Magnetic resonance Index of Activity (MaRIA) is reliable in assessing response to treatment in patients with Crohn's disease (CD).

AIM: To assess the accuracy of Magnetic Resonance Index of Activity (MaRIA) in evaluating therapeutic efficacy in Crohn's disease (CD) patients with different activity levels using ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Forty-eight patients underwent magnetic resonance enterography (MRE) and ileocolonoscopy at baseline, week 26, and week 52, along with the Simple Endoscopic Score for Crohn's Disease (SES-CD) and MaRIA scores. According to the SES-CD score at baseline, all patients were subdivided into mild, moderate, and severe activity subgroups. The identification of endoscopic mucosal healing (MH) was explored primarily. Moreover, the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) levels were collected and analysed. RESULTS: MaRIA correlated significantly with SES-CD and CRP at baseline, week 26, and week 52. The discrepancies in MaRIA and SES-CD were statistically significant before and after treatment. MaRIA = 24.43 and ΔMaRIA = 12.77 as the cut-off points were found to have high diagnostic accuracy for predicting MH. MaRIA (p<0.001), SES-CD (p<0.001), CRP (p<0.05), ESR (p<0.05), and CDAI score (p<0.05) in patients with MH were considerably decreased compared to those in patients without MH. CONCLUSIONS: MRE has good application value in evaluating the therapeutic response of CD patients treated with biological agents. MaRIA is a reliable indicator in the follow-up of CD patients, which is strongly correlated with SES-CD, and it has high accuracy in predicting endoscopic MH.

Single-cell and bulk RNA sequencing reveal heterogeneity and diagnostic markers in papillary thyroid carcinoma lymph-node metastasis.

PURPOSE: Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (RNA-seq) to find diagnostic markers and therapeutic targets. METHODS: ScRNA-seq data were clustered and malignant cells were identified. Differentially expressed genes (DEGs) were identified in malignant cells of scRNA-seq and bulk RNA-seq, respectively. PTC LNM diagnostic model was constructed based on intersecting DEGs using glmnet package. Next, PTC samples from 66 patients were used to validate the two most significant genes in the diagnostic model, S100A2 and type 2 deiodinase (DIO2) by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC). Further, the inhibitory effect of DIO2 on PTC cells was verified by cell biology behavior, western blot, cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, and xenograft tumors. RESULTS: Heterogeneity of PTC LNM was demonstrated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. A total of 19 differential genes were used to construct the diagnostic model. S100A2 and DIO2 differ significantly at the RNA (p < 0.01) and protein level in LNM patient tissues (p < 0.001). And differed in PTC tissues with different pathologic typing (p < 0.001). Further, EdU (p < 0.001) and cell biology behavior revealed that PTC cells overexpressed DIO2 had reduced proliferative capacity. Cell cycle proteins were reduced and cells are more likely to be stuck in G2/M phase (p < 0.001). CONCLUSIONS: This study explored the heterogeneity of PTC LNM using scRNA-seq. By combining with bulk RNA-seq data, diagnostic markers were explored and the model was established. Clinical diagnostic efficacy of S100A2 and DIO2 was validated and the treatment potential of DIO2 was discovered.

[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

[Application of computational fluid dynamics in the evaluation of left ventricular function in cardiomyopathies and coronary disease].

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient's heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

[The expression and significance of protease activated receptor 2 in ovarian epithelial carcinoma].

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/ß-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/ß-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.

[Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer].

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

[Evaluation of the efficacy of TIPS in 27 patients with hepatic sinus obstruction syndrome in the near and medium term].

Objective: intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS). Methods: A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ (2) test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results: PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt (t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt (t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion: TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

[Clinical presentation of acute primary angle-closure glaucoma during the 2019-nCoV epidemic of Omicron variants: a single-center retrospective study].

