[Prediction of the vaulting after posterior chamber intraocular lens implantation].

Objective: To investigate the influencing factors on the vaulting one month after implantable collamer lens (ICL) implantation, and to develop and verify a prediction formula. Methods: The first half of this study was retrospective case series study, and the second half was cross-sectional stydy. A total of 83 eyes of 83 patients who underwent ICL implantation in the Lixiang Eye Hospital of Soochow University were included in the first half of the study, with an average age of (27±5) years, from August 1, 2019 to December 30, 2019. All patients underwent a complete preoperative examination, including axis length, anterior chamber depth, comprehensive optometry, intraocular pressure, central corneal thickness, white-to-white diameter, horizontal and vertical sulcus-to-sulcus diameter (STS), crystalline lens thickness (LT), corneal curvature, and bright and dark pupil diameter. Multiple linear regression (stepwise) was used to develop a prediction formula. In the validation part, a total of 65 people (65 eyes) were included, with an average age of (26±5) years, from March 1, 2020 to June 1, 2020. The accuracy and reliability of the formula were verified by the intergroup correlation coefficient and Bland-Altman consistency test. Results: At 1 month after surgery, ICL size had the greatest impact on the vaulting (ß=0.942, P<0.001), followed by horizontal STS (ß=-0.517, P<0.001), LT (ß=-0.376, P<0.001), and vertical STS (ß=-0.257, P=0.017). The influence of other factors was not statistically significant (all P>0.05). The regression equation was as follows: the vaulting (µm)=-1 369.05+657.12×ICL size-287.41×horizontal STS-432.50×LT-137.33×vertical STS (the fitting degree R=0.813, R2=0.660, and corrected R2=0.643). In the verification part, the predicted average vaulting was (497.31±102.75) µm, while the actual vaulting was (514.62±152.99) µm. About 96.92% (63/65) of the patients were fitted in the moderate vault, and 3.08% (2/65) were in the high vault. The intergroup correlation coefficient was 0.581. According to the Bland-Altman test, the actual vaulting was 17.31 µm, higher than the predicted value, and the 95% confidence interval of the difference was -260.28 to 294.90 µm. Conclusion: The ICL size, horizontal and vertical STS and LT are the factors that affect and predict the vaulting one month after ICL implantation, and our prediction formula has good accuracy and reliability. (Chin J Ophthalmol, 2021, 57: 519-525).

[Roles of interleukin-6/signal transduction and activator of transcription 3 pathway and ß-catenin in mechanical stress-induced hypertrophic scar formation in mice].

