Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.

The intestinal epithelial cells (IECs) constitute the primary barrier between host cells and numerous foreign antigens; it is unclear how IECs induce the protective immunity against pathogens while maintaining the immune tolerance to food. Here, we found IECs accumulate a less recognized 13-kD N-terminal fragment of GSDMD that is cleaved by caspase-3/7 in response to dietary antigens. Unlike the 30-kD GSDMD cleavage fragment that executes pyroptosis, the IEC-accumulated GSDMD cleavage fragment translocates to the nucleus and induces the transcription of CIITA and MHCII molecules, which in turn induces the Tr1 cells in upper small intestine. Mice treated with a caspase-3/7 inhibitor, mice with GSDMD mutation resistant to caspase-3/7 cleavage, mice with MHCII deficiency in IECs, and mice with Tr1 deficiency all displayed a disrupted food tolerance phenotype. Our study supports that differential cleavage of GSDMD can be understood as a regulatory hub controlling immunity versus tolerance in the small intestine.

A mouse model to distinguish NLRP6-mediated inflammasome-dependent and -independent functions.

The NOD-like receptor (NLR) family pyrin domain containing 6 (NLRP6) serves as a sensor for microbial dsRNA or lipoteichoic acid (LTA) in intestinal epithelial cells (IECs), and initiating multiple pathways including inflammasome pathway and type I interferon (IFN) pathway, or regulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. NLRP6 can exert its function in both inflammasome-dependent and inflammasome-independent manners. However, there is no tool to distinguish the contribution of individual NLRP6-mediated pathway to the physiology and pathology in vivo. Here, we validated that Arg39 and Trp50 residues in the pyrin domain (PYD) of murine NLRP6 are required for ASC recruitment and inflammasome activation, but are not important for the RNA binding and PYD-independent NLRP6 oligomerization. We further generated the Nlrp6R39E&W50E mutant mice, which showed reduced inflammasome activation in either steady state intestine or during viral infection. However, the type I IFN production in cells or intestine tissue from Nlrp6R39E&W50E mutant mice remain normal. Interestingly, NLRP6-mediated inflammasome activation or the IFN-I production seems to play distinct roles in the defense responses against different types of RNA viruses. Our work generated a useful tool to study the inflammasome-dependent role of NLRP6 in vivo, which might help to understand the complexity of multiple pathways mediated by NLRP6 in response to the complicated and dynamic environmental cues in the intestine.

Pancreatic Acinar Cells-Derived Sphingosine-1-Phosphate Contributes to Fibrosis of Chronic Pancreatitis via Inducing Autophagy and Activation of Pancreatic Stellate Cells.

BACKGROUND & AIMS: Studies have demonstrated that activated pancreatic stellate cells (PSCs) play a crucial role in pancreatic fibrogenesis in chronic pancreatitis (CP); however, the precise mechanism for PSCs activation has not been fully elucidated. We analyzed the role of injured pancreatic acinar cells (iPACs) in the activation of PSCs of CP. METHODS: Sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) signaling was evaluated in experimental CP induced by cerulein injection or pancreatic duct ligation, as well as in PACs injured by cholecystokinin. The activation of PSCs and pancreatic fibrosis in CP samples was evaluated by immunohistochemical and immunofluorescence analyses. In vitro coculture assay of iPACs and PSCs was created to evaluate the effect of the SPHK1/S1P pathway and S1P receptor 2 (SIPR2) on autophagy and activation of PSCs. The pathogenesis of CP was assessed in SPHK1-/- mice or PACs-specific SPHK1-knockdown mice with recombinant adeno-associated virus serotypes 9-SPHK1-knockdown, as well as in mice treated with inhibitor of SPHK1 and S1P receptor 2 (S1PR2). RESULTS: SPHK1/S1P was remarkably increased in iPACs and acinar cells in pancreatic tissues of CP mice. Meanwhile, the pathogenesis, fibrosis, and PSCs activation of CP was significantly prevented in SPHK1-/- mice and recombinant adeno-associated virus serotypes 9-SPHK1-knockdown mice. Meanwhile, iPACs obviously activated PSCs, which was prevented by SPHK1 knockdown in iPACs. Moreover, iPACs-derived S1P specifically combined to S1PR2 of PSCs, by which modulated 5' adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway and consequently induced autophagy and activation of PSCs. Furthermore, hypoxia-inducible factor 1-α and -2α promoted SPHK1 transcription of PACs under hypoxia conditions, which is a distinct characteristic of the CP microenvironment. Coincidently, inhibition of SPHK1 and S1PR2 activity with inhibitor PF-543 and JTE-013 obviously impeded pancreatic fibrogenesis of CP mice. CONCLUSIONS: The activated SPHK1/S1P pathway in iPACs induces autophagy and activation of PSCs by regulating the S1PR2/5' adenosine monophosphate-activated protein kinase/mammalian target of rapamycin pathway, which promotes fibrogenesis of CP. The hypoxia microenvironment might contribute to the cross talk between PACs and PSCs in pathogenesis of CP.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Association between body stature with ocular biometrics and refraction among Chinese preschoolers.

