ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

PURPOSE: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. METHODS: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. RESULTS: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. CONCLUSION: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

Epigallocatechin-3-gallate increases autophagic activity attenuating TGF-ß1-induced transformation of human Tenon's fibroblasts.

We previously found that epigallocatechin-3-gallate (EGCG) could inhibit the myofibroblast transformation of human Tenon's fibroblasts, however, the underlying mechanism remained unclear. We therefore investigated whether the autophagic regulation involved in the anti-fibrotic function of EGCG. The fibroblasts were subjected to transforming growth factor beta-1 (TGF-ß1) induction followed by EGCG treatments. The autophagic flux was examined by transmission electron microscopy and autophagic flux analysis. The levels of autophagy-related proteins (LC3ß and p62) and alpha-smooth muscle actin (α-SMA) were measured by Western blot and immunofluorescence. Results showed that TGF-ß1 partially inhibited the autophagic function of Tenon's fibroblasts. But this inhibition effect was rescued by LY2157299, a TGF-ßR1 selective inhibitor. Compared with the cells treated with TGF-ß1 alone, EGCG treatments increased the amount of autophagosomes and autolysosomes, evaluated the ratio of LC3-II to LC3-I and decreased p62 level. Our results indicated that EGCG could recover the activity of autophagy in the TGF-ß1-treated cells. Moreover, treatments with EGCG significantly decreased the α-SMA expression. Taken together, these findings revealed that autophagic regulation involved in the action of EGCG against TGF-ß1-induced transformation of Tenon's fibroblasts. Through increasing intracellular autophagy, EGCG could be a potential anti-fibrotic reagent for preventing subconjunctival fibrosis after glaucoma filtration surgery.

Anti-inflammatory active components of the roots of Datura metel.

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-ß-D-apisoyl-6-O-(2-hydroxybenzoyl)]-ß-D-glucopyranoside (1), together with 10 known compounds (2-11), were isolated from the roots of Datura metel. The structures of these compounds were elucidated on the basis of their spectroscopic data. Furthermore, the in vitro anti-inflammatory activities of compounds 1-11 were evaluated.[Formula: see text].

Epigallocatechin-3-gallate (EGCG) inhibits myofibroblast transformation of human Tenon's fibroblasts.

Myofibroblast transformation of human Tenon's fibroblasts severely challenges the outcome of glaucoma filtration surgery. epigallocatechin-3-gallate (EGCG) is considered as a potential reagent to overcome this issue for its anti-fibrosis effect on various human diseases, but it is unclear on the fibrosis of Tenon's fibroblasts. This study was conducted to investigate the effect of EGCG on TGF-ß1-induced myofibroblast transformation of human Tenon's fibroblasts. The human Tenon's fibroblasts were incubated in the medium containing 10 ng/mL TGF-ß1, and subsequently treated with EGCG or mitomycin C (MMC). The cell proliferation and migration were analyzed. The expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col-I), and p-Smad2/3 were also evaluated. It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF-ß1 alone. Scratch-Wound assay showed that 48 h after TGF-ß1 induction, only 10% of the wound width remained. But cells treated with EGCG still showed over 93% wound width. Further, EGCG effectively inhibited TGF-ß1-induced expression of α-SMA and Col-I as well as phosphorylation of Smad2/3 in Tenon's fibroblasts. Altogether, we concluded that EGCG suppressed the myofibroblast transformation in Tenon's fibroblasts through inactivating TGF-ß1/Smad signaling. These findings demonstrate that EGCG can be considered as one of the possible antifibrotic reagents for preventing postoperative scarring in glaucoma filtration surgery.

Elevated level of uric acid in aqueous humour is associated with posterior subcapsular cataract in human lens.

IMPORTANCE: Age-related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive. BACKGROUND: To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC). DESIGN: Retrospective study and experimental investigation. PARTICIPANTS: A total of 180 patients with PSC or non-PSC were included. METHODS: Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated. MAIN OUTCOME MEASURES: Aqueous humour UA and urate deposits. RESULTS: The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non-PSC. Treatment with UA-induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC. CONCLUSIONS AND RELEVANCE: These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.