Objective: To establish mechanical stress-induced hypertrophic scar mouse models, and to examine the roles of interleukin-6/signal transduction and activator of transcription 3 (IL-6/STAT3) pathway and ß-catenin. Methods: The experimental research method was used. Sixteen female C57/BL6 mice of 12-week-old were collected and two straight full-thickness skin incisions of 2 cm in length were inflicted on the back of each mouse. On the fourth day post injury, the two wounds on the back of each mouse were divided into mechanical traction group and blank control group according to the random number table method, with 16 wounds in each group. The wounds in mechanical traction group were given continuous mechanical traction for 14 days, while the wounds in blank control group were given no treatment. After 14 days of mechanical traction for wounds in mechanical traction group, the appearances of the scar tissue in wounds of 2 groups were visually observed, and the areas of scars were measured; the morphological changes of the scar tissue in wounds of 2 groups were observed by hematoxylin-eosin staining, and the cross-sectional areas of scars were measured; the content of IL-6 in supernatant of the scar tissue in wounds of 2 groups was detected by enzyme-linked immunosorbent assay; the protein expression of phosphorylated STAT3 (p-STAT3) of the scar tissue in wounds of 2 groups was detected by Western blotting; and the expression of ß-catenin of the scar tissue in wounds of 2 groups was detected by immunohistochemistry. Data were statistically analyzed with paired sample t test. Results: Red hairless area similar to human scar tissue formed in wounds of mechanical traction group after 14 days of mechanical traction, with large area of scar, thickened local area, hardened texture, and some even slightly raised, while scar in wounds of blank control group was linear and not obvious. After 14 days of mechanical traction for wounds in mechanical traction group, the scar area of wounds in mechanical traction group was (5.65±0.95) mm2, which was significantly larger than (1.07±0.28) mm2 in blank control group (t=26.333, P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the skin appendages of scar tissue were absent, and the dermis hyperplasia was active and obviously thickened, while skin appendages of scar tissue of wounds in blank control group were still present, with unconspicuous dermis hyperplasia; the cross-sectional area of scar in wounds of mechanical traction group was (0.82±0.23) mm2, which was significantly larger than (0.29±0.07) mm2 of blank control group (t=8.879, P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the content of IL-6 in the supernatant of scar tissue and the protein expression of p-STAT3 in scar tissue of wounds in mechanical traction group were significantly higher than those in blank control group (t=37.552, 25.863, P<0.01). The expression of ß-catenin was high in the scar tissue of wounds in mechanical traction group after 14 days of mechanical traction, while that in blank control group was low. Conclusions: The study successfully establishes mechanical stress-induced hypertrophic scar mouse models. Mechanical stress can participate in wound healing and induce scar hyperplasia of mice wounds through continuous or overexpression of IL-6/STAT3 pathway, and ß-catenin can also promote the formation of hypertrophic scar.

[Methylene blue play a role in preventing septic liver injury by inducing macrophage polarization].

Thirty mice were used to establish a sepsis model with cecal ligation and puncture. 15 mg/kg methylene blue or isotonic saline were injected intraperitoneally to observe liver tissue pathological changes. Changes in macrophage frequency and expressional condition of M1 and M2-type hepatic inflammatory factors were detected. After LPS stimulation, the expression level of macrophage inflammatory factor were detected. The results showed that the pathological liver injury was significantly reduced in the MB mice group (P < 0.05), and the frequency of liver macrophage was not statistically significantly different (P > 0.05). MB elevation had promoted the expression of M2-type hepatic inflammatory factor (P < 0.05) and macrophage inflammatory factor (P < 0.05). MB can play a role in preventing septic liver injury by inducing macrophages polarization to M2-type.

[Phosphonate inhibits steatosis and lobular inflammation of non-alcoholic steatohepatitis through depleting macrophages].

Objective: To explore the role of macrophages in non-alcoholic steatohepatitis (NASH) in order to provide directions for the therapeutic target of metabolic liver disease. Methods: Twenty C57BL/6 wild-type male mice at 6-8 weeks were randomly divided into two groups: 5 in the control group, methionine-and choline-deficient diet (MCD); 15 in the experimental group, MCD diet + intraperitoneal injection of disodium chlorophosphonate liposomes (to clear macrophages). Mice were fed for 4 weeks to establish NASH model. Blood, liver and spleen were collected to analyze the body mass index, liver index, spleen index, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Non-alcoholic steatosis (NAS) activity score was evaluated by HE and Oil Red O staining. The relative expression level of F4/80 mRNA was compared by RT-PCR. Data comparison between groups was analyzed by t-test. Results: NASH model was successfully established by feeding the mice with MCD for four week. The expression of F4/80 mRNA (t = 4.167, P < 0.01), hepatic steatosis (t = 10.70, P < 0.05), interlobular inflammatory infiltration (t = 3.08, P < 0.05), and NAS score were decreased (t = 8.06, P < 0.05) in the experimental group. At the same time, ALT level [(817.00 ± 128.90) U/L vs. (231.20 ± 36.28) U/L, t = 5.71, P < 0.01], AST level [(1 211.00 ± 248.90) U/L vs. (505.30 ± 88.20) U/L, t = 3.32, P < 0.01] was decreased significantly. However, the spleen volume and spleen index of the experimental group were larger (0.24 ± 0.01 and 0.32 ± 0.02, t = 2.41, P < 0.05), and there was no significant effect on liver ballooning, body mass index and liver index. Conclusion: In NASH, phosphonate can consume macrophages to inhibit liver inflammation and protect the damaged liver.

