Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin.

AIM: To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis (FVA) in a Chinese Han family. METHODS: Pars plana vitrectomy (PPV) surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment, without evidence of cardiac, renal, gastrointestinal, central nervous system or peripheral nervous system dysfunction. During the surgery, the patient presented with a gray-white dense and thick cotton wool-like change in the vitreous body, accompanied by complete retinal detachment. Additionally, hard, free and movable yellow-white deposits were observed in the posterior pole and surrounding retina, the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination, and whole exome sequencing was performed on blood samples from the patient and her cousin. RESULTS: During the operation, it was discovered that there was a complete detachment of the retina and a significant amount of hard, free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina. This is an exceedingly rare ocular manifestation. Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining, as well as elevated vascular endothelial growth factor (VEGF) expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination. The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin (TTR) gene, resulting in a substitution of glycine (Gly) at position 103 with arginine (Arg). CONCLUSION: FVA may present with various ocular manifestations, but panretinal detachment is a rare occurrence. In cases where retinal detachment persists for an extended period of time, amyloid deposits may form under the retina through retinal tears, leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis. Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state, necessitating careful postoperative follow-up. The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

[Clinical features and TTC21B genotype of a child with nephronophthisis type 12].

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary ß2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.

Clinical features and prognosis of patients with thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a review of 25 cases.

OBJECTIVE: To report the clinical features of patients with systemic lupus erythematosus (SLE) associated with thrombotic thrombocytopenic purpura (TTP). Their diagnosis, treatment, and prognosis were also discussed. METHODS: A total of 25 TTP-SLE pediatric patients were included in this study. Their clinical symptoms, laboratory findings, disease activity, and renal biopsy were retrospectively reviewed. RESULTS: The median age of the patient cohort was 14 years old. Nine patients were first diagnosed with SLE, followed by the diagnosis of TTP-SLE, whereas 15 patients were diagnosed with TTP and SLE concurrently. All the 25 TTP-SLE patients had decreased platelet count and microangiopathic hemolytic anemia. Fever, rash, edema and neurological symptoms were the main clinical symptoms. Fragmentation of erythrocytes on blood smear and increased LDH were found in all patients. Nineteen patients (76%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (20%) and TMA (20%). 13 patients (52%) were treated with glucocorticoids in combination with immunosuppressive agent, and 10 patients (40%) were treated with plasma exchange combined with glucocorticoids plus immunosuppressive agent. One patient died due to lung infection; others had disease remission. Fifteen patients had follow-up regularly, and their conditions were stable. CONCLUSION: Patients with TTP-SLE often had moderate to severe lupus disease activity. Testing of LDH level and blood smear should be performed when kidney and neurological symptoms arise in children with SLE. The use of combination therapy, glucocorticoids plus immunosuppressive agent, provided satisfactory clinical outcome. Patients with refractory TTP-SLE will also need plasma exchange therapy.

Cerebellopontine Angle Tumors Are Associated with a Greater Incidence of Unruptured Intracranial Aneurysms.

OBJECTIVE: We tested the hypothesis that cerebellopontine angle (CPA) tumors are associated with a greater incidence of unruptured intracranial aneurysms (IAs). METHODS: Patients with intracranial tumors (ITs) undergoing computed tomography angiography and magnetic resonance imaging were enrolled in an observational cohort study that prospectively collected age, sex, hypertension, diabetes, cerebral arteriosclerosis, tumor type, tumor location, hydrocephalus, smoking, alcohol intake, CPA tumor size, cerebral aneurysms, and cerebral arteriosclerosis. Patients with the coexistence of IA and ITwere classified as group II, whereas the others with IT as group I. RESULTS: We included 1218 patients with IT for analysis. The incidence of IA was 7.1% (86/1218). A total of 31% of patients with aneurysms had CPA tumors. In a multivariate logistic regression model, a greater incidence of IA was found in female patients (odds ratio [OR] 1.726, 95% confidence interval [CI] 1.050-2.836, P=0.031) and in patients with CPA tumors (OR 3.002, 95% CI 1.822-4.947, P=0.000) after adjustment for tumor type, cerebral arteriosclerosis, and age. In female patients, CPA tumors were a unique independent risk factor of a greater incidence of IA (OR 2.270, 95% CI 1.194-4.317, P=0.012). Furthermore, cerebral arteriosclerosis was a unique independent risk factor of IA in patients with CPA tumors (OR 7.626, 95% CI 2.928-19.860, P=0.000). CONCLUSIONS: These data support the hypothesis that CPA tumors are associated with a greater incidence of unruptured IAs, especially in female patients. Cerebral arteriosclerosis contributed to elevated risk of IA in patients with CPA tumors.

