Lactic acidosis is a rare but severe complication of B-cell lymphoma, often associated with rapid disease progression and poor prognosis. We present a case of a 60-year-old male admitted with fever, splenomegaly, hemophagocytic tendencies, and lactic acidosis. The patient underwent several dialysis sessions before bone marrow flow cytometry finally confirmed B-cell lymphoma. However, hyperlactatemia persisted and recurred. The case underscores the challenges in diagnosing lymphomas with atypical presentations and emphasizes the critical role of timely bone marrow analysis. Additionally, the paper discusses the association between B-cell lymphoma and lactic acidosis, highlighting the importance of early recognition and intervention.

Quantitative analysis of acetylcarnitine in additional 58 serum samples.

A 60-year-old Chinese female patient was admitted to the hospital with complaint of intermittent fever for more than seven months. The main clinical manifestations were acute kidney injury and nephrotic syndrome which developed into a hemophagocytic syndrome. The symptoms did not improve with antibiotics. Moreover, prednisone could only reduce the fever. Finally, a kidney biopsy showed many CD20-positive cells in the glomerulus and some in the peritubular capillaries. This led to a diagnosis of renal intravascular large B-cell lymphoma.

Objective To explore the effect and mechanism of chemokine CX3CL1 on mouse liver fibrosis model.Methods C57BL/6 mice were randomly divided into CCl-4 model group and normal control group with 8 animals in each group.The model group was injected with 10%CCl-4 intra peritoneally for 6 weeks.After 6 weeks,the mice were sacrificed,and the pathological changes of the mouse liver were observed by HE staining.The level of CX3CL1 in peripheral blood of the mice was measured,and the expression level of CX3CL1 mRNA in the liver tis-sue of the mice was detected.In addition,in order to explore the mechanism of CX3CL1,the level of IFN-γ in mouse serum was detected as well.Results After the 6-week modeling,the liver pathology microscopy showed a successful modeling of liver fibrosis.The serum CX3CL1 level and liver tissue CX3CL1 expression in the model group were found to be significantly up-regulated,which suggested a potential impact on the pathogenesis of liver fi-brosis.In addition,the level of IFN-γ in the serum of mice in the model group increased significantly.Conclusions CX3CL1 is related to liver fibrosis in mice,and its mechanism might be explained by promoting the production of IFN-γ so to prevent liver fibrosis.

Chemoresistance remains the foremost challenge in cancer therapy. Targeting reactive oxygen species (ROS) manipulation is a promising strategy in cancer treatment since tumor cells present high levels of intracellular ROS, which makes them more vulnerable to further ROS elevation than normal cells. Nevertheless, dynamic redox evolution and adaptation of tumor cells are capable of counteracting therapy-induced oxidative stress, which leads to chemoresistance. Hence, exploring the cytoprotective mechanisms of tumor cells is urgently needed to overcome chemoresistance. Heme oxygenase-1 (HO-1), a rate-limiting enzyme of heme degradation, acts as a crucial antioxidant defense and cytoprotective molecule in response to cellular stress. Recently, emerging evidence indicated that ROS detoxification and oxidative stress tolerance owing to the antioxidant function of HO-1 contribute to chemoresistance in various cancers. Enhanced HO-1 expression or enzymatic activity was revealed to promote apoptosis resistance and activate protective autophagy, which also involved in the development of chemoresistance. Moreover, inhibition of HO-1 in multiple cancers was identified to reversing chemoresistance or improving chemosensitivity. Here, we summarize the most recent advances regarding the antioxidant, antiapoptotic, and pro-autophagy properties of HO-1 in mediating chemoresistance, highlighting HO-1 as a novel target for overcoming chemoresistance and improving the prognosis of cancer patients.

