Incidence and Risk Factors of Moderate to Severe Postoperative Pain Following the Placement of Primary and Secondary Orbital Implants: A Prospective Observational Study.

PURPOSE: To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. METHODS: One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. RESULTS: Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. CONCLUSIONS: Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.

Integrative transcriptomic and proteomic analysis reveals CD9/ITGA4/PI3K-Akt axis mediates trabecular meshwork cell apoptosis in human glaucoma.

Glaucoma has been the leading cause of irreversible blindness worldwide. High intraocular pressure (IOP) is a high-risk factor of glaucoma, repression of which has been the important treatment of glaucoma in clinic. Trabecular meshwork is crucial for maintaining IOP in aqueous humour out-flow system. It is urgent to reveal the molecular mechanism of trabecular meshwork in glaucoma. Previous studies found that some pathways were related to glaucoma, such as extracellular matrix (ECM)-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and apoptosis. To identify novel molecules in glaucoma, we performed high-throughput transcriptome and proteome analysis to immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM3 ), respectively. Twenty-six up-regulated genes/proteins and 59 down-regulated genes/proteins were identified as the high-risk factors based on differential analysis, including some known factors of glaucoma. Furthermore, a glaucoma-related protein-protein interaction (PPI) network was constructed for investigating the function roles of risk factors. Some genes were identified as potential regulator in the pathogenesis of glaucoma based on the topology analysis and module analysis to the network. Importantly, we identified and demonstrated that CD9 played key roles in glaucoma by biological experiment. CD9 is down-regulated in glaucoma, overexpression of CD9 can active integrin α4 (ITGA4), PI3K and Akt, which lead to the decreased apoptosis and attenuate glaucoma. All these results provide a novel molecular therapy of glaucoma.

Expressional and functional involvement of gap junctions in aqueous humor outflow into the ocular trabecular meshwork of the anterior chamber.

Purpose: The ocular trabecular meshwork (TM) responsible for aqueous humor (AH) drainage is crucial for regulating intraocular pressure (IOP) of the eye. An IOP elevation that causes distended TM is involved in the pathogenesis of glaucoma, suggesting intercellular connections important for the TM pathophysiology. The goal of this study was to examine whether gap junction proteins between endothelial cells in the TM are expressional and functional. Methods: The expression levels of the gap junction channels in normal human TM cells were determined with real-time PCR and western blot assays. Immunohistochemistry (IHC) staining was performed to examine the localization of gap junction proteins in normal human TM cells and tissues. IOP and the outflow of AH were measured after intercameral injection of gap junction blockers in C57/BL6 mice. Results: Gap junction proteins GJA1, GJA8, GJB6, and GJC1 were robustly expressed in human TM cells from three individuals. Among the four gap junction channels, GJA1 and GJA8 exhibited the most abundance in the TM. The IHC analysis further confirmed that these proteins were expressed on the membrane between adjacent cells. In the human TM tissues, GJA1, GJA8, GJB6, and GJC1 were also observed along the trabecular beams. Inhibition of gap junctions with intracameral injection of blockers resulted in a statistically significant increase in aqueous humor outflow resistance and IOP elevation in mice. Conclusions: The GJA1 and GJA8 gap junction proteins, in particular, are robustly expressed in human TM cells and tissues. Pharmacological inhibition of gap junction channels causes an increased resistance of AH outflow and an elevation of IOP in mice. The present findings suggest the functional role of gap junction channels for regulation of AH outflow in the TM, and activation of gap junctions might represent a therapeutic strategy for treatment of glaucoma.

The Risk Factors for New-Onset Calf Muscle Venous Thrombosis after Hip Fracture Surgery.

BACKGROUND: Calf muscle venous thrombosis (CMVT) is among the most important medical complications after hip surgery. CMVT has been known for many years, but many opinions about the incidence and risk factors of CMVT are still controversial. The objective of this retrospective study was to investigate the incidence and associated risk factors of postoperative CMVT in patients with hip fractures. METHODS: Patients with hip fractures from January 2020 to April 2022 (n = 320) at Shenzhen Second People's Hospital were recruited in this study. The personal characteristics and clinical data of CMVT and no-CMVT patients were compared and analyzed. Binary logistic regression analyses were performed to identify potential risk factors of CMVT in patients with hip fractures. Finally we performed a receiver operating characteristic (ROC) curve analysis to compare the diagnostic values of different variables. RESULTS: The overall incidence of new-onset CMVT in patients with hip fractures was 18.75% (60 of 320). Among the 60 CMVT patients, 70% (42 of 60) were diagnosed with femoral neck fractures, 28.3% (17 of 60) with intertrochanteric fractures, and 1.7% (1 of 60) with subtrochanteric fractures. No pulmonary embolism (PE) occurred. High preoperative D-dimer (OR = 1.002, 95%CI 0.97-1.03), sex (OR = 1.22, 95%CI 0.51-2.96), the caprini score (OR = 2.32, 95%CI 1.05-5.16) and the waterlow score (OR = 1.077, 95%CI 0.35-3.36) significantly increased the risk of developing postoperative new-onset CMVT. CONCLUSIONS: CMVT has become a common clinical disease, and its harm should not be underestimated. Our study found that D-dimer, sex, the caprini score and the waterlow score were independent risk factors for postoperative CMVT. According to our clinical work, we should pay attention to identifying the risk factors of CMVT formation and targeted intervention measures to prevent new-onset CMVT.

