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Purpose: To investigate the anti-rheumatic potential of Wu-Wei-Gui-Shao decoction (WGD) and its possible mechanism of action. Methods: Adjuvant arthritis (AA) rats were established using complete Freund's adjuvant. The rats were then given different doses of WGD (100, 200, and 400 mg/kg, for 28 days). The anti-arthritic effects of WGD were evaluated. Furthermore, the in vitro anti-arthritic effects of WGD and its related mechanisms were also determined in MH7A cells. Results: WGD (100 - 400 mg/kg) exhibited significant anti-rheumatic properties after 28 days of treatment, inhibiting paw edema in AA rats, reducing arthritis score and thymus and spleen index, and inhibiting the tumor necrosis factor (TNF)-α and the interleukin (IL)-6. In addition, the results of in vitro cell experiments also confirmed that WGD reduced the release of cytokines, as well as mRNA levels of matrix metalloproteinase (MMP) -2, -3, and -9. Conclusion: These findings suggest that WGD can be further developed as a traditional Chinese medicine to treat rheumatic arthritis. Keywords: Wu-Wei-Gui-Shao decoction, Complete Freund's adjuvant, Arthritis, Molecular mechanism, Traditional Chinese Medicine

老人の骨髄異形成症候群 (MDS) の治療では, 薬剤の効果は不十分である。輸血依存性の症例ではさらに治療に苦慮する。加味帰脾湯は血液学分野では特発性血小板減少性紫斑病に有効であったという報告が散見される。その使用目標には貧血も認められるので輸血依存性のMDSへの効果も期待される。そこで老人のMDS患者に加味帰脾湯を投与し, 血液学的所見の推移の検討および全身状態の推移の評価を行った。症例は74歳, 男性, 虚証。8年来のMDSでプレドニゾロン, 後にメテノロンを内服していた。2週に2単位程度の赤血球輸血が必要で, ヘモクロマトーシスを併発し, 食欲不振を呈していた。加味帰脾湯を投与し, 約2ヵ月後, 白血球数と血小板数が増加した。赤血球数は改善しなかった。骨髄所見は殆ど不変であった。食欲および活動性等の全身状態は, 投与6週後より著明に改善した。ヘモクロマトーシス併発の本症例で血液学的効果とは別に食欲不振および全身倦怠感の改善を認めた。今後補剤のより優れた効果として検討してゆく必要性があるものと思われた。

Combined treatment with high-dose methylprednisolone and Kampoherbal medicine (Xiao-Chai-Hu-Tang and Jia-Wei-Gui-Pi-Tang) brought about a striking clinical improvement in a 24-year-old woman with severe hepatitis-associated aplastic anemia. Laboratory findings on admission were summarized as follows: granulocytes 325/μl, erythrocytes 2, 450, 000/μl, platelets 10, 000/μl, bone marrow nucleated cells 27, 000/μl, and GPT 569IU/l. Neither anti-lymphocyte globulin, high-dose methylprednisolone alone nor oxymetholone was effective on any hematological finding although intravenous administration of high-dose glycyrrhizin improved the liver dysfunction. The patient needed repeated transfusions of leukocyte-poor washed red blood cells and HLA-matched platelet concentrates for a period of 1.5 years until the hematopoietic function recovered 3 months after combined treatment with high-dose methylprednisolone and Kampo-herbal medicine. Laboratory findings on discharge were as follows: granulocytes 1, 050/μl, erythrocytes 3, 460, 000/μl, reticulocytes 100, 000/μl, platelets 47, 000/μl, bone marrow nucleated cells 118, 000/μl, and GPT 52IU/l. Six months later hematopoietic depression recurred, and this combined treatment was performed again with favorable response.

In order to examine the effects of Kami-kihi-to (KKT or Jia-Wei-Gui-Pi-Tang) on osteopenia, we measured bone mineral density using computed X-ray absorptometry and monitored metabolism and bone tissue in an ovariectomized (OVX) rat model. Bone mineral density was significantly lower in the OVX group than in normal group 3 months after ovariectomy. However, the bone mineral density of the OVX group administered KKT was clearly higher than that of the untreated OVX group. Locomotor activity was regular in the normal group and in the OVX groups before administration of KKT. After 6-month administration of KKT, in OVX groups, the pattern of locomotor activity became diphasic with clear active and resting phases, as was also observed in the normal group. The locomotor activity did not decrease in the OVX groups after administration of KKT. At 6 months, the continuity of the trabecular bone was higher in the OVX group administered KKT than in the untreated OVX group. These results indicate that KKT improved the menopausal symptoms and increased the locomotor activity of the OVX group, thereby increasing bone mineral density.

