[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Waveguide Mach-Zehnder interferometer to enhance the sensitivity of quantum parameter estimation.

The waveguide Fabry-Perot interferometer (FPI) (see, e.g., in Phys. Rev. Lett.113, 243601 (2015)10.1103/PhysRevLett.115.243601 and Nature569, 692 (2019)10.1038/s41586-019-1196-1), instead of the free space's one, have been demonstrated for the sensitive quantum parameter estimations. Here, we propose a waveguide Mach-Zehnder interferometer (MZI) to further enhance the sensitivity of the relevant parameter estimations. The configuration is formed by two one-dimensional waveguides coupled sequentially to two atomic mirrors, which are served as the beam splitters of the waveguide photons to control the probabilities of the photons being transferred from one waveguide to another. Due to the quantum interference of the waveguide photons, the acquired phase of the photons when they pass through a phase shifter can be sensitively estimated by measuring either the transmitted or reflected probabilities of the transporting photons. Interestingly, we show that, with the proposed waveguide MZI the sensitivity of the quantum parameter estimation could be further optimized, compared with the waveguide FPI, in the same condition. The feasibility of the proposal, with the current atom-waveguide integrated technique, is also discussed.

[The mediating effect of perceived social support in the relationship between maternal personality traits and pregnancy-related anxiety].

Objective: Exploring the mediating effect of perceived social support between the maternal personality traits and pregnancy-related anxiety. Methods: Singleton pregnant women who underwent antenatal checkups in the obstetrics department of general hospital affiliated to Ningxia Medical University from July to December 2021 were enrolled in this study to investigate perceived social support, pregnancy-related anxiety and conscious personality traits. Pearson correlation analysis was used to analyze the association between the maternal personality traits, perceived social support, and pregnancy-related anxiety, and the mediating effect of perceived social support was analyzed using Bootstrap method. Results: A total of 1 259 subjects were included in the study, of which 170 (13.50%) pregnant women felt introverted. The total score of perceived social support was (46.37±8.38), and 31.45% of pregnant women had high perceived social support. The total score of pregnancy-related anxiety was (21.48±5.53). The score of worry about fetal health was (10.09±3.24), and 368 (29.23%) of pregnant women had pregnancy-related anxiety. Maternal personality traits and pregnancy-related anxiety were negatively correlated (r=-0.076, P<0.05) and positively correlated with perceived social support during pregnancy (r= 0.127, P<0.05). Perceived social support during pregnancy and pregnancy-related anxiety were negatively correlated (r=-0.236, P<0.05). Perceived social support partially mediated the relationship between the maternal personality traits and pregnancy-related anxiety, with a relative effect value of 37.50%. Conclusion: The maternal personality traits, level of perceived social support and pregnancy-related anxiety are all related. Perceived social support could mediate the relationship between the maternal personality traits and pregnancy-related anxiety.

[Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis].

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.

[Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E].

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

[Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease].

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Clinical practice of traditional Chinese medicine for the treatment of postmenopausal osteoporosis: a literature review.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) for postmenopausal osteoporosis (PMOP). METHODS: We conducted a computer literature search in five databases and comprehensively extracted all kinds of information from each article. Traditional Chinese medicine inheritance support system (TCMISS) V2.5 was adopted to perform association analysis. The effectiveness, safety and methodological quality were analyzed using randomized controlled clinical trials (RCTs). RESULTS: A total of 2880 related articles were collected. Finally, 423 articles which included 312 RCTs were included for in-depth analysis. We collected 369 Chinese medicine prescriptions and found that the top three frequently used herbs in the treatment of PMOP were Epimedii Folium (Yinyanghuo), Rehmanniae Radix Praeparata (Shudihuang) and Angelicae Sinensis Radix (Danggui). The top Chinese patent medicine was Gushukang capsule. No serious adverse reaction (AR) had been reported in the Chinese medical treatment group. CONCLUSION: The effectiveness of TCM in treating PMOP needs to be further explored, and the safety is good. Therefore, high-quality evidence is urgently needed to supplement.

[Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis].

Objective: To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE3) levels and XLI. Methods: A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results: Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant (Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions: The decrease levels of uE3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

[Association of SCN2A, ABCB1 and CYP2C19*3 with genetic susceptibility to major depressive disorder].

