Points of interest linear attention network for real-time non-rigid liver volume to surface registration.

BACKGROUND: In laparoscopic liver surgery, accurately predicting the displacement of key intrahepatic anatomical structures is crucial for informing the doctor's intraoperative decision-making. However, due to the constrained surgical perspective, only a partial surface of the liver is typically visible. Consequently, the utilization of non-rigid volume to surface registration methods becomes essential. But traditional registration methods lack the necessary accuracy and cannot meet real-time requirements. PURPOSE: To achieve high-precision liver registration with only partial surface information and estimate the displacement of internal liver tissues in real-time. METHODS: We propose a novel neural network architecture tailored for real-time non-rigid liver volume to surface registration. The network utilizes a voxel-based method, integrating sparse convolution with the newly proposed points of interest (POI) linear attention module. POI linear attention module specifically calculates attention on the previously extracted POI. Additionally, we identified the most suitable normalization method RMSINorm. RESULTS: We evaluated our proposed network and other networks on a dataset generated from real liver models and two real datasets. Our method achieves an average error of 4.23 mm and a mean frame rate of 65.4 fps in the generation dataset. It also achieves an average error of 8.29 mm in the human breathing motion dataset. CONCLUSIONS: Our network outperforms CNN-based networks and other attention networks in terms of accuracy and inference speed.

Eliminating mother-to-child transmission of hepatitis B virus: practice and progress in Baoan, a national pilot district of China.

BACKGROUND: While mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years. METHODS: Data was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT. RESULTS: From 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of - 3.50 (95% CI -6.28 ~ - 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk. CONCLUSIONS: The implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.

Trophoblastic mitochondrial DNA induces endothelial dysfunction and NLRP3 inflammasome activation: Implications for preeclampsia.

AIMS: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE. MATERIALS AND METHODS: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O2) or hypoxic conditions (1 % O2 for 48 h) for subsequent treatments. Primary human umbilical veinendothelial cells (HUVECs) were isolated from the human umbilical cord and then exposed to a vehicle (phosphate-buffered saline [PBS]), mtDNA, hypo-mtDNA, or hypo-mtDNA with INF39 (nucleotide oligomerisation domain-like receptor family pyrin domain containing 3 [NLRP3]-specific inhibitor) for 12 h before flow cytometry and immunoblotting. The effects of trophoblastic mtDNA on the endothelium were further analysed in vivo using enzyme-linked immunosorbent assay (ELISA) and vascular reactivity assay. The effects of mtDNA on vascular phenotypes were also tested on NLRP3 knockout mice. RESULTS: Elevated interleukin (IL)-1ß in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1ß p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1ß levels and endothelium-dependent vasodilation in mice. CONCLUSION: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1ß signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE.

Bilateral occurrence of sperm granulomas in the left spermatic cord and on the right epididymis: A case report.

BACKGROUND: Sperm granuloma is a rare disease in clinical andrology and its incidence is still unclear worldwide. According to the existing literature, sperm granuloma often occurs unilaterally. Clinical and ultrasound features are similar to epididymal tuberculosis, chronic epididymitis and other diseases. Sperm granuloma is usually diagnosed based on postoperative histopathological and immunohistochemical examination. CASE SUMMARY: A 46-year-old man was admitted to the hospital due to the presence of a left scrotal mass for 3 mo and aggravation of pain for 1 wk. The lesions at both sites were surgically resected. Postoperative pathological examination showed that the left spermatic cord mass and the right epididymal mass were consistent with sperm granuloma. The sperm granulomas then recurred 3 mo after surgery. There is little change in the local mass so far. CONCLUSION: The case report is helpful for our understanding of this disease. In clinical diagnosis, it should be distinguished from epididymal tuberculosis, chronic epididymitis and other diseases. Color Doppler ultrasound can be used as a preferred examination method but postoperative pathological examination is still needed for diagnosis.

iNOS regulates activation of the NLRP3 inflammasome through the sGC/cGMP/PKG/TACE/TNF-α axis in response to cigarette smoke resulting in aortic endothelial pyroptosis and vascular dysfunction.

