Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375- 3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3'-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

SISS-MCO: large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans.

Objective.Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013).Approach.In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots.Main results.Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar.Significance.The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System.

AIMS: Clinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. MATERIALS AND METHODS: Using linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. RESULTS: We identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). CONCLUSIONS: In this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

Factors influencing the detection rate of fumarate peak in 1H MR spectroscopy of fumarate hydratase-deficient renal cell carcinoma at 3 T MRI.

AIM: To identify factors that may be associated with fumarate detection rate in 1H-magnetic resonance spectroscopy (MRS) in fumarate hydratase-deficient renal cell carcinoma (FH-RCC). MATERIALS AND MEHODS: Between February 2018 and March 2022, 16 FH-RCC patients with 30 lesions underwent 1H-MRS. Detection results were classified as having a detected fumarate peak (n=12), undetected peak (n=10), or technical failure (n=8). Factors including tumour size, tumour location, treatment history, and metastasis status were collected and analysed. A Bayesian logistic regression model was applied to evaluate the association between these factors and the detection result. RESULTS: Bayesian analysis demonstrated significant associations between fumarate detection results and the following factors: long-axis diameter (odds ratio [OR] of 1.64; 95% confidence interval [CI] of 1.07-2.53), short-axis diameter (OR of 1.90; 95% CI of 1.19-3.06), voxel size (OR of 2.85; 95% CI of 1.70-4.75), treatment history (OR of 0.35; 95% CI of 0.21-0.58), non-metastatic state (OR of 2.45; 95% CI of 1.48-4.06), and lymph node metastasis (OR of 0.35; 95% CI of 0.21-0.58). Technical failure results were associated with factors such as treatment history (OR of 2.59; 95% CI of 1.37-4.66), non-metastatic state (OR of 0.36; 95% CI of 0.19-0.66), and lymph node metastasis (OR of 2.61; 95% CI of 1.39-4.74). CONCLUSION: Tumour size, treatment history, and metastasis character were associated with the detection of abnormal fumarate accumulation. This finding will serve as a reference for interpreting 1H-MRS results and for selecting suitable scenarios to evaluate FH-RCC.

[Progress in the application of alveolar organoids in common lung diseases].

Organoids are tissue cultures formed by culturing cells in three-dimensional environments that simulate the physiological or pathological conditions of the human body. The cultivation of organoids is used to study the temporal and spatial transformation of cells during the development of tissues or organs, to investigate changes in cellular functions and inter-communications caused by various risk factors, and to discover potential therapeutic targets. This article provided an overview of the cultivation and identification methods of alveolar organoids, as well as the research progress in their application to common respiratory diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, viral pneumonia, and so on. The limitations and future applications of alveolar organoids are also analyzed and discussed.

DWI-Based Radiomics Predicts the Functional Outcome of Endovascular Treatment in Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Endovascular treatment is a reference treatment for acute basilar artery occlusion (ABAO). However, no established and specific methods are available for the preoperative screening of patients with ABAO suitable for endovascular treatment. This study explores the potential value of DWI-based radiomics in predicting the functional outcomes of endovascular treatment in ABAO. MATERIALS AND METHODS: Patients with ABAO treated with endovascular treatment from the BASILAR registry (91 patients in the training cohort) and the hospitals in the Northwest of China (31 patients for the external testing cohort) were included in this study. The Mann-Whitney U test, random forests algorithm, and least absolute shrinkage and selection operator were used to reduce the feature dimension. A machine learning model was developed on the basis of the training cohort to predict the prognosis of endovascular treatment. The performance of the model was evaluated on the independent external testing cohort. RESULTS: A subset of radiomics features (n = 6) was used to predict the functional outcomes in patients with ABAO. The areas under the receiver operating characteristic curve of the radiomics model were 0.870 and 0.781 in the training cohort and testing cohort, respectively. The accuracy of the radiomics model was 77.4%, with a sensitivity of 78.9%, specificity of 75%, positive predictive value of 83.3%, and negative predictive value of 69.2% in the testing cohort. CONCLUSIONS: DWI-based radiomics can predict the prognosis of endovascular treatment in patients with ABAO, hence allowing a potentially better selection of patients who are most likely to benefit from this treatment.

Experimental Evidence of t_{2g} Electron-Gas Rashba Interaction Induced by Asymmetric Orbital Hybridization.

