[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

[Application of transbronchial cryobiopsy in the diagnosis of postoperative complications after lung transplantation: a report of 6 cases].

Objective: To investigate the efficacy and safety of transbronchial cryobiopsy (TBCB) after lung transplantation. Methods: The clinical characteristics, TBCB procedure, diagnosis and treatment, and outcomes of lung transplant recipients of 6 patients (all male, aged 33-67 years) with TBCB in China-Japan Friendship Hospital from May to November 2021 were retrospectively analyzed. Results: Among the 6 patients diagnosed by TBCB, there were 2 cases of organizing pneumonia, 1 acute cellular rejection, 1 antibody-mediated rejection, and 1 bronchiolitis obliterans, and 1 diffuse alveolar damage. After the clinical diagnosis was confirmed, the condition improved after adjustment of the treatments followed. There were no serious complications related to the TBCB procedure. Conclusion: TBCB is valuable and relatively safe in the diagnosis of complications after lung transplantation, but the indications need to be strictly controlled.

[A comparison of C+SCAV and SEAM conditioning regimens in efficacy and safety in autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma patients].

Objective: This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin's lymphoma (NHL) . Methods: A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively. Results: ① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups (P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group (P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM (P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group (P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) (P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) (P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) (P=0.389) , respectively. Conclusion: C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.

[Clinical characteristics of patients with antisynthetase syndrome and interstitial pulmonary disease].

Objective: To provide reference for clinicians in diagnosis and treatment of antisynthetase syndrome with interstitial pulmonary disease (ASS-ILD) by analyzing the clinical features, imaging features and pulmonary function changes of ASS-ILD patients. Methods: A total of 92 patients with ASS-ILD diagnosed in the Respiratory Center of China-Japan Friendship Hospital from January 2015 to May 2018 were included, clinical manifestations, high-resolution computed tomography (HRCT), pulmonary function test, treatment and outcome were retrospectively analyzed. Results: The average age of the 92 patients was (58.6±12.2) years with a ratio of male to female 1∶1.79. The main types of anti-synthetase antibody were anti-Jo-1 antibody (37 cases, 40.2%) and anti EJ antibody (26 cases, 28.3%). The most common symptoms of ASS-ILD were cough (79 cases, 85.9%), shortness of breath (60 cases, 65.2%), expectoration (54 cases, 58.7%), fever (34 cases, 36.9%), and common signs were craftsman's hand (30 cases, 32.6%) and joint pain (23 cases, 25.0%). The most common imaging findings in HRCT were ground-glass opacities(68 cases, 73.9%), reticulations (45 cases, 48.9%), tractive bronchiectasis (40 cases, 43.5%) and consolidation (39 cases, 42.4%). The most common types of ILD were non-specific interstitial pneumonia (NSIP) (63 cases, 68.5%), followed by NSIP-organic pneumonia (OP) (12 cases, 13.0%). The main type of lung function impairment was mild restrictive ventilation dysfunction. There were no significant differences in clinical features, imaging findings and pulmonary function changes in different subtypes of ASS-ILD patients (all P>0.05). Corticosteroids was used in 78 (84.8%) of ASS-ILD patients, and 34 cases (37.0%) were given cyclophosphamide. A total of 91 patients (98.9%) were discharged with improvement and 1 anti-EJ positive patient died. Conclusions: ASS-ILD occurs frequently in middle-aged and old women. Respiratory symptoms, craftsman's hands and arthritis are the most common clinical manifestations. The most common imaging types of ILD are NSIP and NSIP-OP. Corticosteroids is commonly used for treatment.

[When COVID-19 encounters interstitial lung disease: challenges and management].

In December 2019, a new type of coronavirus pneumonia (COVID-19) emerged in Wuhan, Hubei, and spread rapidly to China. The lung injury and repair caused by COVID-19 has many similarities with the onset and progression of interstitial lung disease (ILD) . Therefore, it is difficult to distinguish between COVID-19 and some types of new-onset ILD or other causes leading to acute exacerbation of ILD. Clinicians need to comprehensively analyze the epidemic history, disease onset characteristics, clinical manifestations, image characteristics, serological andpathogenic microorganism test results to confirm diagnosis. Because of this, the article will discuss the issues related to the differential diagnosis and management of COVID-19 and ILD, and try to provide reasonable suggestions.

