[The distribution of peripheral anterior synechiae in patients with primary angle-closure glaucoma].

Objective: To describe the distribution and characteristics of peripheral anterior synechiae (PAS) in patients with primary angle-closure glaucoma (PACG). Methods: Retrospective case study. A total of 285 PACG patients (406 eyes) diagnosed in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University from January 2017 to August 2019 were included. They were 102 males and 183 females, with a median age of 67 years old (range, 21 to 95 years old). The PAS range was detected by gonioscopy examination, and the frequency distribution of PAS at 12 clock points was counted by clockwise. The PAS distribution at the middle point of PAS with continuous distribution and ≤6 clock points was assessed. Results: In all cases, PAS of the right eye was concentrated at 11:00 to 4:00 regions [range, 62.0% (129/208) to 78.8% (164/208)]. PAS of the left eye was concentrated at 7:00 to 1:00 regions [range, 50.0% (99/198) to 75.8% (150/198)]. When the PAS range of the atrial angle was ≤6 clock regions, it was mainly at 12:00 to 3:00 [range, 58.3% (74/127) to 67.7% (86/127)] in the right eye and at 10:00 to 12:00 [range, 54.8% (68/124) to 66.1% (82/124)] in the left eye. Among 121 cases (242 eyes) with both eyes involved, the PAS region was at 11:00 to 5:00 [range, 52.1% (63/121) to 79.3% (96/121)] in the right eye and at 8:00 to 1:00 [range, 50.4% (61/121) to 76.9% (93/121)] in the left eye. When the PAS range of the atrial angle was ≤6 clock regions, it was mainly at 12:00 to 4:00 [range, 53.2% (41/77) to 71.4% (55/77)] in the right eye and at 10:00 to 12:00 [range, 50.6% (39/77) to 64.9% (50/77)] in the left eye. In all cases, there were 171 cases of right eyes and 175 cases of left eyes with continuous angle PAS. The central PAS clock position of the right eye was mainly at 11:00 to 3:00 [range, 15.2% (26/171) to 24.0% (41/171)], and that of the left eye was mainly at 8:00 to 12:00 [range, 15.4% (27/175) to 20.6% (36/175)]. Among cases with both eyes involved, there were 98 cases of right eyes and 104 cases of left eyes with continuous angle PAS. The clock distribution of the middle position of the right eye angle PAS was concentrated at 11:00 to 3:00 [range, 17.3% (17/98) to 26.5% (26/98)], and that of the left eye was concentrated at 8:00 to 12:00 [range, 13.5% (14/104) to 20.2% (21/104)]. Conclusions: The PAS of PACG patients is mainly located in the upper and nasal sides, and the closer to the temporal side, the smaller the PAS frequency, showing a gradual downward trend. The PAS distribution of binocular angles is of obvious mirror symmetry. (Chin J Ophthalmol, 2021, 57: 666-671).

[The 484th case:asthma, limb numbness, diplopia, headache].

A 47-year-old female who had a history of asthma and sinusitis in the past was admitted to hospital with limbs numbness and pain for ten days. The symptoms were aggravated for eight hours. On admission, significant peripheral eosinophilia was noted. Paranasal sinusitis and transient bronchiolitis were found by CT scan.Electromyogram demonstrated multiple mononeuropathy. Eosinophilia was indicated by bone marrow biopsy. The diagnosis of eosinophilic granulomatous polyangiitis(EGPA) was determined. The patient got better after applying glucocorticoid and cyclophosphamide.Later she developed abdominal pain and partial oculomotor nerve palsy, while her condition improved after continued immunosuppression and anticoagulant therapy. She was hospitalized for the third time because of headache. Subarachnoid hemorrhage was diagnosed after lumber puncture and cranial MRI+MRA+MRV and other examinations. She was relieved after conservative treatment. Subarachnoid hemorrhage with EGPA is rare. This case may improve physicians' understanding of EGPA complicated with subarachnoid hemorrhage.