Objective: Due to genetic factors might increase the risk of depression, this study investigated the genetic risk factors of depression in Chinese Han population by analyzing the association between 13 candidate genes and depression. Methods: 439 depression patients and 464 healthy controls were included in this case-control study. Case group consisted of 158 males and 281 females, aged (29.84±14.91) years old, who were hospitalized in three departments of the affiliated Brain Hospital of Guangzhou Medical University including Affective Disorders Department, Adult Psychiatry Department and Geriatrics Department, from February 2020 to September 2021. The control group consisted of 196 males and 268 females, aged (30.65±12.63) years old. 20 loci of 13 candidate genes in all subjects were detected by MALDI-TOF mass spectrometry. Age difference was compared using the student's t-test, the distributions of gender and genotype were analyzed with Pearson's Chi-square test. The analyses of Hardy-Weinberg equilibrium, allele frequency and the genetic association of depression were conducted using the corresponding programs in PLINK software. Results: PLINK analysis showed that SCN2A rs17183814, ABCB1 rs1045642, CYP2C19*3 rs4986893 and NAT2*5A rs1799929 were associated with depression before Bonferroni correction (χ2=10.340, P=0.001; χ2=11.010, P=0.001; χ2=9.781, P=0.002; χ2=4.481, P=0.034). The frequencies of minor alleles of above loci in the control group were 12.07%, 43.64%, 2.59% and 3.88%, respectively. The frequencies of minor alleles of loci mentioned above in the case group were 17.43%, 35.99%, 5.47% and 6.04%, respectively. OR values were 1.538, 0.726, 2.178 and 1.592, respectively. After 1 000 000 permutation tests using Max(T) permutation procedure, the four loci were still statistically significant, the empirical P-value were 0.002, 0.001, 0.003 and 0.042, respectively. However, only three loci including SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19 rs4986893 had statistical significance after Bonferroni correction, the adjusted P-value were 0.026, 0.018 and 0.035, respectively. Conclusion: SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19*3 rs4986893 were associated with depression's susceptibility in Chinese Han population. The A allele of SCN2A rs17183814 and CYP2C19*3 rs4986893 were risk factors for depression, while the T allele of ABCB1 rs1045642 was a protective factor for depression.

[Clinical features of 19 cases of lower respiratory papillomatosis].

Objective: To explore the clinical characteristics and prognosis of lower respiratory papilloma(LRP)and therefore to improve clinical diagnosis and treatment. Methods: We performed a retrospective analysis of patients who were diagnosed with LRP in our department from October 2008 to October 2020. Results: Nineteen patients were enrolled and 12 were male and 7 were female. The average age of the 7 adult patients was (41.3±17.5)years and that of the 12 pediatric patients was (5.5±3.5)years. Ten (83.3%)of the pediatric patients showed disease onset at an age of less than 5 years. The main symptoms were cough and sputum production (13/19), dyspnea (15/19), hoarseness (10/19) and signs of stridor or wheezing (7/19). Chest CT examination was performed in 9 patients, which showed nodules or masses (9/9), cystic thin-walled cavity (4/9), obstructive pneumonia (2/9), atelectasis (2/9), and spicule sign (1/9). The upper respiratory tract was affected in all the pediatric patients (12/12) and 3/7 of the adult patients. Eighteen cases (18/19) were diagnosed by bronchoscopy, 1 (1/9) by thoracoscopy. Eighteen cases (18/19) showed mulberry-like and papillary lesions under bronchoscopy. All the cases were histologically confirmed as squamous cell papilloma, with 17 cases(17/19)showing tissue HPV6/11(+), 2 negative (2/19). The positive rate of HPV6 was 36.8%, ant that of HPV11 was 21.1%, while the double positive rate of HPV6/11 was 31.6%, and HPV16/18 were negative in all the 19 cases. Isolated respiratory papillomatosis was found in 4 cases (4/19), and multiple papillomatosis in 15 cases (15/19). Seventeen cases (17/19) underwent endoscopic interventional therapy, and the result showed that 15 cases relapsed, and 2 cases had no recurrence. One patient was treated with thoracoscopic lobectomy, and died 4 months after surgery. One patient gave up treatment. Conclusions: LRP is a rare clinical disease with a chronic course, and isolated LRP is even rarer. Young patients often suffer from upper respiratory tract involvement, and the main symptoms are cough, sputum production, dyspnea and hoarseness. CT scanning showed nodules and masses, cystic thin-walled cavities or signs of airway obstruction. Bronchoscopy often demonstrates papillary lesions. The diagnosis depends on pathology, with squamous cell papilloma being the most common, and most tests are positive for HPV6/11. It is suggested that the incidence is associated with low-risk HPV infection. Endoscopic resection is the main treatment, which is prone to relapse. The treatment should take into account the pathological changes of upper respiratory tract, and the etiological treatment of HPV should be stressed.

