[Clinical study on early predictors of concurrent bile duct injury following TACE in patients with liver cancer].

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.

[Progress of clinical application in extraocular muscle transposition].

Extraocular muscle transposition, including adjacent extraocular muscle transposition and transmuscular transposition, is often used to correct different types of strabismus, especially special forms of strabismus, instead of conventional surgery, which could not correct large-angle strabismus or improve the eye movement function. With the popularity of individualized surgical schemes, various types of extraocular muscle transposition procedures are available. In this article, the research progress of extraocular muscle transposition in the treatment of strabismus is reviewed, and the indications, advantages and disadvantages of various extraocular muscle transposition procedures are discussed, so as to provide reference for clinicians to further understand and reasonably carry out the treatment.

[The research of liver failure in Banna miniature pigs caused by amanita exitialis].

Objective: To explore the characteristics of Banna miniature pig liver failure induced by amanita exitialis. Methods: From September to October 2020, a reverse high performance liquid chromatography (RP-HPLC) method was used to determine the toxin content of amanita exitialis solution, and 2.0 mg/kg amanita exitialis solution (α-amanitins+ß-amanitins) was administered orally to Banna miniature pigs. Toxic symptoms, blood biochemical indexes and histopathological changes of liver, heart and kidney were observed at each time point. Results: All Banna miniature pigs died within 76 h of exposure, and different degrees of digestive tract symptoms such as nausea, vomiting and diarrhea appeared between 6 and 36 h. The biochemical indexes of alanine aminotransferase, aspartate aminotransferase, total bilirubin, lactate dehydrogenase, myoglobin, creatine kinase isoenzyme, blood urea nitrogen and creatinine increased significantly at 52 h after exposure, and the differences were statistically significant compared with 0 h (P<0.05). The bleeding of liver and heart was obvious under macroscopic and microscopic observation, hepatocyte necrosis, renal tubule epithelial cell swelling. Conclusion: Large dose of amanita exitialis can cause acute liver failure of Banna miniature pigs, which is in line with the pathophysiological characteristics of acute liver failure, and lays a foundation for further research on the toxic mechanism and detoxification drugs of amanita exitialis induced liver failure.

[Survival analysis of different kinds of tyrosine kinase inhibitors in the treatment of patients with epidermal growth factor receptor mutated non-small cell lung cancer and leptomeningeal metastasis].

Objective: To explore the prognosis of patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) treated with different kinds of tyrosine kinase inhibitors (TKIs). Methods: From January 2016 to June 2021, the clinicopathological data of 70 patients confirmed by histologically or cytologically EGFRm LM who received different types of TKIs in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. According to treatment patterns, patients were divided into the first-and second-generation EGFR-TKIs treatment group and the third-generation EGFR-TKIs treatment group [Osimertinib 80 mg once a day], and the prognosis and prognostic factors (with Cox proportional hazards model) of patients in different treatment group were assessed. The next-generation sequencing (NGS) of paired samples of cerebrospinal fluid (CSF) and plasma from 64 patients at the time of LM diagnosis was performed simultaneously. Results: There were 20 males and 50 females in 70 EGFRm NSCLC patients with LM. The age ranged from 35 to 69 years, with a median age of 56 years. A total of 24 patients received the first-and second-generation EGFR-TKIs treatment, and 46 received the third-generation EGFR-TKIs treatment. Twenty-four patients developed disease progression on the first-and second EGFR-TKIs treatments, followed by treatment with the third-generation EGFR-TKIs (Osimertinib) in 12 cases, chemotherapy or anti-angiogenesis therapy in 4 cases, and the optimal supportive treatment in 8 cases. Among the 70 patients, 18 had partial response (PR), 48 had stable disease (SD), and 4 had progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 26% (18/70) and 94% (66/70), respectively. The median follow-up time was 16.5 months. The median progression-free survival (PFS) was 5.3 months(95%CI: 2.8-7.8)in the first-and second-generation EGFR-TKIs and 10.8 months (95%CI: 7.9-13.6) in the third-generation EGFR-TKIs, and the difference was statistically significant (P=0.019). The median overall survival (OS) was 14.9 months (95%CI: 9.7-20.0) and 15.7 months (95%CI: 13.3-18.1) in the two groups, respectively, but no statistical differences was observed (P=0.713). Univariate analysis showed that the PFS of patients with EGFRm LM were related to gender and different types of EGFR-TKIs (P˂0.05). Multivariate analysis demonstrated that male (HR=2.30, 95%CI: 1.31-4.03, P=0.004) and the first-and second-generation EGFR-TKIs (HR=2.03, 95%CI: 1.20-3.41, P=0.008) were independent risk factors for PFS in patients with EGFRm LM. The EGFR mutation was detected in 61 (95%) CSF and in 27 (42%) plasma samples. Conclusion: In EGFRm NSCLC patients with LM, the dose of Osimertinib 80 mg (once a day) has a significant PFS benefit compared with the first-and second-generation EGFR-TKIs.