[shRNA-Mediated Suppression of γ-Synuclein Leading to Downregulation of p38/ERK/JNK Phosphorylation and Cell Cycle Arrest in Endometrial Cancer Cells].

In this study, we explored the effects of treating human endometrial cancer cells with γ-synuclein-specific short hairpin RNA (shRNA) and elucidated the associated mechanisms in vitro and in vivo through the p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways. Cell proliferation and migration were assessed using CCK8, Transwell, and scratch wound healing assays. Flow cytometry and laser scanning confocal microscopy were used to detect cell cycle changes. Relative levels of phosphorylated and non-phosphorylated (p) p38, ERK1/2 and JNK1/2/3 were determined in vitro and in vivo using simple western blotting assays. Cell proliferation in the experimental group decreased significantly and cells transfected with shRNA showed reduced migration rates (P < 0.05). p-p38, p-ERK1/2, and p-JNK1/2/3 levels were downregulated in the experimental group in vitro and in vivo. Tumor volumes and weights in the experimental group were significantly lower (P < 0.05). Tumor formation time in the negative control group was significantly shorter (P < 0.05). Flow cytometry showed that the number of cells in the G1 and mitotic phases increased and that in the S phase decreased after SNCG silencing (P < 0.05). Confocal microscopy showed that the percentage of cells in the mitotic phase increased after SNCG gene silencing (P < 0.05). We conclude that shRNA-mediated suppression of γ-synuclein decreased the proliferation, migration, and tumorigenicity of endometrial cancer cells via downregulation of p38, ERK, and JNK phosphorylation. High SNCG expression is closely related to the growth cycle of endometrial cancer cells.

[A multicenter, large-sample, randomized clinical trial on improving the median survival time of advanced non-small cell lung cancer by combination of Ginseng Rg3 and chemotherapy].

Objective: To observe the efficacy of the combination of chemotherapy and Ginseng Rg3 on advanced non-small cell lung cancer(NSCLC). Methods: In the multi-center, large-sample, randomized, double blind trial, 414 patients with Ⅲ-Ⅳ NSCLC were enrolled.199 were in the experimental group and 215 the control group. The patients in the experimental group were treated with the standard first-line chemotherapy combined with Ginseng Rg3. The patients in the control group were treated with the same chemotherapy combined with placebo. Median overall survival (OS), Karnofsky performance scale (KPS), Traditional Chinese Medicine (TCM) symptoms score and side effects of two groups were observed as main indexes. Results: The median OS were 12.03 months in the experimental group, which was significantly better than that in the control group (8.46 months, P<0.05). Hemoglobin and white blood cells were decreased after the first and second cycle of treatment in both groups. Both adverse events were significantly milder in the treatment group (P<0.05). In addition, after two courses of treatment, the KPS of patients was 78.95±9.14 in the experimental group and 76.77±9.15 in the control group, while the TCM symptoms score was 2.45±1.73 in the experimental group and 2.92±2.06 in the control group, with significant difference (P<0.05). Conclusions: Combination of TCM with Western medicine such as chemotherapy could prolong the survival of patients with advanced NSCLC. The combined therapy improved patients' symptoms and reduced chemotherapy induced myelosuppression.

Early improvement in PANSS-30, PANSS-8, and PANSS-6 scores predicts ultimate response and remission during acute treatment of schizophrenia.

