The clinical features and perfusion density in paracentral acute middle maculopathy by optical coherence tomography angiography study.

PURPOSE: To observe the clinical features of the paracentral acute middle maculopathy (PAMM) and to investigate the changes in perfusion density of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in PAMM by optical coherence tomography angiography (OCTA). METHODS: Twelve patients (12 eyes) diagnosed with PAMM and 13 healthy participants (13 eyes) were enrolled. The clinical features of 12 PAMM patients were recorded. The perfusion density of SCP and DCP in the parafovea and perifovea (divided into Temporal, Superior, Nasal, and Inferior) was measured by OCTA in PAMM and healthy eyes. Automated macular maps, including SCP and DCP, were also performed. RESULTS: The mean age of patients was 48.08 (range 14-72) years. The best corrected visual acuity (BCVA) was from finger count (FC) to 1.0. Risk factors included hypertension, diabetes mellitus, COVID-19, etc. The patients had signs of retinal vascular disease except for one patient with isolated PAMM. A spectral-domain OCT image of the PAMM eye showed hyperreflectivity in the inner nuclear layer (INL). Compared with healthy eyes, SCP and DCP in PAMM eyes were significantly reduced in all sectors (all p < 0.05) in the parafovea and perifovea. The average perfusion density of SCP in parafovea and perifovea in PAMM eyes were 46.94±4.34% vs 52.21±3.98 % (p = 0.002), 44.01±3.95% vs 50.51±3.14 (p = 0.000) in healthy eyes. The average perfusion density of DCP in parafovea and perifovea in PAMM eyes were 51.22±4.16% vs 57.15±3.87 % (p = 0.002), 47.375±6.23% vs 54.27±5.33 % (p = 0.002) in healthy eyes. CONCLUSION: PAMM often accompanies concurrent ocular and systemic diseases. OCTA results confirm that the perfusion density of SCP and DCP in the parafovea and perifovea significantly reduced in PAMM patients.

Electroacupuncture improves retinal function in myopia Guinea pigs probably via inhibition of the RhoA/ROCK2 signaling pathway.

Objective: To investigate the effect of electroacupuncture (EA) on retinal function in guinea pigs with negative lens-induced myopia (LIM) by inhibiting the RhoA/ROCK2 signaling pathway. Methods: Guinea pigs were randomly divided into normal control (NC) group, LIM group, EA group, SHAM acupoint (SHAM) group, and electro-acupuncture + ROCK pathway inhibitor Y27632 (EA + Y27632) group. The refraction, axial length, retinal blood flow density, choroidal vascular index, retinal physiological function, the contents of total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) of each group were determined. The changes in retinal tissue structure were observed by hematoxylin and eosin (H&E) staining, and the expression of the RhoA/ROCK2 signaling pathway-related molecules in the retina was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Results: Myopic refraction, AL, and MDA content in the LIM and SHAM groups were significantly increased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were decreased. After EA intervention, myopic refraction, AL, and MDA content decreased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were increased. H&E staining showed that the thickness of the guinea pig retina, the thickness of the inner and outer layers of the nucleus, and the number of cells were significantly increased after EA intervention. qPCR and western blot analyses showed that the expression of RhoA、ROCK2、MLC、CollagenⅠ、MMP-2、TIMP-2 and α-SMA were elevated in the LIM and SHAM group than those in the NC group. Compared with the LIM group, the expression of EA group was significantly decreased. Conclusions: Electroacupuncture can improve retinal function by improving retinal blood flow, reducing retinal oxidative damage, inhibiting RhoA/ROCK2 signaling pathway and controlling extracellular matrix remodeling, thus delaying the occurrence and development of myopia.

The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease from Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), as a typical intracellular pathogen, possesses several putative restriction-modification (R-M) systems, which restrict exogenous DNA's entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from Mtb H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in Escherichia coli BL21(DE3)pLysS strain. The Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay indicates that Rv2528c cleaves genomic DNA in vivo. The plasmid transformation efficiency of BL21(DE3)pLysS strain harboring Rv2528c gene was obviously decreased after plasmids were in vitro methylated by commercial DNA methyltransferases such as M.EcoGII, M.HhaI, etc. These results are consistent with the characteristics of type IV REases. The in vitro DNA cleavage condition and the consensus cleavage/recognition site of Rv2528c still remain unclear, similar to that of most Mrr-family proteins. The possible reasons mentioned above and the potential role of Rv2528c for Mtb were discussed.