Investigation of the Difference in the Pulse Current in the Double Pulsed Gas Metal Arc Welding of Aluminum Alloys.

In this paper, a double pulse gas metal arc welding (DP-GMAW) for an AA6061-T6 aluminum alloy based on fewer basic welding parameters than the traditional DP-GMAW is proposed. This study compared the difference in pulse base currents (ΔIb) and the difference in the pulse peak currents (ΔIp) by analyzing the electrical signal and morphology properties of welded samples. The results indicated that changing ΔIp caused welding defects or even welding failure easily. The welding stability after changing ΔIb was much better than that after changing ΔIp. The individual fish-scale width of the weld joint remained unchanged when ΔIb was at different values. In addition, the average absorbed work, tensile strength, yield strength and elongation of the weld joints obtained by different ΔIb values reached 31.1%, 60.2%, 52.9% and 37.9% of the base metal, respectively.

ITGA8 positive cells in the conventional outflow tissue exhibit Schlemm's canal endothelial cell properties.

AIMS: Elevated intraocular pressure is primarily induced by the increased resistance of conventional outflow of aqueous humor. Dysfunction of the juxtacanalicular region of trabecular meshwork (TM) and Schlemm's canal (SC) endothelium, as the main conventional outflow tissue, have been implicated as the major reasons for the increased resistance. Integrins are widespread in these tissues, especially alpha8 integrin (ITGA8). We aim to investigate the properties of cells expressing ITGA8 in the conventional outflow tissue. MAIN METHODS: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to detect the mRNA and protein levels of ITGA8 in human conventional outflow tissue. ITGA8-positive cells were isolated from the cultured human TM cells through a magnetic bead-based approach. Flow Cytometry was used to determine the purification efficiency. The expressions of TM and SC biomarkers and dexamethasone-induced myocilin secretion capacity of ITGA8-positive cells was assessed by Real-time PCR, IF and Western blot. A gel contraction assay was performed to evaluate contractility of ITGA8-positive cells after endothelin 1 treatment. KEY FINDINGS: ITGA8 was found with robust expression near the inner wall of SC endothelium. After purification, the proportion of ITGA8-positive cells were increased by about 10%. ITGA8-positive cells were identified with the properties as SC endothelial cells, such as more robust expressions of SC biomarkers, less dexamethasone-inducible myocilin expression, and stronger contractility. SIGNIFICANCE: This study demonstrated that cells expressing ITGA8 in SC region possess more properties as SC endothelial cells. Our data implicate a crucial role of ITGA8 in aqueous humor (AH) outflow resistance regulation.

Rho-Associated Protein Kinase Inhibitor Treatment Promotes Proliferation and Phagocytosis in Trabecular Meshwork Cells.

PURPOSE: Continuous reductions in trabecular meshwork (TM) cellularity inhibit aqueous humor (AH) outflow, which is the main cause of primary open-angle glaucoma. Rho-associated protein kinase inhibitor (ROCKi) targets the TM to reduce intraocular pressure (IOP) and increase AH outflow facility. However, the underlying mechanisms are not entirely clear. Here, we aimed to investigate the effect of a ROCKi (Y-27632) on TM cell proliferation and phagocytosis. METHODS: Immortalized human TM (iHTM) cells, glaucomatous TM (GTM3) cells, and primary human TM (pTM) cells were cultured and identified. The effects of various concentrations of Y-27632 on F-actin cytoskeleton were assessed using immunofluorescence. Cell proliferation effects were evaluated using a cell counting kit-8 (CCK8), cell counting, and Ki67 immunostaining. Cell phagocytosis was evaluated using immunofluorescence and flow cytometry in immortalized TM cells. C57BL/6J and Tg-MYOC Y437H mice were used to investigate the proliferative effects of Y-27632 on TM cells in vivo. The effect of Y-27632 on IOP was monitored for 2 weeks, and the outflow facility was detected 2 weeks after IOP measurement. TM cells in mice were counted using immunohistochemistry. RESULTS: Y-27632 (100 µM) significantly promoted the proliferation of both immortal TM cells and pTM cells. In GTM3 cells, phagocytosis was significantly greater in the Y-27632 group than in the control group, nearly reaching the level of phagocytosis in iHTM, as determined using immunofluorescence and flow cytometry. In Tg-MYOC Y437H mice, treatment with Y-27632 significantly decreased IOP and increased outflow facility, which greatly influenced the long-term IOP-lowering effect. The number of TM cells in Tg-MYOC Y437H mice was significantly improved after Y-27632 administration. CONCLUSION: Y-27632 promoted cell proliferation and phagocytosis of TM cells, and its proliferative effect was demonstrated in a transgenic mouse model. These results revealed a new IOP-lowering mechanism of Y-27632 through effects on TM cells, suggesting the potential for a correlation between TM cellularity and long-term recovery of IOP.

