Correction to: Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

[This corrects the article DOI: 10.14740/wjon1817.].

Knockdown of HSPA13 Inhibits TGFß1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.

Purpose: This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms. Methods: HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFß1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition. Results: HSPA13 was found in human ERMs and its expression increased with TGFß1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFß1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFß1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFß1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFß1-induced RPE cells. Conclusions: Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFß1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.

An immune-related eleven-RNA signature-drived risk score model for prognosis of osteosarcoma metastasis.

This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan-Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.

SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia.

BACKGROUND: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear. RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway. CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).

Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

Background: Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management. Methods: A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines. Conclusion: These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

A comprehensive stem cell laboratory module with blended learning for medical students at Tongji University.

The laboratory practice "Primary culture and directional differentiation of rat bone marrow mesenchymal stem cells (BMSCs)" is part of a required course for sophomore medical students at Tongji university, which has been conducted since 2012. Blended learning has been widely applied in medical courses. Based on a student-centered teaching philosophy, we reconstructed a comprehensive stem cell laboratory module with blended learning in 2021, aiming to facilitate students in enhancing their understanding of the multi-lineage differentiation potential of stem cells and improve their experimental skills, self-directed learning ability, and innovative thinking. First, we constructed in-depth online study resources, including videos demonstrating laboratory procedures, a PowerPoint slide deck, and published literature on student self-learning before class. In class, students performed a primary culture of BMSCs, freely chose among adipogenic, osteogenic, or chondrogenic differentiation, and used cytochemical or immunofluorescence staining for identification. After class, the extracurricular part involved performing quantitative polymerase chain reaction to examine the expression of multi-lineage differentiation marker genes, which was designed as an elective. After 2 years of practice, positive feedback was obtained from both students and faculty members who achieved, the learning goal as expected. The reconstructed stem cell laboratory module provides comprehensive practice opportunities for students. Students have a better understanding of BMSC at the molecular, cellular, and functional levels and have improved their experimental skills, which forms a basis for scientific research for medical students. Introducing blended learning into other medical laboratory practices thus seems valuable.

Amniotic membrane transplantation combined with conjunctival flap covering surgery for the treatment of corneal perforations in fungal keratitis.

Purpose: To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations in fungal keratitis (FK). Methods: In this non-comparative, retrospective case series, 16 participants of corneal perforation in FK were successfully treated by a combination of multilayer AMT and bipedicle conjunctival flap with partial tenon's capsule. Corneal healing, recurrence of FK, visual acuity, and relevant complications were reported as outcome measures. Results: Sixteen patients (13 male, 3 female) had a mean age of 58.8 ± 10.3 (range 29-72) years. The mean diameter of corneal perforation was 1.9 ± 0.7 (range 0.5-2.8) mm. Corneal perforations healed and all the patients preserved their eyeballs. During the 11.0 ± 4.4 (range 6-18) months of follow-up, there was no recurrence of FK in any of these cases. Visual acuity improved in 15 eyes (93.8 %) and remained unchanged in 1 patient (6.3 %) who had no light perception when first admitted. All 6 patients who accepted secondary keratoplasty showed improved best corrected visual acuity of more than 4 lines. The most frequently found fungi were Aspergillus species (6 of 16, 37.5 %) and Fusarium species (4 of 16, 25.0 %), followed by 1 Scedosporium apiospermum (1 of 16, 6.3 %). Conclusions: Combination AMT with CFCS is a safe and effective surgery for patients with corneal perforations in FK, particularly where eye banks and fresh corneas are not available. This surgery could preserve the integrity of the eyeball and avoid the recurrence of FK. Besides, it provides a greater opportunity for further optical keratoplasty.

Conjunctival Limbal Autograft Combined with Amnion-Assisted Conjunctival Epithelial Redirection for Unilateral Total Limbal Stem Cell Deficiency after Severe Chemical Burn.

(1) Background: To evaluate the efficacy of conjunctival limbal autograft (CLAU) combined with the amnion-assisted conjunctival epithelial redirection (ACER) procedure for patients with unilateral total limbal stem cell deficiency (LSCD) caused by severe chemical burn. (2) Methods: A retrospective interventional case series of unilateral total LSCD after chemical burn who underwent CLAU combined with ACER surgery between September 2021 and July 2023 was collected. Outcome measures included epithelialization of the cornea with donor limbus-derived epithelium, best corrected visual acuity (BCVA), and complications. (3) Results: Nine males and one female were included in this study. The mean age was 40.9 ± 9.63 (range, 26 to 55) years. The average duration between injury and CLAU combined with the ACER procedure was 7.67 ± 3.97 (range, 4 to 18) months. All patients achieved corneal epithelialization and improved BCVA. Postoperative complications occurred in four cases, including delayed corneal epithelial healing in one case, delayed amniotic membrane dissolution and detachment in two cases, and recurrence of symblepharon in one case. No complications were noted in the healthy donor eyes. (4) Conclusions: CLAU combined with ACER is a safe and effective treatment for unilateral total LSCD caused by severe chemical burn. This combined surgery restores visual function for patients with corneal blindness caused by chemical burn, reducing the burden on the families and society.

