instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Pirfenidone (5 methyl-1-phenyl-2(1H)-pyridone) is a novel anti-fibrotic agent, which has been shown to decrease collagen deposition in a variety of animal models in vivo, and recently in hepatic fibrosis also. At cellular level, we have recently demonstrated that pirfenidone is able to inhibit proliferation of hepatic stellate cells induced by platelet-derived growth factor, as well as collagen type I accumulation and alpha1(I) procollagen mRNA expression.', 'To evaluate if pirfenidone maintains its anti-fibrotic properties also when administered after the induction of hepatic damage and to further investigate the molecular mechanisms leading to the anti-fibrotic effect of pirfenidone.', 'Rats treated with dimethylnitrosamine (10 mg/kg) for 5 weeks received a liquid diet containing 0.5% pirfenidone starting from the third week. Pirfenidone treatment reduced the degree of liver injury, as determined by alanine aminotransferase values and necro-inflammatory score, which was associated with reduced hepatic stellate cells proliferation and collagen deposition. Treatment with dimethylnitrosamine increased transcripts levels for transforming growth factorbeta1, procollagen alpha1(I), tissue inhibitors of metalloproteinase-1 and matrix metalloproteinase-2 by 7-, 7-, 4- and 15-fold, respectively. Pirfenidone administration downregulated elevated levels of those transcripts by 50-60%, and this was associated with a 70% reduction in collagen deposition.\Question: Is the anti-fibrotic effect of pirfenidone in rat liver fibrosis mediated by downregulation of procollagen alpha1 ( I ) , TIMP-1 and MMP-2?
answer:
(1) Pirfenidone is effective also if administered after the induction of the hepatic damage; (2) the anti-fibrotic effect of pirfenidone is mainly due to the reduced expression of profibrogenic procollagen alpha1(I) and TIMP-1, most likely through the downregulation of transforming growth factorbeta1 mRNA, and of matrix metalloproteinase-2, which is mainly implicated in the degradation of the normal extracellular matrix.

question:
Context: To investigate the impact of prophylactic hyperoxic ventilation with Fio2 0.6 on the physiologic limit of acute normovolemic anemia.', 'Prospective, controlled, randomized experimental study.', 'Experimental animal laboratory of a university hospital.', 'Fourteen anesthetized domestic pigs.', 'Animals were randomly ventilated with either Fio2 0.21 (group 0.21, n = 7) or Fio2 0.6 (group 0.6, n = 7), and acute anemia was induced by isovolemic blood-for-hydroxy-ethylstarch (HES) exchange using a 6% HES solution (130/0.4).', 'The blood-for-HES-exchange was continued until a sudden decrease of total body oxygen consumption indicated the onset of oxygen supply dependency (primary end point); the corresponding hemoglobin (Hb) concentration was defined as "critical" (Hb(crit)). Secondary end points were changes in myocardial function, central hemodynamics, oxygen transport, and tissue oxygenation. Compared with room air ventilation (Fio2 0.21), hyperoxic ventilation with Fio2 0.6 enabled a larger blood-for-HES-exchange (139%, 124/156) of circulating blood volume vs. 87% (68/94, p < .05), until Hb(crit) was reached (1.5 g/dL [1.4/2.1] vs. 2.4 g/dL [2.0/2.8], p < .05). At Hb 2.4 g/dL (i.e., Hb(crit) in group 0.21), animals of group 0.6 still presented with superior oxygen transport, tissue oxygenation, and hemodynamic stability. However, hemodynamic and oxygen transport variables were found deteriorated more severely at Hb 1.5 g/dL (i.e., Hb(crit) of group 0.6) compared with group 0.21 at Hb 2.4 g/dL.\Question: Does hyperoxic ventilation increase the tolerance of acute normovolemic anemia in anesthetized pigs?
answer:
During cell-free volume replacement, hyperoxic ventilation with Fio2 0.6 generates a readily usable plasmatic oxygen reserve and thereby increases the tolerance toward acute normovolemic anemia.

question:
Context: To evaluate whether tumor invasion depth can be a reliable and easily applicable pathologic assessment strategy to predict outcomes using surgically resected cervical squamous cell carcinoma specimens from patients who have received neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).', "We included 173 patients with cervical squamous cell carcinoma who received neoadjuvant CCRT (n=125) or RT (n=48) and underwent subsequent radical hysterectomy. Data for the pre-operative clinical International Federation of Gynecology and Obstetrics (FIGO) stage, post-operative pathologic FIGO stage, World Health Organization (WHO) double diameter measurement evaluation, response evaluation criteria in solid tumors (RECIST 1.1) criteria, tumor necrosis rate (TNR), and tumor regression grade (TRG) were investigated to identify correlations with outcomes related to distant metastasis and survival. The tumor invasion depth (TID) and the tumor invasion depth with cytokeratin immunostaining correction (TIDC) at the cervical internal surface were measured to assess their relations to patients' outcomes.", 'Based on measurements taken via transvaginal ultrasound, the pre-operative clinical and post-operative pathologic FIGO staging as well as the WHO double diameter measurement evaluation and RECIST 1.1 criteria were predictive of distant metastasis and survival-related outcomes. Also, lymph node involvement was found to be an independent prognostic factor for recurrence and distant metastasis. Finally, univariate analysis showed both the TID and TIDC were highly related to distant metastasis, overall survival, and progression-free survival, irrespective of the clinical stage of carcinomas.\Question: Is tumor invasion depth a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy?
answer:
The TID or TIDC measured at the cervical internal surface is a useful and easily applied pathologic prognostic factor for distant metastasis and survival outcomes in patients with cervical squamous cell carcinoma treated with neoadjuvant RT or CCRT.