HigA2 (Rv2021c) Is a Transcriptional Regulator with Multiple Regulatory Targets in Mycobacterium tuberculosis.

Toxin-antitoxin (TA) systems are the major mechanism for persister formation in Mycobacterium tuberculosis (Mtb). Previous studies found that HigBA2 (Rv2022c-Rv2021c), a predicted type II TA system of Mtb, could be activated for transcription in response to multiple stresses such as anti-tuberculosis drugs, nutrient starvation, endure hypoxia, acidic pH, etc. In this study, we determined the binding site of HigA2 (Rv2021c), which is located in the coding region of the upstream gene higB2 (Rv2022c), and the conserved recognition motif of HigA2 was characterized via oligonucleotide mutation. Eight binding sites of HigA2 were further found in the Mtb genome according to the conserved motif. RT-PCR showed that HigA2 can regulate the transcription level of all eight of these genes and three adjacent downstream genes. DNA pull-down experiments showed that twelve functional regulators sense external regulatory signals and may regulate the transcription of the HigBA2 system. Of these, Rv0903c, Rv0744c, Rv0474, Rv3124, Rv2603c, and Rv3583c may be involved in the regulation of external stress signals. In general, we identified the downstream target genes and possible upstream regulatory genes of HigA2, which paved the way for the illustration of the persistence establishment mechanism in Mtb.

Comprehensive Analysis of Immune Signatures in Primary Biliary Cholangitis and Autoimmune Hepatitis.

Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+TEMRA, CD4+TEM, and CD4+TEMRA cells, and a concurrent reduction in Treg cells. In contrast, PBC displayed a pronounced presence of Tfh cells and a contraction of CD4-CD8-T cell populations. Correlation analysis revealed that NKP46+NK frequency was closely tied to ALT and AST levels, and TIGIT expression on T cells was associated with GLB level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. And γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.

Design and development of a disease-specific clinical database system to increase the availability of hospital data in China.

Purpose: In order to meet restrictions and difficulties in the development of hospital medical informatization and clinical databases in China, in this study, a disease-specific clinical database system (DSCDS) was designed and built. It provides support for the full utilization of real world medical big data in clinical research and medical services for specific diseases. Methods: The development of DSCDS involved (1) requirements analysis on precision medicine, medical big data, and clinical research; (2) design schematics and basic architecture; (3) standard datasets of specific diseases consisting of common data elements (CDEs); (4) collection and aggregation of specific disease data scattered in various medical business systems of the hospital; (5) governance and quality improvement of specific disease data; (6) data storage and computing; and (7) design of data application modules. Results: A DSCDS for liver cirrhosis was created in the gastrointestinal department of a 3A grade hospital in China and had more than nine data application modules. Based on this DSCDS, a series of clinical studies are being carried out, such as retrospective or prospective cohorts, prognostic studies using multimodal data, and follow-up studies. Conclusion: The development of the DSCDS for liver cirrhosis in this paper provides experience and reference for the design and development of DSCDSs for other specific diseases in China; it can even expand to the development of DSCDSs in other countries if they have the demand for DSCDS and the same or better medical informatization foundation. DSCDS has more accurate, standard, comprehensive, multimodal and usable data of specific diseases than the general clinical database system and clinical data repository (CDR) and provides a credible data foundation for medical research, clinical decision-making and improving the medical service quality of specific diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00211-4.

Effect of ASA on the risk of cerebrovascular ischemic events in patients with PFO.