Novel Role of ER Stress and Mitochondria Stress in Serum-deprivation Induced Apoptosis of Rat Mesenchymal Stem Cells.

The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy. In this study, the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms. Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining. Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting. The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment. Serum deprivation was shown to lead to protein expression alterations in Bax, Bcl-2, casepase-3, casepase-8, GRP78, and CHOP during experiments. The data suggested that the mitochondria death pathway, the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis. The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.

Comparison of surgical and endovascular approaches in the management of multiple intracranial aneurysms.

OBJECTIVE: To investigate the outcomes and safety of endovascular compared with surgical clipping for multiple intracranial aneurysms. MATERIAL AND METHODS: 98 patients with 260 multiple intracranial aneurysms were treated with endovascular, surgical clipping, combined treatment, and observation. Data were retrospectively studied following treatment and at follow-up. RESULTS: In the endovascular group, 44 aneurysms were treated with coils only and 29 aneurysms were treated with stent deployment. The complete occlusion rate was 65%, and the total complication rate was 12% with no permanent deficit. After angiographic follow-up for 1-90 (mean 62) months, the total recurrence rate was 18.3%. In the clipping group, 65 aneurysms were clipped. The complete occlusion rate was 90.8%, and the complication rate was 10.9% with 1 permanent deficit. After follow-up for 11-71 (mean 49) months, the angiographic recurrence rate was 1.5%. In the combination group, 20 aneurysms were treated endovascularly. The complete occlusion rate was 78.9%, and the complication rate was 15.8% with no permanent deficit. Twenty-eight aneurysms were treated surgically with the complete occlusion rate of 89.3%, the complication rate of 20% and 3 permanent deficits. After follow-up for 1-93 (mean 58) months, the angiographic recurrence rate was 33.3% for embolization and 3.6% for clipping. Seventy-four aneurysms for observation had 2.7% regrowth rate within 1-3 years. CONCLUSION: Endovascular embolization has an accepted complication rate but no neurological deficits compared with surgical clipping and may be a better approach for multiple intracranial aneurysms than surgical clipping.

Distribution and prognosis of uncommon metastases from non-small cell lung cancer.

BACKGROUND: According to the literature and our experience, the most common sites of non-small cell lung cancer (NSCLC) metastases include the brain, bone, liver, adrenal glands, contralateral lung and distant lymph nodes. Metastases to other organs are relatively rare. There have been numerous case reports and a few small case series of uncommon metastases derived from NSCLC. METHODS: We defined all organs except the common metastatic sites mentioned above as uncommon sites of metastasis. Patients with uncommon metastases among 2,872 consecutive NSCLC patients with stage IV disease at the Guangdong Lung Cancer Institute (GLCI) from 2006 to 2012 were included in this study. The diagnosis of uncommon metastases was based on pathology or imaging studies. RESULTS: Uncommon metastases were diagnosed in 193 cases at anatomical sites such as the soft tissue, kidney, pancreas, spleen, peritoneum, intestine, bone marrow, eye, ovary, thyroid, heart, breast, tonsil and nasal cavity. Uncommon metastases were identified as independent poor prognostic factors through a multivariate analysis with a HR (hazard ratio) of 1.29 [95% confidence interval (CI) 1.09-1.52, P < 0.01]. Those patients who received systemic therapy plus local treatment had a better survival rate than did those who received systemic therapy only (P < 0.01); all patients received best supportive care. CONCLUSIONS: Metastases to the above mentioned sites are infrequent. The presentation of uncommon metastases tends to indicate a poor outcome, and selected patients may benefit from local treatment.

Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor.

OBJECTIVES: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for EGFR-mutant patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether frontline EGFR TKIs affect subsequent chemo-sensitivity in EGFR-mutant patients. This study compared chemo-sensitivity in patients treated with post-TKI chemotherapy and first-line chemotherapy controls. MATERIALS AND METHODS: This study included 203 EGFR-mutant patients. The study group contained 68 patients treated with chemotherapy after first-line EGFR-TKI and the control group contained 135 patients who received first-line chemotherapy. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: In study group, the RR of chemotherapy was 13.2% compared with 34.1% in the control group (P=0.002). The median PFS of chemotherapy in the control group was significantly longer than in the study group (6.9 vs. 3.9 months, P<0.001), while the RR (76.5% vs. 68.9%, P=0.259) and PFS (11.0 vs. 10.2 months) of EGFR-TKI were similar between first- and second-line treatment. Cox regression analyses indicated that prior EGFR-TKI treatment had a higher risk for disease progression during chemotherapy treatment [hazard ratio (HR)=3.06; 95% CI=2.12-4.42, P<0.001]. Median overall survival was 31.7 months in the control group and 23.5 months in the study group (P<0.001). The adjusted HR for death in the study group was 1.91 (95% CI=1.33-2.76; P<0.001). CONCLUSION: In EGFR-mutant patients, frontline EGFR-TKI significantly reduced the sensitivity of subsequent chemotherapy compared with that of TKI-naïve frontline chemotherapy. These findings need to be validated in further randomized trials.

Lung cancer treatment disparities in China: a question in need of an answer.

BACKGROUND: Substantial progress has been made in the treatment of malignancies in the People's Republic of China in recent years. The goal of this study was to identify the extent to which national treatment guidelines are being used to customize patient care in lung cancer and to analyze the reasons for treatment disparities. METHODS: Patient characteristics and treatments were investigated retrospectively for the period from October 2004 to January 2013 using the outpatient database of the Guangdong Lung Cancer Institute (GLCI) in China. RESULTS: A total of 2,535 outpatients with lung cancer were studied in this retrospective analysis. The treatment disparity was 45.3%. Overall, 20.6% of patients with stage I non-small cell lung cancer (NSCLC) were overtreated, and 20.1% of stage II patients were undertreated. Only 19.6% of stage IIIA patients and 30.7% of stage IIIB patients underwent the recommended combination of chemotherapy and radiotherapy, respectively. For advanced NSCLC, the greatest treatment disparity appeared in the second-line setting and beyond. Patients who were positive for epidermal growth factor receptor (EGFR) and receiving EGFR tyrosine kinase inhibitors experienced significant prolongation of survival compared with patients who were EGFR negative or whose EGFR mutation status was unknown (hazard ratio: 0.79; p = .037). The treatment disparities were significantly larger among patients aged younger than 65 years and in patients from developing regions compared with patients aged 65 years and older and from developed regions, respectively (p < .001, p = .046). The difference in treatment disparity was statistically significant between GLCI and other hospitals (p < .001). CONCLUSION: This retrospective study of a large number of patients from an outpatient oncology database demonstrated large disparities in the treatment of lung cancer in China. It is important to develop a new guideline for recommendations that are based on resource classification.

Prognostic significance of genotype and number of metastatic sites in advanced non-small-cell lung cancer.