BACKGROUND: Cigarette smoke (CS) is associated with vascular injury and dysfunction, which may be mediated by iNOS and NLRP3. However, the exact mechanism is unknown. METHODS: iNOS-knockout and NLRP3-knockout C57BL/6 mice were exposed to air or CS. The vascular structure was examined by hematoxylin-eosin staining. The vascular tension was measured by a vascular reactivity assay. The expression of iNOS, NLRP3, caspase-1p20, IL-1ß and eNOS were measured by western blotting. Human aortic endothelial cells (HAECs) were exposed to L-NIL (iNOS inhibitor), MCC950 (NLRP3 inhibitor), ODQ (sGC inhibitor), KT5823 (PKG inhibitor) or TAPI-1 (TACE/ADAM17 inhibitor) for 1 h prior to cigarette smoke extract (CSE) treatment. The cell viability and lactate dehydrogenase activity were assessed and pyroptosis was determined by scanning electron microscopy. The mRNA expression of TNF-α, and protein expression of iNOS, active-TACE, NLRP3, caspase-1p20, IL-1ß, and eNOS were measured. RESULTS: CS resulted in shrinkage of endothelial cells, impaired aorta relaxation, reduced eNOS expression, and induced expression of iNOS, NLRP3, caspase-1p20 and IL-1ß, which could be prevented by knockdown of iNOS and NLRP3. CSE reduced cell viability, induced LDH release and pyroptosis, and promoted iNOS, NLRP3, caspase-1p20, and IL-1ß expression and reduced eNOS reduction, which could be reversed by inhibition of iNOS or NLRP3 in HAECs. Altogether, activation of the NLRP3 inflammasome by iNOS in CS-exposed HAECs may be mediated by the sGC/cGMP/PKG/TACE/TNF- α pathway. CONCLUSION: These results link iNOS to NLRP3 in CSE-stimulated HAECs through the sGC/cGMP/PKG/TACE/TNF-α pathway. The findings identify a mechanism through which iNOS and NLRP3 contribute to the pathogenesis of CS-induced pyroptosis and impaired aorta relaxation in HAECs.

Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473. However, which site plays the main role in regulating phosphorylation of eNOS Ser1177 is still controversial. The purpose of the present study is to explore the specific regulatory mechanism of phosphorylated Akt in eNOS activation. Inhibition of Akt Thr308 phosphorylation by a specific inhibitor or by siRNA in vitro led to a decrease in eNOS phosphorylation at Ser1177 and to lower NO concentration in the cell culture medium of HUVECs. However, inhibiting p-Akt Ser473 had no effect on eNOS phosphorylation at Ser1177. Next, we administered mice with inhibitors to downregulate p-Akt Ser473 or Thr308 activity. Along with the inhibition of p-Akt Thr308, vascular p-eNOS Ser1177 protein was simultaneously downregulated in parallel with a decrease in plasma NO concentration. Additionally, we cultured HUVECs at various temperature conditions (37, 22, and 4 °C). The results showed that p-Akt Ser473 was gradually decreased in line with the reduction in temperature, accompanied by increased levels of p-Akt Thr308 and p-eNOS Ser1177. Taken together, our study indicates that the phosphorylation of Akt at Thr308, but not at Ser473, plays a more significant role in regulating p-eNOS Ser1177 levels under physiological conditions.

Differential diagnosis of coronavirus disease 2019 pneumonia or influenza A pneumonia by clinical characteristics and laboratory findings.

BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.

Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient.

We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.

Investigation of antibiotic resistance determinants and virulence factors of uropathogenic Escherichia coli.

Multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) are prevalent throughout the world resulting in a major public health burden. In this research, we isolated and identified 28 MDR UPEC from one university hospital in China, investigated MDR and pathogenic mechanisms by PCR, including 55 antibiotic resistance determinants (ARDs) genes, 13 genetic markers of mobile genetic elements (MGEs) and 6 virulence factors (VFs) genes. In these isolates, we identified 23 ARDs genes and 6 genetic markers of MGEs that played a key role in MDR phenotypes. In addition, we found 2 VFs genes, hofQ and ompT, which could be associated with pathogenicity and invasiveness of these strains in urinary tract infections (UTIs).

Effect of glucose, soya oil and glutamine on protein expression and mammalian target of rapamycin complex 1 pathway of jejunal crypt enterocytes in weaned piglets.

The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isoenergetic diets formulated with glucose, soya oil or glutamine for 28 d. On day 14 or 28, the proteins in crypt enterocytes were analysed with isobaric tags for relative and absolute quantification and proteins involved in mTORC1 signalling pathway in villus or crypt compartment cells were determined by Western blotting. Our results showed no significant differences (P > 0·05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of eukaryotic initiation factor-4E binding protein-1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soya oil. On day 28, higher protein expression of phosphor-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soya oil. In conclusion, the isoenergetic glucose, soya oil or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared with soya oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better understand the molecular mechanisms of JAK/STAT signaling pathway in antifungal immune response in silkworm.

[Th17 and Treg cell levels in patients with sarcoidosis and their relation to disease activation].

OBJECTIVE: To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment. METHODS: Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated. RESULTS: Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all P<0.01). After the treatment of glucocorticoids, these index in peripheral blood were significantly improved (Th17 cells 2.16% ± 0.68%，Treg cells 2.21% ± 0.42%, ROR-γt mRNA 10.15 ± 1.93, Foxp3 mRNA 2.44 ± 0.38) ( all P<0.05). The changing trends of Th17 and Treg cell cytokines levels in serum were consistent with two type cells. Meanwhile, the changing trends of above index in BALF of patients treated by glucocorticoids were consistent with those in sarcoidosis patients in active stage. The increased ratios of Th17 cells to Treg cells were positively correlated with the level of serum SACE (r= 0.781). CONCLUSION: The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis, which was associated with the activity of disease, and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance.