BACKGROUND: Whether atrial septal aneurysm (ASA) increases the risk of cerebrovascular ischemic events in patients with patent foramen ovale (PFO) remains controversial. OBJECTIVE: We constructed a detailed meta-analysis to assess the effect of ASA on risk of cerebrovascular ischemic events in patients with PFO. METHODS: Randomized controlled trials (RCTs) and observational studies (cohort studies and case-control studies) that compared PFO-ASA against PFO alone were included. Pooled odds ratios (OR) estimates and 95% CI were calculated using the fixed-effect and random-effect models. RESULTS: Four RCTs and twelve observational studies (five cohort studies and seven case-control studies) contributed to the meta-analysis. The pooled results of case-control studies showed that ASA increased the risk of cerebrovascular ischemic events in patients with PFO (fixed-effect model: OR = 3.69; 95% CI: 2.67-5.09; p < 0.01, random-effect model: OR = 3.63; 95% CI: 2.51-5.24; p < 0.01). However, poole results from RCTs (fixed-effect model: OR = 1.24; 95% CI: 0.78-1.95; p = 0.36, random-effect model: OR = 1.27; 95% CI: 0.78-2.08; p = 0.34) and cohort studies (fixed-effect model: OR = 1.35; 95% CI: 0.81-2.23; p = 0.25, random-effect model: OR = 1.40; 95% CI: 0.84-2.33; p = 0.20) found no evidence. Overall analysis showed that ASA increased the risk of cerebrovascular ischemic events (fixed-effect model: OR = 2.30; 95% CI: 1.84-2.87; p < 0.01, random-effect model: OR = 2.11; 95% CI: 1.48-3.01; p < 0.01). The sensitivity analysis confirmed the stability of all results. CONCLUSIONS: Although case-control studies support ASA to increase the risk of cerebrovascular ischemic events in patients with PFO, RCTs and cohort studies challenged the credibility. Further prospective studies are needed to confirm the effect of ASA on patients with PFO.

The Joint Toxicity of Organic Three-dimensional Layered Double Hydroxide and Methyl Orange to Green Algae Chlorella Vulgaris.

Organic modified layered double hydroxides (O-LDHs), known as attractive adsorbents for organic pollutants, may pose severe toxicity to the aquatic organisms during their large-scale application. However, little information is available on the toxicity of O-LDHs and the joint toxicity with the coexisted organic pollutants. Herein, we employed organic three-dimensional layered double hydroxide (O3D-LDH) and methyl orange (MO) as representative to investigate the toxicity mechanisms of single substance and its binary mixture on green algae Chlorella vulgaris. Results showed that O3D-LDH and MO presented concentration-dependent toxicity, the binary mixture showed additive effect after exposed to low O3D-LDH concentration (≤ 50 mg/L), but antagonism was observed for the other. It revealed that the agglomeration of O3D-LDH and microalgae influenced chlorophyll content, eventually inhibiting the growth of algae. Overall, this toxicity investigation was critical for understanding the environmental risk of organic LDHs to provide theorical guidance for their practical application in the water purification.

Pd-Catalyzed Enantioselective (3+2)-Cycloaddition of Vinyl-Substituted Oxyallyl Carbonates with Isocyanates and Ketones.

The vinyl-substituted oxyallyl carbonates were exploited as a new C,O-dipole for enantioselective Pd-catalyzed (3+2) cycloaddition. The corresponding oxyallyl-Pd species was weakly nucleophilic to react with activated carbonyl compounds, affording multisubstituted and enantioenriched oxazolidinones and 1,3-dioxolanes with a high degree of chemo- and stereoselectivity. The synthetic transformations of oxazolidinone product were carried out to build enantioenriched α-chiral aminoketone and epoxy derivatives.

Clinical presentation of gastric Burkitt lymphoma presenting with paraplegia and acute pancreatitis: A case report.

BACKGROUND: The incidence of gastric Burkitt lymphoma (BL), presenting as paraplegia and acute pancreatitis, is extremely low. BL is a great masquerader that presents in varied forms and in atypical locations, and it is prone to misdiagnosis and missed diagnosis. The prognosis of BL remains poor because of the difficulty in early diagnosis and the limited advances in chemotherapy. CASE SUMMARY: A 53-year-old man was referred to our hospital from the local county hospital due to abdominal pain for two weeks and weakness in the lower extremities for one day. Magnetic resonance imaging of the abdomen and lumbar spine showed a swollen pancreas and gallbladder, with peripancreatic exudation and liquid collection, indicating acute pancreatitis and acute cholecystitis. Additionally, we observed abnormally thickened lesions of the gastric wall, multiple enlarged retroperitoneal lymph nodes and a well-demarcated, posterolateral extradural mass lesion between T9 and T12, with extension through the spinal foramen and definite bony destruction, suggesting metastasis in gastric malignancy. Subsequent whole-body positron emission tomography/computed tomography examination showed multifocal malignant lesions in the stomach, pancreas, gallbladder, bone, bilateral supraclavicular fossa, anterior mediastinum, bilateral axillary and retroperitoneal lymph nodes. Gastroduodenal endoscopy revealed primary BL with massive involvement of the gastric body and duodenum. The patient refused chemotherapeutic treatment and died one week later due to upper gastrointestinal hemorrhage. Afterward, we reviewed the characteristics of 11 patients with BL involving the stomach, pancreas or spinal cord. CONCLUSION: Clinicians should be aware that BL can be the potential cause of acute pancreatitis or a rapidly progressive spinal tumor with accompanying paraplegia. For gastric BL, gastroscopy biopsies and pathology are necessary for a definite diagnosis.

