Predictive value of crossover sign for outcome of ultrasound-guided vacuum aspiration in women with Cesarean scar pregnancy.

OBJECTIVE: To examine the value of the crossover sign (COS) in predicting treatment outcome in women with a Cesarean scar pregnancy (CSP) who were treated with ultrasound-guided vacuum aspiration. METHODS: This was a retrospective cohort study of women with CSP who underwent ultrasound-guided vacuum aspiration. Based on the relationship between the gestational sac, Cesarean scar and anterior wall of the uterus, CSPs were classified by COS type. Analysis was conducted to investigate the association between COS type (COS-1, COS-2) and treatment outcome. The incidence of treatment failure, retained pregnancy tissue, secondary therapy and bleeding ≥ 200 mL were analyzed. RESULTS: In total, 181 eligible patients with CSP, including 90 (49.7%) women with COS-1 and 91 (50.3%) women with COS-2, were analyzed. COS-1 patients had a higher incidence of treatment failure compared with COS-2 patients (25.6% vs 8.8%; P = 0.003), as well as higher rates of retained pregnancy tissue (18.9% vs 6.6%; P = 0.013), secondary therapy (20.0% vs 6.6%; P = 0.002) and bleeding of ≥ 200 mL (13.3% vs 4.4%; P = 0.034). COS-1 and a large gestational sac (30.1-50.0 mm or >50.0 mm in diameter) were associated independently with increased risk of treatment failure (odds ratio, 4.57 (95% CI, 1.66-12.56); P = 0.003, 4.34 (95% CI, 1.35-13.94); P = 0.014 and 10.50 (95% CI, 2.54-43.46); P = 0.001, respectively). CONCLUSIONS: Ultrasound evaluation of the relationship between the gestational sac and the endometrial line (COS classification) in women with CSP may help to predict treatment outcome among those undergoing vacuum aspiration. Among COS-1 patients, especially those with a gestational sac diameter of >30.0 mm, vacuum aspiration may be discouraged. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Interaction of smoking and aging on emphysema and small airways disease in asymptomatic healthy men by CT-based parametric response mapping analysis.

AIM: To explore whether small airway disease and emphysema were affected by the interaction between smoking and aging on chest computed tomography (CT) images of asymptomatic healthy men analysed using a quantitative imaging tool parametric response mapping (PRM). MATERIALS AND METHODS: In this retrospective study, 95 asymptomatic healthy men underwent biphasic chest CT. The PRM classifies lung as a percentage of normal (PRMNormal%), functional small airway disease (PRMfSAD%), and emphysema (PRMEmph%). The patients were divided into groups based on their age and smoking status. Multiple linear regression analysis was applied to explore the factors influencing lung injury. Simple effects analysis was performed to explore the interaction between different age groups and smoking status. RESULTS: The interaction between aging and smoking significantly affected PRMfSAD% and PRMEmph% (p<0.001). The age range 60-69 and smoking were associated with increased PRMfSAD% and PRMEmph% (p<0.05). Futher stratification into different age subgroups showed that smoking was associated with increased PRMfSAD% and PRMEmph% in the 50-59 year age group. Besides, smoking in the 50-59 and 60-69 years group was associated with decreased PRMNormal%, while smoking in the 60-69 years group did not significantly influence the prevalence of PRMfSAD% and PRMEmph% (p>0.05). CONCLUSIONS: PRM reveals the interplay between smoking and aging in the development of lung injury in asymptomatic healthy men. Aging and smoking are important factors of emphysema and small airway disease in the 50-69 years group. In the 60-69 years group, aging poses a greater risk of lung injury compared to smoking.

Effect of quercetin on granulosa cells development from hierarchical follicles in chicken.

