Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Background: and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. Methods: We evaluated the brain MRI data from 87 TGA patients and 20 age- and sexmatched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. Results: TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). Conclusions TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Background/Aims: Noninvasive methods have become increasingly critical in the diagnosis of fibrosis in chronic liver diseases. Herein, we compared the diagnostic performance of serum Mac2 binding protein glycosylation isomer (M2BPGi) and other serological panels for fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and proposed an improved two-step diagnostic algorithm for advanced fibrosis. Methods: We enrolled 231 patients diagnosed with NAFLD who underwent a liver biopsy. We subsequently evaluated the diagnostic performance of serological panels, including serum M2BPGi, a fibrosis index based on four factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), in predicting the stage of liver fibrosis. We then constructed a two-step algorithm to better differentiate advanced fibrosis. Results: The areas under the receiver operating characteristic curves of serum M2BPGi, FIB-4, APRI, and NFS for advanced fibrosis (≥F3) were 0.823, 0.858, 0.779, and 0.827, respectively. To reduce the performance of unnecessary liver biopsy, we propose a two-step algorithm using FIB-4 as an initial diagnostic tool and serum M2BPGi (≥0.6) as an additional diagnostic method for patients classified as intermediate (23%). Using the proposed algorithm, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.812, 0.814, 0.814, 0.600, and 0.927, respectively. Conclusions Serum M2BPGi is a simple and effective test for advanced fibrosis in patients with NAFLD. Application of the two-step algorithm based on FIB-4 and M2BPGi proposed here can improve diagnostic performance and reduce unnecessary tests, making diagnosis easily accessible, especially in primary medical centers.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Objective: To review the characteristics of distal middle cerebral artery (MCA) aneurysm treated by microsurgery, the detailed surgical options, and the clinical result. Methods: We retrospectively reviewed cerebral aneurysm in the M2 and M3 segments of the MCA surgically treated between January 2015 and December 2022. The demographic data, aneurysm-related findings, type of surgical approach, surgical technique, and clinical outcomes of the enrolled patients were analyzed. Results: Sixteen distal MCA aneurysms were treated with microneurosurgery (incidence, 1.0%; female, 12; mean age, 58.1 years; ruptured, three). Twelve aneurysms were in the M2 segment (insular segment), two aneurysms at the M2–M3 junction, and two aneurysms in the M3 segment (opercular segment). Twelve aneurysms were saccular (average size, 4.9 mm; multiplicity, 50%; average aneurysms, 3.0; partially thrombosed, 1; sidewall aneurysm, 2). Three aneurysms were fusiform, of which two were ruptured. Of the ruptured aneurysms, one was a ruptured dissecting aneurysm. The trans-sylvian and trans-sulcal approaches were used in fourteen and two patients, respectively. Neck clipping, wrap clipping, and surgical trapping were performed in twelve, one, and one patient, respectively. Proximal occlusion was performed in one patient. Bypass technique was required in two patients (neck clipping and proximal occlusion). The modified Rankin Score was 6 in the two patients with ruptured aneurysms. The remaining patients did not show further neurological deterioration after microneurosurgery. Conclusions Distal MCA aneurysms had a high incidence of being diagnosed with multiple other aneurysms and were relatively non-saccular.