Investigation and analysis on an outbreak of norovirus infection in a health school in Guangdong Province, China.

Our objective was to describe the epidemiological features of an outbreak of norovirus infection in a health school in Guangdong province, China, to identify the cause of such a large scale outbreak of norovirus among older students, to simulate the transmission dynamics, and to evaluate the effect of intervention measures of GII.17 [P17] genotype norovirus infection. We identified all cases during the outbreak. Descriptive epidemiological, analytical epidemiological and hygiene survey methods were used to described the outbreak epidemic course and identify the cause of the outbreak of norovirus infection. We also used dynamical model to simulate the transmission dynamics of norovirus infection and evaluate the effect of intervention measures. Norovirus genotyping was assigned to the newly obtained strains, with a maximum likelihood phylogenetic analysis conducted. There were 360 cases of 42 classes in five grades with a 12.99% attack rate. Proportionally, more students were in contact with sick students and vomit in the suspected case group than the control group (χ2 = 5.535, P = 0.019 and χ2 = 5.549, P = 0.019, respectively). The basic reproduction number was 8.32 before and 0.49 after the intervention. Dynamical modeling showed that if the isolation rate was higher or case isolation began earlier, the total attack rate would decrease. Molecular characterization identified the GII.17 [P17] genotype in all stains obtained from the health school, which were clustered with high support in the phylogenetic tree. This was an outbreak of norovirus infection caused by contact transmission. The main reasons for the spread of the epidemic were the later control time, irregular treatment of vomit and no case isolation. The transmission dynamics of contact transmission was high, more efficient control measures should be employed.

miR-193a Directly Targets PSEN1 and Inhibits Gastric Cancer Cell Growth, the Activation of PI3K/Akt Signaling Pathway, and the Epithelial-to-Mesenchymal Transition.

BACKGROUND: Gastric cancer, a kind of gastrointestinal malignancy, is the second type of leading death cancer. miR-193a is a key tumor suppressor in several diseases. PSEN1 is mainly related to Alzheimer's disease and may be involved in the cleavage of the Notch receptor. Material and Methods. RT-PCR and western blot were applied to evaluate miR-193a and the expression level of PSEN1. Luciferase reporter assay was applied to verify whether PSEN1 was a target of miR-193a. The Kaplan-Meier method was employed to calculate the 5-year overall survival of gastric cancer patients. RESULTS: miR-193a was downregulated in gastric cancer tissues and cell lines, and downregulation of miR-193a predicted poor 5-year overall survival of gastric cancer. miR-193a inhibited the proliferation and the activation of the PI3K/AKT signaling pathway in gastric cancer cells. miR-193a inhibited gastric cancer tumor growth in vivo. miR-193a impaired cell invasion and epithelial-to-mesenchymal transition (EMT) in HGC-27 cells. In addition, PSEN1 was a direct target of miR-193a and PSEN1 reversed partial functions of miR-193a in cell proliferation and invasion. CONCLUSION: miR-193a prominently decreased the proliferation, invasion, and activation of the PI3K/Akt signaling pathway and the abilities of epithelial-to-mesenchymal transition in gastric cancer cells. The newly identified miR-193a/PSEN1 axis provides novel insight into the pathogenesis of gastric cancer.

High-efficiency water purification for methyl orange and lead(II) by eco-friendly magnetic sulfur-doped graphene-like carbon-supported layered double oxide.