[Preliminary effects of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma].

Objective: To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma. Methods: Clinical data of 50 patients with advanced renal cell carcinoma who received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed. Results: Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95%CI 5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated transaminase, and hand-foot syndrome. Most adverse events were grade 1-2. Conclusion: Toripalimab combined with axitinib was efficient in the treatment of advanced renal cell carcinoma, and had manageable adverse reactions.

[Assessment of disease burden related to non-optimal temperature across China].

Objective: To estimate the excess mortality attributed to non-optimal ambient temperature in China. Methods: Mortality data and meteorological data from 239 counties in 2013-2018 were collected to simulate the quantitative exposure-response relationship between the temperature and mortality using distributed lag nonlinear models for time series studies. Then the number of non-optimal-temperature-related excess deaths was assessed and the spatial distribution was explored. Results: There were averagely (12±8) cases of all-cause deaths per day per county from 2013 to 2018. The average daily temperature was (14.98±10.31)℃, and the daily average relative humidity was (68.79±17.25)%. The daily average O3 concentration was (58.95±34.96) µg/m³, and the daily average PM2.5 concentration was (54.97±45.56) µg/m³. The exposure-response curve between daily average temperature and all-cause mortality showed a "U" shape, and the theoretical minimum mortality temperature (MMT) corresponding to the minimum number of deaths was 21.60 ℃. When the temperature was higher than MMT, the heat-related health effect increased with the temperature rising. When the temperature was lower than MMT, the cold-related effect increased with the temperature decreasing. The attributable fraction (AF) of death caused by non-optimal temperature was 8.76% (95%CI: 8.07%-9.10%), and the AF of death caused by cold effect and heat effect was 7.21% (95%CI: 6.51%-7.57%) and 1.55% (95%CI: 1.46%-1.61%), respectively. The excess deaths from non-optimal temperature in 2015 were 519 122, 72.98% of which could be attributed to low temperature. The number of excess deaths caused by non-optimal temperature mainly showed a decreasing trend from the east to the west, relatively high (117 522) in East China. Heilongjiang Province (in Northeast China) had the most excess deaths (26 924) caused by low temperature, and Guangdong Province(in South China) had the most excess deaths (27 763) caused by high temperature. Conclusion: The non-optimal temperature has a significant impact on health and causes a considerable burden of disease in China with obvious spatial heterogeneity.

Different effects of probiotics and antibiotics on the composition of microbiota, SCFAs concentrations and FFAR2/3 mRNA expression in broiler chickens.

AIMS: The aims of this study were to investigate the effects of probiotics and antibiotics on microbial composition, short chain fatty acids (SCFAs) concentration and free fatty acid receptor 2/3 (FFAR2/3) expression in boiler chickens. METHODS AND RESULTS: A total of 150 1-day-old male broilers were randomly allocated into three groups, control (CON) group, probiotics (PB) group and antibiotics (ATB) group. Results indicated that PB improved the average body weight from 1 to 21 days and feed intake from 21 to 42 days (P < 0·05), while ATB improved the feed efficiency from 1 to 42 days (P < 0·05). Based on 16s rRNA sequencing, PB treatment increased the amount of kingdom bacteria, and the relative abundance of the main bacteria including acetate and butyrate producing bacteria of phylum Firmicutes, family Ruminococcaceae and genus Faecalibacterium. ATB treatment also increased the relative abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, however, it introduced some pathogenic bacteria, such as bacteria of family Rikenellaceae and Enterobacteriaceae. Gas chromatography and mass spectrometry (GC-MS) assay revealed that PB increased acetate and butyrate concentrations at both 21 and 42 days, and propionate at 42 days in the colorectum. Moreover qRT-PCR analysis showed PB treatment significantly activated the FFAR2/3 mRNA expressions. On the contrast, ATB treatment lowered the colorectal propionate at 21 days, and decreased acetate, propionate and butyrate concentrations at 42 days, accompanied with decreased FFAR2/3 mRNA expressions. CONCLUSIONS: Compared to the CON birds, an enriched SCFAs producing bacteria with higher SCFAs contents and activated FFAR2/3 expressions are prominent features of PB birds. However, antibiotics treatment plays the reverse effect compared to PB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings a significant idea that less SCFAs concentration may be another reason why the antibiotics inhibit the immune system development and immunity of the body.