Simultaneous extraction and determination of mono-/polyglutamyl folates using high-performance liquid chromatography-tandem mass spectrometry and its applications in starchy crops.

Folates are typically present in polyglutamyl form in organisms. In traditional extraction methods, polyglutamyl folates are hydrolyzed to monoglutamates, sacrificing valuable information. To advance folate metabolism research, we developed an accurate, sensitive, and reproducible extraction method for polyglutamyl folate species in maize, the main crop in most parts of the world. Twelve folates, including six polyglutamyl folates, were simultaneously determined in maize for the first time using high-performance liquid chromatography-tandem mass spectrometry. The glutamation states of the folates were protected by boiling, which inactivated the native conjugases. α-Amylase and protease were added to obtain better recoveries and decrease difficulties in centrifugation and filtration. The recoveries (n = 5) of six polyglutamyl folates were between 80.5 and 101%. All calibration curves showed good linear regression (r2 ≥ 0.994) within the working range. The instrumental limits of detection and quantitation ranged from 0.070 to 2.4 ng/mL and 0.22 to 8.0 ng/mL, respectively. Intra- and inter-day precision was below 7.81% and 11.9%, respectively (n = 5). Using this method, changes in poly- and monoglutamyl folates during maize germination were determined for the first time. The results suggest that folates were largely synthesized as germination initiated, and 5-methyltetrahydrofolate was the most abundant species. Tetraglutamyl 5-methyltetrahydrofolate contributed more than 50% of the 5-methyltetrahydrofolate species. Inverse changes in contents of 5,10-methenyltetrahydrofolate, and 10-formyl folic acid, monoglutamate, and diglutamate of 5-formyltetrahydrofolate were also observed, indicating potential regulation. Additionally, polyglutamyl folates in sweet potatoes were determined using this method, indicating its applications in starchy crops.

Femtosecond laser-assisted removal of an intracorneal chestnut, a case report.

BACKGROUND: To report a case of femtosecond laser-assisted removal of an intracorneal chestnut. CASE PRESENTATION: A chestnut was obliquely protruding to the stroma of cornea and it was localized at the paracentral region on the left eye of a 32-year-old man. The best-corrected visual acuity (BCVA, in decimal values) was 0.6 in the injured eye. The white ulcers with feathery edges or satellite infiltrates were not observed in the lesion, and the anterior chamber was deep and quiet. Anterior segment optical coherence tomography (AS-OCT) demonstrated that the original entry path of the foreign body had been sealed, spanning a thickness of approximate 152 µm. In view of location of the intraocular chestnut at the paracentral region, femtosecond laser was applied according to the procedures of IntraLase Enabled Keratoplasty (IEK) to create an anterior lamellar flap rapidly and precisely. The lamellar flap was easily separated with a flap lifter, and the chestnut was removed entirely using a pair of forceps. In 3 days after surgery, the patient complained of mild pain and blurred vision. These symptoms were relieved after treatment with the eyedrops. At three-month follow-up, the corneal wound was healed well, and the BCVA was greatly improved to 1.2 in the left eye. A dot-like haze was observed corresponding to the scar at the site of foreign body removal. No surgical induction of corneal astigmatism was found in the corneal topography. CONCLUSIONS: Without induction of a visually significant scar and corneal astigmatism, the IEK procedure of femtosecond laser is of particular interest as it provides a unique method for removal of intracorneal foreign bodies impinging on the visual axis.

A new steroidal saponin from Polygonatum sibiricum.

A new furostan type steroidal saponin, kingianoside Z (1), along with four known compounds (2-5), was isolated from the ethanolic extract of Polygonatum sibiricum Delar. ex Redoute. Their structures were determined by spectroscopical method and by comparison with previously reported spectroscopic data. Compounds 3-5 showed significant cytotoxicity against HepG2 cell lines with IC50 values of 14.2, 12.1 and 8.5 µM, respectively.

Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury.

CONTEXT: Liver disease is a common threat to human health, caused by a variety of factors that damage the liver. Recent studies have shown that active ingredients (for example: flavonoids, saponins, acids, phenols, and alkaloids) from Traditional Chinese Medicine (TCM) can have hepatoprotective benefits, which represents an attractive source of drug discovery for treating liver injury. OBJECTIVE: We reviewed recent contributions on the chemically induced liver injury, immunological liver damage, alcoholic liver injury, and drug-induced liver injury, in order to summarize the research progress in molecular mechanism and pharmacology of TCM, and provides a comprehensive overview of new TCM treatment strategies for liver disease. MATERIALS AND METHODS: Relevant literature was obtained from scientific databases such as Pubmed, Web of Science. and CNKI databases on ethnobotany and ethnomedicines (from January 1980 to the end of May 2018). The experimental studies involving the antihepatic injury role of the active agents from TCM and the underlying mechanisms were identified. The search terms included 'liver injury' or 'hepatic injury', and 'traditional Chinese medicine', or 'herb'. RESULTS: A number of studies revealed that the active ingredients of TCM exhibit potential therapeutic benefits against liver injury, while the underlying mechanisms appear to contribute to the regulation of inflammation, oxidant stress, and pro-apoptosis signaling pathways. DISCUSSION AND CONCLUSIONS: The insights provided in this review will help further exploration of botanical drugs in the development of liver injury therapy via study on the effective components of TCM.

17ß-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts.

Although many studies have suggested that estrogen prevents postmenopausal bone loss partially due to its anti-apoptosis effects in osteoblasts, the underlying mechanism has not been fully elucidated. In the present study, we found that 17ß-estradiol (17ß-E2), one of the primary estrogens, inhibited endoplasmic reticulum (ER) stress-induced apoptosis in MC3T3-E1 cells and primary osteoblasts. Interestingly, 17ß-E2-promoted Grp78 induction, but not CHOP induction in response to ER stress. We further confirmed that Grp78-specific siRNA reversed the inhibition of 17ß-E2 on ER stress-induced apoptosis by activating caspase-12 and caspase-3. Moreover, we found that 17ß-E2 markedly increased the phosphorylated TFII-I levels and nuclear localization of TFII-I in ER stress conditions. 17ß-E2 stimulated Grp78 promoter activity in a dose-dependent manner in the presence of TFII-I and enhanced the binding of TFII-I to the Grp78 promoter. In addition, 17ß-E2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity in MC3T3-E1 cells. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked 17ß-E2-induced TFII-I phosphorylation and Grp78 expression in response to ER stress. Together, 17ß-E2 protected MC3T3-E1 cells against ER stress-induced apoptosis by promoting Ras-ERK1/2-TFII-I signaling pathway-dependent Grp78 induction.

Uric acid-driven NLRP3 inflammasome activation triggers lens epithelial cell senescence and cataract formation.

Excessive uric acid (UA) is associated with age-related cataract. A previous study showed that a high UA level in the aqueous humor stimulated the senescence of lens epithelial cells (LECs), leading to cataract progression. To better understand the underlying mechanisms, we investigated UA-driven senescence in human lens tissue samples obtained during surgery, rat lens organ cultures, and in vivo experiments, using senescence-associated ß-galactosidase (SA-ß-gal) staining, electronic microscopy, Western blotting, and histological analyses. Initially, we identified markedly higher expressions of NLRP3 and caspase-1 in the lens capsules of hyper-uricemic patients compared to normo-uricemic patients. This increase was accompanied by a significant rise in the SA-ß-gal positive rate. We next built a cataract model in which rat lenses in an organ culture system were treated with an increasing dosage of UA. Notably, opacification was apparent in the lenses treated with 800 µM of UA starting on the fifth day. Mechanistically, UA treatment not only significantly induced the expression of NLRP3, caspase-1, and IL-1ß, but also upregulated the levels of SA-ß-gal and the senescence regulators p53 and p21. These effects were fully reversed, and lens opacification was ameliorated by the addition of MCC950, a selective NLRP3 antagonist. Moreover, an in vivo model showed that intravitreal UA injection rapidly induced cataract phenotypes within 21 days, an effect significantly mitigated by co-injection with MCC950. Together, our findings suggest that targeting the UA-induced NLRP3 inflammasome with MCC950 could be a promising strategy for preventing cataract formation associated with inflammageing.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report.