Traditional disposal techniques for the spent layered adsorbents after capturing organics suffer from intractable obstacles, such as resource waste and secondary pollution. To address this diploma, we here developed the "resource-utilization" strategy, i.e., converting the organic layered double hydroxide (as representative) to magnetic sulfur (S)-doped graphene-like carbon-supported layered double oxide (MG/S-LDO) to be reutilized in water purification. The as-prepared MG/S-LDO exhibited outstanding remediation ability toward methyl orange (MO) and lead(II), with the adsorption capacity of 1456 and 656 mg g-1, respectively. Specifically, the residue concentration of Pb2+ was reduced to 0.15 mg L-1 within 1 h, which met the discharge limit of the secondary industrial wastewater. MG/S-LDO could also maintain the preeminent adsorption capability under various interferences (such as wide pH and co-existing ions), even in the authentic water matrices. The removal mechanisms were systematically investigated to unveil that MO removal was dominated by metal-complexation, "memory effect", and π-π electron donor-acceptor (EDA). While for Pb2+ removal, besides the released OH- from LDO as precipitate agent, the vacancy defect resulting from the S doping played a crucial role in electron interaction between Pb2+ and S-doped graphene. Additionally, the MG/S-LDO was further confirmed as an eco-friendly adsorbent with excellent reusability via the acute toxicity tests using green algae and multiple cycle experiments. This work provides a novel resource-utilization strategy for organic layered wastes to construct the functional eco-friendly materials in wastewater purification realm.

Meta-analysis of patent foramen ovale closure versus medical therapy for prevention of recurrent ischemic neurological events: Impact of medication type.

BACKGROUND: The optimal treatment strategy for patent foramen ovale (PFO) patients with cryptic stroke remains controversial. We performed this meta-analysis to evaluate the effect of PFO closure versus different types of medical therapy. METHODS: We searched PubMed, Embase, and Cochrane databases. The primary efficacy endpoints were the composite outcome of recurrent stroke and/or transient ischemic attack (TIA). Secondary efficacy endpoints included separate stroke and TIA. Safety endpoints included new-onset atrial fibrillation (AF)/atrial flutter and bleeding. RESULTS: Compared with antiplatelet therapy, PFO closure significantly reduced the risk of composite outcome (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.51), stroke (OR 0.22, 95% CI 0.13-0.36], and TIA (OR 0.57, 95% CI 0.34-0.98); Compared with the mixed medical therapy group (consist of antiplatelet therapy, anticoagulant therapy, or both), PFO closure still showed some benefits, but the effect was not as significant as that of antiplatelet therapy (composite outcome: OR 0.53, 95% CI 0.41-0.69; stroke: OR 0.48, 95% CI 0.34-0.68; TIA: OR 0.69, 95% CI 0.50-0.96); Compared with anticoagulant therapy, PFO closure showed no benefit (composite outcome: OR 0.77, 95% CI 0.46-1.28; stroke: OR 0.59, 95% CI 0.28-1.25; TIA: OR 1.01, 95% CI 0.50-2.04). In terms of safe endpoints, compared with antiplatelet therapy and anticoagulant therapy, PFO closure increased the risk of AF/atrial flutter (OR 9.56, 95% CI 2.85-32.06; OR 18.96, 95% CI 1.11-323.8, respectively) and reduced the risk of bleeding (OR 0.50, 95% CI 0.24-1.05; OR 0.13, 95% CI 0.04-0.46, respectively); compared with mixed medical therapy, PFO closure increased the risk of AF/atrial flutter (OR 4.40,95% CI 2.24-8.67), but there was no difference in bleeding (OR 0.97, 95% CI 0.56-1.68). CONCLUSIONS: With the addition of anticoagulants, the benefit of PFO closure decreased gradually. Patient groups that adopt individualized medical therapy strategies may benefit more.

Short-term effects of intravitreal Conbercept injection combined with laser photocoagulation on macular edema secondary to ischemic retinal vein occlusion.

