[Enteral nutrition support for lysinuric protein intolerance: a case report and literature review]. / èµ–æ°¨é ¸å°¿æ€§è›‹ç™½è€å—ä¸è‰¯æ‚£å„¿çš„è‚ å† è¥å »æ”¯æŒ1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

OBJECTIVES: To summarize the clinical characteristics and nutrition therapy for children with lysinuric protein intolerance (LPI). METHODS: The clinical manifestations, laboratory test results and enteral nutrition treatment in a girl with LPI diagnosed in Xiangya Hospital, Central South University were retrospective analyzed. Additionally, the data of the children with LPI reported in China and overseas were reviewed. RESULTS: A case of 4-year-old girl was presented, who exhibited significant gastrointestinal symptoms, such as chronic abdominal distension, prolonged diarrhea, recurrent pneumonia, and limited growth. She had a poor response to anti-infection treatment. After receiving enteral nutrition therapy, she did not experience any gastrointestinal discomfort, and there were improvements in the levels of hemoglobin, albumin, and blood ammonia. Unfortunately, due to serious illness, she declined further treatment and later passed away. A total of 92 cases of pediatric patients with LPI have been reported to date, including one case reported in this study. Most children with LPI experienced disease onset after weaning or introduction of complementary foods, presenting with severe digestive system symptoms, malnutrition, and growth retardation. It is noteworthy that only 50% (46/92) of these cases received nutritional therapy, which effectively improved their nutritional status. Among the 92 children, 8 (9%) died, and long-term follow-up data were lacking in other reports. CONCLUSIONS: LPI often involves the digestive system and may result in growth restriction with a poor prognosis. Nutritional therapy plays a crucial role in the comprehensive treatment of LPI.

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

Therapeutic effect of metformin on rats with cisplatin-induced acute kidney injury. / äºŒç”²åŒèƒå¯¹é¡ºé“‚è¯±å¯¼æ€¥æ€§è‚¾æŸä¼¤å¤§é¼ çš„æ²»ç–—ä½œç”¨.

OBJECTIVES: The therapeutic effect of metformin on acute kidney injury remains unclear. The purpose of this study is to observe the therapeutic effect of metformin on cisplatin-induced acute renal injury in rats, and to explore the mechanisms. METHODS: A total of 18 male SD rats were randomly divided into 3 groups: a normal control group, a model group, and a metformin treatment group, 6 in each group. The cisplatin (8 mg/kg) was intraperitoneally injected to establish the acute kidney injury model. Metformin [200 mg/(kg·d)] was given by gavage 48 hours before the cisplatin injection and continuous administration for 9 days in a fixed time. After the last intragastric administration of the drug, the blood samples were collected for measurement of renal function indicators and 24 hours urine samples were collected for the testing of neutrophil gelatinase-associated lipocalin (NGAL). Renal tissues were dyed by HE staining to evaluate the tubular damage, and TUNEL was used to evaluate the number of apoptosis cells. RESULTS: Serum urea nitrogen and creatinine, urinary NGAL, the degree of the renal tubular damage, and the number of apoptotic cells were increased significantly in the model group compared with the normal control group (all P<0.05). After treatment with metformin, serum urea nitrogen and creatinine, urinary NGAL, the degree of the renal tubular damage, and the number of apoptotic cells were decreased significantly (all P<0.05). CONCLUSIONS: Metformin exerts a therapeutic effect on rats with acute renal injury via reduction of apoptosis.

Fluorofenidone protects against acute kidney injury.

Cisplatin (CP) is one of the most effective chemotherapeutics in the treatment of human cancers. However, the beneficial effects of CP are limited by the toxic effects, especially nephrotoxicity. Fluorofenidone (AKFPD) is a promising multifunctional antifibrosis pyridinone drug discovered by our group. But there is no evidence of its protective effects against acute kidney injury (AKI). Therefore, we investigated the protective effects of AKFPD on CP-induced AKI in vivo and in vitro. Compared with the model group, treatment with AKFPD effectively ameliorated kidney damages. In order to elucidate the mechanisms, we discovered that AKFPD treatment notably alleviated generation of reactive oxygen species, reduced the phosphorylation levels of MAPKs (ERK1 and 2, JNKs, and p38), suppressed inflammatory response, inhibited apoptosis, and abated the expression of CP transporters (organic cation transporter 2 and copper transport protein 1) compared with the model group. Moreover, because renal ischemia reperfusion injury (IRI)-induced AKI and LPS-induced AKI are the major models representative of renal transplantation-correlated AKI and sepsis-related AKI, which are also the main causes of AKI, we have also proved the effectiveness of AKFPD on these models. In conclusion, these findings suggest that AKFPD is a potent drug for CP-, IRI-, and LPS-caused AKI and elucidate the underlying mechanism.-Jiang, Y., Quan, J., Chen, Y., Liao, X., Dai, Q., Lu, R., Yu, Y., Hu, G., Li, Q., Meng, J., Xie, Y., Peng, Z., Tao, L. Fluorofenidone protects against acute kidney injury.

HADC regulates the diabetic vascular endothelial dysfunction by targetting MnSOD.

Vascular dysfunction is a common result of diabetes in humans. However, the mechanism underlying diabetic vascular dysfunction is not fully understood. Here in the present study, we showed that the histone deacetylase 2 (HDAC2) promoted the endothelial dysfunction induced by diabetes. The expression and activity of HDAC2 were up-regulated in vascular endothelial cells (ECs) from diabetic patients and mice. The expression of HDAC2 was also increased by high glucose stress in isolated human ECs. HDAC2 knockdown repressed the proliferation rate and promoted high glucose-induced apoptosis of ECs, which was associated with the activation of apoptotic pathways (Bcl-2, Caspase 3, and Bax). By contrast, HDAC2 overexpression led to opposing results. Significantly, we observed that HDAC2 regulated the accumulation of reactive oxygen species (ROS) induced by high glucose in ECs, which accounted for the effects of HDAC2 on proliferation and apoptosis because antioxidants, N-acetyl-l-cysteine (NAC) or MnTBAP treatment blocked the effects of HDAC2 on apoptosis of ECs under high glucose condition. Mechanism study revealed that HDAC2 bound to the promoter of MnSOD and repressed the expression of MnSOD by regulating the level of acetylated H3K9 and H3K27, which led to the promotion of oxidative stress and contributed to the function of HDAC2 in ECs under high glucose condition. Altogether, our evidence demonstrated that HDAC2-MnSOD signaling was critical in oxidative stress and proliferation as well as the survival of ECs under high glucose condition.