We report the control of Rashba spin-orbit interaction by tuning asymmetric hybridization between Ti orbitals at the LaAlO_{3}/SrTiO_{3} interface. This asymmetric orbital hybridization is modulated by introducing a LaFeO_{3} layer between LaAlO_{3} and SrTiO_{3}, which alters the Ti-O lattice polarization and traps interfacial charge carriers, resulting in a large Rashba spin-orbit effect at the interface in the absence of an external bias. This observation is verified through high-resolution electron microscopy, magnetotransport and first-principles calculations. Our results open hitherto unexplored avenues of controlling Rashba interaction to design next-generation spin orbitronics.

[Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome].

OBJECTIVE: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. METHODS: To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. RESULTS: Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-ß (TGF-ß) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to ß-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-ß signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-ß downstream genes. Besides, the serum level of TGF-ß was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-ß, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-ß level by inhibiting the activation of platelet. CONCLUSION: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-ß signaling.

[Application of locating supratrochlear artery and supraorbital artery in combined transfrontal and intranasal endoscopic approaches].

Objective: To investigate the localization methods of supratrochlear artery (STA) and supraorbital artery (SOA), and to explore the clinical benefit of locating nerve via accompanying vascular localization in combined transfrontal and intranasal endoscopic approaches. Methods: From June 2019 to May 2021, 14 patients, including 11 males and 3 females, aging from 18 to 69 years old, were underwent frontal sinus surgery through the combined transfrontal and intranasal endoscopic approaches in the Department of Otorhinolaryngology Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University. Before the surgery, localization of STA and SOA was determined by color doppler flow imaging (CDFI), computerized topographic angiography (CTA) and contrast enhanced magnetic resonance angiography (CE-MRA) respectively, and the distances between STA and SOA from facial midline were measured on 28 eyebrows. The position of external incision was determined according to the preoperative localization of STA and SOA. The examination time, cost and postoperative complications of the three methods were recorded. The accuracy of localization at 14 sides was verified by the surgery. GraphPad Prism 8.3 software was used for statistical analysis. Results: STA and SOA could be located by CDFI, CTA and CE-MRA. There was no significant difference in the measurement of the distance between STA and SOA from the facial midline among 3 methods (all P>0.05). Determining the position of external incision according to the localization of STA and SOA could protect both the blood vessels and accompanying nerves. No postoperative complications such as numbness of the forehead skin occurred. The measurement time of CDFI, CTA and CE-MRA was 22.50 (15.75, 30.00), 30.00 (28.00, 34.25) and 48.00 (44.00, 52.75) min (M (Q1, Q3)), respectively (all P<0.05). CDFI incurred the lowest costs and took the shortest time. Conclusions: CDFI is an efficient and economic localization method. The localization of STA and SOA facilitates the precise selection of the position of external incision, protects the accompanying nerve and reduces postoperative complications.

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.

[Research in evaluation and intervention of cardiovascular complications of patients with type 1 diabetes on demand].

Recently, great progress has been made in the treatment of type 1 diabetes mellitus (T1DM), however the disease still significantly shortens the life expectancy. Cardiovascular complication is the main cause of death in T1DM patients, and the morbidity is even higher than that of type 2 diabetes. The risk factors of cardiovascular complication in T1DM are different from those of type 2 diabetes. Besides hyperglycemia, dyslipidemia, hypertension, microvascular complications and unhealthy lifestyle, non-traditional risk factors also play very important roles in developing cardiovascular complication, such as hypoglycemia, blood glucose variability, insulin resistance, and autoimmune inflammation of heart. At present, there is a lack of risk assessment and prevention measures for cardiovascular complications in T1DM. It is necessary for more studies to explore whether sodium-dependent glucose transporters 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which can improve cardiovascular and renal outcomes in type 2 diabetes mellitus, can be equally effective in T1DM.

Quantitative structure-activity relationship modeling reveals the minimal sequence requirement and amino acid preference of sirtuin-1's deacetylation substrates in diabetes mellitus.