PURPOSE: To evaluate the association of body stature with ocular biometrics and refraction in preschool children. METHODS: A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. RESULTS: A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters. CONCLUSION: Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers.

Simulation and On-Site Detection of the Failure Characteristics of Overlying Strata under the Mining Disturbance of Coal Seams with Thin Bedrock and Thick Alluvium.

When mining deep coal seams with thin bedrock and thick alluvium, the collapse and fracture of thin bedrock layers may cause geological disasters, such as water inrush and sand inrush of the mining face. Comprehensively obtaining the response data of coal mining and reasonably analyzing the failure characteristics of overlying strata are helpful in guiding safe production. In this study, the caving zone heights of overlying strata are obtained by field detection during layered mining. Then, the caving zone heights during the once-full-height mining are evaluated by theoretical analysis. Further, the force and failure characteristics of coal-rock structures under different mining conditions are compared by the simulation detection and analysis. Finally, the results of on-site observation, theoretical analysis, and simulation detection are compared and discussed, and an optimized mining technology is proposed to ensure safe mining. The research shows the caving zone heights of on-site and simulation detections are, respectively, 14.65 m and 13.5 m during bottom-layer mining, which is larger than the caving zone heights of the top-layer coal mining. During once-full-height mining, the maximum caving zone height of simulation detection is 21 m, which is in between two standard results. For the mechanical responses of an aquiclude clay layer under thick loose alluvium, the maximum disturbance displacement of clay aquiclude is 5.8 m during layered mining, which is slightly larger than the disturbance displacement of once full-height mining; however, the maximum stress of the clay layer is 25 MPa during once-full-height mining, which is larger than the maximum stress of clay layer during layered mining. For the clay aquiclude failure, the clay layer during layered mining is in the deflection deformation area, and there is no obvious fracture structure to inrush the water and sand of thick loose alluvium; however, the clay layer during once-full-height mining is prone to produce obvious fracture structure. Therefore, the layered mining technology can effectively reduce and prevent the water/sand inrush disaster of mining working face.

Metabolic stress-induced reciprocal loop of long noncoding RNA ZFAS1 and ZEB1 promotes epithelial-mesenchymal transition and metastasis of pancreatic cancer cells.