OBJECTIVE: PANSS-8 and PANSS-6 are derived from the 30-item Positive and Negative Syndrome Scale (PANSS-30). We investigate whether PANSS-8 or PANSS-6 is a reliable, valid, sensitive to change measure, and scalable, and whether early improvement using them can predict response/remission. METHOD: Data were from 3 trials for 270 schizophrenia inpatients receiving antipsychotics. Internal consistency, validity, sensitivity to change, and scalability using PANSS-30, PANSS-8, and PANSS-6 at each assessment were examined. Early improvement was defined as at least 20% reduction of PANSS-30, PANSS-8, or PANSS-6 scores at week 2. Response was defined as at least 40% reduction of PANSS-30 and remission as a score of PANSS-8 ≤ 3 on each item at endpoint. Receiver operating characteristic analysis was used to determine which rating scale had better discriminative capacity. RESULTS: PANSS-8 and PANSS-6 showed acceptable internal consistency, were highly correlated with PANSS-30, and had sensitivity to change. PANSS-8 and PANSS-6 were scalable at each assessment, except for PANSS-6 at baseline. Early improvement using PANSS-8 or PANSS-6 had comparable predictive values with that of PANSS-30 for response/remission. CONCLUSION: PANSS-8 and PANSS-6 are clinically useful measures. Early improvement, regardless of whether PANSS-30, PANSS-8, or PANSS-6 is used, is a statistically significant predictor of response/remission.

Baseline Vulnerability and Inpatient Frailty Status in Relation to Adverse Outcomes in a Surgical Cohort.

This study aimed to derive measures of baseline vulnerability and inpatient frailty in elderly surgical patients and to study their association with adverse post-operative outcomes. Data from comprehensive geriatric assessment of 208 general surgical and orthopaedic patients aged 70 and over admitted to four acute hospitals in Queensland, Australia, were analysed to derive a baseline and inpatient Frailty Index (FI). The association of these indices with adverse outcomes was examined in logistic regression. The mean (SD) baseline FI was 0.19 (0.09) compared to 0.26 (0.12) on admission, with a predominant increase in domains related to functional status. Both baseline and inpatient FI were significant predictors of one year mortality, inpatient delirium, and a composite adverse outcome, after adjusting for age, sex and acuity of surgery. In summary, detecting baseline frailty pre-hospitalisation may be useful to trigger the implementation of supportive and preventative measures in hospital.

Association of TLR2 and TLR4 non-missense single nucleotide polymorphisms with type 2 diabetes risk in a southern Chinese population: a case-control study.

Toll-like receptors (TLRs), the triggers of the innate and adaptive immune responses, are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Several studies have investigated the effects of genetic polymorphisms in TLR4 and TLR2, but they have yielded limited results. We investigated whether non-missense genetic polymorphisms in the regulatory regions of TLR4 and TLR2 were related to T2DM in a southern Chinese population. Single nucleotide polymorphisms (SNPs) in TLR4 (rs1927911, rs11536889, rs1927907, rs1927906, rs1927914, rs7873784, and rs2149356) and TLR2 (rs1898830, rs3804099, rs4696480, and rs3804100) were genotyped in 552 T2DM and 552 unrelated age- and gender-matched controls by SNaPShot Multiplex assay. Genotypes GG (OR = 0.09, 95%CI = 0.01- 0.83, P = 0.03) and CG (OR = 0.08, 95%CI = 0.01-0.74, P = 0.03) of the 3'-untranslated region (UTR) SNP rs7873784 in TLR4, and genotype AG (OR = 0.67, 95%CI = 0.46-0.97, P = 0.04) and allele G (OR = 0.88, 95%CI = 0.79-0.97, P = 0.01) of the intron SNP rs1898830 in TLR2 were identified as protective against the development of T2DM in southern Chinese people. In contrast, a meta-analysis of rs1927911 and rs1927914 showed no association. Haplotypes AGTT (OR = 0.34, 95%CI = 0.15-0.77, P = 0.01) and AATT (OR = 1.20, 95%CI = 1.01- 1.44, P = 0.05) in TLR2 were significantly associated with susceptibility to T2DM. Our results suggest that the effects of non-missense polymorphisms located in the regulatory regions of TLR4 and TLR2 should not be neglected in T2DM association analysis.

Cantharidins induce ER stress and a terminal unfolded protein response in OSCC.