We studied the effect of Kami-kihi-to (Jia-Wei-Gui-Pi-Tang) on the production of autoantibodies in ten patients with chronic immune thrombocytopenic purpura. After administration of Kami-kihi-to, platelet count was increased in seven of the ten patients ( p

Purpose To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. Methods Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: Results Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. Conclusion Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

OBJECTIVE To investigate whether stressful life events (SLEs) can predict post-stroke fatigue (PSF) in patients with acute ischemic stroke (AIS). METHODS This prospective cohort study included data from patients with AIS who were followed up to 2-year interview. PSF was assessed at admission and at 6 (n = 916), 12 (n = 880), and 24 (n = 857) months with the fatigue severity scale (FSS). SLEs were measured with the Social Readjustment Rating Scale questionnaire at 6, 12 and 24 months' interview. RESULTS A significant dose-response association was found between SLEs and FSS score across all examined time-points: compared with those did not experience SLEs, FSS score was higher for those experiencing SLEs ≥3 at 6 months (β 0.53, 95% CI 0.28-0.78), 12 months (β 0.54, 95% CI 0.30-0.78) and 24 months (β 0.48, 95% CI 0.29-0.68). Longitudinal analyses indicated a significantly positive relationship between the number of SLEs and FSS score (SLEs: ≥3 vs. 0, β 0.14, 95% CI 0.09-0.19). Moreover, a distinct interaction of follow-up time and SLE numbers on FSS score was observed (p

BACKGROUND This study aimed to investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) guided purulence aspiration and local isoniazid injection after lymph node puncture in the treatment of refractory mediastinal tuberculous lymphadenitis (MTLA) as compared to systemic anti-tuberculosis treatment. METHODS This was a retrospective study. A total of 92 patients with MTLA and suppurative lymphadenitis who were treated in the Shanghai Pulmonary Hospital between January 2015 and December 2018 were included into present study and divided into systemic chemotherapy (CT) group and interventional therapy (IT) group. In the CT group, patients received systemic chemotherapy alone; in the IT group, patients received EBUS-TBNA guided lymph node aspiration and local isoniazid injection besides systemic chemotherapy. The recovery of lymphadenitis and adverse effects were observed. RESULTS Seventy patients were included for final analysis, 35 patients in each group. In the IT group, aspiration and local injection were done 137 times; 4R (53.1%) and 7 groups of lymph nodes (30.6%) were the most common site of aspiration; the median number of local treatment was 3 times, and the median duration of local injection was 29 days. The recovery rate of lymphadenitis was 88.6% (31/35) in the IT group and 57.1% (20/35) in the CT group, showing marked difference (χ2=8.741, P

GLOBOCAN estimates 36 types of cancers in 185 countries based on the incidence, mortality, and prevalence in the year 2019. Nowadays, chemotherapy is the most widely used cancer treatment among immune, radio, hormone, and gene therapies. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nano-assembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic Gemcitabine (GEM) drug. The GEM prodrugs were gifted to impulsively self-assemble into excellent steady nanoparticles size on covalent conjugation of linoleic acid hydrophobic through amide group with ∼100 nm. Newly synthesized GEM-NPs morphology was confirmed by various electron microscopic techniques. After successful synthesis, we have evaluated the anticancer property of GEM and GEM-NPs against B-CPAP (papillary thyroid carcinoma) and FTC-133 (human follicular thyroid carcinoma) cancer cell lines. Further studies such as AO-EB (acridine orange-ethidium bromide), nuclear staining and flow cytometry analyses on cell death mechanism signified that the cytotoxicity was associated with apoptosis in thyroid cancer cells. GEM-NPs show excellent biocompatibility compared to GEM. The present study explained that GEM-NPs as a safe and hopeful strategy for chemotherapeutics of thyroid cancer therapy and deserve for further clinical evaluations.

Objective The objective of this study was to evaluate the clinicopathological features and treatment of composite lymphoma (CL) with cervical lymph node enlargement. Methods In this study, two cases of CL are presented. Biopsies of enlarged cervical lymph nodes by excision revealed two distinct types of lymphomas. The diagnoses were confirmed by routine histopathology, immunohistochemistry, in situ hybridization, polymerase chain reactions and flow cytometry. Case 1 was diagnosed with Hodgkin’s lymphoma and cytotoxic T-cell lymphoma complicated by Epstein–Barr virus infection. Case 2 was diagnosed with diffuse large B-cell lymphoma and angioimmunoblastic T-cell lymphoma. Results Case 1 received one cycle of adriamycin, bleomycin, vincristine and dacarbazine (ABVD regimen) combined with chidamide, followed by one cycle of gemcitabine and dexamethasone (GDP regimen) combined with chidamide, and then oral acyclovir. The patient achieved stable disease, but was lost to follow-up. Case 2 received eight cycles of cyclophosphamide, pirarubicin, vincristine and dexamethasone (CTOP regimen) combined with chidamide, and the patient achieved complete remission. Nine months later, relapse was confirmed. She received chidamide monotherapy for 3 months, which was then terminated. One year later, the patient underwent progressive disease and died. Conclusions CL is a kind of rare disease. Due to the complexity of CL, clinicians should consider both disease components in order to increase the likelihood of effective treatment. This is important.

