[Clinicopathological features of breast cancer with HER2 low expression: a real-world retrospective study].

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

Structural insights into peptidoglycan glycosidase EtgA binding to the inner rod protein EscI of the type III secretion system via a designed EscI-EtgA fusion protein.

Bacteria express lytic enzymes such as glycosidases, which have potentially self-destructive peptidoglycan (PG)-degrading activity and, therefore, require careful regulation in bacteria. The PG glycosidase EtgA is regulated by localization to the assembling type III secretion system (T3SS), generating a hole in the PG layer for the T3SS to reach the outer membrane. The EtgA localization was found to be mediated via EtgA interacting with the T3SS inner rod protein EscI. To gain structural insights into the EtgA recognition of EscI, we determined the 2.01 Å resolution structure of an EscI (51-87)-linker-EtgA fusion protein designed based on AlphaFold2 predictions. The structure revealed EscI residues 72-87 forming an α-helix interacting with the backside of EtgA, distant from the active site. EscI residues 56-71 also were found to interact with EtgA, with these residues stretching across the EtgA surface. The ability of the EscI to interact with EtgA was also probed using an EscI peptide. The EscI peptide comprising residues 66-87, slightly larger than the observed EscI α-helix, was shown to bind to EtgA using microscale thermophoresis and thermal shift differential scanning fluorimetry. The EscI peptide also had a two-fold activity-enhancing effect on EtgA, whereas the EscI-EtgA fusion protein enhanced activity over four-fold compared to EtgA. Our studies suggest that EtgA regulation by EscI could be trifold involving protein localization, protein activation, and protein stabilization components. Analysis of the sequence conservation of the EscI EtgA interface residues suggested a possible conservation of such regulation for related proteins from different bacteria.

Preparation and characterisation of novel casein-gum Arabic composite microcapsules for targeted in vivo delivery of Lactiplantibacillus plantarum A3.

The health benefits of probiotics in the body are predicated on their ability to remain viable in harsh gastrointestinal conditions and complex pathological microenvironments. Casein and gum Arabic (GA), with dual emulsifying and stabilising effects in colloidal systems. Therefore, the objective of this research was to develop a novel microcapsule to encapsulate Lactiplantibacillus plantarum A3 using casein and GA as wall materials to improve the survival of the bacteria during gastrointestinal digestion, storage and lyophilization. The casein and GA composite microcapsules were prepared and characterised by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was found that the microcapsules had stable morphology, uniform size and spherical shape. The results revealed that the encapsulation of microcapsules significantly improved the survival of L. plantarum A3 in gastrointestinal fluid environment (5.52 × 109 cfu/ml) and lyophilization treatment (6.25 × 109 cfu/ml). Furthermore, the microencapsulated L. plantarum A3 exhibited an improved ability to regulate intestinal microbiota by effectively increasing the relative abundance of Bacteroidetes, Proteobacteria and Actinobacteria and decreasing the relative abundance of Firmicutes in vivo. The findings of the study will help to design a lactic acid bacteria encapsulation system based on the gastrointestinal environment and provide a basis for the development of probiotic functional products.

[Fabrication and evaluation of composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface].

Objective: To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface. Methods: An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment. Results: After alternative loop immersing, the MN's original microholes (20 µm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point (P<0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN (P<0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 (P<0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN (P<0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 (P>0.05). The Avalue of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) (t=-0.25, P<0.001; t=-0.34, P<0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN (P<0.05). Conclusions: HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

Brusatol attenuated proliferation and invasion induced by KRAS in differentiated thyroid cancer through inhibiting Nrf2.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) can be developed from differentiated thyroid cancer, and this dedifferentiated transformation leads to poor prognosis and high mortality. The role of Nrf2 in the dedifferentiation of differentiated thyroid cancer (DTC) induced by KRAS remains unclear. METHODS AND MATERIALS: In this study, two DTC cell lines, BCPAP and WRO, were used to evaluate the function of Nrf2 in the dedifferentiation caused by wild-type KRAS (KRAS-WT) and G12V point mutation KRAS (KRAS-G12V). RESULTS: The overexpression of KRAS-WT and KRAS-G12V increased the proliferative and invasive ability of BCPAP and WRO cells. Aggressive morphology was observed in KRAS-WT and KRAS-G12V overexpressed WRO cells. These results suggested that overexpression of KRAS-WT or KRAS-G12V may induce dedifferentiation in DTC cells. The expression of Nrf2 was increased by KRAS-WT and KRAS-G12V in DTC cells. In addition, compared with normal thyroid tissues, the expression of Nrf2 protein was considerably higher in thyroid cancer tissues on immunohistochemistry (IHC) staining, and the increased expression of Nrf2 indicated a poor prognosis of thyroid cancer. These results indicated that Nrf2 is the KRAS downstream molecule in thyroid cancer. Functional studies showed that the Nrf2 inhibitor Brusatol counteracted the proliferative and invasive abilities induced by KRAS-WT and KRAS-G12V in BCPAP and WRO cells. In addition, the xenograft assay further confirmed that Brusatol inhibits tumor growth induced by KRAS-WT and KRAS-G12V. CONCLUSION: Collectively, this study suggests that Nrf2 could be a promising therapeutic target in KRAS-mediated dedifferentiation of thyroid cancer.

