UCHL1 contributes to insensitivity to endocrine therapy in triple-negative breast cancer by deubiquitinating and stabilizing KLF5.

BACKGROUND: Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that regulates ERα expression in triple-negative cancer (TNBC). This study aimed to explore the deubiquitination substrates of UCHL1 related to endocrine therapeutic responses and the mechanisms of UCHL1 dysregulation in TNBC. METHODS: Bioinformatics analysis was conducted using online open databases. TNBC representative MDA-MB-468 and SUM149 cells were used for in vitro and in-vivo studies. Co-immunoprecipitation was used to explore the interaction between UCHL1 and KLF5 and UCHL1-mediated KIF5 deubiquitination. CCK-8, colony formation and animal studies were performed to assess endocrine therapy responses. The regulatory effect of TET1/3 on UCHL1 promoter methylation and transcription was performed by Bisulfite sequencing PCR and ChIP-qPCR. RESULTS: UCHL1 interacts with KLF5 and stabilizes KLF5 by reducing its polyubiquitination and proteasomal degradation. The UCHL1-KLF5 axis collaboratively upregulates EGFR expression while downregulating ESR1 expression at both mRNA and protein levels in TNBC. UCHL1 knockdown slows the proliferation of TNBC cells and sensitizes the tumor cells to Tamoxifen and Fulvestrant. KLF5 overexpression partially reverses these trends. Both TET1 and TET3 can bind to the UCHL1 promoter region, reducing methylation of associated CpG sites and enhancing UCHL1 transcription in TNBC cell lines. Additionally, TET1 and TET3 elevates KLF5 protein level in a UCHL1-dependent manner. CONCLUSION: UCHL1 plays a pivotal role in TNBC by deubiquitinating and stabilizing KLF5, contributing to endocrine therapy resistance. TET1 and TET3 promote UCHL1 transcription through promoter demethylation and maintain KLF5 protein level in a UCHL1-dependent manner, implying their potential as therapeutic targets in TNBC.

Integrating machine learning algorithms to systematically assess reactive oxygen species levels to aid prognosis and novel treatments for triple -negative breast cancer patients.

Introduction: Breast cancer has become one of the top health concerns for women, and triple-negative breast cancer (TNBC) leads to treatment resistance and poor prognosis due to its high degree of heterogeneity and malignancy. Reactive oxygen species (ROS) have been found to play a dual role in tumors, and modulating ROS levels may provide new insights into prognosis and tumor treatment. Methods: This study attempted to establish a robust and valid ROS signature (ROSig) to aid in assessing ROS levels. The driver ROS prognostic indicators were searched based on univariate Cox regression. A well-established pipeline integrating 9 machine learning algorithms was used to generate the ROSig. Subsequently, the heterogeneity of different ROSig levels was resolved in terms of cellular communication crosstalk, biological pathways, immune microenvironment, genomic variation, and response to chemotherapy and immunotherapy. In addition, the effect of the core ROS regulator HSF1 on TNBC cell proliferation was detected by cell counting kit-8 and transwell assays. Results: A total of 24 prognostic ROS indicators were detected. A combination of the Coxboost+ Survival Support Vector Machine (survival-SVM) algorithm was chosen to generate ROSig. ROSig proved to be the superior risk predictor for TNBC. Cellular assays show that knockdown of HSF1 can reduce the proliferation and invasion of TNBC cells. The individual risk stratification based on ROSig showed good predictive accuracy. High ROSig was identified to be associated with higher cell replication activity, stronger tumor heterogeneity, and an immunosuppressive microenvironment. In contrast, low ROSig indicated a more abundant cellular matrix and more active immune signaling. Low ROSig has a higher tumor mutation load and copy number load. Finally, we found that low ROSig patients were more sensitive to doxorubicin and immunotherapy. Conclusion: In this study, we developed a robust and effective ROSig model that can be used as a reliable indicator for prognosis and treatment decisions in TNBC patients. This ROSig also allows a simple assessment of TNBC heterogeneity in terms of biological function, immune microenvironment, and genomic variation.

