Objective: To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. Methods: A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. Results: In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients (χ(2)=11.039, P=0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all P>0.05) . Conclusion: The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Pneumonia, Pneumocystis/diagnostic imaging* ; Retrospective Studies ; Pneumocystis carinii ; Hematologic Diseases/complications* ; Tomography, X-Ray Computed ; Fibrosis

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Objective: To investigate the clinical phenotypes and genotypic spectrum of exocrine pancreatic insufficiency in children with cystic fibrosis. Methods: This was a retrospective analysis of 12 children with cystic fibrosis who presented to Children's Hospital of Fudan University from December 2017 to December 2021. Clinical features, fecal elastase-1 level, genotype, diagnosis and treatment were systematically reviewed. Results: A total of 12 children, 7 males and 5 females, diagnosis aged 5.4 (2.0, 10.6) years, were recruited. Common clinical features included chronic cough in 12 cases, malnutrition in 7 cases, steatorrhea in 7 cases, bronchiectasis in 5 cases and electrolyte disturbance in 4 cases. Exocrine pancreatic insufficiency were diagnosed in 8 cases,the main clinical manifestations were steatorrhea in 7 cases, of which 5 cases started in infancy; 6 cases were complicated with malnutrition, including mild in 1 case, moderate in 2 cases and severe in 3 cases; 3 cases had abdominal distension; 2 cases had intermittent abdominal pain; 4 cases showed fatty infiltration or atrophy of pancreas and 3 cases showed no obvious abnormality by pancreatic magnetic resonance imaging or B-ultrasound. All 8 children were given pancreatic enzyme replacement therapy, follow-up visit of 2.3 (1.2,3.2) years. Diarrhea significantly improved in 6 cases, and 1 case was added omeprazole due to poor efficacy. A total of 20 variations of CFTR were detected in this study, of which 7 were novel (c.1373G>A,c.1810A>C,c.270delA,c.2475_2478dupCGAA,c.2489_c.2490insA, c.884delT and exon 1 deletion). Conclusions: There is a high proportion of exocrine pancreatic insufficiency in Chinese patients with cystic fibrosis. The main clinical manifestations are steatorrhea and malnutrition. Steatorrhea has often started from infancy. Pancreatic enzyme replacement therapy can significantly improve the symptoms of diarrhea and malnutrition.
Cystic Fibrosis/genetics* ; Diarrhea/complications* ; Exocrine Pancreatic Insufficiency/genetics* ; Female ; Genotype ; Humans ; Male ; Malnutrition/complications* ; Pancreatic Diseases/genetics* ; Phenotype ; Retrospective Studies ; Steatorrhea/genetics*

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.
Aspartate Aminotransferases ; Biomarkers ; Fibrosis ; Hepatitis C ; Hepatitis C, Chronic/complications* ; Humans ; Infant, Newborn ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Polyesters ; ROC Curve ; Retrospective Studies

Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 μg/L during the induction phase and <100 μg/L during the maintenance phase.
Male ; Humans ; Female ; Hemochromatosis/therapy* ; Hemochromatosis Protein/genetics* ; Carcinoma, Hepatocellular/complications* ; Iron Overload/genetics* ; Ferritins ; Liver Cirrhosis/complications* ; Iron ; Fibrosis ; Liver Neoplasms/complications* ; Transferrins

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease (ILD) of unknown causes, which is characterized by pulmonary fibrosis. The median survival period after diagnosis is about 2-4 years. In recent years, the incidence rate of lung cancer associated with IPF (IPF-LC) is increasing, and the prognosis is worse than that of IPF alone. Pulmonary fibrosis may be closely associated with the occurrence and development of lung cancer. Although the pathogenesis of IPF-LC is still unclear, the current research shows that there are similarities between the pathogenesis of these two diseases at molecular and cellular levels. At present, the research on the cellular and molecular mechanism of lung cancer related to pulmonary fibrosis has become the focus of researchers' attention. This article reviews the related literature, focusing on the latest status of the cellular and molecular mechanisms and treatment of IPF-LC, hoping to help clinicians understand IPF-LC.
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Humans ; Idiopathic Pulmonary Fibrosis/complications* ; Lung Neoplasms/complications*

