Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours.

BACKGROUND: Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs. METHODS: We applied single-cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data-independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining. RESULTS: Tumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer-associated fibroblast-like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter-patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading. CONCLUSIONS: Our study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.

The efficacy of bandage contact lens in relieving the aggravation of dry eye disease after complicated cataract or/and IOL surgery.

PURPOSE: In the present study, we aimed to evaluate the efficacy of the bandage contact lens (BCLs) in the treatment of dry eye disease (DED) after complicated cataract or/and intraocular lens (IOL) surgery. METHODS: In this retrospective, single-centered, observational study, we collected data from 69 patients who underwent complicated cataract or/and IOL surgery. Of these, 35 cases wore their own BCLs immediately after the operation, while the other 34 cases did not have their own BCLs and were instead covered with gauze. The Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp microscope examination, keratograph analysis, and Schirmer I test were measured at baseline, 1 week and 1 month postoperatively. RESULTS: In the BCL group, the score of the OSDI questionnaire was significantly decreased at 1 week and 1 month postoperatively compared with baseline levels (P = 0.000, collectively). Moreover, the fluorescein staining score of the BCL group was remarkably decreased 1-week and 1-month postoperatively compared with the non-BCL group (P = 0.000 and P = 0.000, respectively). Furthermore, the redness score of the BCL group was also better compared with the non-BCL group at 1 week and 1 month postoperatively (P = 0.014 and P = 0.004, respectively). CONCLUSIONS: Complicated cataract or/and IOL surgery would intensify the DED. Early application of BCLs postoperatively improved patients' comfort and alleviated dry eye-related symptoms and signs. Furthermore, this mechanism might involve the acceleration of corneal epithelial healing, the alleviation of ocular stress response and the stabilization of the tear film. TRIAL REGISTRATION: Trial registration ClinicalTrials, NCT04120389. Registered 10 October 2019-retrospectively registered.

Versican core protein aids in the diagnosis and grading of breast phyllodes tumor.

Phyllodes tumors (PTs) are biphasic fibroepithelial lesions that occur in the breast. Diagnosing and grading PTs remains a challenge in a small proportion of cases, due to the lack of reliable specific biomarkers. We screened a potential marker versican core protein (VCAN) through microproteomics analysis, validated its role for the grading of PTs by immunohistochemistry, and analyzed the correlation between VCAN expression and clinicopathological characteristics. Cytoplasmic immunoreactivity for VCAN was identified in all benign PT samples, among which 40 (93.0 %) showed VCAN-positive staining in ≥50 % of tumor cells. Eight (21.6 %) borderline PT samples showed VCAN-positive staining in ≥50 % of the cells with weak to moderate staining intensity, whereas 29 samples (78.4 %) showed VCAN-positive staining in <50 % of the cells. In malignant PTs, 16 (84.2 %) and three (15.8 %) samples showed VCAN-positive staining in <5 % and 5-25 % of stromal cells, respectively. Fibroadenomas showed a similar expression pattern to benign PTs. Fisher's exact test showed that the percentages of positive cells (P < .001) and staining intensities (P < .001) of tumor cells were significantly different between the five groups. VCAN positivity was associated with tumor categories (P < .0001) and CD34 expression (P < .0001). The expression of VCAN gradually decreases as the tumor categories increases, following recurrence. To the best of our knowledge, our results are the first in the literature to reveal that VCAN is useful for diagnosing and grading PTs. The expression level of VCAN appeared to be negatively associated with PT categories, suggesting that dysregulation of VCAN may be involved in the tumor progression of PTs.

Artemether ameliorates adriamycin induced cardiac atrophy in mice.