Volcanic contribution to the 1990s North Pacific climate shift in winter.

It is debatable whether external forcing can change the state of the climate. By investigating decadal changes with and without including the 1990s stratospheric volcanic aerosols, we explored the volcanic eruptions contribution to decadal climate regime shifts occurring in boreal winter over the North Pacific. The volcanic eruptions contribution can be characterized as a series of rapid changes, including the strengthening and poleward shift of the midlatitude westerly jet stream. In addition to the short-lived radiative effects primarily induced by the 1991 Mount Pinatubo eruption, the volcanically driven decadal change can be observed in the mid-to-late 1990s, suggesting a time-lagged characteristic of the volcanic climate impact. Compared with the decadal change irrelevant to volcanic eruption, the decadal state more dramatically enters into the next phase when volcanic forcing is included. The climate oscillation-related pattern shifts that occurred across the 1990s can provide insights into volcanically induced changes in decadal atmospheric circulation.

Permafrost in the Cretaceous supergreenhouse.

Earth's climate during the last 4.6 billion years has changed repeatedly between cold (icehouse) and warm (greenhouse) conditions. The hottest conditions (supergreenhouse) are widely assumed to have lacked an active cryosphere. Here we show that during the archetypal supergreenhouse Cretaceous Earth, an active cryosphere with permafrost existed in Chinese plateau deserts (astrochonological age ca. 132.49-132.17 Ma), and that a modern analogue for these plateau cryospheric conditions is the aeolian-permafrost system we report from the Qiongkuai Lebashi Lake area, Xinjiang Uygur Autonomous Region, China. Significantly, Cretaceous plateau permafrost was coeval with largely marine cryospheric indicators in the Arctic and Australia, indicating a strong coupling of the ocean-atmosphere system. The Cretaceous permafrost contained a rich microbiome at subtropical palaeolatitude and 3-4 km palaeoaltitude, analogous to recent permafrost in the western Himalayas. A mindset of persistent ice-free greenhouse conditions during the Cretaceous has stifled consideration of permafrost thaw as a contributor of C and nutrients to the palaeo-oceans and palaeo-atmosphere.

Tuning intramolecular charge transfer and spin-orbit coupling of AIE-active type-I photosensitizers for photodynamic therapy.

Development of photosensitizers (PSs) featuring type-I reactive oxygen species (ROS) with aggregation-induced emission (AIE) properties is a judicious approach to overcome the deficit of conventional photodynamic therapy (PDT). However, it remains a challenge to design AIE-active type-I ROS PSs using a simple theranostic scaffold paired with a delicate balance between intramolecular charge transfer (ICT) and large spin-orbit coupling (SOC) features to facilitate intersystem crossing (ISC) and hence to intensify triplet excitons for type-I ROS generation as well as to improve optical properties for the desired biomedical applications. In this work, a rationally designed series of PSs based on C-6-substituted tetraphenylethylene-fused benzothiazole-coumarin scaffolds, named TPE-nCUMs, were synthesized via a fused-ring-electron-acceptor (FREA) strategy, endowed with AIE properties in aqueous solution and thus self-monitoring type-I ROS generation under white-light irradiation to study the effects of diverse ICT and SOC potentials on their photochemical and optical properties. Both experimental and theoretical results revealed that the concomitantly increasing strengths of both ICT and SOC features promote type-I ROS generation by TPE-nCUMs. The key role of the SOC-promoting carbonyl group towards the ROS generation ability of TPE-nCUMs was then examined. Among TPE-nCUMs, gem-2OMe-TPE-2CUM displayed highly efficient type-I ROS generation. Importantly, gem-OMe-TPE-1CUM acts as a fluorescent indicator in HeLa cells (in vitro), revealing its excellent diffusion capability in both lysosomal and mitochondrial organelles with low dark toxicity, high cytotoxicity under white-light and remarkable PDT efficiency. Our study has thus elucidated a rationally designed strategy at the molecular level to fine-tune ICT and SOC features for the advance of AIE-active type-I ROS PSs, opening a new avenue for cancer treatment and image-guided therapy.