Mortality and morbidity associated with oral squamous cell carcinoma (OSCC) remain unacceptably high with disfiguring treatment options and a death rate of 1 per hour in the United States. The approval of cituximab for advanced OSCC has been the only new treatment for these patients since the 1970s, although it has not significantly increased overall survival. To address the paucity of effective new therapies, we undertook a high-throughput screen to discover small molecules and natural products that could induce endoplasmic reticulum (ER) stress and enforce a terminal unfolded protein response (UPR) in OSCC. The terpenoid cantharidin (CNT), previously used to treat various malignancies in culture-specific medical practices for over 2,000 y, emerged as a hit. CNT and its analog, cantharidic acid, potently induced protein and gene expression profiles consistent with the activation of ER stress, the UPR, and apoptosis in OSCC cells. Murine embryonic fibroblasts null for the UPR-associated transcription factors Atf4 or Chop were significantly protected from CNT, implicating a key role for the UPR in the death response. These data validate that our high-throughput screen can identify novel modulators of UPR signaling and that such compounds might provide a new therapeutic approach to treating patients with OSCC.

MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets.

MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia.

Abnormal proliferation, apoptosis repression and differentiation blockage of hematopoietic stem/progenitor cells have been characterized to be the main reasons leading to acute myeloid leukemia (AML). Previous studies showed that miR-29a and miR-29b could function as tumor suppressors in leukemogenesis. However, a comprehensive investigation of the function and mechanism of miR-29 family in AML development and their potentiality in AML therapy still need to be elucidated. Herein, we reported that the family members, miR-29a, -29b and -29c, were commonly downregulated in peripheral blood mononuclear cells and bone marrow (BM) CD34+ cells derived from AML patients as compared with the healthy donors. Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited cell proliferation and promoted cell apoptosis. AKT2 and CCND2 mRNAs were demonstrated to be targets of the miR-29 members, and the role of miR-29 family was attributed to the decrease of Akt2 and CCND2, two key signaling molecules. Significantly increased Akt2, CCND2 and c-Myc levels in the AML cases were detected, which were correlated with the decreased miR-29 expression in AML blasts. Furthermore, a feed-back loop comprising of c-Myc, miR-29 family and Akt2 were found in myeloid leukemogenesis. Reintroduction of each miR-29 member partially corrected abnormal cell proliferation and apoptosis repression and myeloid differentiation arrest in AML BM blasts. An intravenous injection of miR-29a, -29b and -29c in the AML model mice relieved leukemic symptoms significantly. Taken together, our finding revealed a pivotal role of miR-29 family in AML development and rescue of miR-29 family expression in AML patients could provide a new therapeutic strategy.

Clinical characteristics, hospital outcome and prognostic factors of patients with ventilator-related pneumothorax.

BACKGROUND: Mechanical ventilation is a common cause of iatrogenic pneumothorax in intensive care units (ICU). Most of the patients with ventilator-related pneumothorax (VRP) have underlying lung diseases and is associated with increased morbidity and mortality. The prognostic factors of VRP are not clear. The objective of this study was to find the possible prognostic factors. METHODS: Analysis of retrospectively collected data of patients with pneumothorax induced by mechanical ventilation. Data were obtained concerning demographics, acute physiology and chronic health evaluation (APACHE) II score, organ failure, underlying diseases, interval between the start of mechanical ventilation and pneumothorax, arterial blood gas, respiratory parameters and patient outcomes. RESULTS: One hundred and twenty-four patients with VRP were included for analysis. The incidence rate of VRP was 0.4% (124/31,660), and the mortality rate was 77.4%. The patients with VRP had higher hospital mortality rate than that of mechanically ventilated patients without pneumothorax (77.4% vs. 13.7%, P<0.001) or patient with procedure-related pneumothorax (77.4% vs. 29.4%, P<0.001). Most cases of VRP occurred in the early phase of mechanical ventilation, and 8.9% of the patients had a later episode of pneumothorax on the opposite lung. The interval between two episodes of VRP was short, at a median time of 2 days. Cox regression analysis showed that tension pneumothorax (P=0.001), PaO2/FiO2<200 (P=0.002), and APACHE II score (P=0.008) were significantly associated with death. CONCLUSION: VRP patients with tension pneumothorax or PaO2/FiO2<200 had a higher risk of death. APACHE II scores were associated with mortality in the VRP patients with PaO2/FiO2≥200 mmHg.

