Renal fibrosis is a common pathway involved in the progression of various chronic kidney diseases to end-stage renal disease. Recent studies show that mitochondrial injury of renal tubular epithelial cells (RTECs) is a crucial pathological foundation for renal fibrosis. However, the underlying regulatory mechanisms remain unclear. Pyruvate carboxylase (PC) is a catalytic enzyme located within the mitochondria that is intricately linked with mitochondrial damage and metabolism. In the present study, the downregulation of PC in various fibrotic animal and human kidney samples is demonstrated. Renal proximal tubule-specific Pcx gene knockout mice (PcxcKO) has significant interstitial fibrosis compared to control mice, with heightened expression of extracellular matrix molecules. This is further demonstrated in a stable PC knock-out RTEC line. Mechanistically, PC deficiency reduces its interaction with sulfide:quinone oxidoreductase (SQOR), increasing the ubiquitination and degradation of SQOR. This leads to mitochondrial morphological and functional disruption, increased mtDNA release, activation of the cGAS-STING pathway, and elevated glycolysis levels, and ultimately, promotes renal fibrosis. This study investigates the molecular mechanisms through which PC deficiency induces mitochondrial injury and metabolic reprogramming in RTECs. This study provides a novel theoretical foundation and potential therapeutic targets for the pathogenesis and treatment of renal fibrosis.

Abstract Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 μM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819–60.761)) and mortality (HR 3.418, 95% CI (1.308–8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.

Pulmonary fibrosis (PF) is a serious pathological change of the lung.The specific mechanism of the initiation and development of PF is still unclear.Currently, it is believed that the abnormal fibrosis repair after repeated alveolar injury caused by multiple factors may be the main reason for the progression of PF disease.Some studies suggest that viruses may act as chronic antigens to stimulate the body repeatedly and cause PF.The studies also found that a large proportion of patients recovering from viral pneumonia will develop PF, affecting the quality of life.These results indicate that chronic inflammation caused by viral infection may be an important cause of the occurrence, development, and deterioration of PF.

Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine workers with silicosis and their co-workers who did not develop silicosis revealed that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. Global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the crystalline silica-induced pulmonary injury in wild-type but not in NLRP3 deficient mice. In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas volumes to resistant crystalline silica-induced lysosomal membrane damage. Thus, these findings provide molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants.

Objective: To analyze the clinical features of primary tracheobronchial pulmonary amyloidosis (PTBA). Methods: The records of 11 patients with PTBA diagnosed by pathology from January 2002 to June 2018 in Xiangya Hospital of Central South University were retrospectively reviewed, including clinical manifestations, laboratory and imaging examination, bronchoscopic manifestations and therapies. Meanwhile, PTBA was staged based on the severity and extent of lesion under bronchoscopy. Results: The most common clinical symptoms were cough and expectoration followed by shortness of breath and hemoptysis. Chest computed tomography (CT) revealed pulmonary infection (4/11), pulmonary nodules and masses (5/11), interstitial lesions (2/11), tracheal bronchial wall thickening (5/11) or airway stenosis (4/11). Bronchoscopy showed mucosal hypertrophy (8/11), nodular bulge (3/11), and luminal stenosis (6/11). According to the lesion involvement, 1 case only involved the lungs, 10 cases involved the trachea and/or bronchus, with (8/10) or without (2/10) lung lesions. According to the bronchoscopic staging, 2 cases (2/10) in the stage Ⅰ, lesions were limited; 2 cases (2/10) in the stage Ⅱ, lesions were diffuse; 6 cases (6/10) in the stage Ⅲ, diffuse lesions with stenosis. Conclusions: PTBA is a rare disease of the respiratory system, with unspecific clinical manifestations and diverse pulmonary imaging findings; airway mucosal hypertrophy and nodular bulging can be seen under bronchoscopy. Patients with advanced stage may present with airway stenosis.

目的:通过OSCE成绩评价临床医学五、八年制医学生临床能力.方法:选取中南大学湘雅医学院2008级五年制临床医学生,2006级八年制临床医学生为研究对象,分析两组学生OSCE成绩资料.结果:五、八年制学生在临床技能考核方面均较为合格,八年制学生在体格检查和文献检索方面表现突出.结论:五年制须更注重临床实践、文献检索能力培养;八年制则需寻求更多突破.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TO) consists of benign lesions of tracheal and bronchial mucosa with multiple nodular hyperplasia of bone or cartilage protruding into the lumen. METHODS: We diagnosed 73 subjects with TO with the use of bronchoscopy in the Department of Respiratory and Critical Care Medicine of Xiangya Hospital between January 2000 and April 2017. Clinical manifestations, radiographic characteristics, bronchoscopic manifestations, histopathological findings, and treatments were analyzed retrospectively. RESULTS: Subjects included 30 women and 43 men (mean age, 52.8 ± 11.7 y). Twenty-seven subjects were diagnosed with other diseases, including tuberculosis in 11 subjects, carcinoma in 13, bronchiectasis in 2, and pulmonary hamartomas in 1 subject. The most common symptom was cough (n = 34). Other initial manifestations included hemoptysis (n = 17), expectoration (n = 15), and chest pain (n = 8). Of those who underwent a computed tomography scan in our hospital, 28 of 32 subjects had noted calcification of the tracheal wall, with 4 of 32 subjects appearing normal. Bronchoscopy revealed typical accumulation of diffuse cartilaginous and osseous nodules of TO, and 9 had observable tracheal stenosis. Histopathologic results included the presence of chronic inflammation (n = 47), ossification (n = 38), and cartilage formation (n = 10). Most subjects received symptomatic treatment, although 3 subjects with severe airway obstruction received bronchoscopic treatment. CONCLUSION: The results indicated that TO lacks clinical specificity, which means that special therapy and bronchoscopy with histopathological and radiographic assistance is important for its diagnosis. The treating physicians' awareness about this condition is also important to its diagnosis and management.