1. The bioflavonoid quercetin is a biologically active component, but its functional regulation of granulosa cells (GCs) during chicken follicular development is little studied. To investigate the effect of quercetin on follicular development in laying hens, an in vitro study was conducted on granulosa cells from hierarchical follicles treated with quercetin.2. The effect of quercetin on cell activity, proliferation and apoptosis of granulosa cells was detected by CCK-8, EdU and apoptosis assays. The effect on progesterone secretion from granulosa cells was investigated by enzyme-linked immunosorbent assay (ELISA). Expression of proliferating cell nuclear antigen (PCNA) mRNA and oestrogen receptors (ERs), as well as the expression of steroid acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA during progesterone synthesis, were measured by real-time quantitative polymerase chain reaction (RT-qPCR). PCNA, StAR and CYP11A1 protein expression levels were detected using Western blotting (WB).3. The results showed that treatment with quercetin in granulosa cells significantly enhanced cell vitality and proliferation, reduced apoptosis and promoted the expression of gene and protein levels of PCNA. The levels of progesterone secretion increased significantly following quercetin treatment, as did the expression levels of StAR and CYP11A1 using the Western Blot (WB) method.4. The mRNA expression levels of ERα were significantly upregulated in the 100 ng/ml and 1000 ng/ml quercetin-treated groups, while there was no significant difference in expression levels of ERß mRNA.

Quercetin ameliorates lipid deposition in primary hepatocytes of the chicken embryo.

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.

[Effect of autologous platelet-rich plasma perfusion on cytokines in uterine drainage fluid of patients with intrauterine adhesions following hysteroscopic adhesiolysis].

Objective: To investigate the effect of autologous platelet-rich plasma (PRP) perfusion on the levels of cytokines in uterine drainage fluid in patients with moderate to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Methods: Thirty patients with moderate to severe IUA who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into two groups: the PRP group (15 patients with placement of intrauterine-suitable balloons and PRP infusion) and the control group (15 patients with placement of intrauterine-suitable balloons only). For all patients, the channel switch was opened 48 hours after the surgery. The drainage fluid of the uterine cavity was collected using syringes through the proximal end of the drainage channel switch at 24 hours after the surgery and through the drainage channel directly at 48, 72, 96, and 120 hours after the surgery, and the levels of related cytokines including platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1) in the drainage fluid of the uterine cavity were evaluated, respectively. Results: (1) The changes in volumes of uterine cavity drainage fluid: the total drainage fluid volumes of the PRP group and the control group in 120 hours after the surgery were (21.8±2.9) and (22.7±2.7) ml, respectively, and there was no statistically significant difference between the two groups (t=-0.847, P>0.05). No significant differences were found in the volumes of drainage fluid between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). (2) Variation in cytokine levels in the uterine cavity drainage fluid: ① PDGF-BB: median PDGF-BB levels at 24 and 48 hours after the surgery in the PRP group (6.6 and 9.6 µg/L, respectively) were significantly higher than those in the control group (4.7 and 2.7 µg/L, respectively; all P<0.05). There were no significant differences in PDGF-BB levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ② VEGF-A: median VEGF-A levels at 24 and 48 hours after the surgery in the PRP group (3.5 and 2.8 µg/L, respectively) were significantly higher than those in the control group (1.6 and 1.2 µg/L, respectively; all P<0.05). There were no significant differences in VEGF-A levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ③ IGF-1: median IGF-1 level at 48 hours after the surgery in the PRP group was significantly higher than that in the control group (39.5 vs 8.6 µg/L, P<0.05). No significant differences were found in IGF-1 levels at 24, 72, 96, and 120 hours after the surgery between the two groups (all P>0.05). ④ TGF-ß1: There were no significant differences in TGF-ß1 levles between the two groups at 24, 48, 72, 96, and 120 hours after the surgery (all P>0.05). Conclusions: PRP perfusion following hysteroscopic adhesiolysis may increase the levels of PDGF-BB, VEGF-A, and IGF-1 in the uterine cavity drainage fluid, which plays a beneficial role in improving wound microvascular formation, reducing adhesion reformation, and promoting endometrial regeneration and repair.

[Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells].

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Exploring the expression and preliminary function of chicken regulator of G protein signalling 3 (RGS3) gene in follicular development.