Objective: To investigate the clinical presentation pattern of acute primary angle-closure glaucoma (PACG) during the 2019 novel coronavirus (2019-nCoV) pandemic over the past three years, and its relationship with 2019-nCoV infections of Omicron variants in Guangdong province. Methods: Ecological study.Patients who were newly diagnosed with acute PACG from February 2020 to January 2023 at the Zhongshan Ophthalmic Center of Sun Yat-sen University were included in the study, and their basic information was collected. Patients were divided into the 2020 group (diagnosed between February 1st, 2020 and January 31st 2021), the 2021 group (diagnosed between February 1st, 2021 and January 31st 2022), and the 2022 group (diagnosed between February 1st, 2022 and January 31st 2023). The clinical presentation pattern of newly diagnosed acute PACG was observed and compared between groups. The daily number of newly diagnosed 2019-nCoV infections in Guangdong province was obtained from the Chinese Center for Disease Control and Prevention. The correlation between the daily number of newly diagnosed acute PACG and that of newly diagnosed 2019-nCoV infections during the epidemic period of Omicron variants between December 2022 and January 2023 was assessed. Results: The study included 1 048 patients with newly diagnosed acute PACG, with 235 for the 2020 group, 274 for the 2021 group, and 539 for the 2022 group. Our results showed that the average weekly number of newly diagnosed acute PACG patients in 2022 [8 (5, 11)] was significantly larger than that in 2020 (4.52±1.95, P<0.05) and 2021 (5.27±2.76, P<0.05). The average weekly number increased to 22.11±20.84 between December 2022 and January 2023. The total number of newly diagnosed acute PACG patients during this period was 199, which was 36.9% (199/539) of the total number of the same year and was 6.63 and 6.42 times as many as that in the same period (December and January) of 2020 and 2021. The proportion of patients with bilateral eye involvement during this period in 2022 was significantly higher than that in 2020 and 2021 (P<0.05). Further analysis found that 88.6% (109/123) of cases had a history of 2019-nCoV infection 2 (0, 3) days before the onset of acute PACG symptoms in average. The estimated daily number of acute PACG onset increased rapidly, peaked on December 23th, 2022, and then dropped gradually. This trend was similar to that of the daily number of new 2019-nCoV infections in Guangdong province. Changes of the daily number of new 2019-nCoV infections in Guangdong province had a positive correlation with the estimated daily number of acute PACG onset (r=0.84, P<0.001). Conclusion: A dramatic increase in the clinical presentation of acute PACG was observed at Zhongshan Ophthalmic Center between December 2022 and January 2023, which was the epidemic period of Omicron variants. There is a correlation between the trend of the estimated daily number of acute PACG onset and that of new 2019-nCoV infections of Omicron variants in Guangdong province, but the exact reason remains to be further studied. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on August 31, 2023).

[Anatomical elucidation and histological study of pelvic autonomic nerve-plane based female fresh cadaver].

Objective: To investigate the rationality of nerve-plane sparing radical hysterectomy (NPSRH) for cervical cancer by observing the anatomical and histological characteristics of pelvic autonomic plane based on fresh cadaver. Methods: From October 2015 to September 2020, 14 fresh female cadavers were anatomically and histologically studied in the Laboratory of Anatomy and Embryology Department, Peking Union Medical College, Chinese Academy of Medical Sciences. The median age of the specimens was 79 years (range: 67 to 92 years). Twenty-eight hemi-pelvic specimens were obtained from 14 fresh female cadavers. NPSRH procedures were simulated in 8 hemi-pelvic cavities to prove its feasibility. Detailed dissection was conducted to recognize nerve plane and to observe the distribution of pelvic nerves in 10 hemipelvis. In the other 10 hemipelvis, whole parametrium tissue was taken from the crossing of ureter and the uterine artery to the ureterovesical entrance and be embedded, then continuous section was performed, and was stained by hematoxylin-eosin staining (HE) to observe the relationship of nerves and vessels. Immunohistochemical staining of S100, tyrosine dehydrogenase (TH), and vasoactive intestinal peptide (VIP) were performed to count and distinguish sympathetic and parasympathetic nerves, respectively. Results: (1) The pelvic autonomic nerve-plane was completely preserved in 7 of 8 hemipelvis by simulating NPSRH. (2) After detailed dissection in 10 hemipelvis, it was found that hypogastric nerve, pelvic splanchnic nerve, and their confluence of inferior hypogastric plexus were distributed in a planar statelocating in the ureteral mesentery and its caudal extension. This nerve plane showed a cross relationship with deep uterine vein and its branches. The bladder branches and vesical venous plexus were closely related to the inferior hypogastric plexus. The middle vesical vein and inferior vesical vein were intact in 7 of 10 hemipelvis, and either vesical vein was missing in 3 of them. It was observed that the vesical venous plexus communicated with the deep uterine vein trunk on the medial side of the nerve plane in 6 hemipelvis, while flowed into the deep uterine vein on the lateral side of the nerve plane in 2 hemipelvis, and in the other 2 hemipelvis it directly flowed into the internal iliac vein. (3) It was revealed that autonomic nerves were continuously distributed beneath the ureteral with sagittal plane by HE staining. The average nerve content below the ureteral width was 70.9% of the total in nerve plane by S100 staining. TH and VIP staining showed that the average number of sympathetic fibers was 13.5 and parasympathetic fibers was 8.2, reminding sympathetic predominated. Conclusion: Pelvic autonomic nerves are mainly distributed within the mesangial plane below the ureter, which provides an anatomic justification for NPSRH.