Co-morbidities in psoriasis: a hospital-based case-control study.

BACKGROUND: Recent researches show that psoriasis is frequently associated with systemic co-morbidities. OBJECTIVES: This study aimed to identify possible associated co-morbidities in psoriatic patients stratified by age and sex. METHODS: In this retrospective hospital-based case-control study, patients diagnosed as psoriasis at the Kaohsiung Veterans General Hospital in Taiwan between January 2008 and December 2009 were enrolled as cases and classified into severe and mild based on their use of systemic therapy. The controls were the patients without psoriasis matched the cases in 1 : 1 ratio with same birth year, sex and calendar date. Odds ratios (ORs) and 95% confidence intervals (CIs) from the conditional logistic regression method were used to assess the risk of co-morbidities between psoriatic and non-psoriatic patients. RESULTS: A total of 447 cases and 447 matched controls, with mean age of 51.3 ± 18.3 years and male-to-female ratio of 2.17 : 1 were enrolled. The ratio of mild-to-severe was 3.5 : 1. Compared with non-psoriatic patients, psoriatic patients had significantly higher OR of hypertension (1.85), diabetes mellitus (2.88) and obesity (1.66). Among those aged ≥51 years old, there was significant risk in male psoriatic patients with ischaemic and hypertensive heart disease (IHHD) (OR = 2.167) after eliminating female IHHD psoriatic patients (OR = 0.125). Psoriasis was significantly negatively associated with cancers (OR = 0.267). Psoriasis patients often had the usual drinking habit (OR = 2.23) and seldom had an occasional drinking habit (OR = 0.25). CONCLUSIONS: Psoriasis is strongly associated with hypertension, diabetes mellitus and obesity. The association between psoriasis and IHHD, stroke, cancers, smoking and alcohol habits warrant more investigation.

Predict the spontaneous resolution of vesicoureteral reflux by direct radionuclide cystography.

OBJECTIVES: To evaluate the prognostic value of initial direct radionuclide cystography (DRC) for spontaneous resolution of vesicoureteral reflux (VUR). METHODS: Fifty-one children with initial diagnosis and 1-6 years' follow-up of VUR by DRC were enrolled in this study. VUR was graded according to the anatomic grading as (1) mild reflux corresponding to tracer just in ureter, (2) moderate reflux with accumulation of activity in a non-dilated collecting system and ureter, and (3) severe reflux equated with a dilated ureter and collecting system. The severity of VUR was also expressed according to the functional classification as (1) transient reflux, which occurred at filling or voiding phase only and (2) persistent reflux, present in both filling and voiding phases. RESULTS: Twenty-nine of the 51 children had unilateral VUR, and the other 22 had bilateral VUR. In the total of 73 refluxing ureters, there were 12 mild, 49 moderate and 12 severe VUR according to anatomic grading, and 30 transient and 43 persistent VUR according to the functional grading. After follow-up, resolution of VUR was found in 92% (11/12) of mild, 59% (29/49) of moderate and 25% (3/12) of severe VUR (P=.04, mild vs. moderate; P=.003, mild vs. severe). Eighty percent (24/30) of transient and 44% (19/43) of persistent reflux showed spontaneous resolution (P=.003). CONCLUSIONS: DRC allows anatomic and functional classification of VUR. It is an ideal method for the diagnosis, staging and follow-up of VUR, and provides valuable information to predict the patient's outcome.

Solubilization of vorinostat by cyclodextrins.

