Corrigendum: Pre-operative evaluation and mid-term outcomes of anomalous origin of the left coronary artery from the pulmonary artery based on left ventricular ejection fraction.

[This corrects the article DOI: 10.3389/fcvm.2022.961491.].

Comparison of Corneal Endothelial Cell Loss in Femtosecond Laser-assisted Cataract Surgery: Impact on Endothelial Cells in Different Regions.

PURPOSE: To compare changes in corneal endothelial parameters following femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification (CPS) in different corneal regions. SETTING: Chang Gung Memorial Hospital, Linkou, Taiwan, 2018- 2022. DESIGN: Single-center, retrospective. METHODS: Before and 1, 3, and 6 months post-op, specular microscopy was performed to measure endothelial cell density (ECD), corneal thickness, hexagonal cell rate (Hex), and coefficient of variation (CoV). Position 1 referred to the central cornea, Position 2 was nearest to the main wound, and Position 3 was at the peripheral zone diagonal to the main wound. RESULTS: This study analyzed 96 eyes in the FLACS group and 110 eyes in the CPS group. Preoperatively, Position 1 had lower ECD and CoV and higher Hex compared to the peripheral regions. FLACS patients had a significantly less phaco time and cumulative dissipated energy. At one month, FLACS patients showed a significantly smaller increase in corneal thickness at Positions 1 and 2. At 3 months, FLACS patients had lower endothelial cell loss (ECL) at Positions 1 and 3. ECL remained lower in FLACS patients at 6 months. The highest ECL was observed at Position 2 in both groups and was progressive up to 6 months. CONCLUSIONS: Following phacoemulcification, ECL varied in different corneal regions. At 3 months, the FLACS group exhibited significantly less ECL at the central cornea; however, the continued ECL at 6 months near the main wound suggested ongoing endothelial remodeling in the region.

The hiPSC-derived corneal endothelial progenitor-like cell recovers the rabbit model of corneal endothelial dystrophy.

INTRODUCTION: Corneal endothelial dysfunction results in cornea opacity, damaging sightedness, and affecting quality of life. A corneal transplant is the current effective intervention. Due to the scarcity of donated cornea, such an unmet medical need requires a novel therapeutic modality. OBJECTIVES: Customizing patients' corneal endothelial progenitor cells with proliferative activity and lineage restriction properties shall offer sufficient therapeutic cells for corneal endothelial dystrophy. METHODS: The customized induced human corneal endothelial progenitor-like cell (iHCEPLC) was obtained through cell fate conversions starting from PBMC (peripheral blood mononuclear cell), hiPSC (human induced pluripotent stem cell), and hNCC (human neural crest cell), while it finally reached the iHCEPLC state via a series of induction. Several molecular diagnoses were applied to depict its progenitor state, including RNAseq, FlowCytometer, immunostainings, and rtPCR. Significantly, it can be induced to gain differentiation maturity through contact inhibition. In addition, a BAK-mediated rabbit model of corneal endothelial dystrophy was established in the present study to test the therapeutic effectiveness of the iHCEPLC. RESULTS: After inducing cell fate conversion, the specific HCEC markers were detected by rtPCR and immunostaining in iHCEPLC. Further, RNAseq was applied to distinguish its progenitor-like cell fate from primary human corneal endothelial cells (HECE). FlowCytometry profiled the heterogeneity subpopulation, consistently displaying a subtle difference from primary HCEC. A terminal differentiation can be induced in iHCEPLC, addressing its progenitor-like fate. iHCEPLC can restore the BAK-based rabbit model of corneal endothelial dystrophy. Immunohistochemistry verified that such acuity restoration of the BAK-treated cornea is due to the introduced iHCEPLC, and such therapeutic effectiveness is observed in the long term. CONCLUSION: Here, we demonstrated that customized iHCEPLC has long-term therapeutic efficacy. As a progenitor cell, our iHCEPLC has a restricted cell lineage nature and can proliferate in vitro, supporting sufficient therapeutic candidate cells. Due to the immune-privileged nature of the cornea, our iHCEPLC proves the principle of therapeutical feasibility in both autogenic and allogeneic modalities.