[Analysis of 53 cases of transjugular liver biopsy].

Objective: To investigate the practicability and safety of transjugular liver biopsy (TJLB). Methods: Data of 53 cases with transjugular liver biopsy from June 2015 to June 2020 were collected. LABS-100 was used in all patients who underwent transjugular liver biopsy. Among them, 45 cases and eight were biopsied via hepatic vein and intrahepatic segment of the inferior vena cava. The surgical indications, related complications, and postoperative pathological diagnosis were analyzed and summarized. Results: TJLB was successful in all patients, with an average of 2.8 punctures per case. Satisfactory liver tissue and histopathological diagnosis was obtained in all patients. Two cases developed a cervical hematoma that was improved spontaneously, and one patient developed an intrahepatic hematoma that was improved after conservative treatment. Conclusion: TJLB is a practical and safe method for patients with contraindications to percutaneous liver biopsy.

[A case of diffuse anterior retinoblastoma].

A female patient presented with redness and visual acuity loss in the left eye for more than 4 months. Ophthalmic examination revealed a large number of gray-white masses and lesions with fuzzy boundaries on the iris surface. Retinoblastoma was diagnosed after enucleation.

Benchmark Experiment to Prove the Role of Projectile Excited States Upon the Ion Stopping in Plasmas.

We report on a precision energy loss measurement and theoretical investigation of 100 keV/u helium ions in a hydrogen-discharge plasma. Collision processes of helium ions with protons, free electrons, and hydrogen atoms are ideally suited for benchmarking plasma stopping-power models. Energy loss results of our experiments are significantly higher than the predictions of traditional effective charge models. We obtained good agreement with our data by solving rate equations, where in addition to the ground state, also excited electronic configurations were considered for the projectile ions. Hence, we demonstrate that excited projectile states, resulting from collisions, leading to capture-, ionization-, and radiative-decay processes, play an important role in the stopping process in plasma.

[Effects of the relationship between adenomyotic lesions and embryo implantation site on pregnancy outcomes in pregnant patients with adenomyosis].

Objective: To investigate the relationship between embryo implantation site and adenomyotic lesions in pregnant patients with adenomyosis and its effects on pregnancy outcomes. Methods: Between January 2018 and December 2020, the clinical data of 95 pregnant patients with adenomyosis who were hospitalized in the Women's Hospital, School of Medicine, Zhejiang University, which could identify the implantation site of embryo or placenta (≥11 weeks of pregnancy) through the nuchal translucency test under ultrasonography were analyzed retrospectively. According to the relationship between embryo implantation site and adenomyotic lesions, 95 patients were divided into two groups:short-distance group (n=59, the embryo or placenta implantation was very close to or over the adenomyotic lesion), and long-distance group (n=36, the implantation site of embryo or placenta was far away from the lesion, or the implantation site and the adenomyotic lesion were on different sides of the uterus). Next, taking 28 weeks of pregnancy as cut-off value, 95 patients were divided into <28 weeks of pregnancy group (pregnancy was terminated because of adverse pregnancy outcome before 28 weeks) and ≥28 weeks of pregnancy group (pregnancy lasted to 28 weeks and later), the differences of pregnancy outcomes between the two groups in different gestation times were analyzed. Results: (1) The age of 95 pregnant patients with adenomyosis was (34.8±3.5) years. There were no significant differences with regard to age, uterine size before pregnancy, the proportions of primipara, assisted reproductive technology conception, endometriosis, history of estrogen and progesterone treatment, diffuse adenomyotic lesions between the short-distance group and the long-distance group (all P>0.05). (2) Among the 95 patients, 12 patients (13%, 12/95) had adverse pregnancy outcomes before 28 weeks of pregnancy (i.e. pregnancy <28 weeks), including 11 cases (19%, 11/59) in the short-distance group and 1 case (3%, 1/36) in the long-distance group, there was significant difference between the two groups (χ²=5.100, P=0.027). Among the 11 patients with adverse pregnancy outcomes at <28 weeks of gestation in the short-distance group, 1 case had threatened rupture of uterus before delivery of twin pregnancy at 26 weeks of gestation, 5 cases had intra uterine fetal death in the second trimester of pregnancy, 4 cases had late inevitable abortion, and 1 case had live birth of singleton at 26 weeks of gestation. In the long-distance group, one patient with adverse pregnancy outcome less than 28 weeks of pregnancy was late inevitable abortion. (3) Of the 95 patients, 83 cases were pregnant for ≥28 weeks (48 cases in the short-distance group and 35 cases in the long-distance group), and their final pregnancy outcome was all live birth. Compared with the long-distance group, the incidence of placental abnormalities (60% vs 14%), fetal distress (27% vs 6%), preterm delivery (67% vs 23%) and intrapartum bleeding [median 350 ml (range: 100-1 500 ml) vs 300 ml (range: 100-800 ml)] in the short-distance group were significantly higher (all P<0.05). While the gestational weeks in the short-distance group [median 37 weeks (range: 30-41 weeks) vs 38 weeks (range: 28-41 weeks)] and neonatal birth weight [median 2 790 g (range: 1 170-4 040 g) vs 3 010 g (range: 980-4 320 g)] decreased significantly (all P<0.05), compared with those in the long-distance group. Conclusion: Patients with pregnancy complicated with adenomyosis are prone to adverse pregnancy outcomes if the embryo implantation is located on or very close to adenomyotic lesions, so close monitoring and early intervention should be carried out to improve pregnancy outcomes.