Histone crotonylation of peripheral blood mononuclear cells is a potential biomarker for diagnosis of colorectal cancer.

BACKGROUND: Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC). RESULTS: Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays. CONCLUSIONS: The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.

Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study.

OBJECTIVES: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS: This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).

Characteristics of mesenchymal stem cells and their exosomes derived from giant panda (Ailuropoda melanoleuca) endometrium.

Conservation of genetic resources is an important way to protect endangered species. At present, mesenchymal stem cells (MSCs) have been isolated from the bone marrow and umbilical cords of giant pandas. However, the types and quantities of preserved cell resources were rare and limited, and none of MSCs was derived from female reproductive organs. Here, we first isolated MSCs from the endometrium of giant panda. These cells showed fibroblast morphology and expressed Sox2, Klf4, Thy1, CD73, CD105, CD44, CD49f, and CD105. Endometrium mesenchymal stem cells (eMSCs) of giant panda could induce differentiation into three germ layers in vitro. RNA-seq analysis showed that 833 genes were upregulated and 716 genes were downregulated in eMSCs compared with skin fibroblast cells. The results of GO and the KEGG analysis of differentially expressed genes (DEGs) were mainly focused on transporter activity, signal transducer activity, pathways regulating pluripotency of stem cells, MAPK signaling pathway, and PI3K-Akt signaling pathway. The genes PLCG2, FRK, JAK3, LYN, PIK3CB, JAK2, CBLB, and MET were identified as hub genes by PPI network analysis. In addition, the exosomes of eMSCs were also isolated and identified. The average diameter of exosomes was 74.26 ± 13.75 nm and highly expressed TSG101 and CD9 but did not express CALNEXIN. A total of 277 miRNAs were detected in the exosomes; the highest expression of miRNA was the has-miR-21-5p. A total of 14461 target genes of the whole miRNAs were predicted and proceeded with functional analysis. In conclusion, we successfully isolated and characterized the giant panda eMSCs and their exosomes, and analyzed their functions through bioinformatics techniques. It not only enriched the conservation types of giant panda cell resources and promoted the protection of genetic diversity, but also laid a foundation for the application of eMSCs and exosomes in the disease treatment of giant pandas.

Two-step strategy-conjunctival flap covering surgery combined with secondary deep anterior lamellar keratoplasty for the treatment of high-risk fungal keratitis.

AIM: To investigate whether the two-step strategy [conjunctival flap covering surgery (CFCS) combined with secondary deep anterior lamellar keratoplasty (DALK)] is effective for patients with high-risk fungal keratitis (FK). METHODS: In this noncomparative, retrospective case series, 10 subjects (6 males, 4 females) with a mean age of 56.5±7.1 (range 47-72)y with high-risk FK undergone the two-step strategy were included. Reported outcome measures were healing of the corneal ulcer, recurrence of FK, reject reaction, improvement in best corrected visual acuity (BCVA) and relevant complications. RESULTS: The average diameter of corneal infiltrates was 7.50±0.39 mm, ranging from 6.94 to 8.13 mm. The mean depth of corneal infiltrates was 422.4±77.1 µm, ranging from 350 to 535 µm. The mean corneal thickness was 597.4±117.3 µm, ranging from 458 to 851 µm. Hypopyon and endothelial plaques were presented in all patients. The period between the two steps was 3.65±0.9 (ranging from 3 to 5)mo. The graft diameter was 7.75±0.39 mm. At the last follow-up (average 9.25±3.39, ranging from 5.5 to 17mo), no fungal recurrence or graft rejection appeared, and all patients showed improvement of BCVA. One patient suffered from liver function impairment due to oral voriconazole for 4wk and recovered spontaneously after 1wk of drug withdrawal. CONCLUSION: The two-step strategy is safe and effective in the treatment of high-risk FK by transforming intentional therapeutic penetrating keratoplasty during acute infection to later optical DALK. It is a practical strategy, especially in areas lacking fresh donor corneas and eye bank services.

The inhibition of p38 MAPK blocked inflammation to restore the functions of rat meibomian gland epithelial cells.

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1ß (IL-1ß) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1ß to identify inflammation levels. RMGECs were exposed to IL-1ß and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1ß was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1ß inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor γ (PPARγ) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1ß. SB203580 effectively diminished the effects of IL-1ß on differentiation, keratinization, and MMP9 expression by blocking IL-1ß-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1ß-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD.