Quantification of peak blood flow velocity at the cardiac valve and great thoracic vessels by four-dimensional flow and two-dimensional phase-contrast MRI compared with echocardiography: a systematic review and meta-analysis.

AIM: To objectively examine the agreement and correlation between four-dimensional (4D) flow magnetic resonance imaging (MRI) and traditional two-dimensional (2D) phase-contrast (PC) MRI with the reference standard of Doppler echocardiography for measuring peak blood velocity at the cardiac valve and great arteries, and to assess if 4D flow MRI offers an advantage over the traditional 2D method. MATERIALS AND METHODS: The literature was searched systematically for studies that evaluate the degree of correlation and agreement between 4D flow MRI or 2D PC MRI and Doppler retrieved from PubMed, EMBASE, and the Cochrane Library. A meta-analysis was conducted to determine the peak velocity pooled bias with 95% limits of agreement (LoA) and correlation coefficient (r) for 4D flow MRI and 2D PC MRI compared with Doppler. RESULTS: Ten studies that compared 4D flow MRI with Doppler and 12 studies that compared 2D PC MRI with Doppler were included. 4D flow MRI showed an underestimation with bias and 95% LoA of -0.09 (-0.41, 0.24) m/s (p=0.079) while 2D PC MRI showed a poorer agreement with a bias and 95% LoA of -0.25 (-0.53, 0.03), p=0.596. 4D flow MRI and 2D PC MRI showed a strong correlation with R=0.80 (95% CI 0.75, 0.84; p<0.001) and R=0.83 (95% CI 0.79, 0.87; p<0.001), respectively. CONCLUSION: In this meta-analysis, 4D flow MRI provides improved assessment of peak velocity when compared with traditional 2D PC MRI. 4D flow MRI can be considered an important complement or substitute to Doppler echocardiography for peak velocity assessment.

Myocardial motion-corrected phase-sensitive inversion recovery late gadolinium enhancement in free breathing paediatric patients: a comparison with single-shot coherent gradient echo ("TrueFISP") phase-sensitive inversion recovery.

AIM: To investigate the value of motion-corrected (MOCO) phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) compared with single-shot balanced steady-state gradient echo ("TrueFISP", Siemens) PSIR in free breathing paediatric patients. MATERIALS AND METHODS: In this retrospective study, 238 paediatric patients underwent clinical contrast-enhanced cardiovascular magnetic resonance imaging (CMRI). Both the single-shot TrueFISP PSIR and MOCO PSIR sequences were performed on each child. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Two radiologists rated the quality of the images on a scale of 1-5 (1 = poor, 5 = very good). Bland-Altman, linear regression, and intraclass correlation coefficient were used to compared the extent of LGE of the single-shot TrueFISP PSIR and MOCO PSIR. Imaging artefacts were described and compared. RESULTS: Children ranged in age from 60 days to 17 years with an average age of 8.1 ± 3.8 years. MOCO PSIR had higher SNR and CNR than the single-shot TrueFISP PSIR (p<0.001). Mean quality ratings for short-axis imaging were 4 (interquartile range, 3-4) for single-shot TrueFISP PSIR and 4 (interquartile range, 4-5) for MOCO PSIR (p<0.001). The scan time was faster for single-shot TrueFISP PSIR than for MOCO PSIR. The myocardial LGE results were similar with high agreement between the single-shot TrueFISP PSIR and MOCO PSIR (ICC = 0.955-0.986). CONCLUSION: The MOCO PSIR sequence is feasible in children. MOCO PSIR is robust at high heart rates and can be performed without breath-holding with higher image-quality ratings than the single-shot TrueFISP PSIR.

Late gadolinium enhancement is a risk factor for major adverse cardiac events in unrecognised myocardial infarction without apparent symptoms: a meta-analysis.

