Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review.

RATIONALE: Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. PATIENT CONCERNS: A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. DIAGNOSES: TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. INTERVENTIONS: After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. OUTCOMES: After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. LESSONS: Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, ß2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.

Perioperative Risk Factors for Post-operative Pneumonia after Type A Acute Aortic Dissection Surgery.

OBJECTIVE: Type A acute aortic dissection (TAAAD) is a dangerous and complicated condition with a high death rate before hospital treatment. Patients who are fortunate to receive prompt surgical treatment still face high in-hospital mortality. A series of post-operative complications further affects the prognosis. Post-operative pneumonia (POP) also leads to great morbidity and mortality. This study aimed to identify the prevalence as well as the risk factors for POP in TAAAD patients and offer references for clinical decisions to further improve the prognosis of patients who survived the surgical procedure. METHODS: The study enrolled 89 TAAAD patients who underwent surgical treatment in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China from December 2020 to July 2021 and analyzed the perioperative data and outcomes of these patients. Logistic regression analyses were used to identify the risk factors for POP. RESULTS: In the study, 31.5% of patients developed POP. Patients with POP had higher proportions of severe oxygenation damage, pneumothorax, reintubation, tracheotomy, renal replacement therapy, arrhythmia, gastrointestinal bleeding, and longer duration of mechanical ventilation, fever, ICU stay, and length of stay (all with P<0.05). The in-hospital mortality was 2.3%. Smoking, preoperative white blood cells, and intraoperative transfusion were the independent risk factors for POP in TAAAD. CONCLUSION: Patients who underwent TAAAD surgery suffered poorer outcomes when they developed POP. Furthermore, patients with risk factors should be treated with caution.

CXCL12 G801A polymorphism and cancer risk: An updated meta-analysis.

Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P<0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P<0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P<0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P<0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.

Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress.

Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. Evidence shows the important role of oxidative stress in the etiopathogenesis of hepatic fibrosis. The aim of this study was to investigate the protective effects of administration of melatonin in rats with carbon tetrachloride-induced fibrosis for 6 weeks. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examinations. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) levels were evaluated in tissue homogenates by spectrophotometry. The nuclear factor-kappaB (NF-kappaB) in liver tissue was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in Kupffer cells (KCs) culture supernatants were measured with ELISA. The rats injected subcutaneously with CCl4 for 6 weeks resulted in hepatic fibrotic changes increased hydroxyproline and MDA levels, and decreased GSH-px and SOD levels, whereas melatonin reversed these effects. Furthermore, melatonin inhibited the expression of NF-kappaB in liver tissue and decreasing production of proinflammatory cytokines such as TNF-alpha and IL-1beta from KCs in fibrotic rats. These present results suggest that melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress and proinflammatory cytokines production.

Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guerin and lipopolysaccharide.

AIM: Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guerin (BCG)/lipopolysaccharide (LPS). METHODS: The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate amino-transferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homogenate were assayed by spectrophotometry. The content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed. RESULTS: In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5, 10, or 20 mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF-alpha and IL-1beta levels in the liver and inhibited the production of TNF- alpha and IL-1beta by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed. CONCLUSION: MT-Se showed a hepatic protective action on immunological liver injury in mice.

Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro.

AIM: To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 micromol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 micromol/L) was lower than that of free 5-Fu (51.2 micromol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepato-carcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.

Pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes in mice.

AIM: To study the pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes (5-Fu-GCL) in mice. METHODS: The concentration of 5-fluorouracil (5-Fu) in serum was detected by high performance liquid chromatography after 5-Fu-GCL (80, 40, 20 mg/kg) and free 5-Fu (40 mg/kg) were injected intravenously into mice. The tissue distribution of 5-Fu-GCL (40 mg/kg) and free 5-Fu (40 mg/kg) was investigated, and concentration-time profile of the two preparations in the liver were studied. Data were analyzed by 3p97 program. RESULTS: Serum concentration-time curves of 5-Fu-GCL and free 5-Fu conformed to one compartment model of first order absorption. 5-Fu-GCL at 80, 40, and 20 mg/kg had T(1/2Ke) of 25.8+/-4.2, 27.3+/-4.4, and 28.2+/-5.6 min; C0 of 24.9+/-4.9, 17.7+/-3.6, and 11.5+/-2.7 mg/L; and AUC of 990.0+/-45.2,622.5+/-38.3, and 340.4+/-25.6 mg x min x L(-1), respectively. In contrast free 5-Fu at 40 kg/mg had T(1/2Ke) of 15.8+/-2.2 min, C0 of 35.8+/-6.2 mg/L, AUC of 639.0+/-35.9 mg x min x L(-1). The tissue distribution of 5-Fu-GCL in the liver and immune organs was significantly increased, while in heart and kidney it was remarkably decreased. The AUC of 5-Fu-GCL in the liver was 3 times higher than that of free 5-Fu. CONCLUSION: The pharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-related and dose-dependent, and exhibits sustained-release and hepatic target characteristics.

A 771726, the active metabolite of leflunomide, inhibits TNF-alpha and IL-1 from Kupffer cells.