1. The following study explored the expression and preliminary function of the RGS3 gene. The spatial and temporal expression patterns of the RGS3 gene were analysed in the ovarian stroma of Shendan No. 6 Green shell hens and Hy-line Brown hens at four time points (6, 28, 40, and 52 weeks old), as well as in various organs and follicles of Hy-line Brown hens.2. Based on the genomic and protein sequences of RGS3 in NCBI database, phylogenetic trees were constructed using MEGA-X. The protein interaction network was analysed using STRING. According to the results of protein-protein interaction network and pathways, the mRNA expression levels of RGS3 and three interaction proteins were explored by qRT-PCR in vitro.3. Spatio-temporal expression data revealed that RGS3 mRNA was expressed in all the organs tested, being highest in the hypothalamus. In different follicles, RGS3 mRNA was highly expressed in post-ovulatory follicles, followed by ovarian stroma and large white follicles. The expression levels of RGS3 mRNA in the ovarian stroma were significantly higher in Shendan No. 6 Green shell hens than that in the Hy-line Brown hens at all egg-laying stages.4. The phylogenetic tree results showed that ducks, geese and chickens had higher homology based on the genomic and protein sequence of RGS3. Moreover, chicken RGS3 interacted with GSK3B, RAF1 and BRAF based on STRING prediction. In vitro follicle stimulating hormone (FSH) treatment showed that mRNA expression levels of RGS3 and those of its predicted interacting proteins BRAF and GSK3B decreased with increasing FSH concentration. The results suggested that RGS3 responds to FSH and may play an important role in the regulation of follicular development in chicken.

Clinical benefits of TNF-α inhibitors in Chinese adult patients with NLRP3-associated autoinflammatory disease.

BACKGROUND: Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)-associated autoinflammatory disease (NLRP3-AID) is a rare, heterogeneous disease entity associated with mutations in NLRP3. Biologic therapy for NLRP3-AID yields diverse results. OBJECTIVES: We aimed to evaluate the clinical features and outcomes of Chinese adult patients with NLRP3-AID who were treated with tumour necrosis factor (TNF)-α inhibitors. METHODS: Five patients with NLRP3-AID were diagnosed and treated with TNF-α inhibitors at Peking Union Medical College Hospital between 2017 and 2020 and were followed up for 6 to 12 months. All patients were systematically studied for treatment outcomes, including clinical manifestations and inflammatory markers. RESULTS: All five adult NLRP3-AID patients were Chinese Han, and four patients were males. The mean age at disease onset was 4.2 ± 4.1 years, and the mean time of diagnosis delay was 19.8 ± 6 years. All patients received TNF-α inhibitors with or without methotrexate/prednisone. During follow-up, all patients achieved remarkable clinical remission of skin lesions and polyarthritis and showed improvements in acute-phase reactants, inflammatory cytokines, patient visual analogue scale, physician global assessment and 36-item Short Form (SF-36). CONCLUSIONS: Early diagnosis and effective therapy for NLRP3-AID are essential for avoiding irreversible organ damage. TNF-α inhibitors might serve as a therapeutic alternative for patients with NLRP3-AID who have unsatisfactory responses or no access to interleukin-1 inhibitors.

Treatment and Outcome in Deficiency of Adenosine Deaminase 2: A Literature Review.

OBJECTIVES: Deficiency of adenosine deaminase 2 (DADA2) is a rare disease with varying phenotypes and disease outcomes. We evaluated the treatment of DADA2 and explored the factors associated with disease outcome. METHODS: A systemic literature review of DADA2 was conducted. Cases were included if they had documented detailed genotypes, phenotypes, treatment protocols, and outcomes. Patients were categorized as having uncontrolled and controlled disease. Factors associated with disease outcome were analyzed using logistic regression models. RESULTS: The study population comprised 242 DADA2 patients with data on treatment protocols and responses, of whom 17 required no treatment. Tumor necrosis factor a inhibitors (TNFi) were effective in 78.6% (103/131). Hematological abnormalities and increased acute phase reactants are independently associated with the effectiveness of TNFi (OR, 0.21 [95%CI, 0.07-0.661; P=.007] and 9.62 [95%CI, 2.31-40.00; P=.002, respectively). Among the 225 patients requiring active treatment, 157 (69.8%) had controlled disease and 68 (30.2%) uncontrolled disease. Neither age of disease onset nor genotype was associated with disease outcome. Increased acute phase reactant values, constitutional symptoms, neurological symptoms, and treatment with TNFi were independently associated with disease control, while recurrent infections and severe vascular events were the main causes of mortality (10/21 and 6/21, respectively). CONCLUSION: In patients requiring treatment, symptoms of systemic inflammation and vasculitis and treatment with TNFi are associated with disease control. Recurrent infections and severe vascular events should be treated intensively, as they are the main causes of death. Hematological abnormalities should be monitored, as they decrease the effectiveness of TNFi.