[Differences in small airway lesions in patients with different types of idiopathic interstitial pneumonia].

Objective: To investigate the differences in small airway lesions in patients with different types of idiopathic interstitial pneumonia (IIPs). Methods: A total of 46 patients with IIPs confirmed by video assisted thoracoscopic or open lung biopsy, hospitalized in the Respiratory and Critical Care Medicine of Beijing Chao-Yang Hospital, from Dec. 1998 through Nov. 2007 were studied, including 19 patients with idiopathic pulmonary fibrosis (IPF group), 14 with nonspecific interstitial pneumonia (NSIP group), and 13 cryptogenic organizing pneumonia (COP group). Pulmonary function and high resolution CT (HRCT) of the patients were examined before lung biopsy, and lung biopsy tissue were stained with hematoxylin-eosin. The abnormality of small airways in pathology, pulmonary function and HRCT were compared among these patients with IIPs. Results: Small airway inflammatory cell infiltration score (53.8±17.7) was significantly higher in the COP group than in the IPF group (38.8±9.7) (P<0.01). The fibrous tissue proliferation score in small airways (42.9±12.1) in the IPF group was significantly higher than that in the NSIP group (31.4±10.5) and the COP group (26.7±16.3) (both P<0.05). In the IPF group, NSIP group and COP group, the small airway function index was significantly reduced, and the maximum expiratory flow rate (V(25%), V(50%)) at 25% and 50% of the lung capacity was<80% predicted, the incidences of small airway dysfunction in the three groups were 63.2%, 69.2%, and 63.6%, respectively. There was no significant difference among the groups (P>0.05). Small airway inflammatory cell infiltration was negatively correlated with V(50%) of small airway function (r=-0.305, P=0.049). The bronchodilation rate in the HRCT of the IPF group (100%) was significantly higher than that of the NSIP group (50.0%) and the COP group (53.8%) (both P<0.01). Conclusion: The patients with IPF, NSIP and COP have abnormal pathologic, physiological and imaging changes of small airways, moreover have different characteristics.

[A clinical study of allogeneic hematopoietic stem cell transplantation in 23 patients with early T-cell precursor acute lymphoblastic leukemia].

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions: Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

[Metformin protects against bleomycin-induced pulmonary fibrosis in mice].

Objective: To explore the effect of metformin on murine model of bleomycin (BLM)-induced lung injury and fibrosis. Methods: A total of 30 mice were divided into 3 groups: control, BLM, and BLM with metformin, in accordance with the random number table and each group had 10 mice. To induce the pulmonary fibrosis model, a concentration of 2 mg/ml bleomycin was intratracheally administered in the BLM group and BLM with metformin group with a volume of 1.75 µl/g, while the control group accepted saline with the same volume. Metformin (200 mg/kg) was given to the mice orally once a day from the day before intratracheal instillation of bleomycin to day 14. The daily survival condition of mice was recorded during 14 days. At day 14, HE-staining was used to assess the severity of fibrosis according to the method proposed by Ashcroft. Total lung collagen content was determined by hydroxyproline assay and Masson's trichrome staining. To examine the expression of fibronectin we used the method of immunohistochemistry staining. The changes of Transforming Growth Factor beta 1 (TGF-ß(1)) in plasm, bronchoalveolar lavage fluid (BALF) and lung were measured by ELISA. Results: The survival rates of control group, BLM group and BLM with metformin group at day 14 were 10/10, 4/10 and 7/10 respectively. According to the method proposed by Ashcroft the score of metformin treated mice was significantly lower than that of the bleomycin model mice[(3.82±0.58) vs (7.79±0.06), (P<0.05)]. The hydroxyproline level in lung tissue were markedly attenuated in metformin treated mice compared with bleomycin model mice [(0.40±0.05) vs (0.73±0.10) µg/mg, (P<0.05)]. The level of TGF-ß(1) in plasma, BALF and lung tissue were also decreased in mice treated with metformin compared with bleomycin model mice [(2.32±0.68) vs (4.59±0.45) ng/ml, (0.81±0.09) vs (1.40±0.06) ng/ml, (17.12±0.83) vs (21.25±0.69) ng/mg, all P<0.05]. Conclusion: Metformin can reduce the severity of pulmonary fibrosis in mice induced by bleomycin.