BACKGROUND: Vorinostat (suberoylanilide hydroxamic acid) is the first histone deacetylase inhibitor approved by US FDA for use in oncology. However, as a hydrophobic acid, its limited aqueous solubility poses a problem for parenteral delivery. Such limited solubility may also affect its oral bioavailability. OBJECTIVE: The aim of this study was to evaluate whether cyclodextrins (CDs), common excipients used in pharmaceutical industry, could increase the aqueous solubility of vorinostat. METHODS: The actual aqueous solubility of vorinostat was investigated by phase-solubility method. Molecular simulation was employed to predict the interaction energy and preferred orientation of vorinostat in CD cavities. RESULTS: Phase-solubility studies indicated that the solubility of vorinostat (7·24×10(-1) mm) was substantially increased when complexed with various CDs, in the following order: randomly methylated-ß-cyclodextrin (RM-ß-CD)>hydroxypropyl-ß-cyclodextrin (HP-ß-CD)>α-cyclodextrin>hydroxypropyl-α-cyclodextrin>Hydroxypropyl-γ-cyclodextrin>γ-cyclodextrin. RM-ß-CD 300 mm increased vorinostat solubility to 70·8 mm, almost two orders of magnitude higher than the baseline solubility. Such findings were in good agreement with the results obtained from molecular simulation. CONCLUSION: CDs, particularly RM-ß-CD and HP-ß-CD, increased vorinostat's solubility. Future studies could be focused on the application of HP-ß-CD in parenteral delivery of vorinostat or using RM-ß-CD as an oral absorption enhancer. Molecular simulation appeared to be a useful tool for the selection of appropriate CD as excipient for drug delivery.

Serotonin transporter gene promoter polymorphism is associated with body mass index and obesity in non-elderly stroke patients.

BACKGROUND: The serotonergic system is involved in the complex behavioral and physiological process in maintaining energy balance. Genetic factors regulating serotonergic function may have links with the development of obesity. AIM: To investigate whether the 5-HTTLPR polymorphism of the serotonin transporter gene is associated with body mass index (BMI) and obesity in stroke patients. SUBJECTS AND METHODS: The study included 376 patients (65.3+/-11.3 yr; male, 61.7%) with stroke. Associations between the 5-HTTLPR and BMI and obesity (BMI > or = 25 kg/m2) were examined in all subjects. In order to test age-dependent effects of the genetic variant, the association was also examined in the non-elderly subgroup (<65 yr) and the elderly subgroup (> or =65 yr) respectively. RESULTS: For non-elderly subjects, the SS genotype was independently associated with increased BMI level (beta=1.84, p=0.037) and obesity (odds ratio 4.17, 95% CI 1.25-14.0, p=0.021) when the LL genotype was used as the reference. The association was not found for all patients or in the elderly subgroup. The LS genotype was not different from the LL genotype in BMI level or risk of obesity, either for all subjects or with regard to the non-elderly and elderly subgroups. CONCLUSIONS: The SS genotype of 5-HTTLPR is an independent determinant of increased BMI level and obesity in non-elderly stroke patients but not in elderly patients. An age-dependent modification for the effect of the 5-HTTLPR on development of obesity is considered.

Emergence of carbapenem-resistant Escherichia coli in Taiwan: resistance due to combined CMY-2 production and porin deficiency.

Eight pairs of Escherichia coli isolates with various carbapenem susceptibilities from 8 patients were prospectively collected to study the development of resistance. All carbapenem-resistant E. coli isolates were resistant to all tested ss-lactams antibiotics except tigecycline. Identical pulsed-field gel electrophoresis (PFGE) patterns were found in carbapenem-susceptible and -resistant isolates but different PFGE patterns occurred among patients. A CMY-2 ss-lactamase was found in all E. coli isolates. No previously reported carbapenemase genes were detected. Examination of outer membrane protein (OMP) profiles revealed that OmpA was not found in all isolates, while OmpC and OmpF were lost in carbapenem-resistant isolates. Loss of both OmpC and OmpF represents the major mechanism of the development of carbapenem resistance in those patients with CMY-2-producing E. coli infections.