Influences of miR-155/NF-κB signaling pathway on inflammatory factors in ARDS in neonatal pigs.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is greatly threatening human health with high morbidity and mortality. The pathogenesis of ARDS is closely related to the inflammatory response in patients. The micro-ribonucleic acid (miR)-155/nuclear factor-κB (NF-κB) signaling pathway is crucial in regulating the expression of inflammation-related genes. Therefore, the influences of miR-155/NF-κB signaling pathway on inflammatory factors in ARDS in neonatal pigs were explored in this study. MATERIALS AND METHODS: The model of ARDS in neonatal pigs was established first. The expression levels of miR-155, NF-κB-related proteins, and inflammatory factors in model group and control group were detected, and their differences were compared. Moreover, after treatment with the miR-155/NF-κB signaling pathway inhibitor, the changes of the inflammatory factors expression in ARDS neonatal pigs were observed at different time points. RESULTS: In the model group, the levels of miR-155 and NF-κB-related proteins were significantly increased, and the levels of inflammatory factors, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6, were also increased synchronously. However, the levels of IL-4 and IL-10 declined significantly. In addition, it was proved that after treatment with the inhibitor in model group the mRNA expressions of miR-155/NF-κB signaling pathway-related proteins were significantly inhibited, and the levels of IL-1ß, TNF-α, and IL-6 were also significantly inhibited (p<0.05). The levels of IL-4 and IL-10 remarkably rose after treatment with the inhibitor for 24 h (p<0.05). CONCLUSIONS: The miR-155/NF-κB signaling pathway influenced the changes of inflammatory factors in ARDS in neonatal pigs, which might be a potential target for eliminating the inflammatory response after ARDS in neonatal pigs.

[Study on the application of oral magnesium sulfate solution in split doses as bowel preparation for colonoscopy in elderly patients].

Objective: To evaluate the efficacy and safety of oral magnesium sulfate solution in split doses as bowel preparation in elderly patients undergoing colonoscopy. Methods: A total of 368 elderly patients undergoing colonoscopy were enrolled at PLA General Hospital. The patients were randomly divided into magnesium sulfate solution orally in split doses group (group A, n=178) and single dose group (group B, n=190). Parameters including general information, defecation frequency, Boston bowel preparation score (BBPS), detection rate of lesions and adverse reactions. Results: The frequency of defecations in group A was (7.6±1.4), more than that in group B (6.6±1.5) with statistical significance (P<0.05). The duration of bowel preparation in group A was (128.6±25.3) min, shorter than that of group B (165.4±29.7) min (P<0.05). The BBPS in group A was (8.09±0.67), better than that of group B (7.34±0.58) (P<0.05). The detection rates of intestinal polyps and micropolyps (diameter<0.5 cm) in group A were 73/178 (41.0%) and 51/178 (28.7%) respectively, compared with 58/190 (30.5%) and 37/190 (19.5%) in group B (both P<0.05). In group A, 8 patients reported adverse reactions as abdominal distension and discomfort. One patient had ST-T abnormality of electrocardiogram (ECG). No nausea or vomiting occurred, yet 2 cases needed enema for inadequate bowel preparation. Twenty-one cases in group B reported adverse events including 7 with nausea and vomiting. There were 13 patients treated with enema. Abnormal ECG was found in 4 patients in group B. The satisfaction rate of group A was 97.8%, higher than that of group B (91.6%) (P<0.05). Conclusions: The effect of bowel preparation of elderly patients with magnesium sulfate solution in split dose has a better tolerance, good cleaning effect and low incidence of adverse reactions. It is an ideal choice for the elderly to prepare colonoscopy.