Con A-induced hepatitis is the most commonly used animal model for simulating autoimmune hepatitis (AIH). In this study, we investigated whether methyl butyrate (MB) alleviates Con A-induced hepatitis and how it affects Con A-stimulated lymphocytes. MB improves liver function in AIH mice, reducing the expression of several inflammatory cytokines and Th1 cell-associated chemokines in the liver, while significantly inhibiting toll-like receptor signaling pathway. Also in the liver, we verified that infiltrating Th1 cells were fewer after MB treatment. In vitro, we found that the activation of both human and mouse Th1 cells by Con A were inhibited by MB and the human-derived cells were even more sensitive. And MB caused a reduction in IFN-γ secretion together with TNF-α and IL-6. The above findings suggest that MB inhibits the activation and homing of Th1 cells to the liver, thereby attenuating Con A-induced liver injury, and may be a potential therapeutic agent for AIH.

本研究依托于新疆干旱区和民勤盆地红崖山灌区水资源和沙区植被调查分析,展开对地下水位回升及地表用水的节水模式科学调控,对土壤水分平衡影响进行探讨,并评价植被特征与植被恢复能力.通过重点规划治理和红崖山灌区水资源科学配置与节水调控模式,运用Origen数据软件线性拟合与Excel数据统计分析地下水开采量与地表水高效利用模式.结果表明:对土壤水分平衡研究,发现降水条件下布设麦草沙障的人工梭梭林比白刺包蒸散量小,其土壤有效储水效果更好,两者降水截留效果基本一致;对植被恢复能力试验得出,在灌区水生态治理时地下水恢复与地表水优化配置两种模式相结合,稳定实现可持续化恢复.

环孢子虫病是一种肠道寄生虫病，人体通过食入被环孢子虫卵囊污染的水和食物而感染，摄入的卵囊通过侵犯小肠上皮细胞进入人体，尤以空肠为主，进而出现慢性肠炎的临床表现。本例患者以腹水为主要表现，血、腹水和骨髓检查结果均提示嗜酸性粒细胞水平增高明显，曾拟诊为"嗜酸细胞性胃肠炎"，并予以糖皮质激素治疗，患者腹胀症状一度出现好转，但在停药3个月后再次出现腹水，最终通过小肠黏膜病理和粪便直接涂片法在光学显微镜下找到环孢子虫卵囊确诊，服用复方磺胺甲噁唑得以痊愈。

1 病例资料 患者女,54岁.因"臀部疼痛3周,右下肢红肿热痛15 d,发热10 d"于2020年10月26日入上海复旦大学附属华山医院感染科住院治疗.患者2020年10月6日晨起出现左侧臀部疼痛明显,皮肤无红肿及皮温升高,伴有左侧臀部及下肢活动障碍,于当地诊所肌注止痛药(具体药物不详) 1次,效果不佳,约3 d后疼痛蔓延至右侧臀部.2020年10月10日至当地诊所进行右侧臀部针灸治疗,针灸后第2天患者右侧臀部疼痛明显加重,伴有红肿及皮温升高,触痛阳性,同时出现右下肢红肿热痛明显.2020年10月14日至当地医院感染科继续治疗,实验室检查:WBC 15.23×109/L, RBC 3.67×1012/L,PLT 31×109/L,Hb 110 g/L,N 0.835,L 0.089,血糖 17.15 mmol/L,红细胞沉降率 80 mm/1 h,C反应蛋白 271.8 mg/L,降钙素原 3.5 μg/L.查CT示:①双侧髋关节周围软组织肿胀,左侧髋关节周围积气;②骶骨右侧见斑片状稍低密度影伴点状积气.