Adriamycin is a widely used and effective antitumor drug; however, its application is limited by various side effects, including irreversible cardiotoxicity. The central role of cardiac atrophy in Adriamycin­induced cardiotoxicity has been revealed; however, the underlying mechanism of this process remains unclear. Artemether is a well­known Chinese herbal medicine, and its pharmacological action is related to the regulation of mitochondrial function and redox status. The present study determined the effects of artemether on Adriamycin­induced cardiotoxicity and investigated the underlying mechanisms. After mouse model establishment and artemether intervention, experimental methods including pathological staining, immunohistochemistry, immunofluorescence, immunoblotting, ELISA and reverse transcription­quantitative PCR were used to evaluate the therapeutic effect. The results demonstrated that artemether prevented Adriamycin­induced cardiac atrophy and recovered the intercombination of connexin 43 and N­cadherin at the intercalated discs. Artemether also regulated the autophagy pathway and restored the unbalanced ratio of Bax and Bcl­2 in myocardial cells. In addition, the increased serum H2O2 levels after Adriamycin exposure were significantly decreased by artemether, and the mitochondrial alterations and redox imbalance in myocardial cells were also improved to varying degrees. In summary, the findings of the present study provide reliable evidence that artemether could ameliorate cardiac atrophy induced by Adriamycin. This therapeutic approach may be translated to the clinic for preventing drug­induced heart diseases.

Prediction of postoperative visual acuity in patients with age-related cataracts using macular optical coherence tomography-based deep learning method.

Background: To predict postoperative visual acuity (VA) in patients with age-related cataracts using macular optical coherence tomography-based deep learning method. Methods: A total of 2,051 eyes from 2,051 patients with age-related cataracts were included. Preoperative optical coherence tomography (OCT) images and best-corrected visual acuity (BCVA) were collected. Five novel models (I, II, III, IV, and V) were proposed to predict postoperative BCVA. The dataset was randomly divided into a training (n = 1,231), validation (n = 410), and test set (n = 410). The performance of the models in predicting exact postoperative BCVA was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The performance of the models in predicting whether postoperative BCVA was improved by at least two lines in the visual chart (0.2LogMAR) was evaluated using precision, sensitivity, accuracy, F1 and area under curve (AUC). Results: Model V containing preoperative OCT images with horizontal and vertical B-scans, macular morphological feature indices, and preoperative BCVA had a better performance in predicting postoperative VA, with the lowest MAE (0.1250 and 0.1194LogMAR) and RMSE (0.2284 and 0.2362LogMAR), and the highest precision (90.7% and 91.7%), sensitivity (93.4% and 93.8%), accuracy (88% and 89%), F1 (92% and 92.7%) and AUCs (0.856 and 0.854) in the validation and test datasets, respectively. Conclusion: The model had a good performance in predicting postoperative VA, when the input information contained preoperative OCT scans, macular morphological feature indices, and preoperative BCVA. The preoperative BCVA and macular OCT indices were of great significance in predicting postoperative VA in patients with age-related cataracts.

Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin. CASE PRESENTATION: A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later. CONCLUSION: Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours.

Effect of two different preoperative calculation schemes on visual outcomes of patients after toric intraocular lens implantation.

PURPOSE: To compare the postoperative visual outcomes of two different preoperative corneal incision schemes in TECNIS toric intraocular lens (IOL) implantation. METHODS: In this randomized controlled study, patients with preoperative corneal astigmatism greater than 1.0 diopter (D) were included. These patients were grouped according to the different preoperative schemes: steep-axis group and minimum-residual refractive astigmatism group. The outcome measurements were the residual refractive astigmatism, visual acuity, changes of corneal astigmatism, and high-order aberration at 1 month postoperatively. RESULTS: This study consisted of 90 eyes (45 eyes steep-axis group, 45 eyes minimum-residual refractive astigmatism group). 1 month after surgery, the refractive astigmatism was statistically lower in the minimum-residual refractive astigmatism group compared with the steep-axis group (0.58 ± 0.40D vs 0.38 ± 0.37D, P = 0.021). The minimum-residual refractive astigmatism group had a smaller difference vector (0.56 ± 0.38D vs 0.36 ± 0.35D; P = 0.047) and a smaller prediction error (0.60 ± 0.44D vs 0.37 ± 0.35D; P = 0.004). In the steep-axis group, corneal astigmatism significantly decreased compared with preoperative value (1.65 ± 0.57D vs 1.17 ± 0.64D; P < 0.001). In the minimum-residual refractive astigmatism group, the changes of corneal astigmatism before and after surgery were not significant. Moreover, total aberration and second astigmatism in ocular aberration were lower in the minimum-residual refractive astigmatism group compared with the steep-axis group (1.86 ± 1.09 vs 1.37 ± 0.95; P = 0.035 and 0.47 ± 0.28 vs 0.31 ± 0.19; P = 0.015, respectively). CONCLUSION: Minimum-residual refractive astigmatism incision had better astigmatism correction and more accurate prediction. The corneal astigmatism was stable 1 month after surgery. It might lead to better visual quality in the early postoperative stage. Trial registration number for prospectively registered trials: clinicaltrials.gov NCT04006912, 07/02/2019.

