Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

BACKGROUND: Bronchopleural fistula (BPF) is one of the most serious and rare postoperative complications, especially the bronchial stump fistula after lobectomy/pneumonectomy. Common treatment options include conservative medical treatment combined with surgery. However, due to the delayed healing of the fistula, the chest cavity continues to communicate with the outside world, and the patient is prone to complicated with severe thoracic infection and respiratory failure, so that the physical condition can hardly tolerate the second surgical procedure. Endoscopic treatment provides a new option for the treatment of this complication. METHODS: A case of right pulmonary squamous cell carcinoma was admitted to the Department of Thoracic Surgery II, Peking University Cancer Hospital in June 2016. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed. RESULTS: A 65 year old male patient was admitted to hospital because of "cough with blood in sputum for 3 months". Chest computed tomography (CT) showed soft tissue density mass shadow in the right lower lobe. A tumor could be seen in the opening of the right middle lobe and basal segment of lower lobe. Biopsy confirmed squamous cell carcinoma. Diagnosis consideration: squamous cell carcinoma of the middle and lower lobe of the right lung (cT2aN2, IIIa). Patients received gemcitabine plus cisplatin neoadjuvant chemotherapy for 2 cycles, and the effect of chemotherapy showed stable disease (SD). Four weeks after chemotherapy, the patient underwent video-assisted thoracic surgery (VATS) assisted right middle and lower lobectomy and mediastinal lymph node dissection. On the 5th day after operation, the patient developed acute respiratory distress syndrome (ARDS) and was transferred to intensive care unit (ICU) again after endotracheal intubation. On the 7th day after operation, the patient developed a right intermediate trunk bronchial stump fistula, but due to ARDS, the patient's physical condition could not tolerate the second operation. Under the support of extracorporeal membrane oxygenation (ECMO), a membrane covered, expandable, hinged stent was inserted into the intermediate trunk bronchial stump through rigid bronchoscope, and was successfully blocked. Due to no improvement in ARDS and irreversible pulmonary interstitial fibrosis, the patient received double lung transplantation successfully after systemic anti-infection treatment. CONCLUSIONS Endoscopic implantation of covered stent is a simple, safe and effective method for closure of bronchial stump fistula. When the patient's clinical situation is not suitable for immediate surgery, endoscopic stent implantation can be used as a preferred treatment method to create opportunities for follow-up treatment.

BACKGROUND: IIIa-N2 non-small cell lung cancer was significant different in survival, although N stage of lung cancer based on anatomic location of metastasis lymph node. Lymph node ratio considered of prognostic factor might be the evaluation index for IIIa-N2 non-small cell lung cancer prognosis. Therefore, the aim of the study was to evaluate the correlation between lymph node ratio and clinicopathological features and prognosis of IIIa-N2 non-small cell lung cancer prognosis. METHODS: A total of 288 cases of pathological IIIa-N2 non-small cell lung cancer were enrolled who received radical resection at the Department of Thoracic Surgery II, Peking University Cancer Hospital from January 2006 to December 2016. The univariate analysis between clinicopathological variables and lymph node ratio used Pearson's chi-squared test. Cox regression was conducted to identify the independent prognosis factors for IIIa-N2 non-small cell lung cancer. RESULTS: There were 139 cases in the lower lymph node ratio group, another 149 cases in the higher lymph node ratio group. Adenocarcinoma (χ²=5.924, P=0.015), highest mediastinal lymph node metastasis (χ²=46.136, P<0.001), multiple-number N2 metastasis (χ²=59.347, P<0.001), multiple-station N2 metastasis (χ²=77.387, P<0.001) and skip N2 lymph node metastasis (χ²=61.524, P<0.001) significantly impacted lymph node ratio. The total number of lymph node dissection was not correlated with the lymph node ratio (χ²=0.537, P=0.464). Cox regression analysis confirmed that adenocarcinoma (P=0.008), multiple-number N2 metastasis (P=0.025) and lymph node ratio (P=0.001) were the independent prognosis factors of disease free survival. The 5-year disease free survival was 18.1% in the higher lymph node ratio group, and 44.1% in the lower. Lymph node ratio was the independent prognosis factor of overall survival (P<0.001). The 5-year overall survival was 36.7% in the higher lymph node ratio group, and 64.1% in the lower. CONCLUSIONS Lymph node ratio was correlative with the pathology, highest mediastinal lymph node metastasis, multiple-number N2 metastasis, multiple-station N2 metastasis and skip N2 lymph node metastasis. Lymph node ratio was the independent prognosis factor for IIIa-N2 non-small cell lung cancer.