Clinical effectiveness of pemetrexed combined with cisplatin chemotherapy for advanced and maintenance treatment for patients with non-small-cell lung cancer.

OBJECTIVE: To evaluate the clinical effectiveness of pemetrexed combined with cisplatin for the first-line chemotherapy of patients with advanced non-small-cell lung cancer (NSCLC) and maintenance treatment. PATIENTS AND METHODS: 240 advanced NSCLC patients were randomly divided into either a control group (treated with gemcitabine combined with cisplatin) or an observation group (treated with pemetrexed combined with cisplatin). The primary treatment was defined as first-line chemotherapy, and the maintenance treatment was defined as retreatment. The demographic data from both groups were statistically similar. Patients were treated for 21 days for each cycle and underwent between 4 to 6 treatment cycles. RESULTS: The mid-and-long term efficacy between groups was compared using efficacy indexes [objective response rate (ORR), disease control rate (DCR), and chemotherapy toxic reaction rate] and progression-free survival (PFS), median survival time, and one-year survival rates. The observation group showed a statically greater (p<0.05) ORR and DCR than the control group. Comparison of the prevalence of toxic reaction above level III between the two groups revealed no statistical difference (p>0.05). The PFS, median survival time, and one-year survival rate of the observation group were statistically longer (p<0.05) than those of the control group. CONCLUSIONS: Pemetrexed combined with cisplatin was both safe and efficacious for the first-line chemotherapy of NSCLC patients at a progressive stage and for maintenance treatment.

[Clinical features of acute diffuse pulmonary exudative disorders].

Objective: To analyze the clinical features of acute diffuse pulmonary exudative disorders. Methods: The data were collected from patients who were hospitalized in respiratory intensive care unit (RICU) of Beijing Chaoyang Hospital affiliated to the Capital Medical University during January 2009 to December 2011, and had acute clinical course with imaging findings of diffuse pulmonary infiltrated shadows (similar to acute respiratory distress syndrome (ARDS)). The causes of disease and clinical features were analyzed. Results: A total of 86 patients with acute diffuse pulmonary exudative disorders were included. Sixty-two (72.1%) were males, with a mean age of (58.6±16.4) years old; 24(27.9%) were females, with a mean age of (48.2±18.3) years old. The duration of the disease before administration was (11.5±5.2) days, and RICU stay was (15.5±9.5) days, with hospital mortality of 40.7% and the average hospitalization cost of 101 thousand RMB. The main cause was infection, which occurred in 53 cases (61.6%) (virus in 21 cases, bacteria in 14 cases, fungus in 11 cases, pneumocystis in 15 cases and others in 3 cases, mixed infection in 11 cases). Interstitial pneumonia occurred in 12 cases (idiopathic interstitial pneumonia in 9 cases: cryptogenic organizing pneumonia in 3 cases, the acute exacerbation of idiopathic pulmonary fibrosis in 3 cases, nonspecific interstitial pneumonia in 1 case, acute interstitial pneumonia in 2 cases, and connective tissue disease in 3 cases), aspiration pneumonia in 10 cases, acute left heart failure in 6 cases, and exogenous pulmonary ARDS in 5 cases. Conclusions: The main cause of acute diffuse pulmonary exudative disorders is pulmonary infection, followed by interstitial pneumonia. The hospital mortality and hospitalization cost are high.

[Effect of water-soluble C(60) fullerenes on pulmonary fibrosis induced by bleomycin in mice].