The effect of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in STEMI patients after PCI.

OBJECTIVE: This study aimed to investigate the effects of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 80 STEMI patients admitted to our hospital from February 2020 to March 2023 were selected and included in the retrospective study, all receiving PCI treatment. They were randomly and retrospectively divided into a control group (40 cases) and an observation group (40 cases), and treated with clopidogrel and ticagrelor, respectively. The clinical effects were compared. RESULTS: The starting perfusion time of the contrast agent in the myocardial infarction area in the observation group was 2.22±0.27 s, and the peak perfusion time was 2.62±0.27 s, which was lower than those in the control group (2.51±0.29 s and 3.21±0.39 s, t=4.629, 7.867, p=0.000). The ratio of peak perfusion intensity between the two groups was significantly different (t=2.363, p=0.021). Left ventricular ejection fraction, stroke volume index, and cardiac index in the observation group were higher than those in the control group (55.03±6.03 vs. 52.33±5.13; 57.39±6.81 vs. 51.11±6.31 L/min·m-2; 3.49±0.45 vs. 3.12±0.38 mL/m2, t=2.157, 4.278, 3.973, p<0.05). The observation group had lower levels of brain natriuretic peptide and C-reactive protein compared to the control group (425.35±55.71 vs. 589.36±70.24 pg/mL; 15.13±1.03 vs. 21.64±2.74 mg/L; t=11.570, 14.066, p=0.000). There was no statistical significance in the incidence of adverse cardiovascular events between the two groups (2.50% vs. 7.50%, χ2=1.920, p=0.166). CONCLUSIONS: The use of ticagrelor can regulate myocardial microcirculation and improve cardiac function in STEMI patients undergoing PCI.

[Identification model of tooth number abnormalities on pediatric panoramic radiographs based on deep learning].

Objective: To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning. Methods: Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results: The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions: In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.

Information-based continuous nursing on pregnant women with gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a serious pregnancy complication, and women with undiagnosed diabetes mellitus can develop chronic hyperglycemia during pregnancy. The purpose of this study is to investigate the impact of information-based continuity of care on glucose levels, health awareness, and maternal and infant outcomes in pregnant women with GDM, thereby providing a basis for the clinical implementation of effective interventions for GDM to reduce or avoid adverse outcomes due to GDM. PATIENTS AND METHODS: One hundred and sixty cases of pregnant women with GDM who underwent treatment in the obstetrics and gynecology department of our hospital from June 2019 to September 2021 were randomly selected as the study population and divided into the control group (n=80) and the study group (n=80). Women in the control group were received with conventional nursing intervention, and those in the study group were obtained with information-based continuity of care on the basis of the control group. Basic clinical data were collected. The levels of fasting blood glucose (FBG), 2h postprandial glucose (2hPG), knowledge of health education, treatment compliance scores, and changes in delivery outcomes were compared between the two groups. According to the maternal blood glucose control level, 160 pregnant women with GDM were divided into the better control group (143 cases) and the poor control group (17 cases). The risk factors affecting the level of maternal glycemic control in gestational diabetes were analyzed. RESULTS: After the intervention, the levels of FBG and 2hPG were significantly lower in both groups than those before the intervention, while the levels of FBG and 2hPG in the study group were notably lower than those in the control group. The health education knowledge score and treatment compliance score after the intervention were significantly higher than those before the intervention, and the health education knowledge score and treatment compliance score in the study group were observably higher than those in the control group (p<0.01). The adverse pregnancy outcomes of pregnant women in the study group were significantly reduced compared with those in the control group (p<0.05). Logistic regression analysis showed that body mass index (BMI), dietary control, literacy, and information-based continuity of care were all influential factors for maternal glycemic control level (p<0.05). Among the influencing factors, dietary control and continuity of care had clinical value in predicting maternal glycemic control levels in gestational diabetes. CONCLUSIONS: Continuous nursing based on informatization can effectively control the blood glucose level of pregnant women with GDM, improve the treatment compliance of pregnant women and the awareness rate of gestational diabetes knowledge so as to reduce the occurrence of adverse pregnancy outcomes and improve the health level. In addition, BMI and dietary control are independent risk factors that affect the blood glucose control level of pregnant women. Relevant intervention measures should be formulated according to the relevant influencing factors to effectively control the blood glucose level of pregnant women with GDM and improve maternal and infant outcomes.

Diagnosis of spinal dural arteriovenous fistula: a multimodal MRI assessment strategy.