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide ([Formula: see text]-dependent deacetylase involved in multiple glucose metabolism pathways and plays an important role in the pathogenesis of diabetes mellitus (DM). The enzyme specifically recognizes its deacetylation substrates' peptide segments containing a central acetyl-lysine residue as well as a number of amino acids flanking the central residue. In this study, we attempted to ascertain the minimal sequence requirement (MSR) around the central acetyl-lysine residue of SIRT1 substrate-recognition sites as well as the amino acid preference (AAP) at different residues of the MSR window through quantitative structure-activity relationship (QSAR) strategy, which would benefit our understanding of SIRT1 substrate specificity at the molecular level and is also helpful to rationally design substrate-mimicking peptidic agents against DM by competitively targeting SIRT1 active site. In this procedure, a large-scale dataset containing 6801 13-mer acetyl-lysine peptides (and their SIRT1-catalyized deacetylation activities) were compiled to train 10 QSAR regression models developed by systematic combination of machine learning methods (PLS and SVM) and five amino acids descriptors (DPPS, T-scale, MolSurf, [Formula: see text]-score, and FASGAI). The two best QSAR models (PLS+FASGAI and SVM+DPPS) were then employed to statistically examine the contribution of residue positions to the deacetylation activity of acetyl-lysine peptide substrates, revealing that the MSR can be represented by 5-mer acetyl-lysine peptides that meet a consensus motif [Formula: see text][Formula: see text][Formula: see text](AcK)0[Formula: see text]. Structural analysis found that the [Formula: see text] and (AcK)0 residues are tightly packed against the enzyme active site and confer both stability and specificity for the enzyme-substrate complex, whereas the [Formula: see text], [Formula: see text] and [Formula: see text] residues are partially exposed to solvent but can also effectively stabilize the complex system. Subsequently, a systematic deacetylation activity change profile (SDACP) was created based on QSAR modeling, from which the AAP for each residue position of MSR was depicted. With the profile, we were able to rationally design an SDACP combinatorial library with promising deacetylation activity, from which nine MSR acetyl-lysine peptides as well as two known SIRT1 acetyl-lysine peptide substrates were tested by using SIRT1 deacetylation assay. It is revealed that the designed peptides exhibit a comparable or even higher activity than the controls, although the former is considerably shorter than the latter.

[Dynamic changes of vestibular autorotation test in patients with unilateral vestibular dysfunction during rehabilitation].

Objective: To explore the dynamic changes of vestibular autorotation test (VAT) before and after vestibular rehabilitation treatment in patients with unilateral vestibular hypofunction (UVH). Methods: A retrospective study was carried out,48 patients who were diagnosed with UVH and under vestibular rehabilitation in department of otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2021 were enrolled. Among them, there were 21 males and 27 females, with an average age of 46.9 years old, including 25 cases of Meniere's disease, 13 cases of sudden deafness with vertigo and 10 cases of vestibular neuritis. The course of disease ranged from 5 days to 10 years. Demographic characteristics, detailed case data and routine examination were collected for the patients. The horizontal gain/phase, vertical gain/phase, and asymmetry of VAT at different frequencies before and after vestibular rehabilitation were collected. The absolute value of the difference between the measured value of 2.0-5.9 Hz before and after rehabilitation and the standard value were statistically analyzed. Results: Before vestibular rehabilitation, the incidence of abnormal gain was 62.5% (30/48), the incidence of abnormal phase was 56.3% (27/48), and the incidence of asymmetry was 16.7% (8/48). After 4-6 weeks of vestibular rehabilitation, the incidence of gain abnormality was 22.9% (11/48), the incidence of phase abnormality was 31.3% (15/48), and the incidence of asymmetry was 12.5% (6/48).The horizontal gain at frequency of 2.0-3.9 Hz showed statistically significant difference compared with before vestibular rehabilitation (P<0.05), and the horizontal gain at frequency of 4.3-5.9 Hz showed that there was no significant difference (P>0.05); the horizontal phase at 5.9 Hz showed that the difference was statistically significant (P=0.043), and there was no significant difference before and after rehabilitation treatment at 2.0-5.5 Hz (P>0.05); the vertical gain at 4.3 Hz showed the difference was statistically significant (P=0.020), and the remaining frequency showed no significant difference (P>0.05); No frequency of asymmetry and vertical phase showed the difference before and after rehabilitation was statistically significant (P>0.05). Conclusion: VAT can be used to monitor the change trend of multiple frequency bands before and after vestibular rehabilitation in UVH, in order to provide reference for the formulation of personalized rehabilitation strategies.

[A comparative study of artificial intelligence nasal polyp classification based on whole-slide imaging and JESREC diagnostic criteria].