Histone deacetylase inhibitors: new hope for rheumatoid arthritis?

Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intra-articular formulations.

Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti-cancer agents, have recently been reported to exhibit potent anti-inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS-275, two HDACi currently undergoing clinical investigations for various oncological indications. EXPERIMENTAL APPROACH: The anti-rheumatic effects of SAHA and MS-275 were assessed in both mouse and rat collagen induced arthritis (CIA) models. KEY RESULTS: SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA-induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS-275 displayed dramatic anti-rheumatic activities. In prophylactic intervention, high doses of MS-275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS-275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS-275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS-275 was also confirmed through its capacity to decrease serum IL-6 and IL-1beta levels in the CIA induced mouse model. The anti-rheumatic activity of MS-275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice. CONCLUSION AND IMPLICATION: This study strongly supported HDACi as an innovative therapeutic strategy for RA.

Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy.

PURPOSE: Intravitreal chemotherapy for primary intraocular lymphoma (PIOL) increasingly is promoted as an alternative to radiotherapy, owing to putative high failure and complication rates of the latter modality. Our aim was to confirm whether these concerns about radiotherapy were borne out in patients treated at our institution over the last decade. DESIGN: Retrospective interventional case series. PARTICIPANTS: A total of 21 eyes of 12 patients with PIOL. METHODS: Comprehensive chart review of ophthalmologic and systemic manifestations, treatments, and outcomes. MAIN OUTCOME MEASURES: Radiation complications and local tumour control. RESULTS: Cytology-confirmed lymphoma involved one eye in three patients and both eyes in nine patients. Initial treatment included external beam radiotherapy and chemotherapy (six patients), chemotherapy alone (four patients), radiotherapy alone (one patient), and no treatment (one patient). Ocular relapses occurred in no patients receiving radiotherapy and in two patients who did not receive radiotherapy. Complications of radiotherapy included dry eye (four patients), cataract (four patients), and mild radiation retinopathy (two patients). CONCLUSIONS: Radiotherapy for PIOL is highly effective with acceptable complications. In the absence of a clear advantage to intravitreal chemotherapy, which involves repetitive injections and associated risks, radiotherapy may still be the most appropriate first-line treatment in most cases.

Role of parents and peers in influencing the smoking status of high school students in Taiwan.

OBJECTIVES: To assess parental influence on smoking behaviour by high school students in an Asian culture and to compare the relative importance of parental and peer influence. METHODS: A 5% nationally representative sample, including 44 976 high school students in 10th to 12th grade (aged 15-18 years) in Taiwan, were surveyed in 1995. Each completed a long self administered questionnaire. Parental influence was measured by examining both parental behaviour (smoking status) and attitudes (perceived "tender loving care" (TLC) by adolescents). Changes in smoking status were used to determine peer influence, defined as the increase in the likelihood of smoking from grade 10 to 12 in a steady state environment. Odds ratios (ORs) were calculated for parental and peer influence, using logistic regression. RESULTS: Adolescents of smoking parents with low TLC had the highest smoking rates and those of non-smoking parents with high TLC had the lowest. The difference was more than twofold in boys and more than fourfold in girls. When either parental smoking status or TLC alone was considered, parental influence was similar to peer influence in boys, but larger than peer influence in girls. However, when smoking status and TLC were considered jointly, it became larger than peer influence for both groups (OR 2.8 v 1.8 for boys and OR 3.9 v 1.3 for girls). CONCLUSION: When parental influence is taken as parental behaviour and attitude together, it plays a more important role than peer influence in smoking among high school students in Taiwan. This study, characterising such relationships among Asian populations for the first time, implies that future prevention programmes should direct more efforts toward the parental smoking and parent-child relationships, and not aim exclusively at adolescents in schools.