BACKGROUND:Hepatic fibrosis is a common response to chronic liver injury. Recently, the role of DZNep (a histone methyltransferase EZH2 inhibitor) in repressing pulmonary and renal fibrosis was verified. However, the potential effect of DZNep on hepatic fibrosis has not been elucidated.METHODS:The hepatic fibrosis model was established in rats treated with CCl4 and in hepatic stellate cells (HSCs) treated with TGF-β1. The liver tissues were stained with H&E and Masson's trichrome. The expression of EZH2, SOCS7, collagen I, αSMA mRNA and miR-199-5p was assessed using qPCR, immunohistochemical or western blot analysis. A dual-luciferase reporter assay was carried out to validate the regulatory relationship of miR-199a-5p with SOCS7.RESULTS:The EZH2 level was increased in CCl4-treated rats and in TGF-β1-treated HSCs, whereas DZNep treatment significantly inhibited EZH2 expression. DZNep repressed hepatic fibrosis in vivo and in vitro, as evidenced by the decrease of hepatic fibrosis markers (α-SMA and Collagen I). Moreover, miR-199a-5p expression was repressed by DZNep in TGF-β1-activated HSCs. Notably, downregulation of miR-199a-5p decreased TGF-β1-induced expression of fibrosis markers. SOCS7 was identified as a direct target of miR-199a-5p. The expression of SOCS7 was decreased in TGF-β1-activated HSCs, but DZNep treatment restore d SOCS7 expression. More importantly, SOCS7 knockdown decreased the effect of DZNep on collagen I and α SMA expression in TGF-β1-activated HSCs.CONCLUSIONS:DZNep suppresses hepatic fibrosis through regulating miR-199a-5p/SOCS7 axis, suggesting that DZNep may represent a novel treatment for fibrosis.

AIM:Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment or serious side effects often occurs in ovarian cancer, and thus, there is an urgent need for effective and combined therapies to overcome such obstacles. In the present study, we aimed to uncover synergistic effects between erastin and cisplatin (CDDP) in inhibiting ovarian cancer cell growth by inducing ferroptosis in vitro and in vivo.METHODS:We performed a CCK-8 assay to detect cell viability in response to erastin alone or in combination with cisplatin and provided further confirmation by western blotting analysis. Transmission electron microscopy and flow cytometry analysis were used to depict the characteristics of ferroptosis. In addition, an ovarian cancer tumor xenograft was built to verify the effects in vivo.RESULTS:CDDP induced multiple modes of cell death-including ferroptosis in ovarian cancer cell lines. Mechanistically, erastin triggered ferroptosis and increased the levels of reactive oxygen species (ROS) so as to augment the cytotoxic effect of cisplatin. Combination therapy based on CDDP and erastin appeared to maximize the therapeutic effects while minimizing side effects in ovarian cancer both in vitro and in vivo.CONCLUSION:Collectively, our results indicate that erastin works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

目的 总结原发性肝结核的临床特征,探讨其早期诊断方法及合理的治疗方案.方法 回顾性分析复旦大学华山医院感染科收治的1例罕见原发性肝结核病理确诊病例的临床表现、治疗和转归,并以"原发性肝结核"为关键词检索万方和中国期刊全文数据库(1984年1月至2020年1月).结果 1例原发性肝结核患者主要表现为午后发热,行胸部CT提示未见明显异常,肝脏MRI及全身PET-CT均提示肝肿瘤,行B超引导下肝穿活检提示肝结核,予规范抗结核治疗后疗效显著.共检索到国内发表的有关原发性肝结核的论文15篇,符合病理确诊标准的22例.其中实验室检查:AFP正常21例,PPD阳性10例,血T-SPOT阳性1例.影像学检查:腹部B超22例,上腹部CT 15例,增强肝脏MRI 4例及全身PET-CT 2例全部误诊;病理结果提示为干酪样坏死、凝固性坏死、上皮样肉芽组织结节、朗格汉氏细胞及淋巴细胞浸润,抗酸染色阳性仅2例;采用规范抗结核治疗,疗效显著.结论 原发性肝结核诊断困难,误诊率高,其临床表现及影像学检查无特异性,PPD试验或血T-SPOT强阳性及AFP阴性对诊断及鉴别诊断有重要意义,对疑诊病例积极进行早期B超引导下肝穿活检并作抗酸染色,可早期确诊,且规范抗结核治疗后疗效显著.