A case-crossover study on association between short-term atmospheric NO2 exposure and outpatient visits due to pediatric neurological system conditions in Shijiazhuang / 环境与职业医学

Background Nitrogen dioxide (NO2), a crucial component of traffic pollutants, has been shown in studies to exert toxic effects on the nervous system. However, there is a limited body of research examining the relationship between NO2 exposure and neurological disorders in children. Objective To explore the impact of short-term NO2 exposure on the outpatient visits due to pediatric neurological diseases in Shijiazhuang. Methods From 2013 to 2021, we collected outpatient data related to neurological diseases at the Children's Hospital in Shijiazhuang, Hebei Province. We also collected air pollution data and meteorological data of the same city. The air pollution data included daily average concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), NO2, carbon monoxide (CO), and daily maximum 8-hour average concentration of ozone (O3). The meteorological data comprised daily average atmospheric pressure, temperature, relative humidity, wind speed, and sunshine duration. Employing a time-stratified case-crossover design, we used conditional logistic regression models to analyze the association between NO2 and pediatric outpatient visits for neurological diseases. Stratification analyses were conducted based on gender (male, female) and age groups (0-6 years, 7-14 years). Results The study included a total of 154348 valid pediatric outpatient visits for neurological diseases. The daily average concentration of NO2 was 49.3 μg·m−3 for the study period. The results from the single-pollutant model indicated that NO2 increased the risk of pediatric neurological outpatient visits, with the highest association observed at lag0. Specifically, for every 10 μg·m⁻³ increase in atmospheric NO2 exposure, there was a 1.40% increase (95%CI: 1.05%, 1.74%) in pediatric neurological outpatient visits. The stratification analyses revealed that increased atmospheric NO2 exposure was associated with an elevated risk of neurological outpatient visits for girls (ER=1.54, 95%CI: 1.01, 2.08) and children aged 7-14 years (ER=2.35, 95%CI: 1.68, 3.02). Even after introducing PM2.5 (ER=1.96, 95%CI: 1.49, 2.43), SO2 (ER=2.09, 95%CI: 1.62, 2.55), and O3 (ER=1.40, 95%CI: 1.06, 1.74) to the models, the impact of NO2 exposure on pediatric neurological outpatient visits remained statistically significant. The results of the multi-pollutant model also indicated a significant association (ER=2.53, 95%CI: 1.97, 3.08). Conclusion The effect of short-term exposure to atmospheric NO2 on the outpatient visits of children with neurological diseases in Shijiazhuang is acute and independent, especially for children aged 7-14.

Clinical Observation on the Joint Needling Method Combined with Ultrasound in the Treatment of Patellofemoral Pain Syndrome of Qi Stagnation and Blood Stasis Type / 广州中医药大学学报

Objective To observe the clinical efficacy of joint needling method combined with ultrasound in the treatment of qi stagnation and blood stasis type of patellofemoral pain syndrome(PFPS).Methods Eighty-six patients with qi stagnation and blood stasis type of PFPS were randomly divided into observation group and control group,with 43 cases in each group.The control group was given western medicine conventional treatment combined with functional exercise,and the observation group was given joint needling method combined with ultrasound treatment on the basis of the control group.Both groups were treated for 2 consecutive weeks.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of knee pain and the Kujala scale scores of the two groups were observed before and after treatment.The changes in active range of motion(AROM)of the affected knee joint were compared before and after treatment between the two groups.Results(1)After treatment,the VAS scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of VAS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the Kujala scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of Kujala scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the AROM of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of AROM,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 95.35%(41/43)in the observation group and 81.40%(35/43)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The joint needling method combined with ultrasound can significantly relieve the pain symptoms of patients with PFPS and promote the recovery of knee joint function,and the clinical efficacy is remarkable.