Ultrasound assistance in treatment with elastic stable intramedullary nail fixation in radial and ulnar fractures in children.

PURPOSE: Radial and ulnar fractures are one of the most common fractures in children. When closed reduction of fractures fails, elastic stable intramedullary nail (ESIN) fixation can mostly be used under the guidance of fluoroscopy. In this study, we evaluated the effect of ultrasound (US) as assistance for radial and ulnar fracture reduction and the insertion of ESINs. METHODS: There were 56 patients with midshaft radial and ulnar fractures included in our hospital from March 2019 to August 2021. After applying the inclusion and exclusion criteria and according to the treatment method, they were divided into the US group (patients treated with US assistance) and the conventional group (C-group, patients treated with fluoroscopy guidance). All patients' clinical data were collected. Operation time, fluoroscopy times, radiation dose, and post-operative complications were analyzed. The elbow function was evaluated using the Mayo Elbow Performance Index. RESULTS: There were 26 patients in the US group and 30 in the C-group. The average operation time was 44.5±19.4 min in the US group and 65.1±16.2 min in the C-group. There were significant differences regarding the surgery time, fluoroscopy time, and radiation dose between the groups (all p = 0.001). The average follow-up time was 13.5±3.1 months. No significant difference was found regarding radial nerve injury, extensor pollicis longus rupture, non-union or delayed union, ulnar nerve injury, or acute compartment syndrome. There was no difference in elbow function at the final follow-up. CONCLUSION: US guidance can be adopted for the treatment of displaced radial and ulnar fracture reduction and the insertion of ESINs. It can significantly decrease fluoroscopy times, radiation doses, and duration of surgery.

The galU gene is required for in vivo survival of pseudomonas plecoglossicida in large yellow croaker (Larimichthys crocea).

Pseudomonas plecoglossicida is an important pathogenic bacterium in aquaculture that causes visceral granulomas in large yellow croaker (Larimichthys crocea). Uridine diphosphate glucose phosphorylase encoded by galU plays a key role in biosynthesis of the bacterial envelope, particularly lipopolysaccharide and the capsule. In this study, we inactivated the galU gene in the P. plecoglossicida isolate XSDHY-P. The galU mutant strain showed impaired growth in the early exponential stage and lacked the O polysaccharide side chain in lipopolysaccharide, but almost no defect in biofilm formation was detected. The galU mutant strain also exhibited significantly more sensitivity to the bactericidal action of normal fish serum mediated by the complement system compared to the wild-type strain. In a cell model originating from the head kidney of large yellow croaker, the galU mutant strain showed lower capacities of adhesion, invasion, and intracellular survival compared to the wild-type strain. In addition, the deficiency of the galU mutant drastically decreased bacterial loads in tissues and attenuated P. plecoglossicida virulence in fish. These results suggest that the galU gene of P. plecoglossicida is required for in vivo survival in large yellow croaker.

Retraction Notice to: Inflammatory-Related P62 Triggers Malignant Transformation of Mesenchymal Stem Cells through the Cascade of CUDR-CTCF-IGFII-RAS Signaling.

[This retracts the article DOI: 10.1016/j.omtn.2018.03.002.].

Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) Transplantation for Recurrent Pterygium with Restrictive Strabismus.

(1) Background: This study aimed to evaluate the clinical outcome of Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) transplantation for recurrent pterygium with restrictive strabismus. (2) Methods: This retrospective study included 11 eyes in 11 patients diagnosed with recurrent pterygium with restrictive strabismus who received sandwich transplantation. The outcomes were measured by pterygium recurrence, best-corrected visual acuity, esotropia (prism diopters), and treatment complications. (3) Results: Eleven patients (six males, five females) had a mean age of 60.5 (range 36-80) years. The previously received pterygium excision surgery number was 1.8 ± 1.02 (range 1-4). The mean follow-up period was 19.9 ± 8.41 (range 12-36) months. All patients had a restriction of abduction in the previously operated eye, causing esotropia in the primary position. Pre-operative esotropia was 17.2 (range 10-30) prims diopter (PD). Five eyes (45.5%) had symblepharon before surgery. All patients were orthotropic until the last follow-up. Symblepharon was released in all eyes. Free ocular motility was present in all eyes. No donor site scar formation, scleral melt, or corneal ulcer was noted. (4) Conclusions: Sandwich transplantation for recurrent pterygium with restrictive strabismus is safe and effective.

Comparison of transcriptome profiles of mesenchymal stem cells derived from umbilical cord and bone marrow of giant panda (Ailuropoda melanoleuca).