Study on Sentinel Lymph Node and Its Lymphatic Drainage Pattern of Breast Cancer by Contrast-Enhanced Ultrasound.

OBJECTIVES: Sentinel lymph node (SLN) and its lymphatic drainage pattern (LDP) of breast cancer were studied by contrast-enhanced ultrasound (CEUS). METHODS: From July 2017 to December 2019, patients with SLN localization of breast cancer in Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital were selected. The sentinel lymph system of breast cancer was observed by CEUS before both operation and blue staining in the surgery. The location, number, and route of sentinel lymphatic channel (SLC) were recorded, along with the number, size, and the depth from skin of SLN. LDPs were summarized according to these basic characteristics of SLC and SLN. RESULTS: A total of 368 cases were included; 465 SLCs and 423 SLNs were detected. Most of the SLCs were originated from the outer upper quadrant of areola. Eleven LDPs were found, including 31 subtypes of LDPs. There were 6 cases of type A (1.63%), 15 cases of type B (4.08%), 223 cases of type C (57.88%), 38 cases of type D (10.33%), 2 cases of type E (0.54%), 3 cases of type F (0.82%), 50 cases of type G (13.59%), 30 cases of type H (8.15%), 2 cases of type I (0.54%), 6 cases of type J (1.63%), and 3 cases of type K (0.82%). CONCLUSIONS: The most common LDP of breast cancer was one SLC originated from the upper quadrant of areola with one SLN. CEUS can identify the LDP before surgery to reduce the false negative rate of SLN biopsy.

Role of eccentricity in early Holocene African and Asian summer monsoons.

The effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro-Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced "dry-gets-wetter" condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India-Pakistan region are unrelated to early-Holocene eccentricity.

miR-183-5p Aggravates Breast Cancer Development via Mediation of RGS2.

This study mainly explores how miR-183-5p pertains to breast cancer (BC) development. Functional assays were employed to test impacts of miR-183-5p in this cancer. Targeting between RGS2 and miR-183-5p was examined with dual-luciferase assay, and how their interaction pertains to cancer progression was further unraveled. miR-183-5p level was noticeably high in cancer tissue/cells. Overexpressing miR-183-5p could remarkably deteriorate cancer progression. The regulatory gene RGS2 levels was markedly low in BC, and two genes we researched were negatively correlated. It was uncovered by rescue assay that miR-183-5p/RGS2 axis mediated tumor-relevant behaviors in BC. Altogether, miR-183-5p aggravates BC development via mediation of RGS2. miR-183-5p supplies a promising target for BC therapy.

The value of contrast-enhanced ultrasound in determining the location of sentinel lymph nodes in breast cancer.

BACKGROUND: This study aimed to explore the sentinel lymph node (SLN) identification rate in breast cancer by subcutaneous and intradermal injection of ultrasound contrast agent in the mammary areola region, compared to the results achieved with methylene blue (MB). METHODS: A total of 390 breast cancer patients with planned sentinel lymph node biopsy from our breast surgery department from July 2017 to February 2019 were enrolled. All patients were subjected to preoperative contrast-enhanced ultrasound (CEUS), that involved an intracutaneous injection of 1 mL ultrasonic contrast agent (UCA) at 3 and 6 o 'clock, as well as a subcutaneous injection of 1 mL UCA at 9 and 12 o'clock. The enhanced lymph nodes along the enhanced lymphatic vessels from the mammary areola were traced. The number of enhanced lymph nodes were recorded, and an ultrasound-guided injection of 1:10 diluted carbon nanoparticles were used to mark all first site enhanced lymph nodes (i.e., SLNs). An intraoperative dye method (MB) was used to track the SLNs and the results were compared with the CEUS findings. RESULTS: Among the 390 cases of breast cancer, enhanced SLNs were observed in 373 patients after an injection of UCA with an identification rate of 95.64 % (373/390), compared to the identification rate of 92.05 % (359/390) using the intraoperative MB. The difference between the two methods was statistically significant (P = 0.016). And among the 390 patients, a total of 808 enhanced lymph nodes were traced by preoperative CEUS, with a median of 2 (1,3). A total of 971 blue-stained lymph nodes were traced using the intraoperative MB, with a median of 2 (2,3), indicating a statistically significant difference (p < 0.001). CONCLUSIONS: Intradermal and subcutaneous injections of UCA in the mammary areola region may have clinical application value for the identification and localization of SLNs in breast cancer patients. The identification rate is higher than that of blue dye method, which can be used as a new tracer of sentinel lymph node biopsy and complement other staining methods to improve the success rate.

