scaffolds have high potential in bone tissue engineering applications.
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http://dx.doi.org/10.1039/d0tb02588gDOI Listing
March 2021

Macromolecular Design of Lithium Conductive Polymer as Electrolyte for Solid-State Lithium Batteries.

Small 2021 Jan 21;17(3):e2005762. Epub 2020 Dec 21.

Qingdao Industrial Energy Storage Research Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.

In the development of solid-state lithium batteries, solid polymer electrolyte (SPE) has drawn extensive concerns for its thermal and chemical stability, low density, and good processability. Especially SPE efficiently suppresses the formation of lithium dendrite and promotes battery safety. However, most of SPE is derived from the matrix with simple functional group, which suffers from low ionic conductivity, reduced mechanical properties after conductivity modification, bad electrochemical stability, and low lithium-ion transference number. Appling macromolecular design with multiple functional groups to polymer matrix is accepted as a strategy to solve the problems of SPE fundamentally. In this review, macromolecular design based on lithium conducting groups is summarized including copolymerization, network construction, and grafting. Meanwhile, the construction of single-ion conductor polymer is also focused herein. Moreover, synergistic effects between the designed matrix, lithium salt, and fillers are reviewed with the objective to further improve the performance of SPE. At last, future studies on macromolecular design are proposed in the development of SPE for solid-state batteries with high energy density and durability.
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http://dx.doi.org/10.1002/smll.202005762DOI Listing
January 2021

Spinster homolog 2 in cancers, its functions and mechanisms.

Cell Signal 2021 01 2;77:109821. Epub 2020 Nov 2.

School of Medicine, South China University of Technology, Guangzhou, Guandong, 510006, PR China. Electronic address:

Spinster homolog 2 (SPNS2) is a multi-transmembrane transporter, widely located in the cell membrane and organelle membranes. It transports sphingosine-1-phosphate (S1P) into the extracellular space and the circulatory system, thus alters the concentration and the distribution of S1P, sphingosine-1-phosphate receptor (S1PRs) and S1P related enzymes, meaning that it exerts its functions via S1P signaling pathways. Studies also show that ectopic SPNS2 mediates parts of the physiological process of the cells. As of now, SPNS2 has been reported to participate in physiological processes such as angiogenesis, embryonic development, immune response and metabolisms. It is also associated with the transformation from inflammation to cancer as well as the proliferation and metastasis of cancer cells. In this review, we summarize the functions and the mechanisms of SPNS2 in the pathogenesis of cancer to provide new insights for the diagnosis and the treatments of cancer.
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http://dx.doi.org/10.1016/j.cellsig.2020.109821DOI Listing
January 2021

A comparison of pregnancy rate between natural cycle and hormone replacement cycle in patients who underwent frozen embryo transfer using 2 consecutive hormone replacement regiments: A STROBE-compliant retrospective study.

Medicine (Baltimore) 2020 Sep;99(37):e22163

Center for Reproduction and Genetics Integrated Traditional Chinese and Western Medicine, The Hospital Affiliated of Shandong University of Traditional Chinese Medicine.

For frozen embryo transplantation patients who failed to use hormone replacement cycle (HRC) transplantation for 2 consecutive times, the third time of transplantation was divided into 2 groups: HRC and natural cycle (NC), and the pregnancy rate of the 2 groups, especially the clinical pregnancy rate, was compared.Retrospective study of 174 patients in the reproductive medicine center of an affiliated hospital of Shandong University of Traditional Chinese Medicine between January 2015 and September 2018.The 174 patients were all infertile with regular menstruation. They had undergone 2 consecutive failed cycles of endometrial preparation with hormone replacement therapy and prepare for the third frozen embryo transplantation.A third cycle of treatment was planned using either NC or HRC for endometrial preparation. All the embryos were obtained during the same oocyte retrieval cycle. Patients were divided into groups based on the method of endometrial preparation: 98 were classified as NC and 76 as HRC.The pregnancy outcomes for the 2 groups were compared. Confounding factors that may affect clinical pregnancy rates were analyzed.We found that on the day of endometrial transformation, estrogen levels and endometrial thickness in the NC group were significantly higher than those in the HRC group. There were no significant differences in the rates of biochemical pregnancy, clinical pregnancy, cumulative pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, or live birth between the 2 groups. It is concluded by binary regression analysis that the different endometrial preparation protocol have no significant effect on the CPR.NC is as effective as HRC after 2 previous cycles of HRC. Because this was a retrospective study design, selection bias is possible, although the baseline characteristics of the 2 groups of patients were matched.
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http://dx.doi.org/10.1097/MD.0000000000022163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489599PMC
September 2020

MYB-QKI rearrangement in angiocentric glioma.