Introduction Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). Methods Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. Results In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26–50%, 51–75%, 76–90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. Conclusion VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

BACKGROUND Gastric duplication cysts (GDCs) are extremely uncommon lesions and the definitive diagnosis of GDCs is challenging for gastrointestinal specialists. It is important that a differential diagnosis is performed to rule out the possibility of other diseases, mainly malignancies with a cystic component. Despite the use of multiple diagnostic modalities including endoscopy, the preoperative diagnosis of GDCs is challenging. CASE SUMMARY A 53-year-old female patient with a GDC was confirmed by positron emission tomography/computed tomography (PET/CT) instead of more conventional procedures such as endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). We propose that 18F-FDG-PET/CT has higher accuracy than EUS-FNA and may be an effective technique for the characterization of duplication cysts. CONCLUSION Preoperative diagnosis of GDCs in adults is difficult largely due to their rarity and the absence of characteristic findings. In addition, few endoscopists include GDCs in the differential diagnosis when they encounter a lesion with cystic characteristics. 18F-FDG-PET/CT with additional imaging data, may complement EUS-FNA in the diagnosis of GDCs.

Poor sleep has been associated with risk of hypertension, but previous studies were limited by treating one or two sleep factors as predictor. Our previous study has developed a sleep factor questionnaire (SFQ) to comprehensively assess wide range of sleep characteristics including sleep duration, sleep quality, light at night (LAN) exposure, night/shift work, daytime napping, and frequency of nighttime waking, insomnia, and snoring. In this cross-sectional study we used the SFQ to evaluated the associations between these sleep domains and hypertension. Comparing with the subjects who slept 7–8 h, subjects with sleep duration 6–7 h (OR = 1.42, 95% CI: 1.01, 2.00), 8–9 h (OR = 1.60, 95% CI: 1.07, 2.40), and over 9 h (OR = 2.39, 95% CI: 1.60, 3.58) had an increased prevalence of hypertension. The associations were significant among individuals under 45 years sleeping 6–7 h and those over 45 years sleeping over 8 h. The OR of prevalent hypertension was 0.80 (95% CI: 0.62, 0.97) for habitual daytime napping compared with never napping, and the association was also significant among individuals over 45 years old. Moreover, among subjects with sleep duration 7–8 h, habitual daytime napping may decrease prevalent hypertension (OR = 0.635, 95% CI: 0.437, 0.924). In conclusion, our data suggested a positive association between both short (6–7 h) and long sleep duration and hypertension, and a preventive pattern for habitual daytime napping among over 45 years old and hypertension. Moreover, interaction analysis indicated that habitual midday nap may decrease prevalent hypertension among subjects with sleep duration 7–8 h.

Background: Investigate factors associated with treatment outcome in patients with nontuberculous mycobacterial pulmonary disease (NTMPD). Methods: This retrospective cohort study examined NTMPD patients in Shanghai from January 2014 to December 2018. The distribution and incidence of the different causative species were determined. The outcomes of patients infected with different NTM species were compared. Univariate and multivariate binary logistic regression analyses were used to determine the odds ratios (ORs) and 95% confidence intervals (CIs) for the association of different factors with treatment failure. Results: The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, PM. abscessus (36.1%, PM. abscessus: aOR=9.355, P<0.001; MAC: aOR=2.970, P=0.021), having an elevated ESR (>60mm/h: aOR=2.658, P P<0.001), middle-aged and elderly (>60 years-old: aOR=1.739, P=0.021; 45–60 years-old: aOR=1.661, P=0.034). Conclusions: The main bacterial species responsible for NTMPD infections in Shanghai were MAC, M. abscessus, and M. kansasii. Patients with M. kansasii infections had a higher rate of treatment success. Multiple factors including infection by M. abscessu or MAC, an elevated ESR, receiving retreatment, middle-aged and elderly were associated with treatment failure.

BACKGROUND: Migraine and major depressive disorder (MDD) are both highly prevalent brain disorders and are often comorbid. However, the common and distinctive neural mechanisms underlying these disorders and the brain function alterations associated with their comorbidity are largely unknown. We aimed to explore the functional abnormalities of the brain associated with the co-occurrence of migraine and depression. METHODS: High-resolution T1-weighted and resting-state functional magnetic resonance images (MRI) were acquired from 93 well-matched patients with comorbid migraine and depression, patients with migraine, patients with MDD, and healthy controls. Voxel-wise analysis of variance (ANOVA) and a two-sample t-test of multiple functional variables were performed among the groups. Furthermore, correlation analysis was conducted to detect the clinical significance of the altered functional regions in the brain. RESULTS: Migraine patients with and without depression revealed widely shared regional networks of functional changes. Brain function changes in the right paracentral lobule and fusiform were specific to patients with comorbid migraine and depression [P