LINC00261/microRNA-550a-3p/SDPR axis affects the biological characteristics of breast cancer stem cells.

Long non-coding RNAs (lncRNAs) have been shown to play key roles in the pathogenesis of breast cancer (BC). The study was to explore the effect of long non-coding RNA LINC00261/microRNA (miR)-550a-3p/serum deprivation response (SDPR) axis on the biological characteristics of BC stem cells (BCSCs). BC and adjacent normal tissues of patients were collected. LINC00261, miR-550a-3p and SDPR expression in BC tissues and cell lines and CD24 and CD44 expression in BC tissues was detected. CD44+ /CD24-/low BCSCs were sorted. CD44+ /CD24-/low MDA-MB-231 and MCF-7 cells were screened and transfected with altered expression of LINC00261 or miR-550a-3p to explore their roles in cell viability, microsphere (MS) formation ability, migration and invasion of CD44+ /CD24-/low BCSCs. The targeting relationships of LINC00261, miR-550a-3p and SDPR were detected. Reduced LINC00261, decreased SDPR and elevated miR-550a-3p exhibited in BC tissues of patients and cell lines. Elevated CD44+/ CD24- were present in BC tissues. LINC00261 up-regulated SDPR expression as a sponge of miR-550a-3p. Elevated LINC00261 suppressed BC cell viability, MS formation ability, migration and invasion of CD44+ /CD24-/low BCSCs. Moreover, up-regulated miR-550a-3p reversed the inhibitive effect of elevated LINC00261 on BCSCs, and reduced SDPR reversed the promotive effect of decreased miR-550a-3p on BCSCs. The study highlights that LINC00261 can adsorb miR-550a-3p to modulate SDPR, thus inhibiting the viability and MS formation of BC cells, reducing migration and invasion of CD44+ /CD24-/low BCSCs, exerting a potential effect on therapy.

CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer.

Immunogenic cell death (ICD) improves the T cell response against different tumors, indicating that ICD can enhance the antitumor immunity elicited by the anti-checkpoint antibody anti-programmed death 1 (anti-PD-1). In the present study, we reported a synergistic and durable immune-mediated antitumor response elicited by the combined treatment of SR-4835, a CDK12/13 specific inhibitor, with PD-1 blockade in a syngeneic mouse model. The developed combination therapy elicited antitumor activity in immunocompetent mouse tumor models. Furthermore, the SR-4835-treated tumor cells exhibited characteristics of ICD, including the release of high mobility group box 1 (HMGB1) and ATP and calreticulin (CRT) translocation. This activity led to a significant T-cell-dependent tumor suppression. The enhanced dendritic cell (DC) and infiltration of T cells activation in the tumors treated with both SR-4835 and anti-PD-1 indicate that this combination treatment promotes an improved immune response. Therefore, the results of the present study demonstrate the potential of CDK12/13 inhibition combined with checkpoint inhibition in breast cancer treatment.

AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion.

