Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

Genetic analysis of a case with mosaicism complex structural aberration of chromosome 18 / 中华医学遗传学杂志

OBJECTIVE@#To determine the karyotype of a patient with mosaicism complex structural aberration of chromosome 18.@*METHODS@#A male patient with a 2-year history of infertility presented at the Center of Reproductive Medicine of the Third Hospital of Peking University in October 2019 was selected as the study subject. Clinical data of the patient was collected. Peripheral blood sample was taken for chromosomal karyotyping, copy number variation (CNV) analysis and fluorescence in situ hybridization (FISH) assay. Semen sample was taken for single sperm CNV analysis.@*RESULTS@#The patient was found to have a karyotype of mos 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1].ish 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1]del(18)(q21q23)(D18Z1+,18p+,18q+,WCP18+),r(18)(q21q23)(WCP18+),r(18)(q21q23×2)(WCP18+). No pathogenic CNV was identified. Sequencing of 20 single sperms showed that 1 sperm was normal, 1 had yielded no result, 9 had harbored del(18q), 7 had harbored dup(18q)×2, and 2 had harbored dup(18q)×3. The dup/del fragments had both spanned approximately 33 Mb.@*CONCLUSION@#It is rare for carriers of complex structural and numerical abnormalities of chromosome 18 to have a normal phenotype. Based on the accurate cytogenetic and molecular analyses and the single sperm CNV analysis, the influence of the aberrant karyotype on the gametogenesis may be evaluated.

Multiple-photon bundle emission in the n-photon Jaynes-Cummings model.

We study the multiple-photon bundle emission in the n-photon Jaynes-Cummings model composed of a two-level system coupled to a single-mode optical field via the n-photon exciting process. Here, the two-level system is strongly driven by a near-resonant monochromatic field, and hence the system can work in the Mollow regime, in which a super-Rabi oscillation between the zero-photon state and the n-photon state can take place under proper resonant conditions. We calculate the photon number populations and the standard equal-time high-order correlation functions, and find that the multiple-photon bundle emission can occur in this system. The multiple-photon bundle emission is also confirmed by investigating the quantum trajectories of the state populations and both the standard and generalized time-delay second-order correlation functions for multiple-photon bundle. Our work paves the way towards the study of multiple-photon quantum coherent devices, with potential application in quantum information sciences and technologies.

A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease / 中华内科杂志

Objective:This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies.Methods:A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed.Results:Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis ( r=0.547, P<0.001). Conclusions:The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Systemic Lupus Erythematosus Combined with Chorea: Report of One Case and Literature Review / 中国医学科学院学报

Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome.@*METHODS@#Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed.@*RESULTS@#(1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05).@*CONCLUSION@#Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules / 中国中药杂志

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure / 中国中药杂志

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.

Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina / 中国中药杂志

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.

Noise-Tolerant Optomechanical Entanglement via Synthetic Magnetism.

Entanglement of light and multiple vibrations is a key resource for multichannel quantum information processing and memory. However, entanglement generation is generally suppressed, or even fully destroyed, by the dark-mode (DM) effect induced by the coupling of multiple degenerate or near-degenerate vibrational modes to a common optical mode. Here we propose how to generate optomechanical entanglement via DM breaking induced by synthetic magnetism. We find that at nonzero temperature, light and vibrations are separable in the DM-unbreaking regime but entangled in the DM-breaking regime. Remarkably, the threshold thermal phonon number for preserving entanglement in our simulations has been observed to be up to 3 orders of magnitude stronger than that in the DM-unbreaking regime. The application of the DM-breaking mechanism to optomechanical networks can make noise-tolerant entanglement networks feasible. These results are quite general and can initiate advances in quantum resources with immunity against both dark modes and thermal noise.

Combined analysis of human chorionic gonadotrophin concentrations at different time points after frozen-thawed blastocyst transfer can improve our ability to predict the pregnancy outcomes of single gestations.

In this study, we conducted a retrospective single-centre study of 1664 singleton pregnancies derived from frozen-thawed blastocyst transfer between January 2017 and December 2018. Analysis showed that there were 596 early pregnancy losses and 1068 ongoing pregnancies. We compared serum HCG (human chorionic gonadotophin) concentrations on days 12, 14, 19, and 21, between the pregnancy loss group and the ongoing pregnancy group. The cut-off level of HCG at each time point was calculated to predict pregnancy outcome. Joint analysis of two single HCG levels taken one week apart was carried out to improve predictive accuracy. The levels of HCG at four time points were significantly lower in the early pregnancy loss group than in the ongoing pregnancy group. According to the area under ROC (receiver operating characteristic curve) curves, all levels of HCG taken at four time points showed good ability to predict the outcome of pregnancy. The joint analysis of two single HCG levels taken one week apart further improved the accuracy of prediction.Impact statementWhat is already known on this subject? Multiple studies have shown that the maternal level of serum HCG is the best parameter for predicting the course of pregnancy.What do the results of this study add? The levels of HCG on days 12, 14, 19 and 21 were significantly lower in the early pregnancy loss group than in the group of ongoing pregnancies. According to the area under ROC curves, all levels of HCG taken at four time points showed a good ability to predict the outcome of pregnancy.What are the implications of these findings for clinical practice and/or further research? The joint analysis of two single HCG levels, taken one week apart, further improved the accuracy of prediction.