Objective::To compare the efficacy and safety of four surgical strategies currently used for the management of deep implantation cesarean scar pregnancy (CSP-II).Methods::This was a retrospective clinical cohort study, and, in total, 131 women diagnosed with CSP-II and primarily treated in our hospital were recruited. Women treated using laparoscopy assisted by operative hysteroscopy (LAOH; Group A, n = 25), uterine artery embolization (UAE) followed by LAOH (Group B, n = 21), ultrasound-guided dilatation and curettage (D&C; Group C, n = 24), and UAE followed by D&C (Group D, n = 61) were evaluated. Univariate and multiple logistic analyses were performed to identify the risk factors. Results::No statistically significant difference was found in patient age, gestational age, size of lesion, and pretreatment serum β-human chorionic gonadotropins (β-hCG) level. Operation time was longer ( P < 0.001) and the success rate was higher ( P = 0.01) in both Group A and Group B than in Group C and Group D. When the cohort was further analyzed regarding patients with myometrial thickness ≤3 mm ( n = 75, defined as CSP-IIb), a lower rate of perioperative complications ( P = 0.036) and a higher success rate ( P < 0.001) remained in Group A ( n = 15) and Group B ( n = 15) but not in Group C ( n = 11) or Group D ( n = 34). In multiple logistic regression analysis, the risk factors related to lower treatment efficacy for patients with CSP-II were thinner myometrial thickness of cesarean scar (CS) (≤3 mm) (odds ratio [ OR] = 5.470, P = 0.062), number of cesarean sections (a2) ( OR = 8.877, P = 0.013), mass protruding into the bladder or abdominal cavity ( OR = 25.507, P < 0.001), and direct D&C modality ( OR = 38.247, P = 0.010). Conclusions::Compared with D&C ± UAE, LAOH ± UAE showed a higher success rate for patients with CSP-II, especially when the zygote was more deeply implanted with a myometrial thickness of CS ≤ 3 mm. CSP-II treatment should be individualized on the basis of many risk factors.

Inexpensive blood tests have been well established as alternatives to liver biopsies to evaluate liver fibrosis in CHB patients. Here, we aim to compare their diagnostic accuracy in assessing liver fibrosis and necroinflammation. A retrospective study was performed to evaluate the predictive value of non-invasive models in chronic hepatitis B patients with liver fibrosis by the area under receiver operating characteristic curve (AUROC). The clinical data of 160 patients were collected from medical records. Of the 160 consecutive treatment-naïve CHB patients, 29 (16%) had significant fibrosis and 34 (21%) had severe necroinflammation. The AUROC of the gamma-glutamyl transpeptidase to platelet ratio (GPR) (0.761, 95% CI 0.671–0.850) for predicting significant fibrosis was significantly higher than that of the aspartate transaminase-to-platelet ratio index (APRI) (0.680, 95% CI 0.585–0.774, p = 0.034), but comparable with the fibrosis index based on four factors (Fib-4) (0.746, 95% CI 0.656–0.836, p = 0.703), while for predicting severe necroinflammation, the performance of the GPR (AUROC = 0.869, 95% CI 0.800–0.937) was better than the APRI (AUROC = 0.816, 95% CI 0.740–0.892, p = 0.085) and Fib-4 (0.792, 95% CI 0.711–0.873, p = 0.023). GPR is a satisfactory model to stage liver fibrosis and to grade necroinflammation activity, representing a convenient non-invasive alternative to liver biopsy in China. los análisis de sangre asequibles se han consolidado como alternativas a la biopsia hepática para evaluar la fibrosis hepática en pacientes con HBC. En este caso, nuestro objetivo es comparar su precisión diagnóstica en la evaluación de la fibrosis hepática y en la necroinflamación. se realizó un estudio retrospectivo para evaluar el valor pronóstico de los modelos no invasivos en pacientes con hepatitis B crónica con fibrosis hepática en el área bajo la curva de rendimiento diagnóstico (AUROC). Se recopilaron los datos clínicos de 160 pacientes a partir de las historias clínicas. De 160 pacientes HBC que no habían recibido tratamiento consecutivo, 29 (16%) presentaron una importante fibrosis y 34 (21%), necroinflamación grave. La AUROC de la gammaglutamiltranspeptidasa respecto a la proporción de plaquetas (GPR) (0,761; IC95%: 0,671-0,850) para pronosticar una fibrosis importante fue considerablemente más alta que el índice de relación aspartato-transaminasa-plaquetas (APRI) (0,680; IC95%: 0,585-0,774; p = 0,034), pero comparable con el índice de fibrosis basado en cuatro factores (Fib-4) (0,746; IC95%: 0,656-0,836; p = 0,703), mientras que para el pronóstico de la necroinflamación grave, el rendimiento de GPR (AUROC = 0,869; IC95%: 0,800-0,937) fue mejor que el de APRI (AUROC = 0,816; IC95%: 0,740-0,892; p = 0,085) y el de Fib-4 (0,792; IC95%: 0,711-0,873; p = 0,023). el GPR es un modelo satisfactorio para clasificar la fibrosis hepática y para calificar la actividad de la necroinflamación, y representa una alternativa práctica y no invasiva a la biopsia hepática en China.