Objective: To explore the types and clinical characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP) based on artificial intelligence and whole-slide imaging (WSI), and to explore the consistency of the diagnostic criteria of the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis (JESREC) in Chinese CRSwNP patients. Methods: The data of 136 patients with CRSwNP (101 males and 35 females, aging 14 to 70 years) who underwent endoscopic sinus surgery from 2018 to 2019 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. The preoperative clinical characteristics of patients were collected, such as visual analogue scale (VAS) of nasal symptoms, peripheral blood inflammatory cell count, total immunoglobulin E (IgE), Lund-Kennedy score and Lund-Mackay score. The proportion of inflammatory cells such as eosinophils, lymphocytes, plasma cells and neutrophils were calculated on the WSI of each patient through artificial intelligence chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0), and the specific type of nasal polyps was then obtained as eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (non-eCRSwNP). In addition, the JESREC diagnostic criteria was used to classify the nasal polyps, and the classification results were compared with the current gold standard for nasal polyps diagnosis (pathological diagnosis based on WSI). The accuracy, sensitivity and specificity of the diagnostic criteria of JESREC were evaluated. The data were expressed in M (Q1, Q3) and statistically analyzed by SPSS 17.0. Results: There was no significant difference between eCRSwNP and non-eCRSwNP in age distribution, gender, time of onset, total VAS score, Lund-Kennedy score or Lund-Mackay score. However, there was a significant difference in the ratio of nasal polyp inflammatory cells (eosinophils 40.5% (22.8%, 54.7%) vs 2.5% (1.0%, 5.3%), neutrophils 0.3% (0.1%, 0.7%) vs 1.3% (0.5%, 3.6%), lymphocytes 49.9% (39.3%, 65.9%) vs 82.0% (72.8%, 87.5%), plasma cells 5.1% (3.6%, 10.5%) vs 13.0% (7.4%, 16.3%), χ2 value was 9.91, 4.66, 8.28, 5.06, respectively, all P<0.05). In addition, eCRSwNP had a significantly higher level of proportion of allergic symptoms (nasal itching and sneezing), asthma, peripheral blood eosinophil and total IgE (all P<0.05). The overall accuracy, sensitivity and specificity of the JESREC diagnostic criteria was 74.3%, 81.3% and 64.3%, respectively. Conclusions: The eCRSwNP based on artificial intelligence and WSI has significant high level of allergic symptoms, asthma, peripheral blood eosinophils and total IgE, and the percentages of inflammatory cells in nasal polyps are different from that of non-eCRSwNP. The JESREC diagnostic criteria has good consistency in our research.

First pregnancy in China after ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first case of pregnancy after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency in China. METHODS: Ovarian tissue cryopreservation was performed in a patient with myelodysplastic syndrome (MDS) before multi-agent chemotherapy and hematopoietic stem cell transplantation. Two years later, she showed complete remission from MDS, and six frozen-thawed ovarian tissue strips were transplanted into the peritoneal pocket. RESULTS: The patient's ovarian activity was restored 3 months after transplantation, and pregnancy occurred spontaneously 27 months after grafting. Until now, the pregnancy has progressed for 30 weeks, and the repeated ultrasound showed normal fetal development. CONCLUSION: This is the first pregnancy resulting from ovarian tissue cryopreservation and transplantation in China.

[Analysis of a pedigree with inherited factor V deficiency caused by compound heterozygous mutation].

Objective: To explore the molecular pathogenesis of a family with hereditary factor Ⅴ (FⅤ) deficiency. Methods: All the exons, flanking sequences, 5' and 3' untranslated regions of the F5 of the proband, and the corresponding mutation sites of the family members were analyzed via direct DNA sequencing. The CAT measurement was used to detect the amount of thrombin produced. The ClustalX software was used to analyze the conservation of mutation sites. The online bioinformatics software, Mutation Taster, PolyPhen-2, PROVEAN, LRT, and SIFT were applied to predict the effects of mutation sites on protein function. The Swiss-PdbViewer software was used to analyze the changes in the protein model and intermolecular force before and after amino acid variation. Results: The proband had a heterozygous missense mutation c.1258G>T (p.Gly392Cys) in exon 8 of the F5, and a heterozygous deletion mutation c.4797delG (p.Glu1572Lys fsX19) in exon 14, which results in a frameshift and produces a truncated protein. Her grandfather and father had p.Gly392Cys heterozygous variation, whereas her maternal grandmother, mother, little aunt, and cousin all had p.Glu1572LysfsX19 heterozygous variation. The ratio of proband's thrombin generation delay to peak time was significantly increased. Conservation analysis results showed that p.Gly392 was located in a conserved region among the 10 homologous species. Five online bioinformatics software predicted that p.Gly392Cys was pathogenic, and Mutation Taster also predicted p.Glu1572Lys fsX19 as a pathogenic variant. Protein model analysis showed that the replacement of Gly392 by Cys392 can lead to the extension of the original hydrogen bond and the formation of a new steric hindrance, which affected the stability of the protein structure. Conclusion: The c.1258G>T heterozygous missense mutation in exon 8 and the c.4797delG heterozygous deletion mutation in exon 14 of the F5 may be responsible for the decrease of FⅤ levels in this family.