[Adrenocortical oncocytic tumors: a clinicopathological analysis of 44 cases].

Objective: To study the clinicopathological features of adrenocortical oncocytic tumors (ACOT) and to compare the diagnostic values of Lin-Weiss-Bisceglia (LWB) score and Helsinki score. Methods: Forty-four cases of ACOT diagnosed at Beijing Friendship Hospital, China from March 2008 to July 2019 were histologically analyzed to evaluate their malignant potential (benign versus malignant) according to two scoring criteria. Immunohistochemical studies (EnVision method) were also used. Results: There were 23 males and 21 females with an average age of 46 years. Histologically, the tumor cells were arranged in trabecular, chrysanthemum-shaped, glandular and microcapsule structures, while clear cells were rare or absent. Most of the tumor cells were moderately atypical, and intranuclear inclusion bodies were conspicuous. Immunohistochemical staining showed that tumor cells were positive for Melan A, inhibin, Syn and calretinin. The average proliferation index was 3% in benign ACOT, about 5% in ACOT of malignant potential, and>20% in malignant ACOT. According to the LWB score, 61.4% (27/44) of the tumors were on the left side and had multiple lesions. The percentage of benign ACOT was 59.1% (26/44), malignant potential 6.8% (3/44), malignant 34.1% (15/44), respectively. Among the 15 malignant ACOT, the mitotic figures>5/50 HPF were found in 13 cases, necrosis in 11 cases and capsule invasion in 10 cases. According to the Helsinki score, 65.9% (29/44) of the tumors were benign, and 34.1% (15/44) were malignant. There was no significant difference between the two scoring standards (P>0.05). During the follow-up of 9 to 144 months, 31 patients survived without disease and 13 patients relapsed or had metastasis. Conclusions: ACOT more likely be benign than malignant. The left side is more common. Malignant tumors are prone to recurrence and metastasis. The morphological parameters (high mitotic index, necrosis, and capsular invasion) in the LWB scoring standards combined with immunohistochemical parameters (Ki-67) in the Helsinki score are helpful for the diagnosis of malignant ACOT and are important predictors of poor prognosis.

[Plasm trimethylamine-N-oxide level and association with lesion severity in coronary heart disease patients with type 2 diabetes mellitus].