AIM: To observe changes in the best-corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) of patients with macular edema (ME) secondary to ischemic retinal vein occlusion (iRVO) following intravitreal Conbercept injection. METHODS: This retrospective study included 33 eyes from 33 patients who received intravitreal injections of Conbercept for ME secondary to iRVO. Treatments were performed on a 3+pro re nata (3+PRN) basis. All of the patients were examined by fundus fluorescein angiography and spectral domain optical coherence tomography at the first visit. Laser photocoagulation was performed in the nonperfusion area of the retina of all eyes after the first injection. BCVA, CMT, and CCT were observed before and after 6mo of treatment. The number of injections necessary to achieve improved vision was also noted. RESULTS: Following Conbercept treatment, the mean BCVA significantly improved from 0.81±0.39 at baseline to 0.41±0.25 and 0.43±0.29 logMAR in the third and sixth months, respectively (both P=0.000). The CMT of the patients at baseline was 556.75±98.57 µm; 304.78±68.53 and 306.85±76.77 µm 3 and 6mo after treatment, respectively (both P=0.000 vs baseline). The CCTs of the patients at baseline, 3 and 6mo after treatment were 304.63±57.83, 271.31±45.53, and 272.29±39.93 µm, respectively (P=0.026 and 0.035 vs baseline). No severe adverse event relevant to the therapy was noted, and the average number of injections delivered was 3.35. CONCLUSION: Intravitreal Conbercept injection combined with laser photocoagulation appears to be a safe and effective treatment for ME secondary to iRVO in the short-term.

Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis.

Fas/Fas ligand (FasL)-mediated cell apoptosis involves a variety of physiological and pathological processes including chronic hepatic diseases, and hepatocytes apoptosis contributes to the development of liver fibrosis following various causes. However, the mechanism of the Fas/FasL signaling and hepatocytes apoptosis in liver fibrogenesis remains unclear. The Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models were investigated. NF-κBp65 wild-type mice (p65f/f), hepatocytes specific NF-κBp65 deletion mice (p65Δhepa), p53-upregulated modulator of apoptosis (PUMA) wild-type (PUMA-WT) and PUMA knockout (PUMA-KO) littermate models, and primary hepatic stellate cells (HSCs) were also used. The mechanism underlying Fas/FasL-regulated hepatocytes apoptosis to drive HSCs activation in fibrosis was further analyzed. We found Fas/FasL promoted PUMA-mediated hepatocytes apoptosis via regulating autophagy signaling and NF-κBp65 phosphorylation, while inhibition of autophagy or PUMA deficiency attenuated Fas/FasL-modulated hepatocytes apoptosis and liver fibrosis. Furthermore, NF-κBp65 in hepatocytes repressed PUMA-mediated hepatocytes apoptosis via regulating the Bcl-2 family, while NF-κBp65 deficiency in hepatocytes promoted PUMA-mediated hepatocytes apoptosis and enhanced apoptosis-linked inflammatory response, which contributed to the activation of HSCs and liver fibrogenesis. These results suggest that Fas/FasL contributes to NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to enhance liver fibrogenesis, and this network could be a potential therapeutic target for liver fibrosis.

Cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis on murine photoreceptor cells.

AIM: To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis (EAU) as well as their secreted interferon (IFN)-γ and interleukin (IL)-17A on murine photoreceptor (661W) cells. METHODS: An EAU model was established in female mice by injection of interphotoreceptor retinoid binding protein (IRBP) emulsion supplemented with complete Freund's adjuvant (CFA) and Mycobacterium tuberculosis (TB). On day 12 after induction of EAU, specific T cells from spleen and lymph node tissues were isolated and cultured for 4d and the levels of IFN-γ and IL-17A in the supernatants were determined by enzyme-linked immunosorbent assays (ELISAs). T cells and their supernatants were added to 661W cells to observe the alteration of cell morphology; IFN-γ and IL-17A were separately added to 661W cells to observe the effect of IFN-γ and IL-17A on cell proliferation. RESULTS: The levels of IFN-γ and IL-17A in the T cell supernatants were 1568.64±38.79 pg/mL and 1456.57±46.98 pg/mL, respectively. The supernatants apparently inhibited 661W cell proliferation (P<0.05). T cells could also attach to the surface of 661W cells, and IFN-γ showed a more serious cytotoxic effect on 661W cells than IL-17A, inhibiting cell proliferation (P<0.01). CONCLUSION: IFN-γ and IL-17A from T cells of EAU mice model can exert cytotoxic effects on murine photoreceptor cell proliferation, and IFN-γ shows more serious cytotoxic effects on murine photoreceptor cells than IL-17A.

A novel model for low-cycle multiaxial fatigue life prediction based on the critical plane-damage parameter.