BACKGROUND: TNM stage remains the most important prognostic factor in clinical practice. The 7th edition lung cancer staging system has not considered some important prognostic factors, such as the number of metastatic organ sites and the molecular biologic characterization. PATIENTS AND METHODS: Using driver gene alternation and tumor burden, advanced NSCLC cases were divided into 3 groups: M1-I group, epidermal growth factor (EGFR)-positive and/or anaplastic lymphoma kinase (ALK)-positive; MI-II, wild-type EGFR and ALK with intrathoracic metastasis or 1 distant metastatic organ with ≤ 3 metastasis lesions; and MI-III, wild-type EGFR and ALK with 1 distant metastatic organ with > 3 metastasis lesions or multiple metastatic organs. Overall survival was comparable between the 7th edition staging system and our category of M descriptors. RESULTS: A total of 627 patients with stage IV NSCLC newly diagnosed at Guangdong Lung Cancer Institute between January 2009 and July 2012 were enrolled in the present study. The median overall survival (OS) was 22.2 (95% CI, 19.590-24.810), 15.5 (95% CI, 13.176-17.824), and 10.0 (95% CI, 8.033-11.967) months for M1-I, M1-II, and M1-III, respectively (P < .001). According to the 7th edition of the TNM staging system, the median OS of the M1a and M1b groups was 22.8 (95% CI, 19.484-26.116) and 13.7 (95% CI, 11.793-15.607) months, respectively (P < .001). The maximum of the absolute values of the M1 category for our study and the 7th TNM staging system was 5.881 and 5.089, respectively. CONCLUSION: Advanced NSCLC could potentially be further divided into 3 subgroups according to the genotype and number of metastatic organ sites and metastasis lesions.

[Reactive epitope analysis of agB subunit antigens of Echinococcus granulosus by using synthetic peptides].

OBJECTIVE: To analyze reactive epitope of three subunit antigens AgB1, AgB2 and AgB4 of Echinococcus granulosus by using synthetic peptides. METHODS: Five synthetic peptides, KK36, RK30, B4-1, B4-2, and B4-3, derived from the sequences of AgB1, AgB2, and AgB4 subunit of E. granulosus, and the three recombinant subunits were used for the detection of serum antibodies by ELISA. A panel of 209 serum samples from patients with cystic echinococcosis (115), alveolar echinococcosis (54), cysticercosis (22), and healthy persons (18) was used in the study. The diagnostic efficiency of the recombinant subunits and peptides for serum detection was estimated and compared using receiver-operating characteristics (ROC) curve. RESULTS: The sensitivity and specificity of peptides KK36 and RK30 in patients with cystic echinococcosis were 89.2% and 62.5%, 85.0% and 59.4%, respectively. Their diagnostic efficiency (84.8% and 80.4%) was similar to AgB1 and AgB2 antigen (84.5% and 81.2%). The ROC curves of peptides KK36 and RK30 were well fitted by that of recombinant subunit AgB1 and AgB2. For the three peptides derived from AgB4 subunit, serum detection indicated that the diagnostic efficiency of B4-1, B4-2 and B4-3 were 49.4%, 57.9%, and 77.4%, respectively. Peptides B4-3 showed best reactivity and B4-2 also showed certain reactivity to the sera from patients with cystic echinococcosis. CONCLUSION: Peptides KK36 and RK30 contain the reactive epitope region of AgB1 and AgB2 subunits. B4-2 and B4-3 contain partial region of the reactive epitope of AgB4. The epitope region of AgB4 may be in the central and back part.

The influence of He-Ne laser on scar formation after trabeculectomy in rabbits.

AIM: To investigate the influence of He-Ne lasers on scar formation in the filtration canal after trabeculectomy in a rabbit model, as well as to explore the mechanisms for preventing scar formation when using He-Ne lasers in vivo. METHODS: Experiment 1: Four groups were established (four eyes in each group). In 12 eyes, the upper nasal limbus area next to the upper rectus muscle received 10 minutes of He-Ne laser irradiation (100, 150, 200mW/cm(2); 60, 90, 120J/cm(2)) every day for three days. Four eyes served as controls. Twenty-four hours after the final irradiation, the rabbits were sacrificed and the irradiated tissue was excised, fixed with paraformaldehyde and tested for proliferating cell nuclear antigen (PCNA), connective tissue growth factor (CTGF) and apoptosis (TUNEL). Experiment 2: Forty-two rabbits were randomly divided into two groups and standard trabeculectomy was performed in the right eyes either after 200mW/cm(2) He-Ne laser irradiation or not in the filtration area. The expression of PCNA and CTGF, apoptosis and collagen density in the filtration area were tested on the 7(th), 14(th) and 28(th) day after surgery. RESULTS: Experiment 1: There were no more PCNA and CTGF positive cells in the He-Ne irradiation group than in the control group. No apoptotic cells were found in either group. Experiment 2: The expression of PCNA and CTGF was lower in the He-Ne irradiation group than in the control group on the 7(th) and 14(th) day after trabeculectomy surgery (P<0.05); no apoptotic cells were detected in either group. Collagen density was significantly lower in the He-Ne irradiation group than in the control group on the 14(th) and 28(th) day after surgery (P<0.05). CONCLUSION: Pretreating the filtration area with 200mW/cm(2) (120J/cm(2)) of He-Ne laser irradiation may be helpful in preventing scar formation after trabeculectomy, possibly due to the downregulation of the expression of PCNA, CTGF and collagen synthesis in fibroblasts.