Multidisciplinary Team Led by Joint Surgeons to Rapidly Identify Spondyloarthritis.

Context: Spondyloarthritis (SpA) is a group of chronic, inflammatory, rheumatic diseases of which axial SpA and peripheral SpA are the two main types. Patients that predominantly have manifestations of axSpA may have additional peripheral-arthritis symptoms, and vice versa. For these hard-to-diagnose SpA patients, symptoms can be nonspecific and difficult to identify, making it easy to miss a diagnosis or misdiagnosis patients, resulting in disability. Objective: The study intended to evaluate the value of a multidisciplinary team (MDT) led by the joint surgeons to rapidly identify spondyloarthritis (SpA). Design: The research team designed a controlled study that analyzed the clinical data of patients with spondyloarthritis. Setting: The study was conducted in the Department of Joint Surgery at Shandong Second Provincial General Hospital in Jinan, China. Participants: Participants were 113 SpA patients at the hospital between January 2019 and January 2020. Intervention: he research team divided participants into an intervention group, the MDT group that used that model to diagnose 83 participants and the control group with 30 participants, for whom diagnoses occurred using the conventional diagnostic model. Outcome Measures: The research team collected data on participants' number of visits and number of departments visited as well as determined the amount of time that elapsed before a diagnosis occurred. The team also measured C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) at baseline and after 3 months and 6 months treatment. Results: In the MDT group, diagnoses included: (1) axial SpA (axSpA)-73 participants, and (2) peripheral SpA-10 participants, including three with reactive arthritis, two with uveitis, and five with psoriatic arthritis. Eight participants in that group were HLA-B27 positive, and 14 had complications from a latent tuberculosis infection. In the control group, diagnoses included: (1) axSpA-25 participants; and (2) peripheral SpA-5 participants, including three with psoriatic arthritis and two with reactive arthritis. Six participants in that group were HLA-B27 positive and four had complications from a latent tuberculosis infection. The number of visits, number of departments visited, and time to diagnosis in the MDT group were significantly lower than those in the control group (P < .001). After three and six months of treatment, the MDT group's CRP, ESR, BASDAI, and BASFI were significantly lower than those at baseline (P < .001). Conclusions: The MDT model of spondyloarthritis led by joint surgeons was accurate and efficient, allowing the medical personnel to quickly identify and intervene in SpA and provide effective treatment for patients. It's a diagnosis and treatment model worthy of promotion.

Efficacy of scleral-fixated 3-looped haptics intraocular lens implantation for surgical management of microspherophakia.

AIM: To evaluate the safety and efficacy of scleral-fixated 3-looped haptics intraocular lens (IOL) implantation for surgical management of microspherophakia. METHODS: A retrospective case series include 10 microspherophakic patients (15 eyes) who underwent lens removal plus a modified surgical treatment of scleral-fixated 3-looped haptics IOL implantation. The primary outcomes involved visual acuity, intraocular pressure (IOP). Secondary outcomes were spherical equivalent (SE), anterior chamber depth (ACD), corneal endothelial cell density and postoperative complications. RESULTS: After a postoperative follow-up of 17.60±15.44mo, improved visual outcomes can be observed. The uncorrected distance visual acuity (UCVA) logMAR improved from 1.54±0.59 preoperatively to 0.51±0.35 postoperatively (P=0.001), and best corrected visual acuity (BCVA) logMAR improved from 0.97±0.91 preoperatively to 0.24±0.23 postoperatively (P=0.003). Moreover, the SE decreased from -9.58±7.47D preoperatively to -0.65±2.21 D postoperatively (P<0.001). In terms of safety profile, the average IOP decreased from 21.10±12.94 mm Hg preoperatively to 14.03±3.57 mm Hg postoperatively (P=0.044), and the previously elevated IOP of three eyes decreased to the normal range. The ACD increased from 2.25±1.45 mm preoperatively to 3.35±0.39 mm postoperatively (P=0.017). The density of corneal endothelial cells did not change significantly after surgery (P=0.140). The posterior chamber IOLs were well centered and no severe complications were found. CONCLUSION: Lens removal plus the modified surgical treatment of scleral-fixated 3-looped haptics IOL implantation can help in improvement of visual acuity, which can be regarded as a relative safe method for the surgical management of microspherophakia.