AIM: To assess the prognostic role of unrecognised myocardial infarction (UMI) detected at late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRII). MATERIALS AND METHODS: Electronic databases including PubMed, EMBASE, Medline, and Cochrane were searched systematically for studies exploring the predictive value of UMI detected by LGE-CMRI for major adverse cardiac events (MACEs) and all-cause mortality in patients without apparent symptoms. Pooled hazard ratios (HRs) along with their 95% confidence intervals (CIs) were obtained from a random-effects model. Subgroup analyses were performed according to the different participants and outcomes. RESULTS: Eight studies (2,009 participants) were identified comprising 442 patients with UMI detected at LGE-CMRI and 1,567 without UMI. The presence of UMI on LGE was associated with a significantly increased risk for MACEs (HRs: 3.44, 95% CI: 2.06 to 5.75; p<0.001) and all-cause mortality (HRs: 2.43, 95% CI: 1.00 to 5.87; p=0.05). In the subgroup analysis, the presence of UMI on LGE remained significantly associated with the risk of MACEs in patients with suspected coronary artery disease (HRs: 3.82, 95% CI: 2.49 to 5.85; p<0.01) and diabetes mellitus (HRs: 4.97, 95% CI: 3.02 to 8.18; p<0.01). CONCLUSION: The presence of UMI detected by LGE-CMRI is associated with an increased risk of MACEs and all-cause mortality in patients without symptoms. LGE-CMRI could provide important prognostic information and guide risk stratification in patients with UMI.

Integrated microRNA-mRNA analysis reveals the roles of microRNAs in the muscle fat metabolism of Yanbian cattle.

Fat deposition is an important economic trait in farm animals. However, it is difficult to genetically improve intramuscular fat deposition via trait-based cattle breeding. The main objectives of this study were to analyze the factors about beef flavor, and to detect functional microRNA (miRNA, miR) associated with intramuscular fat deposition in Yanbian cattle. Longissimus dorsi samples from six steers were separated into high- and low-fat groups (n = 3 each) based on the marbling score, and transcriptomic analysis was performed using miRNA sequencing. A total of 33 miRNAs and 38 genes were found to be differentially expressed in the high- and low-fat groups. Quantitative real-time polymerase chain reaction was performed to validate the sequencing results. Integrated miRNA-mRNA analysis revealed that miRNA-associated target genes were primarily associated with skeletal muscle development. However, some of the miRNAs (miR-424 etc.) and genes (ATF3 etc.) were also associated with fat metabolism. A targeted relationship between miR-22-3p and the WFIKKN2 gene and its involvement in adipocyte differentiation were confirmed experimentally. The study findings may provide potential candidate molecular targets for the selection of cattle with improved meat quality.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

MiR-20b is implicated in preeclampsia progression via the regulation of myeloid cell leukemin-1.

Preeclampsia (PE) may induce gestational failure, threatening a significant number of pregnant women. Recently, microRNAs (miRNAs) have been reported to participate in PE progression, whereas the precise functions and potential mechanisms of miR-20b in placental trophoblast cells as well as in PE progression remain poorly understood. In the present study, real-time quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect expressions of miR-20b and myeloid cell leukemin- 1(MCL-1) mRNA. Cell viability was investigated by cell counting kit-8(CCK-8) assays. Cell invasion and migration abilities were determined by Transwell assays. Western blot was performed to detect MCL-1 protein expressions. The interaction between miR-20b and MCL-1 was investigated by bioinformatics analysis and luciferase activity assay. The results of the study demonstrated that miR-20b was highly expressed in placental tissues of patients with PE. Moreover, miR-20b overexpression inhibited HTR8/ SVneo cell proliferation, invasion and migration. Furthermore, MCL-1 was targeted by miR-20b, and MCL-1 restoration could partially attenuate the effect of miR-20b on HTR8/SVneo cells. In conclusion, the results indicate that miR-20b may contribute to PE through inhibiting proliferation, invasion and migration of placental trophoblast cells by targeting MCL-1. Therefore, miR-20b may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. MiR-20b targeting MCL-1 deserves further investigation in order to explore their potential role in PE.

Bovine bta-microRNA-1271 Promotes Preadipocyte Differentiation by Targeting Activation Transcription Factor 3.