Presence of autoantibodies against ß1-adrenoceptor aggravates the kidney injury in rats.

Since the autoantibodies against the second extracellular loop of ß(1)-adrenoceptor (ß(1)-AABs) have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDCM), the involvement of autoimmune mechanisms in the pathogenesis of many cardiovascular diseases has extensively been investigated. Our previous study found that urinary occult blood and protein excretion were frequently found in the rats with positive ß(1)-AABs, but the mechanisms are unclear. Therefore, we infused the ß(1)-AABs into the vein periodically in an attempt to investigate whether ß(1)-AABs could induce morphological and functional changes in the kidneys of adult and aged rats and explore the possible mechanisms. The synthetic peptide according to the sequences of the second extracellular loop of ß(1)-adrenoceptor (ß(1)-AR-ECII) was used to immunize the adult rats to acquire enough ß(1)-AABs for use. Neonatal rat ventricular myocytes (NRVMs) culture was used to observe the biological effects of ß(1)-AABs on the beating rate. The purified ß(1)-AABs were transfused into the vein of rats. The sera level of blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), urinary specific gravity, protein excretion, occult blood and urinary glucose were detected at the different time points by biochemistry and urine analyzers. HE and Masson's trichrome staining were used to detect the changes in kidney structure of passively immunized rats. Enhanced green fluorescent protein (EGFP) and ß(1)-AR-EGFP plasmids were transfected into the human embryonic kidney 293 (HEK293) cells in order to observe the changes in cell injury with the treatment of ß(1)-AABs. It was found that the sera level of BUN, CR and UA increased gradually and the ratio of BUN to CR decreased progressively with the administration of ß(1)-AABs. The increasing of proteinuria, urinary occult blood and urinary glucose was detected by urine analyzer in ß(1)-AABs group. By HE and Masson's coloration, lots of mononuclear cell infiltration and collagen fibers deposition could be observed at the 24th week of immunization. After the treatment of ß(1)-AABs, the caspase-3 activity increased significantly in the HEK293 cells transfected with ß(1)-AR-EGFP plasmids, while no significant changes were observed for lactate dehydrogenase (LDH) activity. The results indicate that long-term presence of ß(1)-AABs can induce the morphological and functional damage of the kidneys in adult and aged rats.

The Value of Survivin Gene and Proliferation of Hepatocytes in Screening for Hepatocellular Carcinoma.

BACKGROUND: The prospective surveillance programs on patients with liver diseases based on repeat ultrasound examinations of liver and serum α-fetoprotein (AFP) detection were reported having the probability of finding hepatocellular carcinoma (HCC) at its early stage, but it is time-consuming and not cost-effective. To improve the effectiveness and cost-effective of HCC surveillance program, close monitoring has been focused on patients with liver cirrhosis who have particularly high risk of HCC development. It has been found that high liver cell proliferation is a reliable predictor of HCC development, and survivin is a new gene with the role of suppressing apoptosis which has been studied mostly over the past few years. This study aimed to evaluate the usefulness of proliferation cell nuclear antigen (PCNA) and survivin detection in the process of screening cirrhotic patients with high risk of HCC development. METHODS: Total RNA was extracted from fresh specimens of HCC and liver cirrhosis. Survivin mRNA amplification was performed by reverse transcription polymerase chain reaction (RT-PCR). Immunostaining for PCNA was employed to assess liver cell proliferation activity in formalin-fixed, paraffin embedded liver specimens. Five liver specimens obtained from patients operated for hemangioma were used as normal control. The PCNA labeling index was determined as the mean value of positive cells in ten different microscopic fields. RESULTS: RT-PCR was performed in 17 HCC and 10 liver cirrhosis specimens, 11 HCC specimens showed 344bps molecular survivin DNA band in 1% agarose electrophoresis, but none of liver cirrhosis specimens showed positive band. The survivin positive rate in HCC specimens was 64.7% (11/17); The PCNA labeling index was 2.38 ± 2.11 in 30 liver cirrhosis specimens, while 10.08 ± 12.28 in 30 HCC specimens, the latter was significantly higher than the former, P = 0.003. The median PCNA labeling index of 11 survivin positive HCC specimens was 6.8 (from 0.5 to 40), which is significantly higher than that of 6 survivin negative HCC specimens (2.15). CONCLUSIONS: Survivin expressed in HCC tissues but not in liver cirrhosis tissues, this phenomenon indicates that the gene expression may occur at the late phase of liver cell cancer transformation. Compared with survivin detection, the PCNA detection on liver cells of cirrhosis patients is better to differentiate high-risk HCC transformation among liver cirrhosis patients.