Chronic hepatitis C virus (HCV) infection often leads to end‐stage liver disease, including hepatocellular carcinoma (HCC). We have previously observed reduced expression of microRNA‐30e (miR‐30e) in the liver tissues and sera of patients with HCV‐associated HCC, although biological functions remain unknown. In this study, we demonstrated that HCV infection of hepatocytes transcriptionally reduces miR‐30e expression by modulating CCAAT/enhancer binding protein β. In silico prediction suggests that autophagy‐related gene 5 (ATG5) is a direct target of miR‐30e. ATG5 is involved in autophagy biogenesis, and HCV infection in hepatocytes induces autophagy. We showed the presence of ATG5 in the miR‐30e–Argonaute 2 RNA‐induced silencing complex. Overexpression of miR‐30e in HCV‐infected hepatocytes inhibits autophagy activation. Subsequent studies suggested that ATG5 knockdown in Huh7.5 cells results in the remarkable inhibition of sterol regulatory element binding protein (SREBP)‐1c and fatty acid synthase (FASN) level. We also showed that overexpression of miR‐30e decreased lipid synthesis‐related protein SREBP‐1c and FASN in hepatocytes. Conclusion: We show new mechanistic insights into the interactions between autophagy and lipid synthesis through inhibition of miR‐30e in HCV‐infected hepatocytes.

Activation of hepatic stellate cell (HSC), which is the main source of extracellular matrix, plays a pivotal role in liver fibrogenesis. Autophagy of hepatic stellate cell has been recently implicated in liver fibrosis, but the regulation of hepatic stellate cell autophagy during this process remains poorly understood. Here, we first identified miR-96-5p as an aberrantly expressed miRNA in fibrotic liver tissues. Next, we transfected miR-96-5p mimic into human hepatic stellate cell line LX-2 and observed decreased protein and mRNA levels of α-SMA and Col1A1. In addition, transfection of miR-96-5p mimic significantly reduced autophagy activity of LX-2 cells, while transfection of miR-96-5p inhibitor promoted LX-2 cell autophagy. Moreover, autophagy-related protein 7 (ATG7) was predicted as a potential target of miR-96-5p and luciferase assay confirmed its direct interaction with miR-96-5p. Finally, reintroduction of ATG7 into LX-2 cells reversed miR-96-5p-mediated inhibition of autophagy as well as α-SMA and Col1A1 expression. In conclusion, we demonstrated that miR-96-5p can inhibit hepatic stellate cell activation by blocking autophagy via ATG7. These findings provide new insight into the development of miRNA-based anti-fibrotic strategies.KEY MESSAGES:• Altered miRNA expression profile is observed in fibrotic liver tissues. • miR-96-5p can inhibit HSC activation. • Autophagy of HSC is repressed by miR-96-5p during activation. • ATG7 is a direct target of miR-96-5p. • ATG7 can rescue miR-96-5p-mediated inhibition of autophagy and HSC activation.