A Bayesian network meta-analysis of comparison of cancer therapeutic vaccines for melanoma.

Several approaches to active immunotherapy for melanoma, including peptide-based vaccines (PVs), autologous tumour cell vaccines (TCVs), allogeneic TCVs and autologous dendritic cell vaccines (DCVs), have been investigated in clinical trials. However, comprehensive evidence comparing these interventions remains unavailable. The objective of this study was to expand previous work to compare and rank the immunotherapeutic strategies for melanoma in terms of overall survival and toxic effects with a Bayesian network meta-analysis. Methodologically, we performed a network meta-analysis of head-to-head randomized controlled trials comparing and ranking cancer vaccine approaches for patients with melanoma. PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov were searched up to 31 July 2020. We estimated summary hazard ratios for death and risk ratios for toxicity. The effects of the underlying prognostic variable on survival benefits were examined by meta-regression. We performed subgroup analysis for the outcomes based on metastatic categories. Overall, we identified 4776 citations, of which 15 head-to-head randomized controlled trials (3162 participants) were included in the analysis. In terms of efficacy, allogeneic tumour cell vaccines plus immunotherapy adjuvants, peptide-based vaccines plus immunotherapy adjuvants and standard therapy were more effective than peptide vaccines. The proportion of women was inversely associated with mortality risk. For safety, all treatments were inferior to allogeneic tumour cell vaccines except for allogeneic tumour cell vaccines plus chemotherapy. Peptide vaccines plus immunotherapy adjuvants led to an increased risk of adverse events compared to allogeneic tumour cell vaccines plus immunotherapy adjuvants. These results suggest that allogeneic TCV and autologous DCV are better than standard therapy. PV plus immune modulators are the most effective strategy among all comparable strategies but is associated with increased toxicity. Any combination regimens for cancer therapeutic vaccines need to be balanced between risk and benefit profiles.

[Recommendations of diagnosis of autoinflammatory diseases in China].

Autoinflammatory diseases (AIDs) are a group of disorders characterized by dysfunction of innate immunity which caused by gene mutations leading to coded proteins changes, finally causing uncontrolled systemic inflammation. AIDs are a group of rare rheumatic and inflammatory diseases. Here, Chinese Rheumatology Association summarized manifestations of the main AIDs, and to standardize the methods for diagnosis of AIDs.

[Aadult-onset Still's disease: new insights from the rheumatologists].

Adult onset Still's disease (AOSD) is a rare polygenic autoinflammatory disease mainly manifesting as high-spiking fever, rash, arthritis/arthralgia, lymphadenopathy, and leukocytosis. More importantly, life threatening macrophage activation syndrome may occur in AOSD patients. Recently, with the development of research in pathogenesis and therapy strategies of biological agents and small molecule targeted drugs, we have new recognition of AOSD. In this commentary, we attempt to place this syndrome in perspective, including data in the past year on pathogenesis, clinical and laboratory features and therapy.

[Comparison of diagnostic performance of thyroid autoantibodies and high-resolution ultrasound in euthyroid Hashimoto's thyroiditis].