Objective: The comorbidity of migraine and depressive has been recognized, but the pathophysiology remains unknown. Here, we aimed to explore the structural change of amygdala(AMY) and abnormal function in the centromedial amygdala (CMA) among migraineurs with depression. Methods: High-resolution T1-weighted and functional magnetic resonance images were acquired from subjects of 22 migraine comorbid with depression(EMwD ), 22 episodic migraine (EM), 20 major depressive disorder (MDD), respectively, and 18 healthy controls(HC). Apply voxel-based morphometry (VBM ) and resting state functional connectivity (rsFC) to examing inter-group differences in brain structure and function. Results: The volume of bilateral AMY increased in EMwD and EM compared to HC. EMwD showed larger volume than MDD. And the volume of AMY showed positive correlation with duration of illness in patient groups. Compared with EM, EMwD exhibited decreased rsFC between the right CMA and left cerebellum, left dorsolateral prefrontal cortex (DLPFC) , left precuneus(PCC). In addition, rsFC between the left CMA and left DLPFC was negatively correlated with Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD). Conclusions: According to our findings, the larger volume of amygdala and the abnormal functional connectivity may help to determining the common symptoms in migraine with depression, and may be a treatment target for migraine and depression comorbidities.

To investigate the utility of in vivo confocal microscopy (IVCM) in the diagnosis of infectious keratitis (IK). Retrospective chart review of 46 patients with a final diagnosis of IK were included in the study. All patients received IVCM corneal imaging using the Heidelberg Retinal Tomography III system. All available scans were randomized and analyzed in a masked fashion. Sensitivity and specificity of IVCM in diagnosing bacterial keratitis (BK), Acanthamoeba keratitis (AK), fungal keratitis (FK), and HSV viral keratitis (VK) were assessed. The pooled sensitivity and specificity of IVCM in identifying atypical IK (AK and FK cases combined) were 85.3% (95% CI 68.2–94.5%) and 100% (95% CI 74.7–100%), respectively. The sensitivity and specificity of IVCM in identifying BK were 66.7% (95% CI 35.4–88.7%) and 89.2% (95% CI 73.4–96.5%), respectively. The sensitivity and specificity of IVCM in identifying VK were 100% (95% CI 46.3–100%) and 93.2% (95% CI 80.3–98.2%). Additionally, IVCM was able to make the correct diagnosis in 8 out of the 11 atypical keratitis cases misdiagnosed clinically. In the AK subgroup, IVCM was more accurate than clinical assessment (16 vs. 11). In the FK subgroup, IVCM were as accurate as clinical assessment, but did correct one misdiagnosed cases by identfying fungal hyphae. IVCM is an non-invasive imaging modality that can rapidly and accurately diagnose IK even for experienced corneal specialists. In complex cases of polymicrobial infection, IVCM may guide the correct clinical diagnosis and initiation of the appropriate treatment.

Intestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR- and mass spectrometry–based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSH-expressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

Background The accumulation of α-synuclein (α-Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α-Syn, and appendectomy has been reported to affect the incidence of PD. Objective This study investigated appendix abnormality in patients with PD. Methods We assessed appendix morphology in 100 patients with PD and 50 control subjects by multislice spiral computed tomography. We analyzed the clinical characteristics of patients with PD with diseased appendices, which was confirmed in seven patients by histopathological analysis. Results Chronic appendicitis-like lesions were detected in 53% of patients with PD, but these were not associated with the duration of motor symptoms. Appendicitis-like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were risk factors for PD. The following clinical symptoms could be used to identify patients with PD with appendicitis-like lesions: first motor symptoms were bradykinesia/rigidity, onset of motor symptoms in the central axis or left limb, prodromal constipation, high ratio of Unified Parkinson's Disease Rating Scale Part III score to symptom duration, low Montreal Cognitive Assessment score, and high Epworth Sleepiness Scale score. The seven patients with PD who were diagnosed with chronic appendicitis underwent appendectomy, and histopathological analysis revealed structural changes associated with chronic appendicitis and α-Syn aggregation. Conclusions These results indicate an association between chronic appendicitis-like lesions and PD, and suggest that α-Syn accumulation in the diseased appendix occurs in PD. © 2021 International Parkinson and Movement Disorder Society.

Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD(600)), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.

Background: Last winter, a new coronavirus-induced pneumonia, COVID-19, broke out in Wuhan, China, and spread rapidly throughout the country due to its high inf

BackgroundTo describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented.MethodsThis is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented.ResultsRetinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson’s syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up.ConclusionThe characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology ‘Henle fiber layer hemorrhage (HH)’ is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.

The mechanisms by which white button (WB) mushrooms (Agaricus bisporus) may influence health are unclear. WB feeding (1%) resulted in changes in the composition of microbiota in conventional (CV) mice to expand a population of Prevotella that produce propionate and succinate. Microbial propionate and succinate production induced expression of genes important for intestinal gluconeogenesis (IGN) via the gut-brain neural circuit. Reduced hepatic glucose production was a metabolic benefit of IGN that was found in WB fed CV mice. In the absence of microbiota or in mice with disruptions in the ability to sense microbiota there was no WB mediated effect. WB-fed lean mice had a small but significant improvement in glucose sensitivity. WB feeding resulted in shifts in the microbiota that induced IGN and improved glucose homeostasis.