Clin Neuropathol 2020 Nov/Dec;39(6):263-270

Aims: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients.

Materials And Methods: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH).

Results: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance.

Conclusion: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.
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http://dx.doi.org/10.5414/NP301284DOI Listing
October 2021

Analysis of Inflammatory and Homeostatic Roles of Tissue-resident Macrophages in the Progression of Cholesteatoma by RNA-Seq.

Immunol Invest 2021 Aug 23;50(6):609-621. Epub 2020 Jun 23.

Central Laboratory, Ningbo First Hospital, Ningbo City, Zhejiang Province, China.

Background: Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris.

Methods: TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis.

Results: The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs.

Conclusions: The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.
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http://dx.doi.org/10.1080/08820139.2020.1781161DOI Listing
August 2021

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome.

Chin J Integr Med 2021 May 22;27(5):330-335. Epub 2020 Jun 22.

Reproductive and Genetic Center of Integrated Traditional and Western Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China.

Objective: To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR).

Methods: Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells.

Results: EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P<0.05). No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups (P>0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05).

Conclusions: EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).
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http://dx.doi.org/10.1007/s11655-020-3219-zDOI Listing
May 2021

L-Theanine Attenuates Isoflurane-Induced Injury in Neural Stem Cells and Cognitive Impairment in Neonatal Mice.

Biol Pharm Bull 2020 Jun 19;43(6):938-945. Epub 2020 Mar 19.

Department of Anesthesiology, Second Affiliated Hospital of Nanchang University.

The neurodevelopmental toxicity of isoflurane has been proved by many studies, which makes it essential to explore the underline mechanisms and search for protective agents to attenuate its neurotoxcity. Accumulating evidence showed that L-theanine had neuroprotective effects on injured neurons and the developing brain. The present study was designed to investigate whether L-theanine could attenuate isoflurane-induced damage in neural stem cells and cognitive impairment in young mice, and to discuss the role of protein kinase B (Akt)-glycogen synthase kinase 3β (GSK-3β) signaling pathway in this process. Multipotential neural stem cells (NSCs) and C57BL/6J mice were treated with either gas mixture, isoflurane, or L-theanine 30 min prior to isoflurane exposure, respectively. NSC viability was detected by CCK-8 assay. NSC proliferation and apoptosis were assessed by immunofluorescence and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. The levels of cleaved caspase-3 and phosphorylated (p)-Akt and p-GSK-3β in NSCs were tested by Western blotting. Cognitive function of mice was tested by Morris Water Maze at postnatal day (P) 30-35. The results indicated that isoflurane exposure inhibited NSC viability and proliferation, promoted NSC apoptosis as well as increased caspase-3 activation and down-regulated the expressions of p-Akt and p-GSK-3β in NSCs, and that isoflurane exposure on neonatal mice would induce late cognitive impairment. Pretreatment with L-theanine could attenuate isoflurane-caused damage in NSCs and cognitive deficits in young mice. Addinonally, the protective effects of L-theanine on isoflurane-injured NSCs could be reversed by Akt inhibitor Triciribine. Our data showed that pretreatment with L-theanine eliminated the NSC damage and cognitive impairment induced by isoflurane exposure, and that the neuroprotective effect of L-theanine was associated with the Akt-GSK-3β signaling pathway.
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http://dx.doi.org/10.1248/bpb.b19-00790DOI Listing
June 2020

Identification, characterization, and comparison of n-alkanols and anesthetics binding to the C1b subdomain of protein kinase cα: similar function with different binding sites.

J Recept Signal Transduct Res 2020 Apr 13;40(2):109-116. Epub 2020 Feb 13.

Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

Protein kinase C (PKC) is a family of lipid-activated enzymes involved in anesthetic preconditioning signaling pathways. Previously, -alkanols and general anesthetics have been found to activate PKC by binding to the kinase C1B subdomain. In the present study, we attempt to ascertain the molecular mechanism and interaction mode of human PKCα C1B subdomain with a variety of exogenous -alkanols and volatile general anesthetics as well as endogenous activator phorbol ester (PE) and co-activator diacylglycerol (DG). Systematic bioinformatics analysis identifies three spatially vicinal sites on the subdomain surface to potentially accommodate small-molecule ligands, where the site 1 is a narrow, amphipathic pocket, the site 2 is a wide, flat and hydrophobic pocket, and the site 3 is a rugged, polar pocket. Further interaction modeling reveals that site 1 is the cognate binding region of natural PE activator, which can moderately simulate the kinase activity in an independent manner. The short-chain -alkanols are speculated to also bind at the site to competitively inhibit PE-induced kinase activation. The long-chain -alkanols and co-activator DG are found to target site 2 in a nonspecific manner, while the volatile anesthetics prefer to interact with site 3 in a specific manner. Since the site 1 is composed of two protein loops that are also shared by sites 2 and 3, binding of -alkanols, DG and anesthetics to sites 2 and 3 can trigger a conformational displacement on the two loops, which enlarges the pocket size and changes the pocket configuration of site 1 through an allosteric mechanism, consequently enhancing kinase activation by improving PE affinity to the site.
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http://dx.doi.org/10.1080/10799893.2020.1726950DOI Listing
April 2020

promotes hepatocyte proliferation via NF-κB and ERK pathway by targeting , and .

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):3786-3792

Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Jinan University , Guangzhou , Guangdong , China.

Phospholipase Cγ2 (PLCG2) has been implicated in the regulation of cell proliferation, transformation, and tumor growth. In this study, we investigate the mechanism of action using a short interference RNA (siRNA) method. The effects of on rat liver BRL-3A cells treated siRNA were studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT assay), bromodeoxyuridine (BrdU) labelling assay, flow cytometry method (FCM), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The results showed when PLCG2 was reduced, cell vitality and proliferation rate were significantly decreased ( < .05 vs. control). FCM analysis showed that the number of cell division phase (G2 + M) was declined ( < .05 vs. control). RT-PCR and western blot revealed that the expression of signalling related genes and target genes and were remarkably down-regulated in cells treated with PLCG2 siRNAs. Based on these results, we conclude PLCG2 plays an important role in rat liver cell proliferation via ERK and NF-κB pathway by regulating the expression of and .
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http://dx.doi.org/10.1080/21691401.2019.1669616DOI Listing
December 2019

[Prokaryotic expression of human retinol binding protein and preparation of rabbit polyclonal antibody].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Jul;35(7):653-658

Department of Clinical Laboratory, Second Affiliated Hospital of Hainan Medical University, Haikou 570311, China.

Objective To produce rabbit polyclonal antibodies against human retinol-binding protein (RBP). Methods RBP cDNA was amplified by reverse transcription polymerase chain reaction (RT-PCR) and then the amplified products were inserted into prokaryotic expression vector pET-28a(+) to construct recombinant plasmid pET-28a(+)-RBP. The established plasmid was then transformed into E. coli. Isopropylthio-β-D-thiogalactoside (IPTG) was used to induce the expression of recombinant protein His-RBP in E. coli. The expression products were identified by SDS-PAGE from different clones of E. coli to screen positive bacteria, followed by amplifying culture. His-RBP protein was purified from the expression products of positive clones. The purified recombinant His-RBP was used to immunize New Zealand white rabbits. Antisera were acquired after four times of booster immunization. The prepared purified polyclonal antibodies were identified by SDS-PAGE, ELISA and Western blotting. Results We successfully constructed the recombinant plasmid pET-28a(+)-RBP, and acquired recombinant protein His-RBP of high purity. ELISA showed that the antibody titer reached 1:512 000. Conclusion The rabbit polyclonal antibodies against human RBP have been successfully prepared.
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July 2019

Bone morphogenetic protein 6 affects cell-cell communication by altering the expression of Connexin43 in human granulosa-lutein cells.

Mol Cell Endocrinol 2019 12 18;498:110548. Epub 2019 Aug 18.