Background: A 45-year-old man who complained of continuous fever and multiple hepatic masses was admitted to our hospital. Repeated MRI manifestations were similar while each radiological report suggested contradictory diagnosis pointing to infections or malignances respectively. Pathologic examination of the liver tissue showed no direct evidence of either infections or tumor. We performed next-generation sequencing on the liver tissue and peripheral blood to further investigate the possible etiology. Methods: High throughput sequencing was performed on the liver lesion tissues using BGISEQ-100 platform, and data was mapped to the Microbial Genome Databases after filtering low quality data and human reads. Results: We identified a total of 299 sequencing reads of Mycobacterium tuberculosis (M. tuberculosis) complex sequences from the liver tissue, including 8, 2.29 of 4,424,435 of the M. tuberculosis nucleotide sequences, and Mycobacterium afncanum, Mycobacterium bovis, and Mycobacterium canettn were also detected due to the 99.9% identical rate among these strains. No specific Mycobacterial tuberculosis nucleotide sequence was detected in the sample of peripheral blood. Patient's symptom quickly recovered after anti-tuberculosis treatment and repeated Ziehl-Neelsen staining of the liver tissue finally identified small numbers of positive bacillus. Conclusions: The diagnosis of this patient was difficult to establish before the next-generation sequencing because of contradictive radiological results and negative pathological findings. More sensitive diagnostic methods are urgently needed. This is the first case reporting hepatic tuberculosis confirmed by the next-generation sequencing, and marks the promising potential of the application of the next-generation sequencing in the diagnosis of hepatic lesions with unknown etiology. (C) 2018 Elsevier Masson SAS. All rights reserved.

We report human endophthalmitis caused by pseudorabies virus infection after exposure to sewage on a hog farm in China. High-throughput sequencing and real-time PCR of vitreous humor showed pseudorabies virus sequences. This case showed that pseudorabies virus might infect humans after direct contact with contaminants.

BACKGROUND:Talaromyces marneffei, is an opportunistic pathogenic fungus that is most commonly reported in Southeast Asia and disseminated T.marneffei infection predominantly occurs in patients with immunodeficiency. With a potential to invade multiple organs, it can be fatal for patients if diagnosis and treatment are delayed. In current clinical practice, the diagnosis of T.marneffei infection relies heavily on tissue culture and histologic analysis, which may suffer from limited positive rate and is sometimes time consuming. The rapid and accurate diagnosis of disseminated T.marneffei infection remains challenging.CASE PRESENTATION:A 22-year-old man gradually developed fever, cough, lower extremities weakness, jaundice and rash, for which a 3-month extensive investigation failed to reach a diagnosis. After admitted into our hospital, laboratory and radiological tests revealed multiple lesions in the patient's brain, spinal cord, and lungs. We performed next generation sequencing on the patient's skin tissue, bone marrow, blood and cerebrospinal fluid, which all identified numerous Talaromyces marneffei nucleotide sequences and leaded to the rapid diagnosis and treatment of disseminated T.marneffei infection.CONCLUSIONS:This case underline the clinical significance of T.marneffei as a possible pathogen in immune-competent patients. This successful application of the next generation sequencing assisting the rapid diagnosis of disseminated T.marneffei infection provides a new perspective in the clinical approach to the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

We reported a cluster of meningitis cases where next-generation sequencing enabled comprehensive and rapid diagnosis of causative agents. Study attempted a novel application of next-generation sequencing through the dynamic and direct semi-quantitive surveillance of pathogen loads in cerebralspinal fluids, suggesting its potential in reflecting disease progression and therapeutic efficacy evaluation during clinical approach. NGS may perform as a promising tool for infectious disease course surveillance through its ability of revealing the direct connection between pathogen loads and variate disease states in the future.