Pancreatic cancer (PC) development faces significant metabolic stress due to metabolic reprogramming and a distinct hypovascular nature, often leading to glucose and glutamine depletion. However, the adaption mechanisms by which PC adapts to these metabolic challenges have not yet been completely explored. Here, we found that metabolic stress induced by glucose and glutamine deprivation led to an overexpression of ZNFX1 antisense RNA 1 (ZFAS1). This overexpression played a significant role in instigating PC cell epithelial-mesenchymal transition (EMT) and metastasis. Mechanistically, ZFAS1 enhanced the interaction between AMPK, a key kinase, and ZEB1, the primary regulator of EMT. This interaction resulted in the phosphorylation and subsequent stabilization of ZEB1. Interestingly, ZEB1 also reciprocally influenced the transcription of ZFAS1 by binding to its promoter. Furthermore, when ZFAS1 was depleted, the nutrient deprivation-induced EMT of PC cells and lung metastasis in nude mice were significantly inhibited. Our investigations also revealed that ZFAS1-rich exosomes released from cells suffering glucose and glutamine deprivation promoted the EMT and metastasis of recipient PC cells. Corroborating these findings, a correlated upregulation of ZFAS1 and ZEB1 expression was observed in PC tissues and was associated with a poor overall survival rate for patients. Our findings highlight the involvement of a long noncoding RNA-driven metabolic adaptation in promoting EMT and metastasis of PC, suggesting ZFAS1 as a promising novel therapeutic target for PC metabolic treatment.

Photocatalytic Radical Cascade Dehalogenation/Carbo-cyclization/Sulfonylation Leading to Indole- and Benzofuran-Based Benzylic Sulfones.

This study presents a convenient approach to the synthesis of indole- and benzofuran-based benzylic sulfones using unactivated alkynes containing aryl iodides and sodium sulfinates under visible light irradiation. The procedure involves a sequential series of dehalogenation, carbo-cyclization, and radical sulfonylation. Plausible insights into the reaction mechanism are derived from control experiments, leading to the proposal of a radical cascade reaction pathway.

Evaluating the efficacy and timing of blood purification modalities in early-stage hyperlipidemic acute pancreatitis treatment.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is characterized by a violent cytokine storm-driven inflammation and is associated with a predisposition to severe disease. The treatment strategy for HTG-AP consists mainly of conventional symptomatic and lipid-lowering treatments. For early-stage HTG-AP, blood purification (BP) can rapidly and effectively reduce serum triglyceride and inflammatory cytokine levels, block the development of systemic inflammatory response syndrome, and improve patient outcomes. Currently, the primary modalities for BP in patients with HTG-AP include plasma exchange, hemoperfusion, and hemofiltration. When using BP to treat patients with HTG-AP, a comprehensive analysis incorporating the elevated lipid levels and severity of the patient's condition contributes to the selection of different treatment modes. Moreover, the timing of the treatment is also imperative. Early intervention is associated with a better prognosis for patients with HTG-AP requiring lipid-lowering treatment.

An unusual case of abdominal pain: psychogenic vomiting complicated by spontaneous pneumomediastinum.

BACKGROUND: Spontaneous pneumomediastinum (SPM) was defined by the appearance of free air in the mediastinum that was not preceded by trauma, surgery, or other medical procedures. Among the numerous manifestations of SPM, abdominal pain had seldom been described. CASE PRESENTATION: A 25-year-old man presented to the emergency department with nausea, vomiting, and abdominal pain for 7 days. The presenting clinical features and the radiological results were suggestive of psychogenic vomiting with spontaneous pneumomediastinum in a patient who suffered from abdominal pain. CONCLUSIONS: The special feature of this case was the elucidation of a rare cause of abdominal pain, which should be differentiated in patients with vomiting combined with abdominal pain. The importance of this case was that its recognition may prevent unnecessary procedures to rule out or treat other causes of abdominal pain.

CEMIP promotes extracellular matrix-detached prostate cancer cell survival by inhibiting ferroptosis.