[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

[Analysis of the effect of modified cervical cerclage in the treatment of cervical insufficiency].

Objective: To discuss the surgical effect of modified cervical cerclage for the treatment of pregnant women with cervical insufficiency. Methods: The clinical data of 225 pregnant women who underwent modified cervical cerclage in Qilu Hospital (Qingdao) were selected for retrospective analysis from April 2014 to June 2020. Surgical success rate, full-term birth rate, preterm birth rate, prolonged pregnancy weeks and newborn birth weight were compared between singleton and twin pregnancies, preventive cerclage and emergency cerclage, surgery before and after 18 weeks, naturally and in vitro fertilization and embryo transfer (IVF-ET) conceived pregnant women respectively. Results: Among the 225 pregnant women, the gestational weeks of surgery were 14-24+5 weeks, mean gestational weeks of delivery were 38+2 weeks (35+5-39+3 weeks), the number of prolonged gestation were (20.3±5.2) weeks, and the newborn birth weight was (3 065±735) g; the overall surgical success rate was 92.9% (209/225), and the miscarriage rate was 7.1% (16/225); among the surviving newborns, the full-term birth rate was 73.7% (154/209), and the preterm birth rate was 26.3% (55/209). All cases had no intraoperative complications. Among the 225 pregnant women, 202 (89.8%, 202/225) cases were singleton pregnancies, and 23 (10.2%, 23/225) cases were twin pregnancies; 201 (89.3%, 201/225) cases underwent preventive cervical cerclage, and 24 (10.7%, 24/225) cases underwent emergency cervical cerclage; 190 (84.4%, 190/225) cases underwent the surgery before 18 weeks, and 35 (15.6%, 35/225) cases underwent the surgery after 18 weeks; 49 (21.8%, 49/225) cases were conceived by IVF-ET. There was no statistically significant difference in the overall surgical success rate of single and twin group (P>0.05). The full-term birth rate, newborn birth weight and prolonged pregnancy weeks of single group were higher than those of twin group (P<0.05). There were no statistical differences between preventive and emergency cerclage in overall surgical success rate, full-term birth rate, preterm birth rate, and newborn birth weight (all P>0.05). The pregnancy prolonged weeks of preventive cerclage was higher than that of emergency cerclage (P<0.05). There were no statistically significant differences in the overall surgical success rate, full-term birth rate, preterm birth rate and birth weight of newborns at different surgical timings (all P>0.05). The pregnancy prolonged week for those who underwent surgery before 18 weeks was higher than that of surgery after 18 weeks (P<0.05). The premature birth rate of IVF-ET was higher than that of naturally conceived pregnant women (P<0.05). Conclusion: The modified cervical cerclage could effectively prolong the gestational weeks of delivery, reduce the rate of preterm birth, and the operation is simple and easy to promote. It could be used as a surgical option for patients with cervical insufficiency.

[Clinicopathological features and prognosis of primary mediastinal large B-cell lymphoma: a series of sixty cases].