Yanbian yellow cattle are one of the top five largest breeds of cattle in China. We had previously found that bta-miR-1271 is differentially expressed in the longissimus dorsi muscles of Yanbian yellow bulls and steers. However, whether bta-miR-1271 affects bovine fat formation is unclear. In this study, we used target gene prediction, dual-luciferase reporter assay, and transfection-mediated overexpression and inhibition of bta-miR-1271 in a culture of Yanbian yellow cattle preadipocytes to investigate the role of bta-miR-1271 in adipogenesis. We showed that bta-miR-1271 directly targets the 3'-untranslated region (3'-UTR) of the activating transcription factor 3 (ATF3) mRNA and downregulates its expression. Overexpression of bta-miR-1271 enforced by the miRNA mimics promoted triglyceride accumulation and significantly upregulated expression of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα) genes at both the protein and mRNA levels, as demonstrated by RT-qPCR and Western blot analyses. Conversely, inhibition of bta-miR-1271 expression produced the opposite effect. Our results show that bta-miR-1271 regulates differentiation of Yanbian yellow cattle preadipocytes by inhibiting ATF3 expression, which highlights the importance of microRNA-mediated regulation of adipogenesis. miR-1271 and its target gene(s) may provide a new research direction for investigating biological agents affecting intramuscular fat deposition in cattle.

[Diagnostic and therapeutic strategies of lung cancer patients during the outbreak of 2019 novel coronavirus disease (COVID-19)].

With the increasing number of cases and widening geographical spread, the 2019 novel coronavirus disease (COVID-19) has been classified as one of the class B infectious diseases but prevented and controlled as class A infectious disease by the National Health Commission of China. The diagnosis and treatment of lung cancer patients have been challenged greatly because of extraordinary public health measures since the lung cancer patients are a high-risk population during the COVID-19 outbreak period. Strict protection for lung cancer patients is needed to avoid infection. Lung cancer patients are difficult to differentiate from patients with COVID-19 in terms of clinical symptoms, which will bring great trouble to the clinical work and physical and mental health of lung cancer patients. This review will demonstrate how to applicate appropriate and individual management for lung cancer patients to protect them from COVID-19.

[Eosinophilic solid and cystic renal cell carcinoma with TSC2 gene mutations in children].

Objective: To study clinical pathological characteristics, immunohistochemical, molecular genetical changes and prognosis in pediatric eosinophilic solid and cystic renal cell carcinoma (ESC RCC) with TSC2 gene mutations. Methods: The tissue samples were collected from two pediatric ESC RCC patients between 2017 and 2018. The tissues were subjected to histological examination and immunohistochemistry using EnVision system. The TFE3, TFEB gene rearrangements were tested using FISH and molecular genetic study. The paraffin sections were used for DNA extraction, PCR amplification and NGS sequencing. Results: The two patients with ESC RCC were both male, aged at 9 years and 8 months, and 13 years, respectively. The tumors were from the right kidney, 5 cm and 7 cm in size, respectively, with solid and cystic changes in cross section, and grey-reddish or grey-whitish fish meat appearance. Microscopic observation revealed the tumors had fibrous capsules, which were infiltrated by the tumor cells. The tumor cells were diffusely distributed, round-shaped, or polygon-shaped, and had voluminous cytoplasm, eosinophilic cytoplasm, various sizes of vacuoles and clear cell-like appearance. There were papillary structures in some areas, with visible fiber septa. The nuclei were round and vesicular, with multi-nucleated cells and megakaryocytes. The mitoses were not seen. A few cystic structures were visible in different sizes, and capsule walls were covered with a single layer of spike-like tumor cells. Thick-walled blood vessels were seen in the stroma, with focal lymphocytic infiltration, eosinophilic necrosis, calcifications and cholesterol crystals. Immunohistochemistry of the tumor cells was positive for PAX8 (diffuse), CK20 (focal), CKpan (focal), CK10 (1 focal, 1 diffuse), INI1, vimentin, CD68, and Ki-67 (5%~10%); the tumor cells were negative for HMB45, S-100, Melan A, p53, desmin, TFE3, CK7, CK19, EMA, CD56, CgA, Syn, CD30, CD117, WT1 and SMA. Molecular genetic study showed that TFE3 and TFEB gene rearrangements were not detected by FISH. NGS sequencing showed TSC2 p.Lys574Ter (0.198) was found in patient one and TSC2 p.Arg406Ter (0.355) in patient two. Conclusions: ESC RCC in children is a rare disease, and can be misdiagnosed easily. It has unique pathological characteristics, and immunohistochemical, molecular and genetic changes. The prognosis is relatively good.