Artemether attenuates renal tubular injury by regulating iron metabolism in mice with streptozotocin-induced diabetes.

OBJECTIVES: Renal tubular injury plays an important role in the progression of diabetic kidney disease. Previous studies demonstrated that artemether, an antimalarial agent, exerts renal tubular protection in diabetes. However, the detailed mechanisms remain unclear. Several studies have indicated that disorders of iron metabolism have a great impact on renal tubular injury. Therefore, this study was performed to explore whether the therapeutic effects of artemether on diabetic renal tubular injury are related to iron metabolism. METHODS: Male C57BL/6 J mice were randomly divided into three groups. Mice in the type 1 diabetic (T1D) control and streptozotocin (STZ) groups were fed a regular diet; mice in the STZ plus artemether (STZ+Art) group were treated with artemether. RESULTS: Artemether significantly reduced the urinary albumin:creatinine ratio and tubular injury in mice with T1D. Artemether also restored the energy imbalance and restored the changes of mitochondrial cristae in mice with T1D. Increased protein and mRNA levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were observed in renal tubules of diabetic mice. In response to iron overload, levels of iron transport-related proteins and the antioxidant system related to iron metabolism were abnormal in diabetic mice. Artemether significantly restored the protein and mRNA expression levels of both FTH and FTL. Both the iron transport and antioxidant systems were also restored by artemether to varying degrees. CONCLUSIONS: Artemether attenuates renal tubular injury in diabetic mice; this effect might be related to its regulation of iron metabolism.

Imaging manifestations of juvenile hyaline fibromatosis: a case report and literature review.

Objective: Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition caused by a mutation in capillary morphogenesis gene 2 (CMG2) on chromosome 4q21. JHF is an extremely rare genetic disorder, and fewer than a hundred cases have been reported worldwide. In this case report, the clinical features, histopathological features and imaging manifestations of a case of JHF are presented. We present imaging manifestations of one case of JHF to deepen the radiologist's understanding of this condition. The histopathological feature of JHF is hyaline degeneration involving skeletal muscle. Therefore, the lesion has a slightly high density on CT imaging, iso- or hypointense signal on T 1WI and hypointense signal on T 2WI. The boundary between the lesion and skeletal muscle is unclear. Methods: An 8-year-old male (Case 1) was examined in our department with a complaint of multiple masses on the head, neck and back in 2021. The boy was the only child of his parents and was delivered at 40 weeks gestation by caesarean section. His parents were non-consanguineous. Results: JHF displays multiple slowly or rapidly growing subcutaneous nodules. The imaging manifestations can reflect histopathological components, including nodular connective tissue and amorphous, partially calcified hyaline material.

Morphological features of 52 cases of breast phyllodes tumours with local recurrence.

Typical phyllodes tumours (PTs) of the breast are fibroepithelial neoplasms characterised histologically by stromal hypercellularity and leaf-like structures. However, morphological changes may be atypical in some cases, increasing the difficulty of diagnosis and the likelihood of misdiagnosis. To provide more morphological clues for pathological diagnosis of PTs, we retrospectively analysed 52 PT cases with typical morphological features after recurrence, and summarized the clinicopathological characteristics of the paired primary tumours. We found five special histological features in the primary tumours distinct from classic PTs, namely (1) PTs with epithelioid feature (three cases); (2) PTs with gland-rich feature (eight cases); (3) PTs with fibroadenoma-like feature (20 cases); (4) PTs with myxoid fibroadenoma-like feature (five cases); and (5) PTs with pseudohemangiomatoid stromal hyperplasia-like feature (four cases). All the features can exist independently, and a few cases displayed more than two distinctive features at the same time. In this cohort of recurrent PTs, all the primary tumours were absent of recognisable stromal hypercellularity and leaf-like structures that are the critical diagnostic criteria of PTs; however, they showed some other non-classic characteristics which may provide significant clues for the diagnosis of PTs. Particularly, tumours with epithelioid feature displayed high grade at earlier stages, tumours with fibroadenoma-like feature were most likely to be confused with classical fibroadenomas, and tumours with myxoid feature were prone to be neglected because of their hypocellularity.