Purpose To report the first case of a cone dystrophy with central ellipsoid zone loss associated with a mutation in the human retinal fascin gene (FSCN2). Methods Multimodal retinal imaging findings including spectral domain optical coherence tomography and fundus autofluorescence are presented. The results of functional testing and mutational analysis are also discussed. Patients Single patient with a diagnosis of cone dystrophy. Results Spectral domain optical coherence tomography imaging illustrated central loss of the ellipsoid zone band in each eye. Full-field and multifocal electroretinogram testing confirmed a diagnosis of cone dystrophy in a 35-year-old male patient. Subsequent cone dystrophy genetic panel identified a novel mutation (p.Pro406Leu:c.1217C>T) in the FSCN2 gene. Conclusion This is the first case report of a patient diagnosed with cone dystrophy associated with a novel mutation in the FSCN2 gene. FSCN2 genetic testing should be considered in patients with central ellipsoid loss and cone dystrophy, especially as specific gene therapy treatments emerge in the future.

The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem cell growth factor receptor (CD117) markers were specific for the diagnosis of MS. The three patients with NHL survived, and one of the patients survived for 82 months with no evidence of disease; however, was eventually lost to follow-up. The two patients with MS succumbed to the cancer as a result of progressive disease and leukemia. Therefore, pathological examination may be important for the timely diagnosis and appropriate therapeutic regimen for primary hematological malignancy of the uterine cervix.

Purpose To assess the feasibility of imaging extremely low birth weight infants, defined as infants born weighing less than 1000 g or before 27 weeks of gestational age, with an arm-mounted optical coherence tomography angiography (OCTA) device. Methods Cross-sectional case series conducted at a single site in-patient academic center. Subjects included infants who had been born premature and met ROP screening criteria. Birth history such as gestational age and birth weight were collected. Subjects were imaged with OCTA in a supine position during ROP screening and treatment. Segmental errors were manually corrected and FAZ area was calculated from the superficial and deep capillary plexus (SCP, DCP) layers. Main outcomes measures were foveal avascular zone (FAZ) area, ROP stage and treatment. Results Seven ELBW infants were included with an average gestational age of 25 weeks (range = 23-4/7 to 26 weeks) and average postmenstrual age of 54.7 weeks (range = 43–80 weeks) at the time of imaging. Average birth weight was 615 g (range 500–680 grams). Thirteen eyes had ROP treatment including primary laser, anti-vascular endothelial growth factor injection with delayed laser, and scleral buckle. Six infants were imaged under general anesthesia and one infant was imaged without sedation. Average FAZ area was 0.17 mm2 (range = 0.03 mm2–0.37 mm2) in the SCP and 0.04 mm2 (range 0 mm2–0.09 mm2) in the DCP. FAZ area correlated positively to the ratio of outer retinal layer thickness to inner retinal layer thickness at the foveal center in the SCP and DCP (r2 = 0.48, p = 0.02; r2 = 0.46, p = 0.02) and negatively with inner retinal layer thickness in the SCP (r2 = 0.56, p = 0.008). Conclusions and Importance Arm-mounted OCTA was feasible in ELBW infants and provided information about the developing fovea. Measurement of FAZ area and retinal thickness using this modality may be used to study the effects of ELBW, peripheral ROP and ROP treatment on foveal development.

Acanthamoeba keratitis (AK) is a severe vision-threatening ocular infection that is frequently a diagnostic challenge. Treatment course is lengthy and often not fully effective. Contact lens wear has been recognized as the prime risk factor for AK. In vivo confocal microscopy (IVCM) is a noninvasive imaging modality that allows direct visualization of potential causative pathogens in real time with an established utility in the diagnosis of AK. In this study, we aim to assess the utility of IVCM in monitoring disease progression in contact lens wearers with culture-confirmed keratitis.Fourteen eyes from 11 patients with culture-confirmed AK were included in this retrospective study. IVCM was performed during the patient's initial visit and all follow-up visits. All available confocal sequences were reviewed and graded in a masked fashion. Density of Acanthamoeba cyst infiltration and changes in the cyst density as a percentage of baseline cyst density measured at each patient's initial visit were calculated. A univariate regression analysis was performed to assess the association between treatment and changes in cyst density per month of treatment.Acanthamoeba cysts were identified by IVCM in all of these culture-confirmed cases of keratitis. Mean cyst density in the central cornea at presentation was 99 ± 64.9 cells per square millimeter (range, 38-255/mm). Cyst density in our study population significantly decreased by approximately 5.3% with each month of antiamebic treatment (P = 0.001; R = 0.41).Reduction in Acanthamoeba cyst density with treatment can be monitored by IVCM, which in turn can be used clinically in prognostication and disease monitoring of AK.

Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB.

