Venetoclax treatment for chronic lymphocytic leukemia/small lymphocytic leukemia in Japan: post-marketing surveillance.

Venetoclax was approved for relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic leukemia (SLL) in Japan in September 2019; however, clinical data in Japanese patients are limited. This all-case post-marketing surveillance assessed efficacy and safety in Japanese patients with R/R CLL/SLL who started venetoclax treatment between November 2019 and August 2020. Overall, the safety and efficacy analysis sets included 129 and 114 patients, respectively. The overall response rate (ORR) was 57.0%; ORRs were higher in patients with versus without concomitant rituximab (65.4% vs. 54.7%), and in patients with 1 versus ≥ 2 prior lines of therapies (72.5% vs. 44.4%). Adverse events (AEs) were reported in 66.7% of patients (86/129); the most common AEs were neutrophil count decreased (22.5%), white blood cell count decreased (7.8%), and tumor lysis syndrome (TLS; 6.2%). AEs of special interest (TLS, myelosuppression, and infection) were manageable in clinical practice in Japan. Venetoclax is efficacious and safe for R/R CLL/SLL patients in the real-world setting in Japan. ClinicalTrials.gov ID: NCT04198415.

Predicting Therapeutic Intervention for Patients with Quiescent Crohn's Disease Using the Small Bowel Capsule Endoscopy Score.

Introduction: Small bowel (SB) capsule endoscopy (SBCE) is a sensitive modality for screening the entire SB of patients with Crohn's disease (CD); however, the prognostic impact of the results is unclear. We evaluated the ability of the SBCE score to predict therapeutic intervention for patients with CD and SB lesions without clinical symptoms as well as negative C-reactive protein (CRP) levels. Methods: Fifty-six patients who underwent a patency evaluation and had a CD activity index (CDAI) score <150 mg/dL and CRP level <0.5 mg/dL were included. Twenty-one and 35 patients had CD classified as Montreal classifications L1 and L3, respectively. The initial SBCE scores were subsequently grouped according to the presence or absence of intervention based on cutoff values. We examined whether the scores could predict the need for therapeutic intervention at 1 year, 2 years, and 5 years. The CD activity in capsule endoscopy (CDACE) score was used as the SBCE score. Results: The median observation period was 1,326 days. Twenty-one patients received therapeutic intervention. There were significant differences between patients with and without treatment intervention according to the CDACE cutoff value of 420 at 1 year, 2 years, and 5 years. Significant differences between patients with Montreal classification L1 with and without intervention were observed at 1 year and 2 years. The CDACE score was moderately and strongly correlated with the Lewis score and capsule endoscopy CDAI score, respectively (Spearman rank correlation coefficient: ρ = 0.6462 and ρ = 0.9199, respectively; p < 0.0001). Conclusion: A CDACE score ≥420 is predictive of intervention after 1 year for patients with CD, a CDAI score <150, and a CRP level <0.5 mg/dL. A larger study with a prospective design is necessary to validate our findings.

Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn's disease small bowel lesion in capsule endoscopy.

Background/Aims: Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn's disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE. Methods: Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated. Results: Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 µg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 µg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman's rank correlation coefficient ρ = 0.681, P< 0.001). Conclusions: An LRG cutoff value of 14 µg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 µg/mL may be useful in predicting the absence of SB inflammatory findings.

Recovery of phosphorus, magnesium, and potassium from surplus activated sludge using existing sludge treatment facilities and thickened primary sludge.

The separation of P, K, and Mg from surplus activated sludge (SAS) was investigated using existing sludge treatment facilities and the thickened primary sludge (TPS). The addition of the TPS to the SAS storage tank accelerated the anaerobic release of the three elements from SAS with maximum efficiencies of about 60%. The efficiency of P release showed a significant correlation with the oxidation-reduction potential. Increasing the total solid concentration increased the release of elements. The released elements could be transferred to a separate liquid (SL) from a screw-press thickener, and maximum concentrations of P, K, and Mg were about 200, 60, and 35 mg/L, respectively. The addition of CaCl2 and NaOH solutions to SL precipitated P as hydroxyapatite. However, no precipitation of K and Mg occurred simultaneously with P, even when the pH of SL was increased to 9. These findings suggest that about 60% of P, K, and Mg can be separated from SAS into SL using existing sludge treatment facilities and TPS; however, a method other than precipitation would be needed to recover P and K from SL simultaneously.