Objective: To investigate the association between trimethylamine-N-oxide (TMAO) and the degree of coronary atherosclerosis in coronary heart diseases (CHD) patients with type 2 diabetes mellitus. Methods: Consecutive patients, who underwent coronary angiography due to suspected CHD in Beijing Hospital from November 2016 to January 2018, were screened in this cross-sectional study. According to blood glucose level, previous medical history and coronary angiography results, they were divided into CHD without type2 diabetes mellitus(CHD-nDM) group and CHD with type2 diabetes mellitus(CHD-DM) group. Plasma TMAO levels in each group were measured by LC-MS/MS. Spearman correlation analysis was used to evaluate the correlation between TMAO and the number of diseased vessels and Gensini scores. Multivariate logistic regression was used to analyze the correlation between TMAO and high Gensini scores. Results: A total of 590 patients were enrolled in the study, including 238 patients in CHD-DM group and 352 patients in CHD-nDM group. Patients were older, body mass index, blood pressure level, prevalence of history of hypertension and statins use were higher in CHD-DM group than in CHD-nDM group (all P<0.05). The proportion of patients with multivessel disease (2 or more vessels) was also higher in CHD-DM group than in CHD-nDM group (P<0.001). Gensini score was higher in CHD-DM group than in CHD-nDM group (P<0.05). Fasting blood glucose, glycosylated hemoglobin and urea were significantly higher, while low-density lipoprotein cholesterol and hemoglobin were significantly lower in CHD-DM group than in CHD-nDM group (all P<0.05). The levels of TMAO was significantly higher in CHD-DM group than in CHD-nDM group (P<0.001). Spearman correlation analysis showed that TMAO was positively correlated with the number of diseased vessels, Gensini score, age and blood glucose level (r=0.178, 0.189, 0.260, 0.111, respectively, all P<0.01). Multivariate logistic regression analysis showed that, TMAO level was still positively correlated with high Gensini score in CHD-DM group (OR=2.25, 95%CI 1.16-4.38, P=0.017), but not in CHD-nDM group (OR=1.29, 95%CI 0.72-2.31, P=0.386) after adjusting for age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglyceride, history of hypertension, hyperlipidemia, smoking and statin use. Conclusions: In CHD patients with tupe 2 diabetes mellitus, the plasma TMAO level is significantly increased and is independent and positively correlated with the degree of coronary artery disease.

Application of Sarcosaprophagous Insects to Estimate the Postmortem Interval in 11 Cases.

ABSTRACT: Objective To test the feasibility and accuracy of with sarcosaprophagous insects postmortem interval （PMI） estimation with sarcosaprophagous insects and provide references for estimation practice. Methods Eleven cases confirmed by the detection results, with complete entomological evidence were selected. The insect species, estimation results and true results involved in the cases were statistically analyzed and compared. Results Thirteen species of insects were found at the criminal scene, including Chrysomya megacephala （Fabricius）, Chrysomya rufifacies （Macquart）, Chrysomya nigripes （Aubertin）, Lucilia sericata （Meigen）, Hydrotaea spinigera Stein, Muscina stabulans （Fallén）, Sarcophagid （species were not identified）, Megaselia scalaris （Loew）, Hermetia illucens （Linnaeus）, Saprinus splendens （Paykull）, Creophilus maxillosus （Linnaeus）, Dermestes maculatus （De Geer） and Necrobia ruficollis （Fabricius）. The PMI of all eleven cases was within the range of estimated PMI. The estimated results of 72.73% cases were on the same day of the true results. Conclusion Sarcosaprophagous insects can estimate the PMI simply and conveniently. In cases where the PMI is within the time range of one generation of flies or beetles, the estimation results are relatively accurate. However, the estimation is less accurate when the PMI is beyond the time range.

Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients.

Beta-glucosidase (GBA), also known as acid ß-glucosidase, exhibits an activity of glucosylceramidase (EC 3.2.1.45). Three main isoforms of ß-glucosidases have been identified in mammals: GBA1, GBA2, and GBA3. The deficiency of these enzymes leads to glucosylceramide accumulation, resulting in Gaucher's disease. The present study is focused on the cytosolic ß-glucosidase, GBA3, and its relationship with hepatocellular carcinoma (HCC). The expression of GBA3 mRNA in HCC was evaluated first using the TCGA database, and then by immunohistochemistry using tissue microarrays of 328 clinically characterized HCC samples and 151 non-tumor liver controls. Moreover, the presence of a correlation between GBA3 expression and clinicopathological characteristics of patients was examined. The obtained results indicated that the expression of GBA3 mRNA was significantly lower in HCC than in the adjacent non-tumor liver tissues. The expression of GBA3 was inversely related to the number of tumors (p=0.041), tumor size (p<0.001), Edmondson grade (p=0.007), microvascular invasion (p=0.049), patient status (p<0.001), and α-fetoprotein level (p<0.001). Patients exhibiting low GBA3 expression had a shorter survival time than those with high expression (p<0.001). In conclusion, the decreased GBA3 expression is strongly associated with a poor prognosis in HCC patients, and GBA3 may be a potential therapeutic target for HCC.