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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Molecular diagnosis and clinical features of 206 patients with 46, XY disorders of sexual development / 中华内分泌代谢杂志

Objective:To investigate methods of molecular diagnosis and clinical features of 46, XY disorders of sexual development(DSD).Methods:A total of 206 cases of 46, XY DSD patients, who visited the Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, from July 2009 to June 2021, underwent AA chip based on multiplex PCR and probe-capture-targeted next-generation sequencing. Clinical features of patients with genetic diagnosis were analyzed.Results:Among 206 patients, the diagnostic rate of patients with micropenis, hypospadias and cryptorchidism was the highest, up to 75.28%. Almost all patients had different degrees of undermasculinized external genitalia. The most frequent phenotype was micropenis with hypospadias(87.25%). Only one gene variant was detected in 81 patients(39.32%), multiple genetic variants were detected in 104 patients(50.49%), and no gene variant was identified in 21 patients(10.19%). 107 patients had definite genetic diagnosis, with a diagnostic rate of 51.94% by adding the pathogenic and likely pathogenic ratios following the American College of Medical Genetics and Genomics(ACMG) guidelines, including 40 patients of steroid 5α-reductase type 2(SRD5A2) variants(37.38%), 36 patients of androgen receptor(AR) variants(33.64%), 13 patients of steroidogenic factor 1(NR5A1) variants(16.82%), 6 patients of 17β-hydroxysteroid dehydrogenases 3(HSD17B3) variants(5.61%), 2 patients of 17α-hydroxylase/17, 20-lyase enzyme(CYP17A1), Wilms′ tumor 1(WT1) and GATA binding protein 4(GATA4) variants(1.87%), and one patient of luteinizing hormone receptor(LHCGR) variant(0.93%). Gynecomastia was found in 29 of 81 postpubertal patients, of which 25(86.21%) had AR variants.Conclusions:46, XY DSD presents complex clinical manifestations and molecular etiologies. Targeted nextgeneration sequencing has the advantages of high throughput, high efficiency and low cost, which has a high value especially in etiological diagnosis of 46, XY DSD with large genetic heterogeneity.

HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells / 南方医科大学学报

OBJECTIVE@#To explore the role of heat shock protein 90α (HSP90α) and endoplasmic reticulum (ER) stress pathway in allergic airway inflammation induced by house dust mite (HDM) in bronchial epithelial cells.@*METHODS@#A HDM- induced asthmatic cell model was established in human bronchial epithelial (HBE) cells by exposure to a concentration gradient (200, 400 and 800 U/mL) of HDM for 24 h. To test the effect of siHSP90α and HSP90 inhibitor 17-AAG on HDM-induced asthmatic inflammation, HBE cells were transfected with siHSP90α (50 nmol, 12 h) or pretreated with 17-AAG (900 nmol, 6 h) prior to HDM exposure (800 U/mL) for 24 h, and the changes in the expression of HSP90α and ER stress markers were assessed. We also tested the effect of nasal drip of 17-AAG, HDM, or their combination on airway inflammation and ER stress in C57BL/6 mice.@*RESULTS@#In HBE cells, HDM exposure significantly up-regulated the expression of HSP90α protein (P=0.011) and ER stress markers XBP-1 (P=0.044), ATF-6α (P=0.030) and GRP-78 (P=0.027). Knocking down HSP90α and treatment with 17-AAG both significantly inhibited HDM-induced upregulation of XBP-1 (P=0.008). In C57BL/6 mice, treatment with 17-AAG obviously improved HDM-induced airway inflammation and significantly reduced the number of inflammatory cells in the airway (P=0.014) and lowered the levels of IL-4 (P=0.030) and IL-5 (P=0.035) in alveolar lavage fluid. Immunohistochemical staining showed that the expressions of XBP-1 and GRP-78 in airway epithelial cells decreased significantly after the treatment of 17-AAG.@*CONCLUSIONS@#HSP90α promotes HDM-induced airway allergic inflammation possibly by upregulating ER stress pathway in bronchial epithelial cells.

Quantum simulation of tunable and ultrastrong mixed-optomechanics.

We propose a reliable scheme to simulate tunable and ultrastrong mixed (first-order and quadratic optomechanical couplings coexisting) optomechanical interactions in a coupled two-mode bosonic system, in which the two modes are coupled by a cross-Kerr interaction and one of the two modes is driven through both the single- and two-excitation processes. We show that the mixed-optomechanical interactions can enter the single-photon strong-coupling and even ultrastrong-coupling regimes. The strengths of both the first-order and quadratic optomechanical couplings can be controlled on demand, and hence first-order, quadratic, and mixed optomechanical models can be realized. In particular, the thermal noise of the driven mode can be suppressed totally by introducing a proper squeezed vacuum bath. We also study how to generate the superposition of coherent squeezed state and vacuum state based on the simulated interactions. The quantum coherence effect in the generated states is characterized by calculating the Wigner function in both the closed- and open-system cases. This work will pave the way to the observation and application of ultrastrong optomechanical effects in quantum simulators.

Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in China: a nationwide case-control study

OBJECTIVETo formally compare the clinical course of Coronavirus disease 2019 (COVID-19) in pregnant women with their nonpregnant counterparts. METHODSClinical data of pregnant women with confirmed COVID-19 in the designated hospitals of mainland China were retrieved up to April 12, 2020 through an epidemic reporting system maintained at the National Health Commission of the Peoples Republic China. Each pregnant patient was randomly matched to a nonpregnant woman with confirmed COVID-19 in the same hospital as control, then their clinical courses were formally compared. RESULTS138 pregnant women had been identified as confirmed COVID-19 cases. Among them, 17 severe cases and 1 maternal death were recorded, which was less than their nonpregnant peers (23 severe cases and 3 death). 57.2% had been infected with SARS-CoV-2 during the third trimester, including 13 severe cases and 1 maternal death. 7.3% of pregnant patients had diarrhea and 3.6% had nausea or vomiting, compared with related proportion as 15.2% (OR: 0.38, 95%CI: 0.15, 0.96) and 10.1% (OR: 0.25, 95%CI: 0.07, 0.89) in nonpregnant patients. Pregnant patients infected with SARS-CoV-2 in early pregnancy presented similar laboratory tests with their nonpregnant peers, however, with pregnancy progresses, increased inflammation, coagulation and hepatic injury markers happened more and more frequently (p<0.001) in pregnant patients. CONCLUSIONSBeing pregnant did not represent a risk for severe condition when compared with their nonpregnant peers. Patients infected with SARS-CoV-2 in early pregnancy were even at lower risk of severe illness than those infected in late pregnancy. What are the novel findings of this work?Compared with non-pregnant COVID-19 patients, pregnant patients tend to present less symptom, had unique laboratory findings, and tend to at lower risk of COVID-19-related death. Patients infected with SARS-CoV-2 in the early pregnancy tend to be in the less severe condition of illness than those infected in late pregnancy. What are the clinical implications of this work?Vital comparisons of the clinical course upon COVID-19 between pregnant and nonpregnant women in childbearing age are, unfortunately, lacking. Through formally comparisons between the two groups, the present study provides more reliable evidence towards the management of pregnant women with COVID-19.

Comprehensive evaluation of ACE2 expression in female ovary by single-cell RNA-seq analysis

Pneumonia induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) via ACE2 receptor may affect many organ systems like lung, heart and kidney. An autopsy report revealed positive SARS-Cov-2 detection results in ovary, however, the developmental-stage-specific and cell-type-specific risk in fetal primordial germ cells (PGCs) and adult women ovary remained unclear. In this study, we used single-cell RNA-sequencing (scRNA-seq) datasets spanning several developmental stages of ovary including PGCs and cumulus-oocyte complex (COC) to investigate the potential risk of SARS-CoV-2 infection. We found that PGCs and COC exhibited high ACE2 expression. More importantly, the ratio of ACE2-positive cells was sharply up-regulated in primary stage and ACE2 was expressed in all oocytes and cumulus cells in preovulatory stage, suggesting the possible risk of SARS-CoV-2 infection in follicular development. CatB/L, not TMPRSS2, was identified to prime for SARS-CoV-2 entry in follicle. Our findings provided insights into the potential risk of SARS-CoV-2 infection during folliculogenesis in adulthood and the possible risk in fetal PGCs.

Clinical features and treatment outcome of four patients with Kallmann syndrome caused by fibroblast growth factor receptor-1 gene mutation / 中华内分泌代谢杂志

Objective:To investigate the clinical features and treatment outcome of Kallmann syndrome(KS) caused by fibroblast growth factor receptor-1(FGFR1) gene mutation in 4 patients.Methods:Targeted next-generation sequencing(NGS) was performed on thirty KS and normosmic idiopathic hypogonadotropic hypogonadism(nIHH) patients. FGFR1 mutation was identified in four KS patients. The clinical data, laboratory and imaging examinations, and treatment outcome were retrospectively analyzed.Results:Four male patients, aging from 11 to 22 years old, presented as micropenis, and with olfactory dysfunction. Among them, two had history of cryptorchidism, three had history of cleft lip and palate repair surgery. The most severe patient presented with short stature, left microtia and dental agenesis. FGFR1 heterozygous mutation was identified in all four patients, two were point mutation(p.Y374X; p. E670K), and the other was frameshift mutation(p.S346Yfs*61; p.S723*fs*1). One patient, who started treatment of the pulsatile GnRH pump during his youth, succeeded in having two babies.Conclusion:Patients with Kallmann syndrome caused by FGFR1 mutation presents complex clinical manifestations. Besides dysosmia, micropenis, microrchidia, and delayed pubertal development are the main clinical manifestations in male patients. Symptoms such as cleft lip and palate are helpful for early recognition. Genotyping analysis is crucial to confirm the diagnosis. The pulsatile GnRH pump can produce satisfactory therapeutic effect, but the age of initiating therapy should be carefully considered.