Objective: To investigate the clinicopathological features and prognostic factors of primary mediastinal large B-cell lymphoma (PMBL). Methods: The clinical data of 60 patients with PMBL including 44 biopsy cases and 16 consultation cases from September 2000 to November 2019 in the Department of Pathology, China-Japan Friendship Hospital (14 cases) and Peking Union Medical College Hospital (46 cases) were enrolled. Pathologic features, immunophenotype, immunoglobulin (Ig) gene rearrangement and microRNA expression profile were retrospectively studied. Results: Of the 60 patients, 23 were males and 37 were females, age ranged from 15 to 64 years (median 28 years). Immunohistochemical staining showed that the tumor cells were positive for pan-B cell antigens, CD30 (77.4%, 24/31), CD23 (73.1%, 19/26), MUM1 (45.8%, 11/24), Ki-67 index ≥70 % (90.6%, 29/32). EBER in situ hybridization was analyzed in 21 PMBL, only one case (4.8%) was positive. Ig gene rearrangement was performed in 20 cases, and seven were positive (35.0%). MicroRNA gene expression profiles were analyzed in seven cases of PMBL and nine cases of diffuse large B-cell lymphoma, and there were 33 microRNAs with significant difference (P<0.05). Univariate analysis indicated that the poor prognostic factors included serum lactate dehydrogenase (LDH) level,International Prognostic Index (IPI) score ≥3, stages Ⅲ-Ⅳ, chemotherapy not combined with rituximab and MUM1 positivity (P<0.05). Multivariate analysis showed that the treatment combined with rituximab was independently related to prognosis (P<0.05). Conclusions: PMBL is different from diffuse large B-cell lymphoma in clinicopathologic features, immunophenotypic presentation and molecular features. The prognostic factors, molecular genetics and immunological characteristics reveal that this study has enriched our understanding of the biology of PMBL, thus providing evidence and strategies for treatment.

[Clinicopathological characteristics of pulmonary artery intimal sarcoma].

Objective: To describe the clinicopathological features of pulmonary artery intimal sarcoma (PAIS), and to understand its molecular alterations. Methods: Sixty cases of pulmonary artery endarterectomy performed at the China-Japan Friendship Hospital, Beijing, China from January 2017 to January 2020 were reviewed. Clinical data of 5 patients with pulmonary artery intimal sarcoma were collected. Hematoxylin-eosin staining, immunohistochemistry staining and fluorescence in situ hybridization (FISH) were performed to evaluate the pathological features. RNA sequencing was conducted to assess the fusion gene changes in PAIS. Results: The detection rate of PAIS was 8.3% (5/60), with the median age of 49 years and a female predominance. Their clinical manifestations were non-specific. Histopathological examination showed that the tumors were composed of malignant spindle or epithelioid cells, with various degrees of atypia. Focal heterologous osteosarcomatous or leiomyosarcomatous differentiation was noted. The tumor cells could express PDGFRA, CDK4 and MDM2 with co-amplification of MDM2, CDK4 and EGFR genes. RNA sequencing detected multiple in-frame fusions in the tumors. Conclusions: PAIS is a rare, highly heterogeneous, and poorly-or un-differentiated sarcoma accompanied by complex changes of multiple genes.It has no known effective treatments, and thus has a poor prognosis.

[New progress in the diagnosis and treatment of hepatocellular carcinoma: a decade of grinding sword].

Globally, hepatocellular carcinoma (HCC) is one of the most highly morbid, fatal, and malignant tumors, with a poor prognosis in advanced stage. In the past decade, new advances have been emerged in the field of HCC therapy, including surgery, ablation, transvascular intervention, external radiotherapy, and systemic therapy. Among them, systemic treatments, particularly targeted and immune checkpoint drugs have made outstanding progress, significantly improving the five-year survival rate of liver cancer patients. In addition, the management of liver cancer patients, especially the screening management and multidisciplinary collaborative diagnosis and treatment of high-risk populations, has significantly increased the early diagnosis rate and improved the overall treatment efficacy. Considering our country's condition and the development of existing treatment, the most effective strategy to reduce HCC mortality in the future is to accurately identify high-risk populations, increase the early diagnosis rate, and formulate personalized treatment strategies.

[Application of aMAP score to assess the risk of hepatocarciongenesis in population of chronic liver disease in primary hospitals].

Objective: The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening. Methods: The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population. Results: A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion: The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

[Proteomic study on the damage of learning and memory ability of rat offspring caused by chronic stress during pregnancy].