OBJECTIVETo study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia.

METHODSBlood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared.

RESULTSThe hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05).

CONCLUSIONMTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.

Adult ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Hyperlipidemias ; blood ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

ObjectiveTo evaluate the safety and effects of pseudomonas aerug PA-MSHA vaccine on cytoimmunity in advanced gastric cancer patients. MethodsSeventy two patients with advanced gastric cancer were randomly divided into experimental group and control group. Tumor bed was treated intraoperatively by pseudomonas vaccine injection in experimental group.The venous bloods were sampled prior to surgery (preoperative) and on days 10,20,and 30 postoperatively.The total lymphocyte count and lymphocyte subpopulations were detected while the postoperative complications and adverse drug reaction were observed,prognosis was evaluated. ResultsThe total lymphocyte count(P =0.042) and the counts ofCD3+ lymphocyte(P =0.027) and NK cell increased (P =0.012) obviously in experimental group.CD8+ lymphocyte decreased(P =0.037),but the counts of CI4+ lymphocyte and CD4+/CD8+ were not significantly different.Complications were not significantly different in the two groups.One year survival rate was longer ( 94.9％ ) in experimental group than that in the control group ( 83.3％ ) ( P =0.022 ).ConclusionsPeritoneal cavity administration with pseudomonas aerug vaccine was safe,and effectively helps regulate cytoimmunity in postoperative patients of advanced gastric carcinoma.

Objective To compare the efficacy of urinary type Ⅳ collagen( Ⅳ C), N-acetyl-β-D-glucosaminidase( NAG ), serum cystatin C ( CysC ), β2 microglobulin ( β2-MG ) in early diagnosis of diabetic nephropathy(DN) ,and to develop a multiple regression equation using above mentioned indices. Methods One hundred and eight cases of DM patients were enrolled in the study. All those DM patients were divided into two groups according to 24 hr urinary albumin excretion(UAE): non-DN group( UAE ＜30 mg/24 h)and DN group (UAE ≥30 mg/24 h). Receiver operating characteristics (ROC)curve was developed using urinary IVC, NAG,serum CysC and β2-MG,and the efficiency of the four indices for early diagnosis of diabetic nephropathy were assessed by area under the curve ROC (AUCROC). Furthermore, the regression equation of four indicators was developed. All statistical analyses were performed using SPSS 13.0. Results The levels of urine Ⅳ C, NAG,CysC,β2-MG,were(3.91±1.93)ng/ml, ( 12.20 ±3.46)U/L, ( 1.18 ±0.41 )mg/L , (2. 50 ±0. 74)mg/ml in the non-DN group, respectively; and ( 14.14 ± 11.17 ) ng/ml, ( 23.12 ± 13.57 ) U/L, ( 2.69 ± 1.69 ) mg/L and(5.21 ± 2.78)mg/ml in the DN group, respectively. There were significant differences in the comparison of the four indicators between the two groups ( Ps ＜ 0.01 ). AUCROC of Ⅳ C, NAG, CysC and β2-MG were 0. 747,0.732,0.764 and 0.823 respectively;which meant the diagnostic efficacy for DN decended from β2-MG, CysC,Ⅳ C, to NAG in order. All these indices showed significant efficiency in assisting diagnosis of early DN ( Ps ＜0.01 ). The regression equation of UAE and the four indices was: UAE = - 242.624 + 6.362IVC + 8.662NAG + 64. 622CysC + 29.488β2-MG, and the equation had statisticl significance( P ＜ 0.O1 ). Conclusion Urine Ⅳ C, NAG,serum CysC, and β2-MG showed significant value in assisting diagosis of early DN, and could be sensitive indices for DN.