Breast cancer (BC) is a type of malignant tumor originating from the epithelial tissue of the mammary gland, and about 20% of breast cancers are human epidermal growth factor receptor 2 positive (HER2+), which is a subtype with more aggression. Recently, HER2-positive breast cancer is often accompanied by poor prognosis of patients, and targeted therapy showed a promising prospect. To combat this disease, novel therapeutic targets are still needed. Adenylate kinase 4 (AK4) is a member of the adenylate kinase family and is expressed in the mitochondrial matrix. AK4 is involved in multiple cellular functions such as energy metabolism homeostasis. Interestingly, AK4 was observed highly expressed in several tumor tissues, and the involvement of AK4 in cancer development was generally revealed. However, the possible role of AK4 on the growth and development of breast cancer is still unclear. Here, we investigated the possible functions of AK4 on the progression of HER2-positive breast cancer. We found the high expression of AK4 in HER2-positive breast cancer tissues from patients who received surgical treatment. Additionally, AK4 expression levels were obviously correlated with clinical-pathological features, including pTNM stage (P = 0.017) and lymph node metastasis (P = 0.046). We mechanically confirmed that AK4 depletion showed the obvious impairment of cell proliferation and invasion in MCF7 and MDA-MB-231 cells. AK4 also facilitates tumor growth and metastasis of HER2-positive breast cancer in vivo. In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer.

SYCP2 expression is a novel prognostic biomarker in luminal A/B breast cancer.

AIM: To explore the prognostic value of synaptonemal complex protein-2 (SYCP2) in different subtypes of breast cancer. Patients & materials: In silico bioinformatic analysis was conducted using large databases. RESULTS: SYCP2 was only significantly upregulated in luminal B tumors compared with the adjacent normal tissues. SYCP2 expression was an independent indicator of shorter overall survival in luminal A patients (hazard ratio: 2.269; 95% CI: 1.059-4.862; p = 0.035) and luminal B patients (hazard ratio: 2.546; 95% CI: 1.020-6.355; p = 0.045). Its expression was negatively correlated with the methylation status of multiple CpG sites (cg22214414, cg23241473 and cg07347645) in both luminal A and luminal B tumors. CONCLUSION: Increased SYCP2 expression might be an independent indicator of shorter overall survival in both luminal A and luminal B patients.

Paleoclimatic information recorded in fluid inclusions in halites from Lop Nur, Western China.

The homogenization temperature (Th) of primary fluid inclusions in halite can be used for paleoclimate interpretations. Lop Nur, in Central Asia, is an extremely arid zone where large amounts of glauberite were deposited from the late Middle to Late Pleistocene. This deposition was accompanied by formation of large-scale potash-bearing brines. However, quantitative paleotemperature data are still lacking, hindering reconstruction of Quaternary climate conditions and their control over potash formation. We measured the Th of inclusions in halite from the salt field and the top of Upper Pleistocene strata in Lop Nur. The maximum homogenization temperature (Th MAX) of inclusions in halite from the salt field was 41.1 °C, consistent with the maximum ambient temperature (43.4 °C) in the same period. The Th MAX of inclusions in halite from the Upper Pleistocene strata ranged from 35.6 °C to 43 °C, where maximum air temperatures may have reached 37.9 °C to 45.3 °C. The results show that a hot and arid climate prevailed in Lop Nur at the end of the Late Pleistocene. Furthermore, changes of the brine chemical composition due to supply variations instead of climate change, may have caused glauberite deposition to cease at the end of the Late Pleistocene.

Long Non-Coding RNA (lncRNA) Urothelial Carcinoma-Associated 1 (UCA1) Enhances Tamoxifen Resistance in Breast Cancer Cells via Inhibiting mTOR Signaling Pathway.