Objective: To compare the diagnostic performance of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and high-resolution ultrasound (HRUS) in euthyroid Hashimoto's thyroiditis (HT). Methods: From January 2016 to January 2019, patients with complete data of preoperative thyroid function, TPOAb, TgAb and HRUS who had undergone thyroid surgery treatment at the First Affiliated Hospital with Nanjing Medical University were reviewed. The diagnostic value of different diagnostic methods was compared using histopathology (HP) examination result as the gold standard. Results: The data of 792 patients (217 males and 575 females) was retrospectively collected. The M(Q1,Q3)of patients' age was 41(32,52)years and the range was 16-75 years. With HP as the diagnostic gold standard, TPOAb exhibited similar sensitivity (59.3% vs 61.2%, P=0.752), accuracy (85.0% vs 83.6%, P=0.379), area under the receiver operating characteristic curve (AUC) (0.767 vs 0.764, P=0.886) and higher specificity (94.2% vs 91.6%, P=0.033) when compared with TgAb in diagnosing euthyroid HT. They both exhibited a higher sensitivity (59.3% vs 44.5%, P = 0.002; 61.2% vs 44.5%, P<0.001), accuracy (85.0% vs 79.7%, P = 0.001; 83.6% vs 79.7%, P = 0.013) and AUC (0.767 vs 0.684, P<0.001; 0.764 vs 0.684, P<0.001) than HRUS. Compared with each method alone, the sensitivity and AUC of TPOAb combined with TgAb or HRUS were improved. The combination of three methods showed the greatest sensitivity. Concordance analysis demonstrated that TPOAb and HP had a moderate agreement (Kappa=0.580, 95%CI:0.513-0.647,P<0.001). Conclusions: The combination of thyroid antibodies, TPOAb and TgAb, can improve sensitivity, accuracy and AUC of diagnosis in euthyroid Hashimoto's thyroiditis. The two antibodies combined with HRUS exhibited the highest diagnostic performance. Elevated TPOAb showed moderate diagnostic consistency with histopathologic evidence of HT.

[Advance on theoretical epidemiology models research of prevention and control of COVID-19].

COVID-19 has brought a significant impact to the global health system, and also opportunities and challenges to epidemiological researches. Theoretical epidemiological models can simulate the process of epidemic in scenarios under different conditions. Therefore, modeling researches can analyze the epidemical trend of COVID-19, predict epidemical risks, and evaluate effects of different control measures and vaccine policies. Theoretical epidemiological modeling researches provide scientific advice for the prevention and control of infectious diseases, and play a crucial role in containing COVID-19 over the past year. In this study, we review the theoretical epidemiological modeling researches on COVID-19 and summarize the role of theoretical epidemiological models in the prevention and control of COVID-19, in order to provide reference for the combination of mathematical modeling and epidemic control.

[Clinicopathological features of differentiated-type dysplasia of the esophagus].

Objective: To investigate the clinicopathological features of differentiated-type (squamous) dysplasia of the esophagus. Methods: A total of 184 cases of esophageal differentiated-type dysplasia were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), and Beijing Chaoyang Hospital, Capital Medical University, China from 2016 to 2019. Their histological characteristics and immunophenotypes were analyzed, and related literature was reviewed. Results: The median age of the 184 patients was 65 years (range 39-83 years), while the ratio of men to women was 1.7∶1.0. There were 17 cases in the upper esophagus, 143 in the middle esophagus and 24 in the lower esophagus. The median diameter of the dysplasia was 15 mm (range 2-50 mm). According to the Paris classification, 2 cases were 0-Ⅰ, 25 cases were 0-Ⅱa, 70 cases were 0-Ⅱb, 74 cases were 0-Ⅱb and 0-Ⅱc and 13 cases were 0-Ⅱc. Macroscopically, the lesional mucosa was reddish with rough surface and white moss; capillary abnormality was found on narrow-band imaging. Histologically, dysplastic cells had distinct features of squamous epithelium, with abundant eosinophilic cytoplasm, round to irregular nuclei, coarse chromatin, obvious nucleolus, and conspicuous mitoses. The cellularity was increased, the arrangement of cells was disordered, and the polarity of cells in basal layer was lost. When the dysplasia did not completely spread to the whole layer of squamous epithelium, a clear boundary was often formed between the dysplasia and the normal epithelium above it. The neoplastic epithelial protrusions often grew toward the lamina propria and were accompanied by conspicuous inflammatory cell reaction at its frontal edge. Sometimes, abnormal mature single epithelial cells or cell clusters infiltrated into the lamina propria. There were high-grade dysplasia of the common type and superficial invasive squamous cell carcinoma in 98 cases of differentiated-type dysplasia. Immunohistochemical staining showed that the mutation rate of TP53 was 47.7% (53/111). The median of Ki-67 labeling index was 50.0% (range 10%-80%), while that of basal tumor cells was 12/HPF (range 3-65/HPF). The abnormal distribution pattern of Ki-67 was seen in 111 (100%) cases. According to the initial pathological diagnosis, there were 16 cases of low-grade intraepithelial neoplasia, 37 cases of atypical epithelial cells and 131 cases of high-grade intraepithelial neoplasia and superficial invasive squamous cell carcinoma. Conclusions: The morphology of differentiated-type dysplasia of the esophagus is unique. Characteristics of highly differentiated dysplastic cells suggest that they may represent a differentiated type in the morphological lineage of esophageal squamous (high-grade) dysplasia. When the knowledge of the lesion is insufficient, it is easy to be misdiagnosed or missed in pathologic examination.