The influence of timing of oocytes retrieval and embryo transfer on the IVF-ET outcomes in patients having bilateral salpingectomy due to bilateral hydrosalpinx.

Objective: The objective of the study was to investigate whether the sequence of oocyte retrieval and salpingectomy for hydrosalpinx affects pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) patients. Study Design: There were 1,610 bilateral hydrosalpinx patients who underwent laparoscopy salpingectomy and IVF-ET/intracytoplasmic sperm injection (ICSI) from January 2009 to December 2018. They were divided into two groups: oocyte retrieval first group: 235 accepted oocyte retrieval before salpingectomy; operation first group: 1,375 accepted oocyte retrieval after salpingectomy. The basic information and pregnancy outcomes of the two groups were compared. The pregnancy outcomes and influencing factors were analyzed among patients at different starting times of frozen-thawed embryo transfer (FET) or oocyte retrieval after the salpingectomy. Results: Patients in the oocyte retrieval first group had higher levels of basal follicle stimulating hormone and lower anti-Mullerian hormone levels (P < 0.05). There were no cases of pelvic infection or oocyte and embryo contamination after oocyte retrieval in the oocyte retrieval first group. In the frozen cycle, the clinical pregnancy and miscarriage rates of the oocyte retrieval first group were lower than those in the operation first group (P < 0.05), while the live birth rate was not significantly different (P > 0.05). The live birth rates of patients ≥35 years old in the operation first group and the oocyte retrieval first group were not significantly different (29.3% vs. 23.3%, P = 0.240). After adjusting for age and antral follicle count (AFC), oocyte retrieval 4-6 and 7-12 months after the operation had higher accumulated pregnancy rates [OR 1.439 (1.045-1.982), P = 0.026; OR 1.509 (1.055-2.158), P = 0.024] and higher accumulated live birth rates [OR 1.419 (1.018-1.977), P = 0.039; OR 1.544 (1.068-2.230), P = 0.021]. No significant difference was observed in the pregnancy outcomes of frozen embryo transfer at different times after salpingectomy (P > 0.05). Conclusion: No contamination of the embryo or infection was observed in patients who underwent oocyte retrieval before the operation. The interval between the operation and frozen embryo transfer did not affect the pregnancy outcomes. After adjusting for age and AFC, patients who underwent oocyte retrieval 4-6 and 7-12 months after the operation had higher accumulated pregnancy rates and live birth rates.

Guidance of critical thinking of clinical medical students in disease-centered PBL integrated course: taking diabetes as example / 中华医学教育探索杂志

Disease-centered problem-based learning (PBL) integrated course inspires the thinking of medical students in the case scenario to stimulate students' motivation of active learning. In this paper, the study of diabetes cases was taken as an example. Through the design of PBL cases, the scenario was reconstructed and information was provided step by step, so as to induce the students to discuss and learn the related knowledge of glucose metabolism and understand the predisposing factors of diabetes. Furthermore, students' critical thinking could be inspired through the information of the misdiagnose and mistreatment to recognize the clinical presentation and inducement of diabetic ketoacidosis. This teaching model is conducive to the cultivation of medical students' questioning spirit and critical thinking, laying a foundation for the cultivation of innovative medical talents.

Expert consensus on preimplantation genetic testing for spinal muscular atrophy / 中华医学遗传学杂志

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron degenerative disease, which is the most common fatal neuromuscular disease in pediatrics with a high carrier frequency and can lead to progressive symmetrical muscle weakness and atrophy of the trunk and limbs. Preimplantation genetic testing (PGT) can be used to prevent the birth of children with SMA effectively. To standardize PGT technologies for SMA, experts from the fields of neurology, pediatrics and reproductive genetics have discussed and drafted this consensus for guiding its clinical application.

Advance in mutations of steroidogenic factor-1 and the related clinical phenotype / 中华内分泌代谢杂志

Steroidogenic factor-1 (SF-1, NR5A1) is a transcription factor that plays a key role in the development of gonad and adrenal gland. NR5A1 gene mutation is one of the common causes of disorders of sex development(DSD). Heterozygous mutations of NR5A1 gene accounts for the majority of reported cases with various phenotyre. Early reported cases manifested with varying degrees of 46, XY gonadal dysplasia, whereas NR5A1 mutation was revealed to be related with the phenotypes of azoospermia in men and premature ovarian insufficiency in women recently. Adrenocortical insufficiency is absent in most cases. The heterogeneity of the clinical phenotype is considered resulting from the functional impact of different gene mutations on transcriptional activity, dose effect of downstream target gene(such as SOX9)and the genetic background of oligogenic mutation, etc. The process and regulation of gonadal development might be understood comprehensively by investigating the genotype and related phenotype of NR5A1.