Background: In the absence of a positive sputum bacteriological result, pathological and bacteriological examinations of lung lesion biopsies are important methods to confirm bacteriological-negative tuberculosis. Endobronchial ultrasonography with guide sheath (EBUS-GS) and electromagnetic navigation bronchoscopy (ENB) are two new endobronchial diagnostic techniques, the combination of which has greatly facilitated the diagnosis of peripheral pulmonary lesions and is an especially useful, minimally invasive, effective diagnostic method for bacteriologically-negative tuberculosis cases. Methods: A total of 78 patients were included in this study with suspected pulmonary tuberculosis based on clinical manifestations, laboratory tests, and imaging studies. The patients underwent a high-resolution chest CT scan before bronchoscopy, A method was selected (EBUS-GS alone, or EBUS-GS + ENB) based on the lesion site and the level and angle of the bronchus involved. After the lesion was found, a puncture needle, biopsy forceps, and brushing forceps were used to collect a tissue sample. Results: Forty-four patients were diagnosed with tuberculosis; 1, nontuberculous Mycobacteria (NTM) lung disease; 15, lung cancer; 15, pulmonary infection; 1, allergic bronchopulmonary aspergillosis (ABPA); and 2, pneumoconiosis. A total of 25 patients of TB (56.8%) were successfully diagnosed with EBUS-GS plus ENB. Among the patients with confirmed diagnosis, 9 were diagnosed with pathological examination; 4, genetic analysis; 11, positive smear; and 14, positive culture. Conclusions: The introduction of EBUS and ENB in China has provided a new direction for the diagnosis of atypical bacteriological-negative tuberculosis, as the techniques are less invasive and less expensive than thoracoscopy.

Tumor necrosis factor receptor-associated protein-1 (TRAP-1), a mitochondrial chaperone, contributes significantly to the progression of cancer. However, the understanding of its involvement in the clinicopathological characteristics and prognosis of colorectal cancer (CRC) remains limited. The aim of the present study was to assess the significance of TRAP-1 expression in CRC. The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry. The associations between TRAP-1 expression and the clinicopathological parameters and survival rates of patients was assessed. Out of 256 patients with CRC, TRAP-1 expression was detected in 203 (79.3%). TRAP-1 expression was significantly increased in cancerous tissue compared with that in corresponding paracancerous tissues (P

Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug reactions (ADRs). To assess the potential of drug-induced lymphocyte stimulation test (DLST) in screening ADRs in patients treated with anti-TB drugs, we performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without ADRs) treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The ADRs were diagnosed by drug provocation test based on clinical and laboratory examinations. The sensitivities of DLST in the diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and 23.1%, respectively, with the corresponding specificities being 93.4%, 94.0%, 97.5%, and 98.8%. DLST has high specificity and limited sensitivity in the diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation and drug use history, DLST could have a predictive validity of ADRs, especially when a positive result is obtained.

Background Isocyanates are one of the most commonly reported causes of occupational asthma; however, the risks of developing isocyanate asthma in modern production facilities remain poorly defined. We evaluated TDI exposure and respiratory health among an inception cohort of workers during their first year of employment at a new polyurethane foam production factory.

Purpose To report a case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy. Observations A 65-year-old Caucasian woman presented with acute respiratory distress syndrome and septic shock. After treatment with vasopressors and prolonged prone positioning, she was noted to be bilaterally completely blind on hospitalization day 12. Evaluation revealed evidence of bilateral central retinal artery occlusion and bilateral ischemic optic neuropathy. Magnetic resonance imaging of the orbits demonstrated severe restricted diffusion of both optic nerves consistent with ischemia. Both central retinal artery occlusion and ischemic optic neuropathy have been reported in cases of severe hypotension, blood loss, and prone positioning, most often postoperatively after spinal surgery. Conclusions and importance To our knowledge, this is the first reported case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy, presumed due to the combination of severe systemic hypotension, hypoxemia due to the respiratory distress syndrome, and prolonged prone positioning.

Objective To evaluate the treatment of primary pulmonary NK/T cell lymphoma. Method A case report and review of the literature. The tissue material was obtained by transbronchial biopsy, and the diagnosis was confirmed by pathology. He received five cycles of chemotherapy with L-asparaginase-based regimen. Result He remained complete remission for 2 years following the initial diagnosis. Conclusion Primary pulmonary NK/T cell lymphoma is an aggressive disease. It is usually associated with poor outcome in the literature. L-asparaginase based regimen was effective for our newly diagnosed patient.

To compare vision-related (VR-QOL) and health-related quality of life (HR-QOL) in patients with noninfectious uveitis treated with systemic anti-inflammatory therapy versus nonsystemic therapy.A prospective, cross-sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25-Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health Survey (SF-12), respectively. Multivariate regression analysis was performed to assess the VR-QOL and HR-QOL based on treatment.Among the 80 patients, the median age was 51 years with 28 males (35%). The adjusted effect of treatment modality on VR-QOL or HR-QOL showed no statistically significant difference in all subscores of VFQ-25 or physical component score (PCS) and mental component score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL compared to nonsystemic therapy.Systemic therapy can be effectively used to control serious cases of noninfectious uveitis without significant relative adverse impact on quality of life.