BACKGROUND Long non-coding RNA (lncRNA) UCA1 is an oncogene in breast cancer. The purpose of this study was to investigate the role of UCA1 in tamoxifen resistance of estrogen receptor positive breast cancer cells. MATERIAL AND METHODS Tamoxifen sensitive MCF-7 cells were transfected for UCA1 overexpression, while tamoxifen resistant LCC2 and LCC9 cells were transfected with UCA siRNA for UCA1 knockdown. qRT-PCR was performed to analyze UCA1 expression. CCK-8 assay, immunofluorescence staining of cleaved caspase-9, and flow cytometric analysis of Annexin V/PI staining were used to assess tamoxifen sensitivity. Western blot analysis was performed to detect p-AKT and p-mTOR expression. RESULTS LncRNA UCA1 was significantly upregulated in tamoxifen resistant breast cancer cells compared to tamoxifen sensitive cells. LCC2 and LCC9 cells transfected with UCA1 siRNA had significantly higher ratio of apoptosis after tamoxifen treatment. UCA1 siRNA significantly decreased the protein levels of p-AKT and p-mTOR in LCC2 and LCC9 cells. Enforced UCA1 expression substantially reduced tamoxifen induced apoptosis in MCF-7 cells, while rapamycin treatment abrogated the protective effect of UCA1. CONCLUSIONS UCA1 upregulation was associated with tamoxifen resistance in breast cancer. Mechanistically, UCA1 confers tamoxifen resistance to breast cancer cells partly via activating the mTOR signaling pathway.

Predictive model for contrast-enhanced ultrasound of the breast: Is it feasible in malignant risk assessment of breast imaging reporting and data system 4 lesions?

AIM: To build and evaluate predictive models for contrast-enhanced ultrasound (CEUS) of the breast to distinguish between benign and malignant lesions. METHODS: A total of 235 breast imaging reporting and data system (BI-RADS) 4 solid breast lesions were imaged via CEUS before core needle biopsy or surgical resection. CEUS results were analyzed on 10 enhancing patterns to evaluate diagnostic performance of three benign and three malignant CEUS models, with pathological results used as the gold standard. A logistic regression model was developed basing on the CEUS results, and then evaluated with receiver operating curve (ROC). RESULTS: Except in cases of enhanced homogeneity, the rest of the 9 enhancement appearances were statistically significant (P < 0.05). These 9 enhancement patterns were selected in the final step of the logistic regression analysis, with diagnostic sensitivity and specificity of 84.4% and 82.7%, respectively, and the area under the ROC curve of 0.911. Diagnostic sensitivity, specificity, and accuracy of the malignant vs benign CEUS models were 84.38%, 87.77%, 86.38% and 86.46%, 81.29% and 83.40%, respectively. CONCLUSION: The breast CEUS models can predict risk of malignant breast lesions more accurately, decrease false-positive biopsy, and provide accurate BI-RADS classification.

Contrast-enhanced ultrasound improved performance of breast imaging reporting and data system evaluation of critical breast lesions.

AIM: To determine whether contrast-enhanced ultrasound (CEUS) can improve the precision of breast imaging reporting and data system (BI-RADS) categorization. METHODS: A total of 230 patients with 235 solid breast lesions classified as BI-RADS 4 on conventional ultrasound were evaluated. CEUS was performed within one week before core needle biopsy or surgical resection and a revised BI-RADS classification was assigned based on 10 CEUS imaging characteristics. Receiver operating characteristic curve analysis was then conducted to evaluate the diagnostic performance of CEUS-based BI-RADS assignment with pathological examination as reference criteria. RESULTS: The CEUS-based BI-RADS evaluation classified 116/235 (49.36%) lesions into category 3, 20 (8.51%), 13 (5.53%) and 12 (5.11%) lesions into categories 4A, 4B and 4C, respectively, and 74 (31.49%) into category 5. Selecting CEUS-based BI-RADS category 4A as an appropriate cut-off gave sensitivity and specificity values of 85.4% and 87.8%, respectively, for the diagnosis of malignant disease. The cancer-to-biopsy yield was 73.11% with CEUS-based BI-RADS 4A selected as the biopsy threshold compared with 40.85% otherwise, while the biopsy rate was only 42.13% compared with 100% otherwise. Overall, only 4.68% of invasive cancers were misdiagnosed. CONCLUSION: This pilot study suggests that evaluation of BI-RADS 4 breast lesions with CEUS results in reduced biopsy rates and increased cancer-to-biopsy yields.