This study was conducted to investigate the importance of direct contact between Kupffer cells (KCs) and hepatocytes (HCs) during the hepatic inflammatory responses, and the effect of leflunomide's active metabolite, A771726, on cytokines in KCs and HCs (DC cocultures) and KC cultures using an in vitro approach. Lipopolysaccharide (LPS)-induced inflammatory response in monocultures of rats HCs and KCs were compared with DC cocultures. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) concentrations of different culture supernatants were measured with ELISA. TNF-alpha and IL-1 mRNA in KCs of inflammatory liver injury was analyzed with reverse transcription polymerase chain reaction (RT-PCR). Our data showed that DC cocultures exhibited the highest production of TNF-alpha and IL-1 compared with other cultures, and these cytokines were mainly produced by KCs, in particular activated KCs. Time course studies revealed an increased production of TNF-a preceding the IL-1 production, suggesting that increased TNF-alpha levels could be involved in the increased IL-1 production. Leflunomide's active metabolite, A771726, has significantly inhibitory effect on TNF-a and IL-1 at protein and transcription levels, and reduced production of IL-1 by A771726 was associated with inhibitory action of A771726 on TNF-alpha. These results provided evidence that leflunomide significantly inhibited TNF-alpha and IL-1 from KCs.

Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide.

AIM: To investigate the effects and mechanisms of melatonin on immunological liver injury in mice. METHODS: A model of liver injury was induced by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice. Kupffer cells and hepatocytes were isolated and cultured according to a modified two-step collagenase perfusion technique. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO), content of malondiadehyde (MDA), activity of superoxide dismutase (SOD), were measured by biochemical methods. Tumor necrosis factor-alpha (TNF-alpha) activity was determined by RIA. Interleukin (IL)-1 activity was measured by thymocyte proliferation bioassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS: Immunological liver injury induced by BCG+LPS was successfully duplicated. Serum transaminase (ALT, AST) activities were significantly decreased by melatonin (0.25, 1.0, 4.0 mg/kg bm). Meanwhile, MDA content was decreased and SOD in liver homogenates was upregulated. Furthermore, pro-inflammatory mediators (TNF-alpha, IL-1, NO) in serum and liver homogenates were significantly reduced by melatonin. Histological examination demonstrated that melatonin could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. In in vitro experiment, TNF-alpha was inhibited at the concentrations of 10(-8)-10(-6) mol/L of melatonin, while IL-1 production of Kupffer cells induced by LPS (5 microg/mL) was decreased only at the concentration of 10(-6) mol/L of melatonin, but no effect on NO production was observed. Immunological liver injury model in vitro was established by incubating hepatocytes with BCG- and LPS-induced Kupffer cells. Activities of ALT, TNF-alpha, IL-1, and MDA in supernatant were significantly increased. Melatonin had little effect on the level of ALT, but reduced the content of TNF-alpha and MDA at concentrations of 10(-7)-10(-5) mol/L and decreased the content of IL-1 at concentrations of 10(-6)-10(-5) mol/L. CONCLUSION: Melatonin could significantly protect liver injury in mice, which was related to free radical scavenging, increased SOD activity and pro-inflammatory mediators.

Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells.

AIM: To investigate the importance of direct contact between Kupffer cells (KCs) and hepatocytes (HCs) during hepatic inflammatory responses, and the effect of leflunomide's active metabolite, A(771726), on cytokines in KCs, HCs and KC cocultures (DC cocultures). METHODS: KCs and HCs in liver were isolated by digestion with pronase and collagenase. Lipopolysaccharide (LPS)-induced inflammatory response in monocultures of rat HCs and KCs was compared with that in DC cocultures. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) concentrations in different culture supernatants were measured with ELISA. TNF-alpha mRNA in KCs of inflammatory liver injury was analyzed with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: DC cocultures strongly exhibited the production of TNF-alpha and IL-1 compared with other cultures, and these cytokines were mainly produced by KCs, especially by activated KCs. Time course studies revealed an increased production of TNF-alpha preceding the IL-1 production, suggesting that increased TNF-alpha levels could be involved in the increase of IL-1 production. Leflunomide's active metabolite, A(771726), had significantly inhibitory effect on TNF-alpha and IL-1 at protein and transcription levels, and the reduced production of IL-1 by A(771726) was associated with the inhibitory action of A(771726 ) on TNF-alpha. CONCLUSION: Leflunomide can inhibit hepatocyte damage by inhibiting proinflammatory cytokine release from KCs.

Effect of leflunomide on immunological liver injury in mice.

AIM: To study the effect of leflunomide on immunological liver injury (ILI) in mice. METHODS: ILI was induced by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10 microg lipopolysaccharide (LPS) in 0.2 mL saline (BCG+LPS). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) level in plasma and molondiadehyde (MDA), glutathione peroxidase (GSHpx) in liver homogenate were assayed by spectroscopy. The serum content of tumor necrosis factors-alpha (TNF-alpha) was determined by ELISA. Interleukin-1 (IL-1), interleukin-2 (IL-2) and Concanavalin A (ConA)-induced splenocyte proliferation response were determined by methods of (3)H-infiltrated cell proliferation. RESULTS: Leflunomide (4, 12, 36 mg.kg(-1)) was found to significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Leflunomide (4, 12, 36 mg.kg(-1)) significantly lowered TNF-alpha and NO level in serum, and IL-1 produced by intraperitoneal macrophages(PMphi). Moreover, the decreased IL-2 production and ConA-induced splenocyte proliferation response were further inhibited. CONCLUSION: These findings suggested that leflunomide had significant protective action on ILI in mice.