To improve detection performance for weak and small targets signal in complex infrared background,such as the ground and the cloud,a dim and small target background suppression method is presented based on vision cell response model was presented.Firstly,according to simple cell receptive field model,original infrared image is decomposed to two images with different Gabor functions using convolution.And then,the function of nonlinear convergence of complex cell response is used to fusion two images obtained for separation small target with background clutter in infrared image.Finally,target image is obtained by using classical adaptive thresholding method.Several groups of experimental results demonstrate that the proposed method can segment the infrared target image effectively,compared with several classical infrared dim and small target background suppression methods,such as local means remove and max median filter methods.

Objective To observe the effects of serum containing Xiaotan Sanjie Decoction, a compound traditional Chinese herbal medicine, on proliferation and apoptosis of human gastric cancer cell line MKN-45. Methods After coculturing MKN-45 cells with low-, medium- and high-dose Xiaotan Sanjie Decoction-containing serum, inverted microscope was utilized to observe morphological changes and counting chamber was used to count the MKN-45 cells; the proliferation of MKN-45 cells was determined by cell counting kit 8; Annexin V-fluorescein isothiocyanate/propidium iodide double label method was used to detect apoptosis rate of MKN-45 cells. Results Xiaotan Sanjie Decoction-containing serum significantly inhibited the proliferation of MKN-45 cells. The typical morphological changes of apoptotic MKN-45 cells were observed after treating with Xiaotan Sanjie Decoction-containing serum. The cell apoptosis was also observed by flow cytometry and the apoptosis rates of medium- and high-dose Xiaotan Sanjie Decoction-containing serum groups were higher than that of low-dose group. Conclusion Xiaotan Sanjie Decoction-containing serum can inhibit the MKN-45 cell proliferation and induce cell apoptosis, which provides an experimental evidence for its treatment of human gastric cancer.

The objective is to investigate the association between pathological type and clinical features, response to treatment and prognosis of primary gastrointestinal Non-Hodgkin's lymphoma (PGINHL). The clinicopathologic features, response to treatment and survival of 124 patients with PGINHL, were investigated retrospectively. Ninety-one patients were treated with surgery, most of which included combined therapy, while 32 patients received chemotherapy alone. Survival analysis was performed by Kaplan-Meier and Cox regression method. The most common immunophenotype was B-cell subtype. In 115 (92.7%) patients of B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) were 55 and 50 patients, respectively. The patients of two pathological types had different clinical features including stage, B symptoms, sites of tumor, distant involvement, International Prognosis Index Score, size of tumor, and response to treatment. Both overall survival curve and multiple Cox regression analysis indicated that pathological type was statistically significant. The pathological subtype of PGINHL was an important prognostic factor. The patients with MALToma appear to have more favorable prognosis than those with DLBCL.

The aim of this study was to evaluate the effect and safety of autologous peripheral blood stem cell transplantation (APBSCT) in children and adolescents with non-Hodgkin lymphoma (NHL). Ten patients with NHL were analyzed retrospectively. In all the patients, lymph node enlargement was most frequently detected. Patients with a mediastinal mass presented with a cough, palpitation and shortness of breath. Extranodal patients presented with abdominal pain, inability to walk and vaginal bleeding. All patients underwent APBSCT with conditioning regimens BEAM or BuCy. Among them, four patients with B-cell NHL received rituximab in addition to the conditioning regimen. Hematopoietic reconstitution was observed in all patients. Severe toxicity and transplant-related mortality were not observed. Prior to APBSCT, nine patients with a status of complete response (CR) and CR unconfirmed achieved continuing complete remission. Only one patient with partial response succumbed to progressive disease. APBSCT in children and adolescents with NHL is a safe, convenient and efficient treatment. The BEAM conditioning regimen was shown to be effective and tolerable for children and adolescents with NHL. Rituximab is a safe agent in the transplantation. The CR status at the time of transplantation demonstrated a higher survival rate.