Cells detached from the extracellular matrix (ECM) can trigger different modes of cell death, and the survival of ECM-detached cells is one of the prerequisites for the metastatic cascade. Ferroptosis, a form of iron-dependent programmed cell death, has recently been found to be involved in matrix-detached cancer cells. However, the molecular mechanisms by which ECM-detached cells escape ferroptosis are not fully understood. Here, we observed that cell migration-inducing protein (CEMIP) upregulation facilitates ferroptosis resistance during ECM detachment by promoting cystine uptake in prostate cancer (PCa) cells. Meanwhile, silencing CEMIP causes it to lose its ability to promote cystine uptake and inhibit ferroptosis. Mechanistically, the interaction of CEMIP with inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) modulates calcium ion (Ca2+ ) leakage from the endoplasmic reticulum, activating calcium/calmodulin-dependent protein kinase II (CaMKII), which further facilitates nuclear factor erythroid 2-related factor 2 (NRF2) phosphorylation and nuclear localization, leading to elevated transcription of solute carrier family 7 member 11 (SLC7A11), a glutamate/cystine antiporter, in PCa cells. Our findings delineate a novel role of CEMIP in ferroptosis resistance during ECM detachment and provide new insights into therapeutic strategies for metastatic PCa.

WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the function of p53 in suppressing metastasis.

Accumulating evidence suggests that p53 plays a suppressive role in cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3-mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis.

Andrographolide derivative as antagonist of vitamin D receptor to induce lipidation of microtubule associate protein 1 light chain 3 (LC3).

Lipidation of microtubule associated protein 1 light chain 3 (LC3) is the critical step in autophagosome formation, numerous efforts have been made to design and develop small molecules that trigger LC3 lipidation to activate autophagy. In this study, we discovered a series of andrographolide derivatives as potent antagonists of vitamin D receptor (VDR) by luciferase reporter assay. Structure-activity-relationship study revealed that andrographolide derivative ZAV-12 specifically inhibited VDR signaling but not NF-κB or STAT3 activation. Western blot analysis indicates that ZAV-12 markedly triggered lipidation of LC3 in MPP+-induced Parkinsonism in vitro in an mTOR-independent manner. The ZAV-12 triggered lipidation was mediated through SREBP2 activation instead of changing expression levels of lipid synthesis genes. Furthermore, ZAV-12 treatment increased the ratio of LC3-II/LC3-I and oligomerization of A53T α-synuclein (SNCA) in SNCA triggered neurotoxicity. Taken together, these results demonstrate the therapeutic potential of VDR antagonist as novel drug candidate for neurodegenerative diseases.

CHARACTERISTICS OF PERIPAPILLARY INTRACHOROIDAL CAVITATION IN HIGHLY MYOPIC EYES: The Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.

PURPOSE: To characterize peripapillary intrachoroidal cavitation (PICC) in highly myopic participants and its associated risk factors. METHODS: This observational, cross-sectional study recruited 890 Chinese participants with bilateral high myopia, defined as ≤-6.00 diopters spherical power. Fundus photography and spectral-domain optical coherence tomography were used to determine the presence of PICC, defined as a yellow-orange lesion adjacent to the disc border with a corresponding intrachoroidal hyporeflective space. RESULTS: Among 890 participants, 884 right eyes were included for analysis. The rate of PICC was 3.6% (32 eyes). Peripapillary intrachoroidal cavitation was observed in two eyes without myopic retinal lesions, nine eyes with tessellated fundus only, 16 eyes with diffuse chorioretinal atrophy, and five eyes with patchy chorioretinal atrophy. The most commonly affected area was inferior disc border (87.5%), followed by multiple (9.4%) and superior (3.1%) disc borders. The multiple linear logistic regression model showed that older age, more myopic spherical equivalent, and longer axial length were associated with the presence of PICC. CONCLUSION: Peripapillary intrachoroidal cavitation was present in 3.6% of highly myopic eyes. It was more common in eyes with a higher myopic maculopathy category. Older age, more myopic spherical equivalent, and longer axial length were risk factors for the presence of PICC.

Circ_MUC16 attenuates the effects of Propofol to promote the aggressive behaviors of ovarian cancer by mediating the miR-1182/S100B signaling pathway.