Objective: To evaluate the role of water-soluble C(60) fullerenes in mice model of lung injury and fibrosis that induced by bleomycin. Methods: A total of 20 healthy C57BL/6J mice were randomly divided into normal control group, bleomycin group, high dose C(60) group, low dose C(60) group, each group with 5 mice. Mice were induced pulmonary fibrosis by intratracheal injection of bleomycin except the normal control group, which was induced by saline instead. In low dose C(60) group and high dose C(60) group, 1 mg·kg(-1)·d(-1) and 10 mg·kg(-1)·d(-1) water-soluble C(60) fullerenes was injected into mice intraperitoneally every day, which began from one day before intratracheal instillation of bleomycin until the end of observation. Saline was given to mice in the same way in normal control and bleomycin group. This study investigated the variation of weight and survival rate of mice for 14 d. HE-staining and Masson's trichrome staining were used to assess the severity of fibrosis according to the method proposed by Ashcroft at 14th day. Total lung collagen content was determined by hydroxyproline assay. The changes of transforming growth factor-ß(1) (TGF-ß(1)) and tumor necrosis factor α (TNF-α) in plasma, bronchial alveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). And, the amount of reactive oxygen species (ROS) was tested by 2, 7-dichlorofuorescin diacetate (DCFH-DA), and determined by the ratio of fluorescence intensity and protein content (OD/µg). Results: C(60) can protect mice that injured by bleomycin from weight loss. According the method proposed by Ashcroft et al.HE and Masson's trichrome staining showed that collagen deposition in lung tissue were markedly attenuated in C(60) (1 mg·kg(-1)·d(-1) and 10 mg·kg(-1)·d(-1)) treated mice compared with bleomycin model mice[(4.08±0.52), (3.00±0.41) vs (6.75±0.75) points, both P<0.01]. In low dose C(60) group and high dose C(60) group, the content of hydroxyproline in lung tissue were significantly lower than that in bleomycin group[(0.36±0.06), (0.35±0.08) vs (0.55±0.16) µg/mg, both P<0.05]. The level of TGF-ß(1) in BALF and lung tissue were also decreased in mice treated with C(60) (10 mg·kg(-1)·d(-1)) compared with bleomycin model mice, but the difference had no statistical significance[(9.38±5.32) vs (23.60±8.96) pg/ml, (2.89±0.35) vs (6.44±2.95) pg/mg, both P>0.05]. Also, in high dose C(60) group, the content of TNF-α in plasma, BALF and lung tissue were significantly lower than those in bleomycin group[(4.56±0.73) vs (7.21±2.26) pg/ml, (34.58±23.30) vs (151.00±27.34) pg/ml, (22.99±5.83) vs (122.90±22.04) pg/mg, all P<0.05]. In addition, Compared with bleomycin group, ROS in lung tissue was significantly decreased after treatment with C(60) (10 mg·kg(-1)·d(-1))[(19.68±0.91) vs (22.92±1.71) OD/µg, P<0.05]. Conclusion: Water-soluble C(60) fullerenes reduce the severity of pulmonary fibrosis induced by bleomycin in mice.

[The clinical features of primary or metastatic malignancies presenting with multiple lung cavities].

OBJECTIVE: To evaluate the clinical, radiological and pathological features of primary or metastatic malignancies presenting with multiple lung cavities. METHODS: A total of 38 cases met the inclusion criteria and had adequate imaging data for retrospective review between June 2006 and August 2013. There were 30 cases of primary lung cancer, and 8 cases of pulmonary metastasis including 6 gastrointestinal tract malignancies, 1 vulva malignancy and 1 scalp malignancy. There were 21 females and 17 males, with a median age of 63 years. RESULTS: Cough and expectoration were the most common clinical manifestations of primary lung cancer(22/30). There were 4 main types of lung cavities, including thick-walled cavities(n=12), circular cavities (n=24), thin-walled cavities or cystic cavities (n=11), cavities or multi-cystic changes within airspace consolidation or ground glass opacity(n=11). The cavitary lesions were often accompanied by pulmonary nodules, mass and ground glass opacity(32/38, 84%). The presence of internal soft-tissue septa in the cavity was commonly seen(17/38, 45%). The 4(th) type of cavity and presence of air-fluid levels were only found in lung adenocarcinoma, including 5 cases of mucinous adenocarcinoma. In both primary lung cancers and metastatic tumors, adenocarcinoma was the most common histological type (29/30 and 6/8, respectively). The other histological types included 1 case of lung squamous cell carcinoma, 1 vulva adenosquamous carcinoma and 1 scalp angiosarcoma. The possible mechanisms of cavity formation included necrosis, mucin-secretion air-containing cystic spaces in papillary tumors and the check-valve mechanism. CONCLUSIONS: Adenocarcinoma was the most common histological type in multiple cavitary primary lung cancers and metastatic tumors. These cavities showed varied radiological features and were easy to be misdiagnosed as benign cavitary lung diseases.