A 56-year-old female patient was admitted to a hospital because of repeated fatigue, anorexia, fever for more than one year, recurrence for 2 months and sudden left limb twitch for 10 days. In 2017, patient was diagnosed with infective endocarditis, then underwent aortic valve replacement, valve biopsy showed Candida parapsilosis, she took medicine regularly after operation and withdrew medicine after three consecutive negative blood culture. Fever and multiple organ infarction occurred again in 2018, Candida parapsilosis was isolated again from blood culture, it is suggested that fungal endocarditis may be latent and recurrence in human body for a long time, exfoliation of vegetation may embolize various organs and lead to corresponding clinical manifestations, surgery combined with drug therapy and subsequent maintenance of antifungal therapy are extremely important to improve the prognosis of patients.

Objective To investigate the effects of fluorofenidone(AKF-PD)on diabetic kidney disease in db/db mice and its possible mechanisms.Methods(1)Fifty-six mice aged 8 weeks(half male and half female),including 42 db/db mice and 14 wild-type mice were studied.Fortytwo db/db mice randomly were divided into model group(mock-treated diabetic db/db mice),AKF-PD(250 mg· kg-1· d-1)treatment group and losartan(20 mg· kg-1· d-1)treatment group.Wild-type mice and model mice were treated with vehicle(0.5％sodium carboxymethylcellulose),while the treatment groups received either AKF-PD or losartan.After 18 weeks,the blood glucose and urinary albumin were measured,the pathological changes of kidney were observed by PAS staining.The protein expressions of type Ⅳ collagen and fibronectin(FN)in kidney tissue were detected by immunohistochemistry.(2)Mouse glomerular mesangial cells(MES-13 cells)were divided into six groups:normal glucose group(5.5 mmol/L glucose),hypertonic group(5.5 mmol/L glucose+19.5 mmol/L mannitol),high glucose group(25.0 mmol/L glucose),AKF-PD group(25.0 mmol/L glucose+400 mg/L AKF-PD)and losartan group(25.0 mmol/L glucose+2 μmol/L losartan).After 72 h treatment,the expressions of type Ⅰ collagen,type Ⅳ collagen and transforming growth factor-β1(TGF-β1)mRNA were detected by realtime PCR,and the content of TGF-β1 protein in the culture supernatant was detected by ELISA.Results(1)Compared with the wild type mice,model mice had increased weight,blood glucose and glomerulosclerosis index(all P ＜ 0.01),accompanied with heavy albuminuria,glomerular hypertrophy,mesangial area expansion and deposition of collagen type Ⅳ and FN(all P ＜ 0.01).Compared with model mice,in AKF-PD and losartan groups 24 h urinary albumin and glomerulosclerosis index decreased(all P ＜ 0.01),glomerular hypertrophy and mesangial area expansion alleviated,and the protein expressions of collagen type Ⅳ and FN were inhibited(all P ＜ 0.01).(2)Compared with the normal glucose group,the mRNA expressions of type Ⅰ collagen and type Ⅳ collagen increased in high glucose group,meanwhile the mRNA and protein expressions of TGF-β1 increased(all P ＜ 0.01).In AKF-PD and losartan groups the expressions of type Ⅰ collagen,type Ⅳ collagen and TGF-β1 were inhibited as compared with high glucose group(all P ＜ 0.05).Conclusion Fluorofenidone may play an anti-fibrotic effect in db/db mice by reducing the expression of TGF-β1 and inhibiting collagen synthesis in glomerular mesangial cells.

Idiopathic pulmonary fibrosis ( IPF ) is a chronic ,progressive and fatal disease with unknown pathogenesis .It showed that an aberrant wound-healing response following repetitive alveolar injury in genetically susceptible individuals contributes to IPF .Pulmonary infections and application of immunosuppressants in IPF patients lead to the increase in mortality .Recent evidences suggest that there is significant difference between the microbiome in IPF subjects and healthy controls after the improvement of 16SrRNA sequencing , which is used to determine the abundance of microbiome . Meanwhile ,the bacterial burden is related to the progression of this disease .It is suggest that the microbiome may play an important role in the development of IPF .

The etiology of idiopathic pulmonary fibrosis (IPF) is unknown ,and the pathogenesis of IPF is complex and not fully elucidated .In recent years ,the role of immunity in the pathogenesis of IPF has attracted increasing attention .This review summarizes the role of immune cells in the occurrence and development of IPF ,and provides ideas for the study of the pathogenesis and treatment of IPF .

Objective:To explore the feasibility of improving the recovery rate of bronchoalveolar lavage fluid(BALF)in mice with pulmonary fibrosis by improving the experimental method.Methods:Male BALB/C mice were selected.36 male mice from 6 to 8 week were divided into the 3 groups.After 28 days of pulmonary fibrosis,the bronchoalveolar lavage was performed 4 times,0.8 mL/times,and repeated 4 times.Macrophages and lymphocytes were the main inflammatory cells in the lavage fluid.Results:Through this method each mouse can be collected BALF about 2.6~2.8 mL/3.2 mL.There was no statistical difference between groups,and there was no significant difference between groups(P>0.05).The recovery rate was about 81.25%~87.5%,and the cell count could meet the experimental requirements.Conclusion:The recovery rate of alveolar lavage fluid obtained from this method can meet the need of medical scientific research,and it has the characteristics of strong operability and practicability.