Multiaxial fatigue of the components is a very complex behavior. This analyzes the multiaxial fatigue failure mechanism, reviews and compares the advantages and disadvantages of the classic model. The fatigue failure mechanism and fatigue life under multiaxial loading are derived through theoretical analysis and formulas, and finally verified with the results of multiaxial fatigue tests. The model of multiaxial fatigue life for low-cycle fatigue life prediction model not only improves the prediction accuracy of the classic model, but also considers the effects of non-proportional additional hardening phenomena and fatigue failure modes. The model is proved to be effective in low-cycle fatigue life prediction under different loading paths and types for different materials. Compared with the other three classical models, the proposed model has higher life prediction accuracy and good engineering applicability.

Diode laser transscleral cyclophotocoagulation for uveitis-glaucoma-hyphema syndrome: A case report.

RATIONALE: To report a case of diode laser transscleral cyclophotocoagulation (DLTSC) for uveitis-glaucoma-hyphema syndrome (UGH). PATIENT CONCERNS: The patient developed UGH on the right eye (OD) after vitrectomy and intraocular lens (IOL) implantation. DIAGNOSES: Best corrected visual acuity (BCVA) was HM/50 cm, intraocular pressure (IOP) was 51.3 mm Hg on the OD. He was found to have 3+ anterior chamber cells. A B-scan ultrasound showed vitreous opacity. Ultrasound biomicroscopy (UBM) showed the chafing between the IOL and the posterior surface of the iris. Thus, he was diagnosed as UGH on the OD. INTERVENTIONS: The patient was worried about the complications for removal of the IOL, a DLTSC approach was performed. OUTCOMES: BCVA was 20/40 on the OD, IOP was 12 mm Hg on the OD. There were no anterior chamber inflammation and no vitreous opacity. UBM showed there was no contact between IOL and the posterior surface of the iris, the fundus of the eye was clearly visible. LESSONS: UGH syndrome is a severe complication of cataract extraction. IOL extraction has been the traditional approach to treatment. DLTSC can be an option when the IOL is slightly tilted.

Long-term efficacy after closure of patent foramen ovale for ischemic neurological events in young adults: A systematic review and meta-analysis.

BACKGROUND: The efficacy of patent foramen ovale (PFO) closure remains controversial, and it is unclear which patient groups are best benefited. We performed this meta-analysis to clarify the efficacy of PFO closure of younger patients for prevention of recurrent ischemic neurological events. METHODS: We systematically searched for studies of PFO closure for younger patients under the age of 55, and pooled available data on PFO closure of younger vs older patients and on PFO closure of younger patients vs medical therapy. The primary endpoints were the composite outcome of recurrent ischemic neurological events [stroke and/or transient ischemic attack (TIA)]. The secondary endpoints included recurrent stroke, TIA, atrial fibrillation (AF) and bleeding events. We calculated the odds ratios (OR) and 95% confidence interval (CI) using fixed-effect and random-effect models. RESULTS: Three randomized controlled trials (RCT) and 13 observational studies were eligible. Compared with older patients undergoing PFO closure, younger patients undergoing closure had a lower risk of composite outcome (OR: 0.40, 95% CI: 0.28 to .56; P < .001) and AF (OR: 0.25, 95% CI: 0.10-0.61; P = .003). Compared with medical therapy, PFO closure of younger patients reduced the risk of composite outcome (OR: 0.50, 95% CI: 0.33-0.75; P<.001); there was no statistical difference in total complications of AF and bleeding events (OR: 2.15, 95% CI: 0.15-30.37; P = .57). Separate analysis of stroke and TIA showed that PFO closure in younger patients was more effective in preventing stroke (OR: 0.45, 95% CI: 0.28-0.72; P < .001) and TIA (OR: 0.35, 95% CI: 0.21-0.58); P < .001) compared with older patients. Compared with medical therapy, PFO closure of younger patients reduced the risk of stroke (OR: 0.26, 95% CI: 0.13-0.51; P < .001); but there was no difference in the risk of TIA (OR: 1.07, 95% CI: 0.16-7.01; P = .94). CONCLUSIONS: Compared with PFO closure of older patients and medical therapy, PFO closure of younger patients can benefit more for the prevention of recurrent ischemic neurological events. Our results indicate that PFO closure is the best treatment strategy for younger patients under the age of 55.