[Spindle cell type squamous dysplasia of the esophagus: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and significance of spindle cell type squamous dysplasia of the esophagus. Methods: The clinicopathological data of 37 cases of spindle cell type squamous dysplasia of esophagus were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from 2009 to 2019. The histological and immunohistochemical characteristics were analyzed, with a literature review. Results: The median age of the 37 patients was 65 years (range 47-81 years), while the ratio of men to women was 1.5∶1.0. There were 4 cases in the upper esophagus, 31 in the middle esophagus and 2 in the lower esophagus. The median diameter of the lesions was 14 mm (range 3-40 mm). According to the Paris classification, 11 cases were 0-Ⅱa, 14 cases were 0-Ⅱb, 3 cases were 0-Ⅱb and 0-Ⅱa, and 9 cases were 0-Ⅱc. Under endoscope, the lesional mucosa was reddish. The micro-vessels were dilated, with various shapes and density. Histologically, tumor cells and nuclei were spindle shaped or elongated spindle shaped, with considerable homogeneity, dark nuclei and delicate or slightly thickened chromatin. The mitosis was conspicuous, and atypic mitoses were seen; the cytoplasm was acidophilic, and the intercellular bridge was obvious. The cells were dense and often lost polarity, but still arranged in parallel, mostly perpendicular to the basement membrane. Spindle cells often involved the whole layer of epithelium, with no gradient maturation and differentiation of normal squamous epithelium. The tumor was well demarcated. The spindle cells often invaded lamina propria. There were 15 cases with focal high-grade dysplasia and superficial invasive squamous cell carcinoma. Immunohistochemical staining showed that the mutation rate of p53 was 41.4% (12/29), the median of Ki-67 labeling index was 40% (range 20%-80%), and the abnormal distribution pattern of Ki-67 was 29 (100%). According to the initial pathological diagnosis, there were 6 cases of low-grade dysplasia, 4 cases of atypical epithelial cells and 27 cases of high-grade dysplasia and superficial invasive squamous cell carcinoma. Conclusions: Spindle tumor cells have moderate to severe atypia, and some tumors show invasive pattern. P53 mutation and Ki-67 abnormal distribution pattern indicate that they are high-grade dysplasia of esophageal squamous epithelium. The unique characteristics of spindle tumor cells suggest that they may represent a spindle cell subtype in the morphological spectrum of esophageal squamous dysplasia. When the knowledge of the lesion is insufficient, it can be easily misdiagnosed or missed.

[Clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus].

Objective: To investigate the clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus. Methods: Fifty-two cases of basal cell layer type high-grade squamous dysplasia of the esophagus were collected at PLA Joint Logistics Support Force 989 Hospital (34 cases) and Beijing Chaoyang Hospital (18 cases) from 2009 to 2019. The clinical, histological and immunohistochemical features were characterized. Related literature was also reviewed. Results: The median age of the 52 patients was 64 years (range 43-72 years). There were 35 men and 17 women, with a male to female ratio of 2.1∶1.0. There were 8 cases in the upper esophagus, 41 in the middle esophagus and 3 in the lower esophagus. According to the Paris Classification, 24 cases were 0-Ⅱb and 28 cases were 0-Ⅱc. Endoscopic examination showed that the color of the lesions was red and the edge was irregular. The narrow band imaging showed that the lesions were brown, and the microvascular abnormalities on the mucosal surface were observed with high magnification. Iodine staining of the lesions showed no or light staining and irregular border. Histologically, the basal layer of squamous epithelium was hypercellular, with large and hyperchromatic nuclei, and disordered cell arrangement. A high proportion of the cases showed a down-growth pattern and associated invasive squamous cell carcinoma. The immunohistochemical staining of 37 cases showed that the mutation rate of p53 was 48.6% (18/37), the median of Ki-67 labeling index was 60% (range 20%-90%), the median of Ki-67 labeling index of the basal tumor cells was 26/HPF (range 5-70/HPF), and the rate of abnormal Ki-67 distribution pattern was 37(100.0%). According to the initial pathological diagnosis, there were 8 cases of low-grade intraepithelial neoplasia, 2 cases of atypical epithelial cells and 42 cases of high-grade intraepithelial neoplasia. Conclusions: The basal cell layer type high-grade squamous dysplasia of the esophagus has a unique morphology. The dysplasia is mainly limited to the lower half part of the squamous epithelium. With marked cytological atypia and prominent invasiveness pattern, it is likely to develop into invasive squamous cell carcinoma at an early stage of the disease. The rate of pathologic misdiagnosis (such as low-grade lesion) is high. The p53 mutation and Ki-67 abnormal distribution pattern are helpful features for confirming the diagnosis of such high-grade dysplasia.