[Application of image navigation assisted nasal endoscopic surgery in optic nerve decompression].

Objective:To explore the application and to evaluate the advantage of image navigation assisted nasal endoscopic surgery in optic nerve decompression. Method:Sixty patients accepted the image navigation assisted nasal endoscopic surgery therapy in optic nerve decompression were included in this retrospective study and followed up for about six months to four years. Result:The visual acuity was improved in 16 cases with visual acuity above light. One case is 10 cm index, two cases are 40 cm index, one case is 70 cm index, the visual acuity of rest 12 cases was between 0.04 and 0.30, two of them were missing from the field of view, the effective rate was 100%. The 44 cases without light sensation before operation, postoperative visual acuity was improved in 11 cases, four of which were light sensation and visible figure. Visual acuity of seven cases was between 0.03 and 0.08, one of them was missing from the field of view, the effective rate was 25%. No complications occurred. Conclusion:With the help of the image navigation, it is convenient and accurate to locate the anatomical marker sites such as orbital apex, optic canal and fracture site, internal carotid artery and so on, as a result, the accuracy and the success rate of the surgery were greatly improved.

[Clinical analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in thalassemia major].

Objective: To explore the diagnosis, treatment and prognosis of autoimmune hemolytic anemia (AIHA) after allo-HSCT in patients with thalassemia major (TM). Methods: A retrospective analysis of AIHA status after allo-HSCT in 291 TM patients from July 2007 to December 2017 was conducted. Results: Five of the 291 TM patients (1.72%) were diagnosed with post-transplant AIHA. The median time of AIHA was 7 (5-12) months after HSCT. All post-transplant AIHA patients were positive in direct and indirect Coombs test, the main clinical manifestations were dizziness, fatigue, pale complexion, skin and sclera yellow, and soy sauce urine. The incidence of AIHA was higher after unrelated donor transplantation (6.36%, 4/63) compared with that of sibling donor transplantation (0.43%, 1/228). One patient who received only prednison was dead. Four patients who received rituximab combined with prednisolone were alive, Coombs test in two of them were negative. Conclusions: AIHA after allo-HSCT developed in 1.72% patients with TM. Monitoring of Coombs test was important for diagnosis of post-transplant AIHA. The incidence of post-transplant AIHA was higher in unrelated donors compared with that of sibling donors transplantation. Treatment of rituximab combined glucocorticoid was effective strategy for post-transplant AIHA.

[Wegner's granulomatosis of hypolarynx in a patient with laryngemphraxis: case report and review of literature].

Summary A patient suffered from progressive dyspnea and even laryngeal obstruction visited our department in May, 2017 and received emergency tracheotomy for assistance in breathing. There was no dysphagia, sore throat, fever, cough, hemoptysis and hematuresis. The pathological signs including facies dolorosa, three depressions sign, perforation of nasal septum. The laboratory examination showed that there were hematuresis and albuminuria. The urine bilirubin levels were elevated, antineutrophil cytoplasmic antibody (ANCA) was positive and antiproteinase 3 antibody was elevated. The electronic laryngoscope revealed the swelling of infraglottic region and laryngeal CT showed the subglottic area occupation and stenosis. The pulmonary CT showed the irregular mass shadow in lower lobe of right lung which was considered benign pathological changes. Finally, the diagnosis was subglottic Wegner's granulomatosis and result in laryngeal obstruction and need the first aid in clinic.

Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway.