Efficacy and safety of tacrolimus in older adults with ulcerative colitis: a retrospective study.

BACKGROUND/AIMS: The prevalence of ulcerative colitis (UC) has been increasing, also in older adults. Here, we retrospectively compared the efficacy and safety of tacrolimus (TAC) in older and younger patients with UC. METHODS: We included younger (age < 65 years; n = 116) and older patients (age ≥ 65 years; n = 21) with UC who received TAC from April 2009 through December 2022(mean follow-up, 1230 ± 175 days) and achieved remission. Evaluations included age at onset, laboratory values, estimated glomerular filtration rate (eGFR), use of 5-aminosalicylic acid (5-ASA), biological experience, colonoscopy scores, remission at 1 month after treatment initiation, and adverse events. Treatment duration and renal function were assessed in patients with follow-up data (younger patients, n = 110; older patients, n = 19). RESULTS: Older patients had a higher age at onset and treatment initiation but less 5-ASA use and biological experience. Before treatment, hemoglobin, albumin, and eGFR were significantly lower in the older group and CRP was significantly higher. The remission rate was 80.1% in the younger group and 66.6% in the older group (P = 0.1862). Adverse events were similar in both groups. The older group had a shorter treatment duration and significantly less change in renal function at all time points. DISCUSSION: Rates of TAC-induced remission and adverse events were similar in older and younger adults with UC. CONCLUSION: TAC can be used safely in elderly patients with moderate to severe UC with careful monitoring.

A retrospective study to investigate the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis with ulcerative colitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis. METHODS: We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events. RESULTS: Seven of the 10 patients were male. The median (min-max) age was 23 (18-77) years. The most common disease type was right-dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1). CONCLUSIONS: Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.

Nano-displacement sensing by phase-diversity optical digital coherent detection utilizing alternating quadrature phase-modulated reference light.

We have introduced a nanometer-scale non-contact displacement sensing method that relies on phase-diversity optical digital coherent detection. In our prior work, we used a conventional setup involving a 90°optical hybrid, two balanced amplified photodetectors (BAPs), and a narrow-linewidth (NLW) laser, which is complex and costly. However, in this paper, we have streamlined the system configuration by employing alternating quadrature phase modulation (AQPM) reference light, implemented using a phase modulator and a BAP. Moreover, we've employed an economical distributed feedback (DFB) laser, enabling us to achieve displacement sensing at 1.6 nm with a resolution of 0.6 nm. It is notable that there is some degradation in the performance due to the phase noise compared to the NLW laser, which achieves a displacement sensing down to 0.6 nm with a 0.2 nm resolution. Nevertheless, the DFB-AQPM system holds a significant potential for cost-effective, high-resolution nanometer-scale sensing applications.

A Patient with Crohn's Disease Who Gave Birth Despite Sigmoid Volvulus, Venous Thrombosis, Nontraumatic Fracture of the Rib, and Sepsis during Pregnancy.

The patient was a woman in her 40s who was diagnosed with Crohn's disease (CD) of the large and small intestines in 1996. In 2005, she was referred to our hospital for treatment. We treated her for 17 years with corticosteroids, biologics, immunosuppressive agents, 5-aminosalicylic acid, and nutrition care. However, her Crohn's Disease Activity Index remained between 200 and 250, indicating refractory CD. During her medical treatment, the patient also underwent 3 operations. One year ago, the patient became pregnant through in vitro fertilization. Even after pregnancy was confirmed, the patient continued her treatment for refractory CD with ustekinumab, granulocyte apheresis, and budesonide. Nonetheless, her CD was highly active during pregnancy, and she experienced various complications: sigmoid volvulus at gestational week 15, venous thrombosis at gestational week 17, nontraumatic rib fracture due to fetal movement at gestational week 32, and sepsis from central venous catheter infection at gestational week 37. At gestational week 38, the patient gave birth by emergency cesarian delivery. This paper reports details of the case in which delivery was achieved after various complications were overcome and discusses previous relevant reports.

Statistical model of trajectories of reduced mobility in older people with locomotive disorders: a prospective cohort study with group-based trajectory model.