Objective To study the clinical significance of urinary type Ⅳ collagen(IVC)and UmAlb/UCr ratio in the diagnosis of early diabetic nephropathy. Methods We collected 52 cases of diabetes(group A)without DN(UAE ＜30 mg/24 h),35 cases of diabetes(group B)with early DN(UAE as 30-300 mg/24 h),and 50 cases of healthy controls. The differences of urine IVC,UmAlb/UCr were compared among group A,B and the control group. ROC curve was used for evaluating the use of urine IVC and UmAlb/UCr in the diagnosis of early DN. The correlation of urine IVC and UmAlb/UCr with UAE were investigated,and linear model curve were established. IVC in urine was detected by chemiluminescence,UmAlb was detected by immunoturbidimetric assay,UCr was detected by enzymatic. Statistical analysis were performed with SPSS13.0 statistical software. Results The urine IVC testing of group A,B and the control group were(2. 64 ± 0. 91),(3.91 ± 1.93)and(10. 08 ± 6. 50)μg/L,respectively. The UmAlb/UCr(mg/mmol)testing of group A,B and the control group were(1.50 ± 0. 40),(2. 58 ±2. 10)and(17.95 ± 13. 38)mg/mmol,respectively. Urine IVC and UmAlb/UCr were significant difference between group A,B and the control group(Ps ＜ 0. 01);the ROC area under the curve(AUCROC)of urine IVC and UmAlb/UCr were 0. 724,0. 945,the two indicators for early diagnosis of DN were significant(Ps ＜ 0. 01);The pearson correlation coefficients of the urine IVC and UmAlb/UCr were 0. 529,0. 919 ,respectively. They were positive and significant correlation(Ps ＜ 0. 01),On the basis of the correlation coefficient and linear model fitting curve with the UAE,the relationship of UmAlb/UCr with the UAE was better than that of IVC. Conclusions Urine IVC and UmAlb/UCr ratio,which significantly assists diagnosis in diabetic nephropathy ,can be used as a sensitive diagnostic indicator of diabetic nephropathy. Moreover,the relationship of UmAlb/UCr with the UAE is better than that with IVC.

The purpose of this study was to clone human HSP90beta cDNA and construct its eukaryote expression vector . The total RNA was isolated by TRIzol Reagent (Invitrogen) from human NPC and its cDNA was gained by RT-PCR. The purified RT-PCR products and PGEM-T Easy Vector were ligated and transformed into XL1-blue E. coli bacteria. The white clones were selected and the plasmid was purified, which was further identified by double enzyme digestion and sequenced. PGEM-hHSP90beta and pcDNA3.1(+) DNA were digested by AflII and Xbal respectively. After purification, the two fragments obtained were ligased by using T4 DNA ligase (Fermentas). This recombinant DNA was then transformed into E. coli Competent Cells XL1-blue and positive clones were selected on the LB agarose plate containing Ampr (100 microg/ml). Single clones were identified by double digestion with AflII and Xbal, and two fragments with the size 5.4 kb and 2.1 kb were produced as expected. The hHSP90beta gene was successfully inserted into the eukaryote expression vector pcDNA3.1(+) by the recombination technique in vitro.
Cloning, Molecular ; DNA, Complementary ; genetics ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; HSP90 Heat-Shock Proteins ; biosynthesis ; genetics ; Humans ; Plasmids ; genetics ; Recombinant Proteins ; biosynthesis ; genetics