OBJECTIVE: To investigate the relative expression of long non-coding RNA 00673 (lncRNA 00673) in hepatocellular carcinoma (HCC) and HCC cells and study its regulation on the malignant phenotype of HCC cells PATIENTS AND METHODS: Samples of HCC and adjacent tissues from January 2013 to December 2015 were collected. The expression level of lncRNA00673 in HCC tissues and cells was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) assays. lncRNA00673 specific interference sequences were transiently transfected into HCC cells and the effect of HCC cells on the biological behavior of HCC cells was examined by in vitro experiments ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay), flow cytometry, transwell, etc.). A tumor model of nude mice with HCC was established for the study of tumor growth condition of tumor-bearing mice after the interference with lncRNA00673 expression. Changes in expression levels of molecular markers on Notch signaling pathway after the interference with lncRNA00673 were detected by Western blot. RESULTS: lncRNA00673 was highly expressed in HCC tissues and cells. MTT results showed that interfering with lncRNA00673 inhibited cell proliferation. Flow cytometry results showed that HCC cell cycle was retarded in G1-G0 phase, thus promoting apoptosis after the interference with lncRNA00673. Western blot results showed that expression levels of molecular markers on Notch signaling pathway were changed after the interference with lncRNA00763. CONCLUSIONS: lncRNA00673 is highly expressed in HCC tissues and cells, and can promote the proliferation and metastasis of HCC by the regulation on Notch signaling pathway. lncRNA00673 may be a potential target for the treatment of HCC.

CD8(+) T cells with distinct cytokine-producing features and low cytotoxic activity in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: CD8(+) T cells are important effectors of cell-mediated immunity; however, their contribution to the pathogenesis of CRS is unclear. OBJECTIVE: This study aimed to characterize the cytokine-producing features and cytotoxic activity of CD8(+) T cells, and their correlation with inflammation patterns in CRS with nasal polyps. METHODS: The expression of IFN-γ, IL-4, IL-5, IL-17A, forkhead box P3 (FOXP3), perforin, and granzyme B in CD8(+) T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression of CD8(+) T-cell subset relevant chemokines and chemokine receptors was detected by means of real-time RT-PCR or ELISA. The cytotoxic activity of sorted CD8(+) T cells was defined by anti-CD3-redirected killing assay. RESULTS: Compared with controls, elevated percentages of total CD8(+) T cells and cytotoxic T lymphocyte (Tc) 1 (IFN-γ(+) ), Tc2 (IL-4(+) ), and Tc17 (IL-17A(+) ) cell subset, and decreased percentages of FOXP3(+) CD8(+) regulatory T cells, were found in both eosinophilic and non-eosinophilic polyps with a Tc2-skewed and Tc1/Tc17-dominated response in eosinophilic and non-eosinophilic polyps, respectively. Nasal CD8(+) T cells were found to produce similar or even higher levels of IFN-γ and IL-4 compared with CD4(+) T cells. Tc1 and Tc17, and Tc2 (IL-4(+) and IL-5(+) ) cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, the expression of perforin and granzyme B and cytotoxic activity were significantly reduced in nasal CD8(+) T cells compared with their counterparts in peripheral blood. The expression of CXCL16, CCL17, and CCL20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively. CONCLUSION AND CLINICAL RELEVANCE: CD8(+) T cells have low cytotoxic activity; nevertheless, they are a significant and previously underappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinctly biased granulocyte inflammation in eosinophilic and non-eosinophilic polyps.

Dendritic cells in inflammatory sinonasal diseases.

Dendritic cells (DCs) are critical in linking the innate and adaptive immune responses, which have been implicated in the pathogenesis of many immune and inflammatory diseases as well as the development of tumours. The role of DCs in the pathophysiology of lung diseases has been widely studied. However, the phenotype, subset and function of DCs in upper airways under physiological or pathological conditions remain largely undefined. Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two important upper airway diseases with a high worldwide prevalence. Aberrant innate and adaptive immune responses have been considered to play an important role in the pathogenesis of AR and CRS. To this end, understanding the function of DCs in shaping the immune responses in sinonasal mucosa is critical in exploring the pathogenic mechanisms underlying AR and CRS as well as in developing novel therapeutic strategies. This review summarizes the phenotype, subset, function and regulation of DCs in sinonasal mucosa, particularly in the setting of AR and CRS. Furthermore, this review discusses the perspectives for future research and potential clinical utility focusing on DC pathways in the context of AR and CRS.