[Retinal toxicity study of intravitreal ganciclovir in albino rabbit].

Objective: To elevated the retinal toxicity of intravitreal ganciclovir in albino rabbit eyes. Methods: Experimental study. Twenty-four New Zealand albino rabbits (forty-eight eyes) were divided into four groups by random. Three groups were prepared for ganciclovir experiment, named A, B, C. Each group received intravitreal injection ganciclovir dose at 400 µg/0.05 ml, 2 mg/0.05 ml and 5 mg/0.05 ml respectively. The other group named D served as a control accepted intravitreal injection 0.9% normal saline 0.1 ml. Before and after 1, 2 and 4 weeks, flicker full field electroretina gram (ERG) was recorded. After 1, 2 and 4 weeks light and electron microscopic tests were recorded for further toxicity study. Results: There was significant difference in amplitude of maximal combined response a wave in one week(χ(2)=8.319, P=0.04), and pairwise comparison the 5 mg group (140.50 µV) was significantly lower than the control group (165.00 µV) (χ(2)=-2.830, P=0.028). Maximal combined response b wave in four weeks(χ(2)=-10.626, P=0.014), and pairwise comparison the 5 mg group (261.50 µV) was significantly lower than the control group (398.00 µV) (χ(2)=-2.973, P=0.018). 30 Hz flicker response in one, two and four weeks(χ(2)=17.589, 8.225, 8.997, P=0.001, 0.042, 0.02), and pairwise comparison the 5 mg group (71.3µV, 106.00µV, 63.60µV) was significantly lower than the control group (118.50µV, 129.00µV, 116.50µV) (χ(2)=-4.142, -2.826, -2.713, P=0.000, 0.028, 0.040). There was no histologic retinal toxicity evidence of group 400 µg and control group observed by light microscopy in any stage of the study. Histologic changes of group 2 mg four week later, group 5 mg two and four week later include inner nuclear layer loose arranged, nuclear of ganglia were widened and outer plexiform layer stained less in four week later. By electron microscopic observation, the ultrastructure of retina changed to different degrees and became worse in each experimental group with significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors, loosely arranged and disordered in the outer segment of photoreceptors four weeks later. Conclusions: The retinal function and morphology were normal in group 400 µg. Group 2 mg and 5 mg had retinal toxicity, and 5 mg was more severe. Therefore, the clinical application of ganciclovir in the treatment of acute retinal necrosis (ARN) should select the minimum effective dose to avoid the occurrence of retinal toxicity. (Chin J Ophthalmol, 2020, 56:279-285).

[Peripapillary and macular vessel density in eyes with different phases of thyroid-associated ophthalmopathy].

Objective: To analyze the characteristics of vessel density in the optic disc and macular area of patients with different phases of thyroid-associated ophthalmopathy (TAO) and their correlation with visual function. Methods: This case-control study was conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between June 2019 and September 2019. TAO patients and healthy volunteers were included in the study. Patients with a clinical activity score greater than or equal to 3 points were categorized as active TAO. Dysthyroid optic neuropathy (DON) patients with a course less than 6 months were categorized as acute phase of DON, and those more than 6 months were in the chronic group. Healthy volunteers were in the control group. Each group included 12 subjects, with right eyes for analysis. There were 6 males and 6 females in each group. All participants underwent comprehensive ophthalmic examination including best corrected visual acuity and visual field examination for the mean defect (MD). Best corrected visual acuity was subsequently converted to logarithm of minimum angle of resolution (logMAR). Optical coherence tomography was used to measure the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to the peripapillary and macular vessel density. The differences in the vessel densities in the optic disc and macular area between groups and their correlation with different factors were analyzed. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient were conducted for statistical analysis. Results: There was no significant difference in age among the four groups (P>0.05). The logMAR of the acute DON group was 0.1 (0.0, 0.2), worse than the control group, which was 0.0 (0.0, 0.0) (U=114.000, P<0.05). The overall vessel densities of the optic disc in acute DON and chronic DON were significantly lower than the control group (54.70%±2.31% and 54.31%±3.65% vs. 57.54%±2.17%; t=3.104, 2.636; both P<0.05). The overall superficial vessel densities of the macular area in active TAO, acute DON and chronic DON were significantly lower than the control group (46.07%±3.06% and 42.26%±5.05% and 45.63%±3.87% vs. 49.34%±3.08%), and the differences were statistically significant (t=2.614, 4.147, 2.603; all P<0.05). There was no statistically significant difference in the size of the foveal avascular zone or the density of deep blood vessels in the macular area among the four groups (all P>0.05). In the active TAO period, there was no correlation between the MD value, RNFL thickness, GCC thickness and the vessel densities of the optic disc and macular area (all P>0.05). The vascular density of the whole layer of the optic disc in acute DON was negatively correlated with the MD value (r=-0.591, P<0.05) and positively correlated with the RNFL thickness and GCC thickness (r=0.595, 0.693; both P<0.05). In chronic DON, the overall capillary density of the optic disc was negatively correlated with the MD value (r=-0.673, P<0.05); the superficial overall blood vessel density of the macular area was positively correlated with the thickness of RNFL and GCC (r=0.732, 0.712;both P<0.01). Conclusions: In active TAO, only the blood supply to the superficial layer of the macular area is decreased. In the acute and chronic phases of DON, the blood supply to the superficial layer of the macular area and the optic disc is both reduced; the smaller the blood vessel density, the more severe the visual field defect, and the thinner the RNFL and GCC. (Chin J Ophthalmol, 2020, 56:824-831).

[Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma].

Objective: To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods: In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results: Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%, 7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high, medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%, 5/7 and 6/11 in high, medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15, 2/4 and 3/6, respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions: The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.

[The ocular manifestations of human immunodeficiency virus and syphilis coinfection].

Objective: To investigate the ocular manifestations of human immunodeficiency virus (HIV) and syphilis coinfection. Methods: A retrospective analysis of the ocular manifestations was carried out in 27 patients (54 eyes) diagnosed as syphilis and HIV coinfection by the Department of Infectious Medicine in Peking Union Medical College Hospital during the years of 2006-2017. The research included 26 males and 1 female, aging from 24 to 76 years old, with a mean age of 40.40±12.94 years old. Ocular anterior segments were examined with slit-lamp microscope. Fundus examinations were conducted with papillary dilation, fundus photography. Results: At the first visit, there were 2 eyes without light perception, 4 eyes with light perception, 1 eye with hand movement, 1 eye with finger counting, 2 eyes with 0.01-0.09 eyesight, 8 eyes with 0.1-0.2 eyesight, 12 eyes with 0.25-0.4 eyesight, 15 eyes with 0.5-0.9 eyesight, 9 eyes with 1.0-1.5 eyesight. Among the 27 patients (54 eyes) coinfected with HIV and syphilis, keratic precipitates were identified in 20 eyes, aqueous flare positive in 20 eyes, float positive in 15 eyes, and iris posterior synechias in 7 eyes. Nineteen eyes were diagnosed as syphilis uveitis, including 2 eyes with syphilis anterior uveitis and 17 eyes with syphilis panuveitis, among which, vitreous inflammatory opacity was observed in all 19 eyes, disk atrophy in 2 eyes, optic edema in 1 eye, vitreous hemorrhage in 1 eye, retinal detachment in 2 eyes, retinal hemorrhage and white vein in 1 eye. In addition, 8 eyes were diagnosed as HIV retinopathy, all manifested as cotton-wool spot. Among the 8 eyes, 4 were diagnosed as cytomegalovirus retinitis, 3 showed retinal yellow-white lesions, and 1 was in late phase which showed retinal pigmentation. The incidence of both HIV and syphilis coinfection patients and male homosexuality population increased. The most common ocular manifestation of HIV and syphilis coinfection was syphilis panuveitis. Six patients first visited the Department of Ophthalmology, and were then diagnosed as HIV and syphilis coinfection. Conclusions: The ocular manifestations of HIV and syphilis coinfection are diversified, which can be manifested as fundus necrotic lesions as well as anterior and posterior inflammatory. For HIV positive patients, syphilis serologic test should be routinely performed. The same, syphilis positive patients should be tested for HIV serum antibodies, in order to improve the diagnosis level of HIV/syphilis coinfection and give timely etiological treatment, which is of vital importance for saving visual acuity. (Chin J Ophthalmol, 2019, 55:267-272).