Integrative Medicine Research Centre of Reproduction and Heredity, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V6H 3V5, Canada. Electronic address:

Connexin 43 (Cx43)-coupled gap junctions in granulosa cells play an important role in follicular development, oocyte maturation, and corpus luteum maintenance. Bone morphogenetic protein 6 (BMP6) is highly expressed in human oocytes and granulosa cells and is involved in the regulation of female reproduction. Currently, whether oocyte- and granulosa cell-derived BMP6 affects the expression of Cx43 and its related gap junction intercellular communication (GJIC) activity in human granulosa cells remains unknown. In this study, we demonstrate that BMP6 treatment significantly suppressed the expression of Cx43 in both primary and immortalized (SVOG) human granulosa-lutein cells. Using both pharmacological inhibitors and small interfering RNA-mediated knockdown approaches, we demonstrate that ALK2 and ALK3 BMP type I receptors are involved in BMP6-induced suppressive effects on Cx43 expression and GJIC activity in SVOG cells. Furthermore, these cellular activities are most likely mediated by the SMAD1/SMAD5-SMAD4-dependent signaling pathway. Notably, the ChIP analyses demonstrated that phosphorylated SMADs could bind to human Cx43 promoter. Our findings provide new insight into the molecular mechanisms by which an intrafollicular growth factor regulates cell-cell communication in human granulosa cells.
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http://dx.doi.org/10.1016/j.mce.2019.110548DOI Listing
December 2019

Expression of HOXA10 gene in women with polycystic ovarian syndrome and its correlation analysis with lipid metabolism.

Minerva Endocrinol 2019 12 24;44(4):413-415. Epub 2019 Jul 24.

Center for Reproduction and Genetics of Integrated Traditional Chinese and Western Medicine, Affiliate Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

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http://dx.doi.org/10.23736/S0391-1977.19.03064-5DOI Listing
December 2019

Comparison of type I tympanoplasty with acellular dermal allograft and cartilage perichondrium.

Acta Otolaryngol 2019 Oct 16;139(10):833-836. Epub 2019 Jul 16.

Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , PR China.

Acellular dermal allograft (AlloDerm) and cartilage perichondrium are two common materials used for repair of tympanic membrane perforations (TMPs). To date, comparative evaluations of their efficacy have rarely been reported. To compare anatomical and audiological outcomes between AlloDerm and cartilage perichondrium in type I tympanoplasty. A total of 61 patients of TMP were studied. In total, 27 patients (Group 1) underwent AlloDerm myringoplasty, and the remaining 34 patients (Group 2) underwent perichondrium myringoplasty. Operating time, closure rate and hearing gain were compared between Groups 1 and 2. Successful closure rates at 6-month follow-up were 88.9% (Group 1) and 82.4% (group 2). The average improvement of air-bone gap (ABG) was 13.5 ± 11.8 dB for Group 1 and 13.1 ± 13.1 dB for Group 2. The difference in between preoperative and 6 months postoperative ABG values was statistically significant ( < .001). Success rates and improvement of hearing level were similar for the AlloDerm (Group 1) and the cartilage perichondrium (Group 2) groups. However, AlloDerm requires shorter operative time and avoids the incisions in the harvest of allografts. Our results suggest that AlloDerm can be recommended as an attractive alternative to cartilage grafts.
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http://dx.doi.org/10.1080/00016489.2019.1637541DOI Listing
October 2019

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer.

Chin J Integr Med 2019 Apr 25;25(4):252-258. Epub 2019 Jun 25.

Integrative Medicine Research Centre of Reproduction and Heredity, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

Objective: To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism.

Methods: Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.

Results: Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05).

Conclusions: For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).
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http://dx.doi.org/10.1007/s11655-019-2948-3DOI Listing
April 2019

Identification of potential metabolic biomarkers of polycystic ovary syndrome in follicular fluid by SWATH mass spectrometry.

Reprod Biol Endocrinol 2019 Jun 11;17(1):45. Epub 2019 Jun 11.

Integrative Medicine Research Centre of Reproduction and Heredity, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No 42 Wen Hua Xi Road, Jinan, 250011, China.

Background: Polycystic ovary syndrome (PCOS) is a complex disorder associated with multiple metabolic disturbance, including defective glucose metabolism and insulin resistance. The altered metabolites caused by the related metabolic disturbance may affect ovarian follicles, which can be reflected in follicular fluid composition. The aim of this study is to investigate follicular fluid metabolic profiles in women with PCOS using an advanced sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry.

Materials And Methods: Nineteen women with PCOS and twenty-one healthy controls undergoing IVF/ET were recruited, and their follicular fluid samples were collected for metabolomic study. Follicular fluid metabolic profiles, including steroid hormones, free fatty acids, bioactive lipids, and amino acids were analyzed using the principal component analysis (PCA) and partial least squares to latent structure-discriminant analysis (PLS-DA) model.