AIM: To identify more specific screening indicators at magnetic resonance imaging (MRI) for the diagnosis of spinal dural arteriovenous fistulas (SDAVFs) and to determine an efficient diagnostic strategy. MATERIALS AND METHODS: This retrospective study analysed clinical and imaging data of patients diagnosed with SDAVF and alternative myelopathy who underwent conventional MRI examinations. Additionally, three-dimensional (3D) T2-weighted sampling perfection with application-optimised contrasts using different flip-angle evolutions (3D-T2-SPACE) and contrast-enhanced magnetic resonance angiography (CE-MRA) data from patients with SDAVF were compared with digital subtraction angiography (DSA) data. RESULTS: The age of onset, perimedullary flow voids (PFV), distribution of lesions, syringomyelia, degree of spinal oedema, and cauda equina disorder (CED) were factors that showed statistically significance in the identification of SDAVF with alternative myelopathy. After controlling for age, gender, PFV, degree of spinal cord swelling, and syringomyelia, the multivariable ordinal logistic regression model showed that the CED sign (OR = 32.46; 95% confidence interval [CI]: 2.47-427.15; p=0.008) was an independent predictor for SDAVF. The diagnostic model constructed using the PFV and CED signs had better diagnostic performance, with an area under the curve of 0.957 (p<0.001), maximum Youden index of 0.844, sensitivity of 92.9%, and specificity of 91.5%. Both 3D-T2-SPACE (77.8%) and CE-MRA (83.3%) sequences had good localisation values for SDAVF. Combining the two imaging examinations had better diagnostic accuracy than that of DSA. CONCLUSION: CED and PFV on conventional MRI were specific indicators for the diagnosis of SDAVF. To compensate for the lack of fistula localisation on conventional MRI, 3D-T2-SPACE and CE-MRA can be used. Together they complement each other and have good diagnostic potential.

Tissue Distribution of mtDNA Copy Number And Expression Pattern of An mtDNA-Related Gene in Three Teleost Fish Species.

Teleosts are the most speciose vertebrates and have diverse swimming performance. Based on swimming duration and speed, teleosts are broadly divided into sustained, prolonged, and burst swimming fish. Teleosts with different swimming performance have different energy requirements. In addition, energy requirement also varies among different tissues. As mitochondrial DNA (mtDNA) copy number is correlated with ATP production, we speculated that mtDNA copy number varies among fish with different swimming performance, as well as among different tissues. In other species, mtDNA copy number is regulated by tfam (mitochondrial transcription factor A) through mtDNA compaction and mito-genome replication initiation. In order to clarify the tissue distribution of mtDNA copy number and expression pattern of tfam in teleosts with disparate swimming performance, we selected representative fish with sustained swimming (Pseudocaranx dentex), prolonged swimming (Takifugu rubripes), and burst swimming (Paralichthys olivaceus). We measured mtDNA copy number and tfam gene expression in 10 tissues of these three fish. The results showed the mtDNA content pattern of various tissues was broadly consistent among three fish, and high-energy demanding tissues contain higher mtDNA copy number. Slow-twitch muscles with higher oxidative metabolism possess a greater content of mtDNA than fast-twitch muscles. In addition, relatively higher mtDNA content in fast-twitch muscle of P. olivaceus compared to the other two fish could be an adaptation to their frequent burst swimming demands. And the higher mtDNA copy number in heart of P. dentex could meet their oxygen transport demands of long-distance swimming. However, tfam expression was not significantly correlated with mtDNA copy number in these teleosts, suggesting tfam may be not the only factor regulating mtDNA content among various tissues. This study can lay a foundation for studying the role of mtDNA in the adaptive evolution of various swimming ability in teleost fish.

[Clinical features of non-cirrhotic portal hypertension in patients with common variable immunodeficiency].

We wished to summarize the clinical features of common variable immunodeficiency (CVID) complicated by non-cirrhotic portal hypertension (NCPH) and to deepen our understanding of it. The case data of CVID complicated with NCPH admitted to Peking Union Medical College Hospital from January 1983 to May 2021 were analyzed retrospectively to summarize their clinical characteristics. Six patients with CVID combined with NCPH (three of each sex; 16-45 years) were assessed. Four patients had portal hypertension. All patients had anemia, splenomegaly, a normal serum level of albumin and transaminases, and possibly increased levels of alkaline phosphatase and gamma-glutamyl transpeptidase. Two patients were diagnosed with esophagogastric fundic varices by gastroscopy. Two patients underwent splenectomy (which improved hematologic abnormalities partially). Four patients had autoimmune disease. Two cases were diagnosed with nodular regenerative hyperplasia (NRH) upon liver biopsy. Six patients were administered intravenous immunoglobulin-G (0.4-0.6 g/kg bodyweight) once every 3-4 weeks as basic therapy. Often, CVID complicated with NCPH has: (1) The manifestations of portal hypertension as the primary symptom. (2) Autoimmune-related manifestations. Imaging can provide important diagnostic clues. The etiology may be related to hepatic NRH and splenomegaly due to recurrent infections.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Analysis of changes in reporting and diagnosis of pulmonary tuberculosis among children in Liangshan Yi Autonomous Prefecture, Sichuan Province from 2019 to 2021].

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.