Magnetic resonance imaging assessment of the therapeutic effect of combined electroacupuncture and stem cells in acute peripheral nerve injury.

Objectives: This study aimed to evaluate the therapeutic effect of a combination of Bone Mesenchymal stem cells (BMSCs) transplantation and Electroacupuncture (EA) for acute sciatic nerve injury in rats using magnetic resonance. Methods: Ninety-two male adult healthy Sprague-Dawley rats were randomly divided into the EA+BMSCs group, EA group, MSCs group, and PBS group (control). Electroacupuncture was performed on a rat receiving EA treatment at Huantiao (GB30) and Zusanli (ST36). T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunohistochemistry was used to monitor nerve regeneration. Walking track analysis was used to assess nerve functional recovery. Repeated-measures one-way analysis of variance was used to evaluate the significance of T2, DTI, and SFI values among the four groups. One-way analysis of variance was used for comparing the histological characteristics. Bonferroni test was used for multiple pairwise comparisons at each time point. Results: In terms of FA, the EA+BMSCs and EA groups had faster recovery than PBS (control) in all time points after surgery, and the EA+BMSCs group recovered better than the BMSCs group at 3 weeks (P ≤ 0.008). FA values were higher in the EA group than in the BMSCs group at 4 weeks (P ≤ 0.008). In terms of RD, the EA+BMSCs group recovered better than the BMSCs group at 2 and 4 weeks (P ≤ 0.008). Immunofluorescence staining for axon guidance molecule netrin-1 revealed that it was significantly higher in the EA+BMSCs subgroup and EA subgroup than it was in the control (PBS) subgroup at 1-3 weeks (P < 0.001). Immunofluorescence staining for S100 showed the continuity of nerve fibers recovered more quickly in the EA+BMSCs subgroup than in the BMSCs subgroup. Conclusion: Our research revealed that a combination of MSCs and EA can provide both topological and biomolecular guidance to promote axonal extension, myelin regeneration, and functional recovery after PNI. EA not only promotes nerve repair on its own, but also enhanced the beneficial effects of stem cell treatment and the secretion of netrin 1, a guidance regeneration factor, and promotes the orderly growth of nerve fibers. These PNI repairs could be monitored non-invasively and in situ by MRI. The FA and RD values derived from MRI could be sensitive biomarkers to reflect the PNI repair process.

Etiology of granulomatous lobular mastitis based on metagenomic next-generation sequencing.

OBJECTIVES: We aimed to comprehensively explore the etiology of granulomatous lobular mastitis (GLM) to optimize treatment programs. METHODS: We collected 30 fresh mastitis samples for metagenomic next-generation sequencing, morphological observation, and analysis of the clinical information. RESULTS: Of the 30 samples, 25 were GLM; pathogens were detected in 17, these were: Corynebacterium kroppenstedtii (10 of 25, 40%); C. kroppenstedtii and Pseudomonas oleovorans (3 of 25, 12%); C. kroppenstedtii and human gammaherpesvirus 4 (1 of 25, 4%); Acinetobacter baumannii and C. kroppenstedtii (1 of 25, 4%); P. oleovorans (1 of 25, 4%); and Tepidiphilus thermophilus (1 of 25, 4%). Abnormal sex hormone levels (mainly prolactin) and/or autoimmune function were found in 12 of the 25 samples. Lipophilic antibiotics (rifampicin) were found to work effectively in patients with slow-healing wounds after surgery. CONCLUSIONS: The main pathogenic factor of GLM is C. kroppenstedtii infection, but other unusual pathogens (P. oleovorans, human gammaherpesvirus 4, A. baumannii, T. thermophilus) are likely to be closely related to GLM, particularly human gammaherpesvirus 4 (Epstein-Barr virus)-associated mastitis, which may be a new entity of mastitis. Abnormal levels of sex hormones and autoimmune function are also common causes. Therefore, lipophilic antibiotics (rifampicin) and prolactin inhibitors may be an effective treatment.