Results: Levels of free fatty acids, 3-hydroxynonanoyl carnitine and eicosapentaenoic acid were significantly increased (P < 0.05), whereas those of bioactive lipids, lysophosphatidylcholines (LysoPC) (16:0), phytosphingosine, LysoPC (14:0) and LysoPC (18:0) were significantly decreased in women with PCOS (P < 0.05). Additionally, levels of steroid hormone deoxycorticosterone and two amino acids, phenylalanine and leucine were higher in the PCOS patients (P < 0.05).

Conclusion: Women with PCOS display unique metabolic profiles in their follicular fluid, and this data may provide us with important biochemical information and metabolic signatures that enable a better understanding of the pathogenesis of PCOS.
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http://dx.doi.org/10.1186/s12958-019-0490-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560878PMC
June 2019

The caveolin-3 P104L mutation in LGMD-1C patients inhibits non-insulin-stimulated glucose metabolism and growth but promotes myocyte proliferation.

Cell Biol Int 2019 Jun 13;43(6):669-677. Epub 2019 May 13.

Department of Physiology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530022, Guangxi, China.

The caveolin-3 (CAV3) protein is known to be specifically expressed in various myocytes, and skeletal muscle consumes most of the blood glucose as an energy source to maintain normal cell metabolism and function. The P104L mutation in the coding sequence of the human CAV3 gene leads to autosomal dominant disease limb-girdle muscular dystrophy type 1C (LGMD-1C). We previously reported that C2C12 cells transiently transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis after insulin stimulation. The present study aimed to examine whether the P104L mutation affects C2C12 cell glucose metabolism, growth, and proliferation without insulin stimulation. C2C12 cells stably transfected with CAV3-P104L were established, and biochemical assays, western blot analysis and confocal microscopy were used to observe glucose metabolism as well as cell growth and proliferation and to determine the effect of the P104L mutation on the PI3K/Akt signaling pathway. Without insulin stimulation, C2C12 cells stably transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis, decreased CAV3 expression and reduced localization of CAV3 and GLUT4 on the cell membrane. The P104L mutant significantly reduced the cell diameters, but accelerated cell proliferation. Akt phosphorylation was inhibited, and protein expression of GLUT4, p-GSK3β, and p-p70s6K, which are molecules downstream of Akt, was significantly decreased. The CAV3-P104L mutation inhibits glycometabolism and cell growth but accelerates C2C12 cell proliferation by reducing CAV3 protein expression and cell membrane localization, which may contribute to the pathogenesis of LGMD-1C.
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http://dx.doi.org/10.1002/cbin.11144DOI Listing
June 2019

Transcutaneous electrical acupuncture point stimulation improves pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilisation and embryo transfer: a prospective, randomised trial.

Acupunct Med 2019 02 13;37(1):33-39. Epub 2019 Mar 13.

2 The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), Shenzhen, China.

Objective: To evaluate the effect of transcutaneous electrical acupuncture stimulation (TEAS) on pregnancy outcomes in patients with recurrent implantation failure (RIF) undergoing in vitro fertilisation (IVF).

Methods: A total of 122 women with RIF undergoing fresh embryo transfer cycle IVF were randomly allocated to a TEAS or mock TEAS (MTEAS) group. Gonadotrophin therapy using a long protocol was provided in both groups. TEAS consisted of 30 min of stimulation (9-25 mA, 2 Hz) at SP6, CV3, CV4 and Zigong from day 5 of the ovarian stimulation cycle once every other day until the day of embryo transfer. The patients in the control group received MTEAS. Implantation, clinical pregnancy and live birth rates were compared.

Results: In the TEAS group, the implantation rate, clinical pregnancy rate and live birth rate (24.3%, 32.8% and 27.9%, respectively) were significantly higher than in the MTEAS group (12.1%, 16.4% and 13.1%, respectively).

Conclusions: TEAS significantly improves the clinical outcomes of subsequent IVF cycles among women who have experienced RIF.

Trial Registration Number: ChiCTR-TRC-14004730.
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http://dx.doi.org/10.1136/acupmed-2017-011483DOI Listing
February 2019

Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications.

Hum Reprod Update 2019 03;25(2):224-242

Integrative Medicine Research Centre of Reproduction and Heredity, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

Background: Neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary.

Objective And Rationale: The molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities.

Search Methods: Relevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar.

Outcomes: Studies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers.

Wider Implications: A comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.
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http://dx.doi.org/10.1093/humupd/dmy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390169PMC
March 2019
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