BACKGROUND: Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer. METHODS: The expression of circ_MUC16, microRNA-1182 (miR-1182) and S100 calcium-binding protein B (S100B) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). The expression of S100B protein was checked by western blot. Cell proliferation was assessed by 3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide (MTT) assay and colony formation assay. Glycolysis metabolism was assessed by glucose consumption, lactate production and ATP level. Cell migration and cell invasion were assessed by transwell assay. Cell migration was also assessed by wound healing assay. Animal study was conducted in nude mice to determine the role of circ_MUC16 in vivo. The relationship between miR-1182 and circ_MUC16 or S100B was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Propofol inhibited ovarian cancer cell proliferation, glycolysis metabolism, migration and invasion, which were partly recovered by circ_MUC16 overexpression. Circ_MUC16 was downregulated in Propofol-treated ovarian cancer cells. Besides, circ_MUC16 knockdown enhanced the effects of Propofol to further inhibit tumor growth in vivo. MiR-1182 was a target of circ_MUC16, and circ_MUC16 knockdown-inhibited cell proliferation, glycolysis metabolism, migration and invasion were partly restored by miR-1182 inhibition. In addition, S100B was a target of miR-1182, and miR-1182-suppressed cell proliferation, glycolysis metabolism, migration and invasion were partly restored by S100B overexpression. CONCLUSION: Circ_MUC16 overexpression alleviated the effects of Propofol to promote the aggressive behaviors of ovarian cancer by targeting the miR-1182/S100B network.

Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7.

The tumor suppressor p53 plays a prominent role in the protection against cancer. The activity of p53 is mainly controlled by the ubiquitin E3 ligase Mdm2, which targets p53 for proteasomal degradation. However, the regulation of Mdm2 remains not well understood. Here, we show that MARCH7, a RING domain-containing ubiquitin E3 ligase, physically interacts with Mdm2 and is essential for maintaining the stability of Mdm2. MARCH7 catalyzes Lys63-linked polyubiquitination of Mdm2, which impedes Mdm2 autoubiquitination and degradation, thereby leading to the stabilization of Mdm2. MARCH7 also promotes Mdm2-dependent polyubiquitination and degradation of p53. Furthermore, MARCH7 is able to regulate cell proliferation, DNA damage-induced apoptosis, and tumorigenesis via a p53-dependent mechanism. These findings uncover a novel mechanism for the regulation of Mdm2 and reveal MARCH7 as an important regulator of the Mdm2-p53 pathway.

Self-assembly of isomeric naphthalene appended glucono derivatives: nanofibers and nanotwists with circularly polarized luminescence emission.

Two isomeric naphthalene appended glucono derivatives substituted at the 1 or 2-naphthyl positions (Nap-1 and Nap-2) were designed and their self-assembly behaviors and optical properties were investigated. Nap-1 and Nap-2 were found to self-assemble into nanofibers and nanotwists, respectively. While the molecular chirality of the glucono moiety could not be effectively transferred to the naphthalene moiety in the Nap-1 system, this was achieved in the Nap-2 assembly. Thus, the Nap-2 assembly showed obvious circular dichroism (CD) and circularly polarized luminescence (CPL) signals. From the XRD patterns and IR spectra of the supramolecular assemblies, it was found that Nap-2 packed in a more orderly fashion than Nap-1, leading to a hierarchical assembly forming nanotwist structures. Moreover, a light-harvesting system based on Nap-2 supramolecular gels and dyes was established, in which an efficient energy transfer was demonstrated from Nap-2 to an acceptor Eosin Y. It was further found that both chirality and energy transfer enhanced the dissymmetry factor of Eosin Y CPL emission.

Inhibition of zika virus infection by fused tricyclic derivatives of 1,2,4,5-tetrahydroimidazo[1,5-a]quinolin-3(3aH)-one.