Research progress on complications of unilateral biportal endoscopic spinal surgery technique / 临床外科杂志

The unilateral biportal endoscopic spinal surgery(UBE)technique is an emerging endoscopic technique,mainly used as treatment for lumbar degenerative disease.The procedure is characterized by two working channels,one being endoscopic,the second to be employed as an operating channel.Through the use of such dual-channel-technology,it allows the operating instruments to be unrestricted in size.Therefore,it is a highly efficient surgical technique for minimally invasive spinal surgery(MISS).However,the clinical complications of UBE technology must be taken into consideration.Possible side effects include dural injury,epidural hematoma,occult blood loss,postoperative headache,nerve root injury and insufficient decompression.This article reviews the causes,prevention and management of UBE-related complications.

Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial cells exposed to H2 O2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1ß, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A165 , with a dissociation constant of 2.2 × 10-14  M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.

Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model.

BACKGROUND: Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study. AIM: To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming. METHODS: Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels. RESULTS: IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway. CONCLUSION: IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

PURPOSE: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Retrospective comparative case series. METHODS: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used. RESULTS: Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications. CONCLUSIONS: Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.

Peripheral ulcerative keratitis in a patient with granulomatous rosacea.

A 24-year-old woman visited our emergency department due to intermittent dull pain in the right eye, blurred vision, foreign body sensation for 3 weeks, and progressive facial rash with pustules for 3 months. She had a history of recurring skin rash on her face and extremities since early adolescence. Peripheral ulcerative keratitis (PUK) was diagnosed based on slit-lamp examination and corneal topography and then granulomatous rosacea (GR) based on clinical manifestations and skin pathology. Topical prednisolone, artificial tears, oral doxycycline, oral prednisolone, and topical clindamycin were administered. After 1 month, PUK progressed to corneal perforation probably due to eye rubbing. The corneal lesion was repaired with a glycerol-preserved corneal graft. A dermatologist prescribed oral isotretinoin for 2 months in conjunction with topical betamethasone gradually tapered for 14 months. After 34 months of follow-up, no signs of skin and ocular recurrence were noted, and the cornea graft was intact. In conclusion, PUK may present with GR, and oral isotretinoin may be an effective therapy for PUK in the setting of GR.

Diterpenoids and Their Glycosides from the Stems of Tinospora crispa with Beta-Cell Protective Activity.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.

Transcription Factor ATF3 Participates in DeltaNp63-Mediated Proliferation of Corneal Epithelial Cells.

Understanding the regulatory mechanisms underlying corneal epithelial cell (CEC) proliferation in vitro may provide the means to boost CEC production in cell therapy for ocular disorders. The transcription factor ΔNp63 plays a crucial role in the proliferation of CECs, but the underlying mechanisms is yet to be elucidated. TP63 and ΔNp63 are encoded by the TP63 gene via alternative promoters. We previously reported that both ΔNp63 and activating transcription factor (ATF3) are substantially expressed in cultured CECs, but the regulatory relationship between ΔNp63 and ATF3 is unknown. In the present study, we found that ΔNp63 increased ATF3 expression and ATF3 promoter activity in cultured CECs. The deletion of the p63 binding core site reduced ATF3 promoter activity. CECs overexpressing ATF3 exhibited significantly greater proliferation than control CECs. ATF3 knockdown suppressed the ΔNp63-induced increase in cell proliferation. Overexpression of ATF3 in CECs significantly elevated protein and mRNA levels of cyclin D. The protein levels of keratin 3/14, integrin ß1, and involucrin did not differ between ATF3-overexpressing CECs, ATF3-downregulated CECs, and control cells. In conclusion, our results suggest that ΔNp63 increases CEC proliferation via the ΔNp63/ATF3/CDK pathway.

Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

GSK3α phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells.

Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2) in catalyzing GLUT4 endocytosis is negatively regulated by insulin signaling in muscle cells. Mechanistically, the fission activity of Dyn2 is inhibited by binding with the SH3 domain of Bin1. In the absence of insulin, GSK3α phosphorylates Dyn2 to relieve the inhibition of Bin1 and promotes endocytosis. Conversely, insulin signaling inactivates GSK3α and leads to attenuated GLUT4 internalization. Furthermore, the isoform-specific pharmacological inhibition of GSK3α significantly improves insulin sensitivity and glucose tolerance in diet-induced insulin-resistant mice. Together, we identify a new role of GSK3α in insulin-stimulated glucose disposal by regulating Dyn2-mediated GLUT4 endocytosis in muscle cells. These results highlight the isoform-specific function of GSK3α on membrane trafficking and its potential as a therapeutic target for metabolic disorders.

Microbial Keratitis in Patients With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Experience From a Tertiary Centre in Taiwan.

PURPOSE: The purpose of this study was to analyze the clinical features, causative microorganisms, antibiotic susceptibility, and treatment outcomes in culture-proven microbial keratitis (MK) in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and to analyze the potential risk factors. METHODS: We reviewed the medical records of all patients with SJS/TEN who attended our department between 2009 and 2018. Patients with a diagnosis of MK who underwent corneal cultures were enrolled. Demographics; clinical characteristics including ocular findings, treatment, time between onset of SJS/TEN and keratitis; changes in visual acuity; culture results; and antibiotic susceptibility were analyzed. Culture results from prior conjunctival swabs and keratitis were also compared. RESULTS: Sixteen eyes from 12 patients (mean age 40.1 ± 27.7 years) with MK were identified. These patients had the most severe ocular involvement in the acute stage and had more severe ocular complications (SOCs) in the chronic stage compared with patients with SJS/TEN without MK. There were 26 infection episodes during 4.4 ± 6.9 (1.0-25.8) years of follow-up. Oral nonsteroidal anti-inflammatory drugs accounted for half of the causative drugs. Severe dry eye was the most common predisposing factor, followed by topical steroid use, trichiasis, and lid margin keratinization. Staphylococcus was the most common pathogen, and over half of the gram-positive bacteria were resistant to oxacillin/methicillin. Fungal infections (notably Candida ) accounted for nearly one-third of the causative microorganisms. Culture reports from periodic conjunctival swabs were not consistent with those from corneal scrapings. Recurrence of infection was associated with inferior visual outcome. CONCLUSIONS: Patients with SJS/TEN with SOCs are subject to recurrent corneal infections, which are responsible for deterioration of vision. Identifying the risk factors and aggressive treatment as early as possible is pivotal for infection control.

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations / 中华病理学杂志

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Isolation of GLP-1 enhancing indolizidine alkaloids from Boehmeria formosana.

Boehmeria formosana, with its related species, demonstrates anti-glycemic effect, inhibition of HBV production, anti-cancer activities, etc. Some indolizidine alkaloids from the same genus are bioactive but sensitive to light. To overcome this problem and obtain more phenanthroindolizidine alkaloids, isolation was performed in darkness, yielding 10 new indolizidine alkaloids and 17 known compounds. Among them, seven enhanced glucagon-like receptor 1 (GLP-1) activity at 50 mM, especially 14 and 6 (3.5- and 2.3-fold than the negative control). This procedure yielded bioactive indolizidine alkaloids with novel structures.

Components with Anti-Diabetic Activity Isolated from the Leaves and Twigs of Glycosmis pentaphylla Collected in Vietnam.

A phytochemical investigation of the leaves and twigs of Glycosmis pentaphylla (Rutaceae), collected in Vietnam, yielded three new compounds named glyfuran (1), glyphyllamide (2), and glyphyllazole (3), along with twenty-five known compounds (4-28). The structures of isolates were determined by IR, MS, NMR, and UV data analyses. In the anti-diabetic activity screening, (+)-isoaltholacton (4), glycoborinine (17), 2',4'-dihydroxy-4,6'-dimethoxychalcone (24), and flavokawain A (25) simultaneously exhibited inhibition of dipeptidyl peptidase-4 (DPP4) and stimulation of the glucagon-like peptide-1 (GLP-1) secretion on the murine intestinal secretin tumor cell line (STC-1).