[Investigation on contamination of Cryptosporidium and Giardia in drinking water and environmental water in Shanghai].

OBJECTIVE: To understand the contamination status of Cryptosporidium sp. and Giardia lamblia in drinking water, source water and environmental water in Shanghai. METHODS: All water samples collected from drinking water, source water and environmental water were detected by a procedure of micromembrane filtration, immune magnetic separation (IMS), and immunofluorescent assay (IFA). RESULTS: Cryptosporidium oocysts and Giardia cysts were not found in 156 samples of the drinking water including finished water, tap water, or pipe water for directly drinking in communities. Among 70 samples either source water of water plants (15 samples), environmental water from Huangpu River(25), canal water around animal sheds(15), exit water from waste-water treatment plants(9), or waste water due to daily life(6), Cryptosporidium oocysts were detected in 1(6.7%), 2(8.0%), 7(46.7%), 1(11.1%), and 1(16.7%) samples, respectively; and Giardia cysts were detected in 1(6.7%), 3(12.0%), 6 (40.0%), 2(22.2%), and 2(33.3%), respectively. The positive rate of Cryptosporidium oocysts and Giardia cysts was 17.1% (12/70) and 20.0% (14/70), respectively. CONCLUSION: No Cryptosporidium oocysts and Giardia cysts have been detected in drinking water, but found in source water and environmental water samples in Shanghai.

[Clinical manifestations, laboratory test, treatment and outcome of neuropsychiatric involvement in pediatric systemic lupus erythematosus patients].

OBJECTIVE: To investigate the clinical manifestations, laboratory test, treatment and outcome of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (SLE) patients. METHODS: Seventy-seven patients with NP syndromes of SLE (NPSLE) seen from 1987 to 2007 were retrospectively reviewed. The relationship between the relative factors and the relapse of NPSLE was analyzed with logistic regression model. RESULTS: NPSLE was found in 17.3% of the SLE patients and 75% of the NPSLE patients the NP involvements occurred in the first 2 years of the onset of SLE. The most frequent NP manifestations were headache (31.8%) and seizure disorder (29.1%). In the active phases, the levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores of the 92.2% patients were higher than 15 and belonged to severe lupus. The patients were accompanied frequently with fever (88.3%) and rash (84.4%). The most frequently involved organs were kidney (76.6%) and blood system (67.5%). In the active phases, the ANA was positive (98.7%), the level of ESR increased (86.3%), the level of complement profile decreased (72.7%). The cerebrospinal fluid (CSF) study, the CT, the MRI and the EEG were abnormal (90.1%, 60.7%, 54.8%, 73.9%, respectively). All the patients received glucocorticoids and immunodepressant treatment in which 79.2% received IV high-dose methylprednisolone (MP), 51.9% received intrathecal (IT) methotrexate (MTX) and dexamethasone (DXM), 26.0% received IVIG, 2 patients received autologous peripheral blood stem cell transplantation. The mortality was 9.0%. The rate of relapse was 22.0% and in 75.0% of relapsed patients the relapse occurred within 24 months from the onset of NPSLE. The SLEDAI scores related to the relapse of the NPSLE (chi(2) = 3.987, P = 0.0459, OR = 1.172, 95% CI 1.003 and 1.370). CONCLUSION: SLEDAI scores were significantly helpful in predicting recurrence of NPSLE.