Mesenchymal stem cells (MSCs) have pluripotent differentiation ability and play an important role in human clinical cell therapy. While, the research on MSCs in endangered wild animals is extremely rare. In our previous studies, the bone marrow mesenchymal stem cells (bmMSCs) and umbilical cord mesenchymal stem cells (ucMSCs) of giant panda (Ailuropoda melanoleuca) were successfully isolated. We aimed to characterize the differences in gene expression profiles between these two types of MSCs using RNA sequencing (RNA-Seq) and to determine which potential pathways are involved in functional regulation. In total, 1079 significantly differentially expressed genes (DEGs) were identified, of which 478 genes were upregulated and 601 genes were downregulated. The significantly enriched Gene Ontology (GO) terms mainly contained cell adhesion, biological adhesion, intracellular signal transduction, molecular function regulator, Ras protein signal transduction, small GTPase mediated signal transduction, and regulation of Rho protein signal transduction. The most enrichment pathways of DEGs enriched in Kyoto Encyclopedia of Genes Genomes (KEGG) were PI3K-AKT signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, Hippo signaling pathway, Wnt signaling pathway, cGMP-PKG signaling pathway and Signaling pathways regulating pluripotency of stem cells. In addition, quantitative real time polymerase chain reaction (qRT-PCR) showed that the AKT3, CDK2, MAPK3, mTOR, PI3K and PTK2 genes associated with PI3K-AKT pathway were highly expressed (P < 0.01), and Caspase-3 was low expressed (P < 0.05) in ucMSCs group when compared with bmMSCs. After treatment with the PI3K inhibitor LY294002, genes AKT3, CDK2, MAPK3, mTOR, and PTK2 were significantly decreased in ucMSCs (P < 0.01), and Caspase-3 was significantly up regulated (P < 0.001). In conclusion, we for the first time compared and analyzed the transcriptome profiles of giant panda ucMSCs and bmMSCs, and found the PI3K-AKT pathway was highly activated and might be a key signaling pathway in the ucMSCs regulation. This study will be beneficial for the research on MSCs proliferation regulation and differentiation of giant pandas in the future, and lay the foundation for MSCs application and clinical therapy for endangered wild animals.

Topical Chemotherapy for Treating Ocular Surface Squamous Neoplasia with a Combination of Interferon α-2b and 5-Fluorouracil.

INTRODUCTION: This study evaluated the efficacy of combined interferon α-2b (IFNα2b) and 5-fluorouracil (5-FU) as primary treatment for ocular surface squamous neoplasia (OSSN). METHODS: In this retrospective study, 27 eyes with OSSN followed by topical application of combined IFNα2b and 5-FU were examined. Reported outcome measures were tumor response, visual acuity, time to complete resolution, recurrence and treatment complications. RESULTS: Twenty-six patients (17 male, 9 female) had a mean age of 63.9 (median, 67; range 22-83) years. Complete tumor response was observed in 24 eyes (88.9%). Three eyes (11.1%) showed partial response to the chemotherapy agents and later underwent surgical tumor removal. The median time to complete resolution was 6 (mean, 6.1; range, 3-11) weeks. Of these, the patients received between one to three cycles of 5-FU therapy (median, 2; mean, 1.8). Complications noted were transient irritation at 5-FU cycle (11 eyes, 40.7%). There was no tumor recurrence at mean follow-up of 16.1 (median, 12; range 6-38) months. CONCLUSIONS: Combination therapy of IFNα2b and 5-FU was a safe and effective treatment, inducing a short duration of administration and low recurrence rate for OSSN. TRIAL REGISTRATION: Retrospectively registered, UHCT22048.

Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis.

PD-L1 is a ligand for PD-1, and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. In this study, PD-L1 expression correlated negatively with rates of apoptosis in human neutrophils harvested from patients with sepsis. Coimmunoprecipitation assays on control neutrophils challenged with interferon-γ and LPS showed that PD-L1 complexes with the p85 subunit of phosphatidyl 3-kinase (PI3K) to activate AKT-dependent survival signaling. Conditional CRE/LoxP deletion of neutrophil PD-L1 in vivo further protected against lung injury and reduced neutrophil lung infiltration in a cecal ligation and puncture (CLP) experimental sepsis animal model. Compared with wild-type animals, PD-L1-deficient animals presented lower levels of plasma tumor necrosis factor-α and interleukin-6 (IL-6) and higher levels of IL-10 after CLP, and reduced 7-day mortality in CLP PD-L1-knockout animals. Taken together, our data suggest that increased PD-L1 expression on human neutrophils delays cellular apoptosis by triggering PI3K-dependent AKT phosphorylation to drive lung injury and increase mortality during clinical and experimental sepsis.