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

[Potential Oncogenic Role of Genes in PLC Family on T-ALL Cell Lines by Suppression of Apoptosis].

OBJECTIVE: To explore the role of phospholipase C(PLC) family in the progression of acute T lymphoblastic leukemia (T-ALL). METHODS: The apoptosis of T-ALL cells was determined by Annexin V-PE/7-AAD staining after treatment of PLC inhibitor U73122 and Edelfosine. Cox regression and Kaplan-Meier were used to analyze the impact of PLC expressions on the event-free survival (EFS) of T-ALL patients. PLC expression in each subtype of T-ALL were analyzed by One-way ANOVA. The siRNA expression plasmids targeting the PLCß1, PLCγ1, PLCη1 gene were constructed, and T-ALL cells were infected with retrovirus packaging in HEK-293T cells. The mRNA and protein level were tested by RT-PCR and Western blot. RESULTS: P12-ICH and CCRF-CEM cell line were sensitive to U73122 and Edelfosine treatment, while Jurkat and MOLT4 were resistant to them. In the TARGET-ALL database, the prognosis of T-ALL patients with high expression of PLCß1, PLCγ1 and PLCη1 was poor, and PLCß1, PLCγ1, PLCη1 were unevenly distributed in T-ALL subtypes. PLCß1, PLCγ1 and PLCη1 maintained the survival of P12-ICH and CCRF-CEM cell lines, respectively, while they had no effect on the survival of MOLT4. CONCLUSION: PLCß1, PLCγ1 and PLCη1 can maintain the growth of T-ALL cell lines in vitro and promote the malignant progression of T-ALL, which are potential therapeutic targets.

Primary lacrimal sac lymphoma: a case-based retrospective study in a Chinese population.

AIM: To determine the clinical characteristics, pathological types, tumor markers, treatments, and outcomes of Chinese patients with primary lacrimal sac lymphoma. METHODS: This case-based retrospective study analyzed 15 Chinese patients with primary lacrimal sac lymphoma. The clinical data collected included gender, age at diagnosis, symptoms, imaging examination results, pathologic diagnosis, pathogen identification, tumor markers, treatments, follow-up, and prognosis. Descriptive statistics were used to characterize the patients. Progression-free survival (PFS) was defined as the time from surgery to the last follow-up, first record of tumor recurrence, or death. RESULTS: There were 7 males and 8 females with unilateral primary lacrimal sac lymphoma in the left eye (n=6) or right eye (n=9). The initial symptom in 13 patients was epiphora, and 2 patients had redness and swelling in the lacrimal sac area. All patients ultimately developed epiphora, and 12 had masses in the lacrimal sac area. Analysis of preoperative plasma tumor markers indicated 14 patients had elevated homocysteine, 9 had elevated ß2-microglobulin, and 2 had elevated lactate dehydrogenase (LDH); 2 patients had elevations of all three markers, and 1 patient had no elevation of any marker. All patients underwent surgical resection and 12 patients received postoperative chemotherapy. The pathological types were DLBCL (n=8), MALT lymphoma (n=5), and NK/T-cell lymphoma, nasal type (n=2). The mean follow-up time was 25.8mo (range: 4-41) and 2 patients died. Seven patients who underwent mass excision combined with dacryocystorhinostomy (DCR) had no postoperative epiphora. Eight patients who only underwent mass excision had varying degrees of postoperative epiphora. Preoperative LDH elevation and NK/T-cell lymphoma, nasal type were associated with poor prognoses. CONCLUSION: Early diagnosis and treatment can lead to a good prognosis for most patients with primary lacrimal sac lymphoma. Mass resection combined with DCR can reduce the occurrence of post-surgical epiphora. The pathology type and tumor marker status are associated with prognosis.