Efficacy of bandage contact lens for the management of dry eye disease after cataract surgery.

PURPOSE: We aimed to evaluate the efficacy of bandage contact lens (BCL) for the management of dry eye disease (DED) after cataract surgery. METHODS: A total of 120 patients (140 eyes) with age-related cataract and DED were enrolled in this study. Patients underwent standard micro-incision phacoemulsification surgeries and were divided into control or BCL groups. Slit-lamp biomicroscopic examination, Ocular Surface Disease Index, keratograph analysis and Schirmer I test were executed, and the levels of tear inflammatory molecules were detected. RESULTS: In the control group, the NIAvg-BUT and Schirmer I test scores were significantly decreased at 1 week post-operation compared with baseline levels (P = 0.035 and P = 0.009, respectively). In the BCL group, the NIF-BUT and Schemer I test scores were significantly improved at 1 month after operation compared with the control group (P = 0.012 and P < 0.001, respectively). Levels of IL-6, IL-8 and ICAM-1 were significantly increased in the control group at 1 month after the operation (P = 0.005, P = 0.038 and P = 0.022, respectively), while there was no difference in the BCL group. The increase in the IL-6 level in the control group was significantly higher compared with that in the BCL group (P = 0.047). In DED patients, there were significant correlations between ocular surface parameters and inflammatory molecules. CONCLUSIONS: Cataract surgery could lead to the development or worsening of DED. The application of BCLs after cataract surgery could stabilize the ocular surface and tear film, improve the corneal healing and reduce the inflammation. Collectively, our findings suggested that proper use of BCLs after cataract surgery played an effective role in the management of DED. TRIAL REGISTRATION: ClinicalTrials, NCT04100031. Registered 18 September 2019-retrospectively registered.

Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma.

Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.

Diagnosis and treatment of microspherophakia.

As a rare congenital disease, microspherophakia (MSP) is characterized by small and spherically shaped crystalline lenses. The common complications of MSP include secondary glaucoma and crystalline lens dislocation or subluxation. Patients with MSP often show high lenticular myopia. The special morphological characteristics and complex complications bring challenges to the treatment of patients with MSP. Although there are some studies on MSP, most are case reports. In this article, the morphological characteristics, complications, genetic diagnosis, and treatment of MSP were systematically reviewed, providing valuable insight into the clinical diagnosis and treatment of this disease.

Early-stage clinical outcomes and rotational stability of TECNIS toric intraocular lens implantation in cataract cases with long axial length.

BACKGROUND: A major focus of toric intraocular lens (IOL) implantation is the rotational stability, especially in the patients with long axial length (AL). In this study, we aimed to evaluate the clinical outcomes after implantation of TECNIS toric IOL in eyes with long AL and identify factors influencing their early-stage stability with preoperative corneal astigmatism. METHODS: The study population consisted of 64 eyes from 52 cataract patients, and these patients had preoperative corneal astigmatism between 1.0 and 3.7 diopters (D) and underwent phacoemulsification and TECNIS toric IOL implantation. Ophthalmic biological measurements were carried out preoperatively, including AL, anterior chamber depth (ACD), lens thickness (LT), vitreous length (VL), anterior chamber volume (ACV), sulcus-to-sulcus (STS) and keratometric value (K). Clinical examinations, including visual acuity, manifest refraction, keratometry, digital anterior segment photographs with pupillary dilation, were performed at 1 and 3 months after surgery. RESULTS: The mean best corrected distance visual acuity (BCDVA) was improved from 0.93 ± 0.35 logarithms of the minimal angle of resolution (logMAR) preoperatively to 0.07 ± 0.10 logMAR postoperatively at 3 months after surgery. The mean residual astigmatism (RAS) was 0.91 ± 0.74D at 3 months, which was significantly decreased compared with the preoperative corneal astigmatism of 1.71 ± 0.55 D. The mean absolute rotation of TECNIS toric IOL at 1 and 3 months was 7.42 ± 11.32 degree (°) (0-79°) and 7.48 ± 11.19°(0-79°), respectively. The mean area of capsulorhexis and the overlapped area between capsulorhexis and IOL optic intraoperatively was 21.04 ± 3.30 mm2 and 7.40 ± 2.87 mm2.A positive correlation was found between IOL rotation and the area of capsulorhexis (p = 0.017) at 3 months after surgery. No correlation was found between IOL rotation and AL (p = 0.876), ACD (p = 0.387), LT (p = 0.523), VL (p = 0.546), ACV (p = 0.480), STS (p = 0.884), K1 (p = 0.429), K2 (p = 0.644), average of K1 and K2 (p = 0.520), intraoperative IOL axial direction (p = 0.396), preoperative corneal astigmatism (p = 0.269) or the overlapped area between capsulorhexis and IOL optic intraoperatively (p = 0.131) . CONCLUSIONS: The large CCC was a risk factor for toric IOL rotation. An appropriately smaller sized CCC was conducive to increase the rotational stability of TECNIS toric IOL implantation in cataract cases with long AL.