Objective: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) for aggressive lymphoma and to study the problem of minimal residual disease (MRD). Methods: 14 lymphoma patients who had lymphoma with high risk factors, relapsed lymphoma or refractory lymphoma received autologous bone marrow transplantation (ABMT). 14 lymphoma patients who were similar to ABMT group received autologous peripheral blood stem cells transplantation (APBSCT). Regimen of CBV (cyclophos phamide 50∼60 mg/kg/d×2 d, carmustine 15 mg/kg/d×1 d, etoposide 45∼60 mg/kg/d×1 d) was received by all the patients as conditioning regimen in the transplant pretreatment followed by ABMT or APBSCT. Autologous peripheral blood stem cell (APBSC) was mobilized by CTX 2g∼3g/m2/d×2 d iv and G-CSF 5 µg/kg/d for five to seven days. MRD was continually supervised by PCR in bone marrow before and after transplantation. Cellular immunocyte function, such as natural killer cell (NK), CD3, CD4, CD8 and sIL-2R was tested before and twenty days after transplantation. Results: In ABMT group, the median time for hematopoietic recovery of absolute neutrophilia counts ≥0.5×109/L and platelet counts ≥20×109/L was +18 days and +20 days respectively. In contrast, the APBSCT group was both at 12 days. Patients who have undergone ABMT all got complete remission (CR), while 81.8% patients in APBSCT group got CR. The 3-year disease free survival (DFS) in APBSCT and ABMT group was 75% and 72.7% respectively (P>0.05). The mean days of immunity recovering in APBSCT was ±20 days. After transplantation, MRD in 11 patients were positive, in whom 6 patients died. Conclusion: Aggressive lymphoma patients’ hemapoiesis recovered more rapidly in APBSCT group than that in ABMT group, but 3-year DFS had no statistical difference. Patients positive for IgH/TCR-γ by molecular PCR analysis had poor DFS. Molecur monitoring of MRD using PCR techniques seems to represent a reliable prognostic indicator. Immunotherapy in the patients whose bone morrow was positive for MRD post-AHSCT may intensify remission and reduce relapse rates.

The accuracy and sensitivity of prostate-specific antigen (PSA) for prostate cancer diagnosis is often poor; however, the reasons for its inaccuracy have rarely been investigated, especially with respect to age. In this study, 476 healthy males, aged 10–89 years, were stratified into eight age groups, and levels of seven markers were determined: total PSA (tPSA), free PSA (fPSA), %fPSA, isoform [-2]proPSA (p2PSA), p2PSA/tPSA, %p2PSA, and the prostate health index (PHI). Both tPSA and fPSA levels increased with age. The tPSA level was highest (1.39 ng ml−1) at 70–79 years; %fPSA was highest (0.57 ng ml−1) at 10–19 years; and %p2PSA was lowest (18.33 ng ml−1) at 40–49 years. Both p2PSA and p2PSA/tPSA had relatively flat curves and showed no correlation with age (P = 0.222). PHI was a sensitive age-associated marker (P < 0.05), with two peaks and one trough. The coverage rates and radiance graphs of PHI and %p2PSA were more distinctive than those of tPSA and the other markers. In subjects older than 69 years, PHI and %p2PSA both began to decrease, approximately 10 years earlier than the decrease in tPSA. Our results suggest that the clinical diagnosis of prostate cancer using PSA should be investigated more comprehensively based on patient age. Moreover, %p2PSA and PHI could be considered as earlier markers that may be more suitable than PSA alone.

To address the role of the transforming growth factor beta (TGFβ)-Smad3 signaling pathway in dendrite growth and associated synaptogenesis, we used small inhibitory RNA to knockdown the Smad3 gene in either cultured neurons and or primary astrocytes. We found that TGFβ1 treatment of primary neurons increased dendrite extensions and the number of synapsin-1-positive synapses. When Smad3 was knockdown in primary neurons, dendrite growth was inhibited and the number of synapsin-1-positive synapses reduced even with TGFβ1 treatment. When astrocyte-conditioned medium (ACM), collected from TGFβ1-treated astrocytes (TGFβ1-stimulated ACM), was added to cultured neurons, dendritic growth was inhibited and the number of synapsin-1-positive puncta reduced. When TGFβ1-stimulated ACM was collected from astrocytes with Smad3 knocked down, this conditioned media promoted the growth of dendrites and the number of synapsin-1-positive puncta in cultured neurons. We further found that TGFβ1 signaling through Smad3 increased the expression of chondroitin sulfate proteoglycans, neurocan, and phosphacan in ACM. Application of chondroitinase ABC to the TGFβ1-stimulated ACM reversed its inhibitory effects on the dendrite growth and the number of synapsin-1-positive puncta. On the other hand, we found that TGFβ1 treatment caused a facilitation of Smad3 phosphorylation and translocation to the nucleus induced by status epilepticus (SE) in wild-type (Smad3(+/+)) mice, and this treatment also caused a promotion of γ-aminobutyric acid-ergic synaptogenesis impaired by SE in Smad3(+/+) as well as in Smad3(-/-) mice, but more dramatic promotion in Smad3(+/+) mice. Thus, we provide evidence for the first time that TGFβ-Smad3 signaling pathways within neuron and astrocyte differentially regulate dendrite growth and synaptogenesis, and this pathway may be involved in the pathogenesis of some central nervous system diseases, such as epilepsy.

Primary thunderclap headache (TCH) is a rare condition, of which the onset can be triggered by coughing, exercise, and sexual activity. Micturition is a recognized trigger of secondary TCH with pheochromocytoma in bladder, but not of primary TCH. We describe a patient with an apparent primary TCH, which repeatedly occurred immediately after micturition until she achieved a therapeutic dosage of nimodipine.