[Fingerprint of sophorolipids based on ultra-high performance liquid chromatography-charged aerosol detection].

Sophorolipids are secondary metabolites produced during fermentation by nonpathogenic yeasts. These molecules are amphiphilic and consist of a hydrophilic sophora sugar moiety and a hydrophobic hydroxylated fatty acid. Based on their degree of esterification, sophorolipids can be divided into the acid and lactone types. Sophorolipids are highly promising biosurfactants with good antibacterial, antiviral, and other biological activities. Moreover, they are characterized by mildness, low toxicity, and environmental friendliness. However, their composition is quite complex, and effective methods for their quality evaluation are lacking. Since sophorolipids do not absorb ultraviolet (UV) light, common UV detectors are unsuitable for fingerprint establishment. In this study, we first selected a charged aerosol detector (CAD) to establish the ultra-high performance liquid chromatography (UHPLC) fingerprint of sophorolipids. The detector had high sensitivity, good reproducibility, and excellent suitability for the detection of substances with no or weak ultraviolet absorption. We then evaluated the similarities between 17 batches of sophorolipid samples. The samples were extracted by ultrasound for 10 min in 80% ethanol aqueous solution at a liquid-solid ratio of 10∶1 (mL/g) and then separated on a Thermo Fisher Scientific Hypersil Gold chromatographic column (150 mm×2.1 mm, 1.9 µm). Separation was performed using acetonitrile-0.01% (v/v) formic acid aqueous solution as the mobile phase via gradient elution. The flow rate was 0.2 mL/min, and the column temperature was 40 ℃. The CAD was used under the following conditions: power function of 1.0, data rate of 5 Hz, filter constant of 3.6, and evaporation temperature of 45 ℃. The chromatograms and retention times of the sophorolipids were compared, and 16 common peaks with strong responses, good resolutions, and stable retention times were selected as characteristic peaks. Oleic acid was chosen as the reference peak because it achieved good separation and a strong chromatographic response in all batches of samples. UHPLC-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to identify chromatographic peaks in the sophorolipid fingerprints. The results were combined with the retention time rule of the sophorolipids, leading to their identification based on matching with the results of the primary database, the precise relative molecular mass and fragmentation rule of secondary fragments, a self-built database, and the PubChem database. Sixteen compounds were identified, including eight acid sophorolipids, six lactone sophorolipids, and two aliphatic acids. The results of precision, repeatability, and 24 h stability tests indicated that the relative standard deviations (RSDs) of the retention times and peak areas of the 15 characteristic peaks relative to the control peak (oleic acid) were less than 3.0% (n=6). Seventeen batches of sophorolipid samples were analyzed, and the similarity values of all fingerprints were found to be 0.965 or higher. Little differences in chemical composition were observed among the different batches of sophorolipid samples, and the quality of the sophorolipids was relatively consistent. The fingerprint established in this study is stable and reliable; it can be used for the quality evaluation of sophorolipids and lays a solid foundation for future research on production technology and the development and utilization of sophorolipids. The successful application of a universal CAD to the fingerprint establishment of sophorolipids also provides a reliable solution for the fingerprint establishment of substances with no or weak ultraviolet absorption.

[Corrigendum] Anti­osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome.