Zika virus (ZIKV) infection represents a significant threat to the global health system, and the search for efficient antivirals to ZIKV remains necessary and urgent. In this study, we extended the exploration of our previously discovered scaffold of 1H-pyrrolo[1,2-c]imidazol-1-one and revealed that two trans isomers of compounds 2 and 7 and one mixture with major trans isomer of compound 3 as novel tetrahydroquinoline-fused imidazolone derivatives are active against ZIKV infection but they are not virucidal. Western Blot and ELISA analyses of ZIKV NS5 and NS1 further demonstrate that compounds of (±)-2, (±)-3 and (±)-7 act as effective agents against ZIKV infection. We show that the N10's basicity is not the basic requirement for these compounds' antiviral activity in the current work. Importantly, tuning of some pharmacophores including substituents at arene can generate promising candidates for anti-ZIKV agents.

Efficacy of Eutectic Mixture of Local Anesthetics on Pain Control During Extracorporeal Shock Wave Lithotripsy: A Systematic Review and Meta-Analysis.

BACKGROUND The efficacy of a eutectic mixture of local anesthetics (EMLA) for pain control in extracorporeal shock wave lithotripsy is unclear. The aim of this study was to assess the effect of EMLA cream on pain control during extracorporeal shock wave lithotripsy. MATERIAL AND METHODS We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials to identify relevant randomized controlled trials that compared the pain control efficacies of EMLA vs. placebo. Study eligibility criteria, participants, and interventions: Randomized controlled trials that compared the effect of EMLA with placebo cream for patients underwent extracorporeal shock wave lithotripsy. Study appraisal and synthesis methods: Two review authors extracted data independently using a designed data extraction form and risk of bias by Cochrane Collaboration's tool. RESULTS Nine studies, including 10 randomized controlled trials with 1167 patients, were eligible. The EMLA group experienced less pain (mean difference, -0.47; 95% confidence interval, -0.78 to -0.16; p=0.003) and shorter duration of lithotripsy (mean difference, -1.70, 95% confidence interval: -2.31 to -1.10, p<0.0001) than the placebo group. There were no significant differences in the number of patients who needed extra intravenous medication (p=0.610), number of patients with insufficient extracorporeal shock wave lithotripsy pain control (p=0.530), and number of patients with opioid adverse effects (p=0.320). Limitations: Long interval between the studies, different kinds of lithotripters. CONCLUSIONS EMLA can reduce pain during the ESWL procedure.

DIFFUSE CHORIORETINAL ATROPHY IN CHINESE HIGH MYOPIA: The ZOC-BHVI High Myopia Cohort Study.

PURPOSE: To explore the associations between diffuse chorioretinal atrophy (DCA) and age, sex, axial length, spherical equivalent, and best-corrected visual acuity (BCVA) among highly myopic eyes. METHODS: This study included right eyes of 857 bilaterally highly myopic individuals from the ZOC-BHVI Cohort Study. Participants underwent examinations, including BCVA, ocular biometry, autorefraction, and color fundus photography. An Early Treatment Diabetic Retinopathy Study grid was applied on the fundus photographs to evaluate the location of DCA, which was graded into four categories (D0-D3). The characteristics and ocular biometry were compared between participants' eyes with and without DCA. RESULTS: Diffuse chorioretinal atrophy was found in 177 (20.6%) eyes. The proportion of participants with DCA in age groups of 7 to 11, 12 to 18, 19 to 39, and ≥ 40 years old was 20.9%, 9.2%, 23.1%, and 52.9%, respectively. The proportion of DCA significantly increased with longer axial length and worse myopic spherical equivalent. Eyes with DCA had poorer BCVA (Snellen visual acuity 20/36, logarithm of minimal angle of resolution 0.26 ± 0.25) than those without DCA (Snellen visual acuity 20/23, logarithm of minimal angle of resolution 0.06 ± 0.14) (P < 0.001). The BCVA gradually declined as the lesion got closer to the fovea (P for trend < 0.001). CONCLUSION: The proportion of DCA increased with older age, longer axial length, and more myopic spherical equivalent. Diffuse chorioretinal atrophy is a vision-threatening complication of high myopia where BCVA gradually worsens with foveal involvement.