Vitamin D Deficiency Is Associated With Metabolic Risk Factors in Women With Polycystic Ovary Syndrome: A Cross-Sectional Study in Shaanxi China.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women at reproductive age, which is characterized by obesity, hyperandrogenemia, and insulin resistance (IR). This study aimed to investigate the vitamin D status, and analyze the relationship between vitamin D deficiency and metabolic risk factors in PCOS women in Shaanxi China. Methods: A cross-sectional study included 169 women diagnosed with PCOS and 114 control women without PCOS. The serum 25(OH)D and metabolic markers were measured. Vitamin D deficiency was defined as serum 25(OH)D concentration less than 20 ng/mL. The primary outcome was the difference in vitamin D status between the PCOS and control groups, the secondary outcomes were correlations between serum 25(OH)D concentration and metabolic risk factors in women with PCOS. Results: The serum 25(OH)D concentration was significantly lower in women with PCOS than in controls (P < 0.05), and the prevalence rates of 25(OH)D deficiency and insufficiency were significantly higher in women with PCOS than in controls (P < 0.05). The serum 25(OH)D concentration was significantly lower in PCOS women with obesity or IR than in women without obesity or IR (P < 0.05), and the prevalence of 25(OH)D deficiency in PCOS women with obesity or IR was significantly higher than in women without obesity or IR (P < 0.05). Serum 25(OH)D concentration was significantly negatively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP) (P < 0.05). In comparison, serum 25(OH)D concentration was significantly positively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Increased BMI and WHR, high levels of fasting insulin, HOMA-IR, total cholesterol, LDL-C and hs-CRP were regarded as risk factors, but high level of HDL-C was considered to be protective factor of vitamin D deficiency in PCOS women. Conclusions: Vitamin D deficiency is prevalent in PCOS women in Shaanxi China, especially in those with obesity and IR. The serum 25(OH)D level was correlated with metabolic risk factors in PCOS women. Multi-center randomized controlled trials with large sample sizes are needed to probe the metabolic effect of vitamin D supplementation in PCOS women.

[DNA hypomethylation in villi of patients with unexplained recurrent spontaneous abortion and its mechanism].

Objective To explore the genome-wide DNA methylation level and the expression of DNA methylation-related enzymes in the villi tissue of patients with unexplained recurrent spontaneous abortion (URSA). Methods The villi samples were obtained from thirty-one URSA patients (URSA group) and thirty pregnancy women who underwent induced abortion (control group). Total DNA methylation was determined by ELISA. Real-time quantitative PCR was used to detect mRNA levels of DNMT1, DNMT3a, DNMT3b, TET1, TET2 and TET3, and Western blot analysis was used to detect protein levels of DNMT1, DNMT2, DNMT3, TET1, TET2 and TET3. Immunohistochemistry was performed to detect the expression and distribution of DNMT1, DNMT3a, DNMT3b, TET1, TET2 and TET3 in villi tissues. Results Methylation level of total DNA in the URSA group was significantly lower than that of the control group. Compared with the control group, mRNA and protein expression levels of DNMT1 and DNMT3b significantly decreased, while TET1 and TET2 significantly increased in the villi of the URSA group. Conclusion The methylation level is reduced in the villi of URSA women, which may be correlated with up-regulated expression of DNMT1 and DNMT3b and down-regulated expression of TET1 and TET2.