AIM: To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene. METHODS: Ophthalmological examinations, including slit-lamp biomicroscopy and lacrimal duct probing, and computed tomography dacryocystography (CT-DCG) were performed for all participants. The family pedigree was drawn, genetic features were analyzed, and the genomic DNA of the subjects was extracted. Pathogenic genes were screened via whole exome sequencing (WES) and confirmed using Sanger sequencing. RESULTS: Six patients belonged to this three-generation family, and their clinical manifestations included congenital nasolacrimal duct obstruction, congenital absence of lacrimal puncta and canaliculi, lacrimal fistulae, and limb deformities. This pattern indicates autosomal dominant inheritance. Diagnosis was based on the clinical characteristics of LADD syndrome, which presented in all the patients in this family. A novel frameshift mutation in the FGF10 gene (NM_004465.1), c.234dupC (p.Trp79Leus*15), was identified in all patients via WES. The variant was confirmed by Sanger sequencing and classified as a "pathogenic mutation" according to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines. CONCLUSION: A novel frameshift mutation in the FGF10 gene is found in all patients. This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode.

BACKGROUND: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. METHOD: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI. RESULTS: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. CONCLUSIONS: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.

Guidewire-Assisted Reduction Technology Combined with Postural Reduction Improves the Success Rate of Internal Vein Catheterisation.

Objective: To investigate the value of guidewire-assisted reduction technology (which increases the stiffness of a catheter through the use of a guidewire, thereby protecting the puncture point and distal vein from breakage) combined with postural reduction for malpositioned catheters in the internal jugular vein during peripherally inserted central venous catheter catheterisation. Methods: From January 2015 to August 2020, we used ultrasound to perform guided puncture and monitoring. We identified the tip of the catheter as malpositioned in the internal jugular vein in 99 patients during the catheterisation process. These patients were divided randomly into a control group and an experimental group. In the control group, 43 cases received guidewire-assisted reduction technology, while in the experimental group, 56 patients received guidewire-assisted reduction technology combined with an upright posture. This study compared the efficacy of these two methods. Results: The results showed that 30 catheters were reduced successfully in the control group, with a success rate of 69.8%. In the experimental group, 53 cases were successfully reduced, with a success rate of 94.6%. The catheter reduction success rate in the experimental group was significantly higher than in the control group; this was a statistically significant difference (P=0.001). Conclusion: Guidewire-assisted reduction technology combined with postural reduction can improve the success rate of the reduction of malpositioned catheters in the internal jugular vein.

Definition of catheter jamming: A mechanical analysis of catheter fracture tension and fracture strain.

BACKGROUND: Catheter jamming is an emerging and possibly underrated complication. OBJECTIVE: To find the criteria for determining if the catheter cannot be removed through the mechanical analysis of fracture tension and fracture strain (εf) of Peripheral Inserted Central Catheters (PICC). METHOD: We removed 30 pieces of PICC catheters from patients and recorded the indwelling time. Those with an indwelling time shorter than 12 weeks belonged to the short-term group. Those with an indwelling time longer than 12 weeks belonged to the long-term group. The first half of the same catheter is section A, and the second half is section B. The fraction tension and fracture strain of the catheter were measured, and statistical analysis was conducted. RESULTS: The fracture tension of catheter in sections A and B were 5.8917 ± 1.0095 and 6.0670 ± 0.8066 Newtons respectively (p= 0.393) and the fracture strain of catheter in sections A and B were 6.0611 ± 1.0810 and 6.2543 ± 0.7187 Newtons respectively (p= 0.343). The fracture tension of catheter in short-term and long-term group were 6.0696 ± 0.9414 and 5.9192 ± 0.8972 Newtons respectively (p= 0.535) and the fracture strain of catheter in short-term and long-term group were 6.0067 ± 0.7227 and 6.2584 ± 1.0212 respectively (p= 0.301). CONCLUSION: It is objective and consistent to take the catheter fracture tension as the standard. This standard would be able to accurately define the concept of catheter failure and reduce the risk of catheter fracture and the misdiagnosis of catheter failure. The catheter fracture tension and fracture strain was not affected by the catheter indwelling time. It is recommended to set the tensile force as 5 Newtons and carry it out at a speed of 100 mm/min for the catheter drawing of the PICC single-lumen silicone catheter (4.0F) from Budd Company.