Azithromycin-induced torsade de pointes.

Although erythromycin frequently induces long QT interval and torsade de pointes, the newer drug, azithromycin, has rarely been reported to be associated with torsade de pointes. We report here the occurrence of a significant typical QT prolongation within a few hours after taking azithromycin which lead to torsade de pointes.

TT viral infection through blood transfusion: retrospective investigation on patients in a prospective study of post-transfusion hepatitis.

AIM:To investigate the role of blood transfusion in TT viral infection(TTV).METHODS:We retrospectively studied serum samples from 192 transfusion recipients who underwent cardiovascular surgery and blood transfusion between July 1991 and June 1992. All patients had a follow-up every other week for at least 6 months after transfusion. Eighty recipients received blood before screening donors for hepatitis C antibody (anti-HCV), and 112 recipients received screened blood. Recipients with alanine aminotransferase level > 2.5 times the upper normal limit were tested for serological markers for viral hepatitis A, B, C, G, Epstein-Barr virus and cytomegalovirus. TTV infection was defined by the positivity for serum TTV DNA using the polymerase chain reaction method.RESULTS: Eleven and three patients, who received anti-HCV unscreened and screened blood, respectively, had serum ALT levels > 90IU/L. Five patients (HCV and TTV 1; HCV, HGV, and TTV 1; TTV 2; and CMV and TTV 1) were positive for TTV DNA, and four of them had sero conversion of TTV DNA.CONCLUSION:TTV can be transmitted via blood transfusion.Two recipients infected by TTV alone may be associated with the hepatitis. However, whether TTV was the causal agent remains unsettled, and further studies are necessary to define the role of TTV infection in chronic hepatitis.

Nutritional status in non-alcoholic sub-clinical porto-systemic encephalopathy.

AIM:To understand the role of nutritional status in cirrhotic patients without clinical porto-systemic encephalopathy (PSE).METHODS:Fifty-one non-alcoholic patients with cirrhosis without PSE were studied prospectively and compared with 20 healthy volunteers. The nutritional evaluation included serum prealbumin, albumin, transferrin, body mass index (BMI), mid-arm muscle circumference (MAMC), and grip power. The occurrence of subclinical PSE (SPSE) was defined when N20-N65 inter-peak latencies of median nerve-stimulated somatosensory evoked potentials were > 2.5 standard deviations of control means. Blood chemistries were tested within 12h of somatosensory evoked potentials test and nutritional evaluation.RESULTS:Twenty-five, 17 and 9 cirrhotic patients were graded as Child-Pugh class A, B, and C, respectively. Twenty-four (47.1%) patients developed SPSE. Cirrhotic patients with SPSE had lower serum albumin (2.8g/dL ± 0.5g/dL vs 3.1g/dL ± 0.7g/dL, P < 0.001) levels than those without SPSE. Prealbumin (10.6mg/dL ± 5.7mg/dL vs 12.5mg/dL ± 5.8mg/dL), transferrin (164mg/dL ± 46mg/dL vs 178mg/dL ± 58mg/dL), BMI (23.7kg/m(2) ± 2.7kg/m(2) vs 25.3kg/m(2) ± 3.6kg/m(2)), MAMC (22.2cm ± 2.6cm vs 22.7cm ± 3.5cm), and grip power (26.3kg ± 6.4kg vs 26.9kg ± 6.8kg) were not different between cirrhotic patients with and without SPSE. N20-N65 inter-peak latencies were correlated with serum albumin levels (P =0.01) but not with prealbumin, transferrin, BMI, MAMC,or grip power. Serum albumin, prealbumin and transferrin levels were different among cirrhotic patients with Child-Pugh classes A, B, and C (P < 0.05). BMI, MAMC, and grip power were not different among Child-Pugh classes A, B and C.CONCLUSION:Our data suggest that serum albumin level is a simple test in the evaluation of nutritional status in patients with cirrhosis.