Toll-like receptor 4 promotes fibrosis in bleomycin-induced lung injury in mice.

The specific role of Toll-like receptor 4 (TLR4) in bleomycin-induced lung fibrosis of mice, a model of human idiopathic pulmonary fibrosis, has not been characterized. We injected bleomycin intratracheally into TLR4 knockout (TLR4(-/-)) and wild-type (WT) mice. Twenty-one days after injection, mice were sacrificed and their lungs were harvested for pathological, hydroxyproline, mRNA expression, and collagen I analyses. Body weight changes and mortality were observed. Light microscopy showed that lung fibrosis was minimal in TLR4(-/-) compared to that in WT mice on day 21 after bleomycin instillation. The Ashcroft score was significantly lower in TLR4(-/-) than in WT mice (3.667 ± 0.730 vs 4.945 ± 0.880, P < 0.05). Hydroxyproline content was significantly lower in TLR4(-/-) than in WT mice on day 21 after bleomycin injection (0.281 ± 0.022 vs 0.371 ± 0.047, P < 0.05). Compared to WT mice, bleomycin-treated TLR4(-/-) mice expressed significantly lower type I collagen mRNA levels (mesenchymal marker; 11.069 ± 2.627 vs 4.589 ± 1.440, P < 0.05). Collagen I was significantly lower in TLR4(-/-) than in WT mice (0.838 ± 0.352 vs 2.427 ± 0.551, P < 0.05). Bleomycin-treated TLR4(-/-) mice had a significantly lower mortality rate on day 21 than WT mice (33 vs 75%, P < 0.05). Body weight reduction was lower in TLR4(-/-) mice than in WT mice; this difference was not statistically significant (-3.735 ± 5.276 vs -6.698 ± 3.218, P > 0.05). Thus, bleomycin-induced pulmonary fibrosis is TLR4-dependent and TLR4 promoted fibrosis in bleomycin-challenged mice.

Clinical and pathological features of adult pulmonary tuberculosis with reversed halo sign.

OBJECTIVE: To understand the pathological correlation of the reversed halo sign (RHS) in adult pulmonary tuberculosis (PTB) patients, and to compare the clinical characteristics of PTB patients with RHS with those without RHS. MATERIALS AND METHODS: The study included 80 patients consecutively diagnosed with PTB by pathology or smear-positive sputum or bronchoalveolar lavage fluid from 1 January to 31 August 2012. All patients underwent high-resolution computed tomography (HRCT) scan, and were divided into two groups based on HRCT findings: RHS and non-RHS. All patients in the RHS group underwent CT-guided transthoracic lung biopsy to evaluate histopathological abnormalities. Clinical features such as smoking history, TB-related symptoms and comorbidities were compared. RESULTS: The 'ring' in the RHS corresponded to granulomata, with or without acid-fast stain positivity, and with or without caseating necrosis. Compared with the non-RHS group, patients in the RHS group were significantly younger, were less likely to have a smoking history and had fewer TB-related symptoms and comorbidities. CONCLUSIONS: Our study shows that younger PTB patients with relatively better baseline status tended to present with RHS on HRCT, have fewer TB-related symptoms and present atypically.

Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree.

Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1, keratin 9, keratin 16, desmoglein 1 and plakoglobin. Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain-of-function mutation highlights the role of domain 2B in mediating filament assembly.