[Pathological characteristics of colorectal adenoma with submucosal pseudoinvasion].

Objective: To investigate the pathomorphological characteristics of colorectal adenoma with submucosal pseudoinvasion and to summarize the corresponding pseudoinvasion patterns. Methods: The clinicopathological data of 9 cases of colorectal adenoma were collected at 989 Hospital of PLA Joint Logistics Support Force (4 cases) and Beijing Chaoyang Hospital, Capital Medical University (5 cases), from 2016 to 2019. retrospectively, and the histomorphological characteristics and immunophenotypes were analyzed, and discussed in light of the relevant literature. Results: There were 8 cases of adenoma with stalk. Tumor glands were found in the submucosa at the head end of adenoma, similar to infiltrating adenocarcinoma. The structure and cellular morphology of submucosal glands were very similar to the intramucosal tumor while the local submucosal tumor showed continuity with the intramucosal tumor. The submucosal tumors were lobule-like or nest-like with clear boundary. The outline of the gland was smooth and blunt-round, and there was loose fibromyxoid stroma around the gland, similar to the mucosa propria stroma. Some cases of the submucosal glands were cystic dilated with mucocele formation and hemosiderin deposition. One case with broad stalk-base showed an elevated adenoma with local high grade dysplasia involved in the aggregated lymphoid nodule, forming the lymphoglandular complexes, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates. Submucosal cancer tissue and intramucosal cancer tissue had continuity, and their morphology was the same. The submucosal tumor was round in the outline, smooth and blunt in the edge, and surrounded by lymphoid tissue. There was no stromal response around the gland to promote the proliferation of connective tissue, neither was there single-cell or small-cell cluster, sharp angle branch of gland, or vascular infiltration. Conclusions: There are two unique morphological patterns in colorectal adenoma with submucosal pseudoinvasion. Morphologically, the data show that one is lobular-like pattern, and the other is lymphoglandular complexes-like pattern. The main features of the two patterns are the same-morphology and continuity of submucosal tumor and intramucosal tumor. The pushed glands were surrounded by the intrinsic membrane stroma and muscularis mucosae in proper order, lacking the typical morphological characteristics of invasive adenocarcinoma.

[Prognostic values of spindle checkpoint protein BUB1B in triple negative breast cancer].