Mitogen-activated protein kinase signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor-mediated amyloid-ß uptake in SH-SY5Y cells.

Intraneuronal accumulation of beta-amyloid protein (Aß) is an early pathological change in Alzheimer's disease (AD). Recent studies demonstrate that α7 nicotinic acetylcholine receptor (α7nAChR) binds to soluble Aß with a high affinity. In vitro and in vivo experiments also show that Aß activates p38 MAPK and ERK1/2 signaling pathways via the α7nAChR. Interestingly, it has been reported that p38 MAPK and ERK1/2 signaling pathways affect the regulation of receptor-mediated endocytosis. These data suggest that MAPK signaling pathways maybe involved in the regulation of α7nAChR-mediated Aß uptake. However, the evidence for this hypothesis is lacking. In the present study, we examined whether Aß1-42 oligomers activate MAPK signaling pathways via α7nAChR, and assessed the role of MAPK signaling pathways in the regulation of Aß1-42 uptake by α7nAChR. We confirm that undifferentiated SH-SY5Y cells are capable of taking up extracellular Aß1-42. The internalization of Aß1-42 accumulates in the endosomes/lysosomes and mitochondria. MAPK signaling pathways are activated by Aß1-42 via α7nAChR. Aß1-42 and α7nAChR are co-localized in SH-SY5Y cells and the expression of α7nAChR involves in Aß1-42 uptake and accumulation in SH-SY5Y cells. Our data demonstrate that Aß1-42 induces an α7nAChR-dependent pathway that relates to the activation of p38 MAPK and ERK1/2, resulting in internalization of Aß1-42. Our findings suggest that α7nAChR and MAPK signaling pathways play an important role in the uptake and accumulation of Aß1-42 in SH-SY5Y cells. Blockade of α7nAChR may have a beneficial effect by limiting intracellular accumulation of amyloid in AD brain and serves a potential therapeutic target for AD.

Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns.

BACKGROUND: The remodeling patterns in different types of chronic rhinosinusitis (CRS) have rarely been compared, particularly the difference between eosinophilic and noneosinophilic CRS with nasal polyps (CRSwNP). Moreover, whether there is a link between remodeling and inflammation remains controversial. OBJECTIVE: To directly compare the remodeling features of different CRS and to explore their relationship with inflammation in Chinese patients. METHODS: Histologic characteristics of surgical samples were analyzed in 33 controls, 72 eosinophilic and 76 noneosinophilic CRSwNP, and 72 CRS without nasal polyps (CRSsNP) patients. Tissue samples from 38 controls, 26 eosinophilic and 26 noneosinophilic CRSwNP, and 32 CRSsNP patients were measured for mRNA and/or protein expression of profibrotic growth factors, metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), hypoxia-inducible factor (HIF)-1α, interleukin (IL)-8, eosinophil cationic protein (ECP), and myeloperoxidase (MPO). RESULTS: The amount of collagen decreased, whereas the edema scores increased, from CRSsNP to noneosinophilic CRSwNP and to eosinophilic CRSwNP. Transforming growth factor (TGF)-ß2 protein levels were enhanced in CRSsNP compared with CRSwNP. TIMP-4 protein levels decreased in eosinophilic CRSwNP compared with noneosinophilic CRSwNP and CRSsNP. The number of neutrophils decreased from CRSsNP to noneosinophilic CRSwNP and to eosinophilic CRSwNP. ECP levels were only up-regulated in eosinophilic CRSwNP. ECP levels and neutrophil number correlated positively with the severity of edema and fibrosis, respectively. Neutrophils were the major sources of TGF-ß2 in CRSsNP and noneosinophilic CRSwNP. CONCLUSION: Distinct remodeling patterns are revealed for different types of CRS, particularly for eosinophilic and noneosinophilic CRSwNP. Tissue remodeling associates with inflammation in CRS.