Compound heterozygous mutations in CYP1B1 gene leads to severe primary congenital glaucoma phenotype.

AIM: To identify the novel mutation alleles in the CYP1B1 gene of primary congenital glaucoma (PCG) patients at Shandong Province of China, and investigate their correlation with glaucomatous features. METHODS: The DNA from the peripheral blood of 13 congenital glaucoma patients and 50 ethnically matched healthy controls from the affiliated hospital of Qingdao University were extracted. The coding region of the CYP1B1 gene was amplified by PCR and direct DNA sequencing was performed. Disease causing-variants were analyzed by comparing the sequences and the structures of wild type and mutant CYP1B1 proteins by PyMOL software. RESULTS: Two missense mutations, including A330F caused by c.988G>T&c.989C>T, and R390H caused by c.1169G>A, were identified in one of the 13 PCG patients analyzed in our study. A330F mutation was observed to be novel in the Chinese Han population, which dramatically altered the protein structure of CYP1B1 gene, including the changes in the ligand-binding pocket. Furthermore, R390H mutation caused the changes in heme-protein binding site of this gene. In addition, the clinical phenotype displayed by PCG patient with these mutations was more pronounced than other PCG patients without these mutations. Multiple surgeries and combined drug treatment were not effective in reducing the elevated intraocular pressure in this patient. CONCLUSION: A novel A330F mutation is identified in the CYP1B1 gene of Chinese PCG patient. Moreover, in combination with other mutation R390H, this PCG patient shows significant difference in the CYP1B1 protein structure, which may specifically contribute to severe glaucomatous phenotype.

[Prevalence and related factors of carcinoma among population in Macao during 2003 - 2007].

OBJECTIVE: Understanding the prevalence of cancer among Macao residents to better carry out tertiary prevention and control program. METHODS: Data was gathered from annual reports of Macao Cancer Registry of Health Bureau in 2003 - 2007, and demographic statistics of Statistics and Census Bureau Macau SAR Government in 1997 - 2006. Both International Statistical Classification of Diseases and Related Health Problems 10(th) Revision (ICD-10) were used to classify the diseases and causes of death. Excel 2003 was used for data input and data was analyzed with crude rate, velocity of increase of crude rate and cumulative risk. RESULTS: The average crude incidence rate of cancer was 237.2 per 100 000 among the Macao population, with age standardized incidence rate as 194.4 per 100 000;and crude mortality rate as 101.0 per 100 000. Lower gastrointestinal cancer had the highest crude incidence, with the crude incidence rate of prostate cancer rapidly increasing. Respiratory cancer and breast cancer appeared to be the highest crude incidences in both men and women, with the crude mortality rate (25.0 per 100 000) of respiratory cancer the highest. 72.9% of the tumors occurred at the age of 50 and above. However, 81.1% of the tumors occurred at 50 years old and above in men, with the occurrences of tumors of women distributed more evenly. Breast cancer and epithelial tumor commonly occurred in adolescents and young adults while respiratory cancer mostly seen in adulthood and the elderly. Residents were usually diagnosed of cancer at 61.0 years of age and death occurred at 70.5 year old. The prognosis of cancer of men was worse than women's. The worst prognosis of cancer was seen in liver and esophagus, with death occurred within 1 year after diagnosis was made. Breast cancer had the highest cumulative incidence rate, but respiratory cancer had the highest cumulative mortality rate. Both cumulative rates of incidence and mortality in women were lower than in men. CONCLUSION: The increase of crude cancer incidence rate was fast among Macao residents, but relatively slow with crude mortality rate. Respiratory and lower gastrointestinal tumors took the majority while prostate and breast cancer were by no means unimportant, which also called for tertiary prevention. People above 50 years old and all males should be listed as target population to receive preventive program on cancer.