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

OBJECTIVE: To investigate the clinical features and outcome of hydronephrosis induced by retroperitoneal fibrosis (RPF), and to evaluate the effect of corticosteroid based therapy combined with surgical intervention of ureteral obstruction. METHODS: A total of 17 RPF patients with hydronephrosis hospitalized in Peking University International Hospital from May 2016 to December 2019 were analyzed retrospectively. RESULTS: The median age was 56 (53, 65) years, the male to female ratio was 2.4 : 1, and the disease duration was 4.00 (0.83, 8.00) months. The initial symptoms included back pain (9 cases), abdominal pain (6 cases), oliguria (2 cases) and lower limb edema (3 cases). Eight patients presented left hydronephrosis, 1 right hydronephrosis and 8 bilateral hydronephrosis. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were both elevated in 13 patients (76.5%, n=17). Immunoglobin (Ig) G4 increased in 5 cases (29.4%, n=17). IgG, IgE and IgA increased in 4 cases (30.8%, n=13), 4 cases (30.8%, n=13) and 1 case (7.7%, n=13), respectively. Among 12 patients who underwent biopsy, 3 patients were diagnosed with IgG4-relate disease. The level of IgG4 in the tissues varied, 6 cases expressed less than 10 per high power field (HPF) or no expression (50.0%). Only 2 cases expressed 10-30/HPF (16.7%), and 4 cases revealed more than 30/HPF (33.3%). Among the 17 patients with ureteral obstruction, no urinary drainage procedure was needed in 4 patients who had mild ureteral obstruction, whereas, ureteral stenting was carried out in the other 13 cases before drug treatment. Time was too short to evaluate the effect of urinary drainage procedures in 4 patients. For the rest, ureterolysis had to be performed in 3 cases after failed ureteral stent insertion. Successful drain removal was accomplished in all of these 9 patients and the mean time to drain removal was (6.7±3.0) months. In addition, 10 patients had complete medical records after an average follow-up time of 5 (3-13) months. Levels of ESR, CRP, IgG4, IgG, IgE, IgA were 54.0 (36.3, 98.5) mm/h, 26.8 (8.7, 53.0) mg/L, 1.34 (0.55, 3.36) g/L, 16.3 (13.0, 21.1) g/L, 40.5 (31.4, 203.0) IU/mL, 2.51 (1.82, 3.25) g/L at baseline, which all decreased predominantly after treatment. ESR, CRP, IgG4, IgG, IgE and IgA dropped by 38.5 (23.5, 54.3) mm/h (P < 0.01), 23.0 (5.5, 52.0) mg/L (P < 0.05), 0.92 (0.40, 2.85) g/L (P < 0.01), 6.5 (1.7, 9.1) g/L (P < 0.05), 23.7 (4.8, 162.0) IU/mL (P < 0.05) and 0.77 (0.32, 1.26) g/L (P < 0.05), respectively. Size of mass measured by CT/MRI imaging became smaller significantly and hydronephrosis relieved. CONCLUSION Onset of RPF is insidious and lack of specific initial symptoms. Corticosteroid based therapy combined with surgical intervention of relieving obstruction is effective.
Aged ; Female ; Humans ; Hydronephrosis/etiology* ; Male ; Retroperitoneal Fibrosis/complications* ; Retrospective Studies ; Ureter ; Ureteral Obstruction

OBJECTIVE: To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. METHODS: Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. RESULTS: The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. CONCLUSIONS Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Angiotensin II Type 1 Receptor Blockers ; Animals ; Antihypertensive Agents ; Extracellular Matrix Proteins ; metabolism ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; Random Allocation ; Telmisartan ; pharmacology ; Transforming Growth Factor beta1 ; pharmacology ; Ureteral Obstruction ; complications ; metabolism

OBJECTIVE: To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism. METHODS: Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot. RESULTS: Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups. CONCLUSION These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.
Animals ; Enzyme Inhibitors ; pharmacology ; Fibrosis ; complications ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rhodanine ; analogs & derivatives ; pharmacology ; Thiazolidines ; pharmacology ; Ureteral Obstruction ; complications ; drug therapy