Objective: To study the differential protein and signal pathway related to the impairment of learning and memory ability of offspring caused by chronic stress during pregnancy and explore the possible mechanism. Methods: From July to October 2019, sixteen SPF free female SD rats aged 80-90 days, weighing (200±20) g. Twelve SPF grade male SD rats aged 90-100 days, weighing (220±20) g. After a week of adaptive feeding, the female rats were randomly divided into control group and model group (8 rats in each group) , male rats were divided into control mating group (n=8) and model mating group (n=4) . Chronic unpredictable mild stress (CUMS) model was established and stimulated continuously for 21 days. One day before stress, the first, seventh, fourteenth and 21th day after stress, the blood was collected from the inner canthus vein of the female rats, and the content of corticosterone was determined. Morris water maze test was used to detect the spatial learning and memory ability of offspring rats. The morphological changes of hippocampus were observed by HE and Nissl staining. The proteomic correlation analysis of offspring rats' hippocampus was performed by isobaric tags for relative and absolute quantification (iTRAQ) technique. Results: Compared with the control group, the content of plasma corticosterone in the model group was significantly higher (F=7.717, P<0.05) , and the model was successfully established. In Morris water maze test, compared with the control offspring group, the escape latency was longer, the average swimming speed was lower, the number of crossing platform was less, and the target quadrant run was shorter in the model offspring group (P<0.05) . The pathological results showed that the morphology of cells in the hippocampal tissue of the model offspring group was irregular, the number of neurons was small, Nissl body was unevenly distributed, the volume was small and the number was small. Mass spectrometry analysis showed that a total of 5065 proteins were screened out in the two offspring groups, and 26 proteins were differentially expressed (P<0.05) , of which 19 proteins were up-regulated and 7 proteins were down regulated. The differential proteins were mainly involved in 23 biological processes, 14 cellular components and 9 molecular functions. Kyoto Encyclopedia of genes and genomes (KEGG) enrichment analysis showed that 57 pathways were enriched, of which 8 signaling pathways were significantly enriched (P<0.05) . There were 5 signaling pathways that might be involved in the impairment of learning and memory ability of offspring, including neuroactive ligand receptor interaction, cGMP-PKG signaling pathway, adhesion and connection, adhesion and connection FoxO signaling pathway and Notch signaling pathway, mainly including tyrosine protein kinase receptor, tyrosine kinase receptor and Notch signaling pathway, and α2A adrenergic receptor, cGMP dependent protein kinase and other differential proteins may be involved in the injury process. Conclusion: The damage of learning and memory ability of offspring may be caused by chronic stress during pregnancy rats. The enriched signal pathway and key differential proteins of proteomics may play an important role in the process of damage.

[Effects of chronic stress during pregnancy on composition and diversity of intestinal microbiota in female rats and offspring].

Objective: To investigate the effect of chronic stress of pregnant rats on the gut microbiota of female rats and offspring, and explore the role of intestinal microbiota in chronic stress during pregnancy. Methods: In November 2019, SPF-grade healthy adult SD rats were selected. 16 female rats were randomly divided into control group and model group, with 8 in each group; 12 male rats were randomly divided into model mating group (8) and control mating group (4) . A model of chronic unpredictable mild stress (CUMS) during pregnancy was established. Blood samples were collected from the iliac vein of the female rats 1 day before and 1, 7, and 14 days after the CUMS protocol, and measured for plasma corticosterone content by radioimmunoassay. After the stress was completed, fresh feces of the female rats were collected for testing. The offspring's fresh stool samples were collected on postnatal day 20 (PND20) , and they were divided into control offspring group and model offspring group samples. The sequence of 16S rRNAV3-V4 regions of microorganisms in the feces of offspring was determined by Illumina MiSeq technique; and the interaction between microbial community structure and diversity were analyzed. Results: The content of plasma corticosterone in the model group was higher than that in the control group on the 7th and 14th day of stress (P<0.05) . Compared with the control group, the Sobs index, Chao index, ACE index and Shannon index of the model group were decreased (P<0.05) . The number of unique species abundance (OTU) in the control group was 130, and 91 in the model group. The relative abundance of female Firmicutes in the control group (64.87%) was higher than that in the model group, and the relative abundance of Bacteroides (31.72%) was lower than that of the model group (46.35%) . The Sobs index, Chao index, ACE index, Simpson index and Shannon index of the control offspring group were higher than those of the model offspring group (P<0.05) . The number of unique OTUs in the model offspring group was 75, and 93 in the control offspring group. The relative abundance of Firmicutes (60.24%) in the control offspring group was higher than that of the model offspring group (52.95%) . Conclusion: Chronic stress during pregnancy can not only lead to the disorder of intestinal flora in female rats, but also lead to the change of intrauterine environment, thus affecting the diversity of intestinal flora in offspring.