Objective: To identify important prognostic molecular markers of triple negative breast cancer (TNBC) using high throughput sequencing technology and to explore the correlation of spindle checkpoint protein BUB1B and clinicopathological features with patients' prognosis. Methods: The clinicopathological data and prognostic information of TNBC diagnosed at the West China Hospital of Sichuan University from 2009 to 2017 were collected. Forty-seven fresh tumor samples and 139 formalin fixed paraffin-embedded samples were selected. The fresh tumor samples were subject to RNA sequencing (RNA-seq). The enrichment analysis and protein-protein interaction (PPI) analysis were performed after intersection of difference analysis between RNAseq and GEO (Gene Expression Omnibus) datasets GSE38959 and GSE65194. Kaplan-Meier plotter database was used to analyze the relationship between expression of BUB1B and prognosis. Immunohistochemical staining was used to verify its expression in TNBC and correlation with clinicopathological features and prognosis. Results: Using edgeR to perform differential expression analysis between 47 TNBC tumor tissues and 12 normal tissues, 1 559 up-regulated genes and 1 376 down-regulated genes were identified, while only 131 differentially expressed genes were overlapping with those in GSE38959 and GSE65194. Enrichment analysis was mainly enriched in cell cycle, JAK-STAT signaling pathway and p53 signaling pathway. The top 10 genes ranked by degree of association were TOP2A, BUB1B, MKI67, PLK1, RRM2, PCNA, KPNA2, SMC4, PBK and IGF1. Kaplan-Meier plotter database analysis showed that the expression of BUB1B was significantly correlated with the prognosis of TNBC [overall survival, hazard ratio (HR)=0.52, 95%CI (0.35-0.77), P=0.001; distant metastasis-free, HR=0.72, 95%CI (0.52-0.98), P=0.038]. The immunohistochemical analyses of 139 formalin fixed paraffin-embedded samples showed that the low expression of BUB1B was correlated with poor prognosis in TNBC [HR=0.41, 95%CI (0.18-0.95), P=0.024]. Conclusions: The low expression of BUB1B protein is associated with poor prognosis in TNBC patients, and the molecular mechanism related with prognosis and potential therapeutic targets need to be further studied.

[Application of remote "Internet+" interactive mode in the management of patients with hypertension during normalized epidemic prevention and control of COVID-19].

Objective: To explore the effect of remote "Internet+" interactive management strategy on blood pressure control in patients with hypertension during normalized epidemic prevention and control of COVID-19. Methods: This is a randomized controlled study. A total of 394 patients with hypertension who were treated in Chinese People's Liberation Army General Hospital from October 2019 to December 2020 were randomly divided into experimental group (197 cases) and control group (197 cases). The experimental group adopted remote "Internet+" interaction mode to carry out remote blood pressure intervention, and the control group received traditional blood pressure control mode, and the intervention time was 6 months. Evaluation indicators included blood pressure level, blood pressure lowering speed, time to target blood pressure, blood pressure measurement times, communication times with doctors, medication compliance, blood pressure measurement compliance and disease awareness after 6 months of intervention. The evaluation indexes of the two groups were compared, and the bivariate Pearson correlation analysis was used to explore the relationship between the speed of blood pressure reduction and the times of blood pressure measurement and doctor communication in all patients. Results: A total of 394 patients with hypertension were included in this study, including 209 males, aged (67.6±2.8) years old. After 6 months of intervention, the systolic and diastolic blood pressure of the two groups were both lower than the baseline blood pressure before intervention (both P<0.05), the systolic blood pressure ((125.7±11.7) mmHg (1 mmHg=0.133 kPa) vs. (132.6±12.9) mmHg, P<0.001) and diastolic blood pressure ((72.4±10.7) mmHg vs. (79.8±11.6) mmHg, P<0.001) in the experimental group were lower than those in the control group. The blood pressure reduction speed of the experimental group was faster than that of the control group ((18.63±1.59) mmHg/d vs. (13.26±2.85) mmHg/d, P<0.001), and the time to reach the target blood pressure in the experimental group was shorter than that in the control group ((23.69±2.93) d vs. (47.12±5.81) d, P<0.001). Compared with the control group, the blood pressure measurement times ((0.98±0.13) times/d vs. (0.20±0.40) times/d, P<0.05) and the number of communications with doctors ((0.97±0.16) times/week vs. (0.12±0.32) times/week, P<0.05) were significantly higher in the experimental group. Correlation analysis showed that the speed of blood pressure reduction was positively correlated with the number of blood pressure measurements (r=0.419, P<0.01) and the number of communications with doctors (r=0.857, P<0.01). The proportion of standardized medication (93.91% (185/197) vs. 51.78% (102/197), P<0.001), timely measurement (97.46% (192/197) vs. 47.21% (93/197), P<0.001) and high-degree disease awareness (94.42% (186/197) vs. 49.24% (97/197), P<0.001) were significantly higher in the experimental group than those in the control group. Conclusions: The remote "Internet+" interactive management strategy can effectively improve patients' blood pressure control. The doctor-patient interaction can improve medication compliance and measurement compliance of patients, and help shorten the time to reach the target blood pressure.