BACKGROUND: Today we experience "Super-aged society", and a drastic increase in the number of older people needing assistance is an urgent matter for everyone from medical and socio-economical standpoints. Locomotive organ dysfunction due to musculoskeletal disorders is one of the main problems in these patients. Although the concepts of frailty and sarcopenia have been proposed for functional decline, pain remains the main and non-negligible complaint in these of such disorders. This prospective cohort study aimed to observe the changes of reduced mobility in patients with locomotive disorders and to determine the risk factors for functional deterioration of those patients using statistical modeling. METHODS: A cohort of older adults with locomotive disorders who were followed up every 6 months for up to 18 months was organized. Pain, physical findings related to the lower extremities, locomotive function in performing daily tasks, and Geriatric Locomotive Function Scale-25 (GLFS-25) score were collected to predict the progress of deterioration. Group-based trajectory analysis was used to identify subgroups of changes of GLFS-25 scores, and multinomial logistic regression analysis was performed to investigate potential predictors of the GLFS-25 trajectories. RESULTS: Overall, 314 participants aged between 65 and 93 years were included. The participants were treated with various combinations of orthopedic conservative treatments on an outpatient basis. The in-group trajectory model analysis revealed a clear differentiation between the four groups. The mild and severe groups generally maintained their GLFD-25 scores, while the moderate group included a fluctuating group and a no change group.　This study showed that comorbidity of osteoporosis was related to GLFS-25 score over 18 months. Age was a weak factor to be moderate or severe group, but gender was not. In addition, the number of pain locations, number of weak muscles, one-leg standing time, grip strength and BMI significantly contributed to the change in GLFS-25 score. CONCLUSIONS: This study proposes an effective statistical model to monitor locomotive functions and related findings. Pain and comorbid osteoporosis are significant factors that related to functional deterioration of activities. In addition, the study shows a patient group recovers from the progression and their possible contributing factors.

CD98 expression can be a predictive factor of resistance to radiotherapy in head and neck squamous cell carcinoma.

CD98 is a marker of cancer stem cells, and it regulates radiosensitivity in head and neck squamous cell carcinoma (HNSCC). The current study aimed to investigate whether CD98 can be used as a prognostic factor and marker of radioresistance. CD98 immunostaining was performed using biopsy specimens collected from patients diagnosed with HNSCC. The average period of postoperative monitoring was 31.6 months. The treatment options were radiation therapy with either cisplatin or cetuximab, and surgery. The participants were divided into groups of low and high fluorescence intensity. CD98 was an independent prognostic factor of radioresistance. In total, 103 patients were treated with chemoradiotherapy or bioradiotherapy. The overall survival rates of patients receiving chemoradiotherapy or bioradiotherapy were 69.2% in the low group and 36.2% in the high group. The progression-free survival rates were 60.0% and 24.6%, respectively. CD98 expression was considered an independent prognostic factor of overall survival and progression-free survival. In total, 99 patients underwent surgical treatment. The surgery group did not differ according to CD98 expression. Via CD98 immunostaining, sensitivity to radiotherapy can be determined in advance. In HNSCC, knowledge about sensitivity to radiotherapy can significantly improve prognosis.

Direct binding of calmodulin to the cytosolic C-terminal regions of sweet/umami taste receptors.

Sweet and umami taste receptors recognize chemicals such as sugars and amino acids on their extracellular side and transmit signals into the cytosol of the taste cell. In contrast to ligands that act on the extracellular side of these receptors, little is known regarding the molecules that regulate receptor functions within the cytosol. In this study, we analysed the interaction between sweet and umami taste receptors and calmodulin, a representative Ca2+-dependent cytosolic regulatory protein. High prediction scores for calmodulin binding were observed on the C-terminal cytosolic side of mouse taste receptor type 1 subunit 3 (T1r3), a subunit that is common to both sweet and umami taste receptors. Pull-down assay and surface plasmon resonance analyses showed different affinities of calmodulin to the C-terminal tails of distinct T1r subtypes. Furthermore, we found that T1r3 and T1r2 showed the highest and considerable binding to calmodulin, whereas T1r1 showed weaker binding affinity. Finally, the binding of calmodulin to T1rs was consistently higher in the presence of Ca2+ than in its absence. The results suggested a possibility of the Ca2+-dependent feedback regulation process of sweet and umami taste receptor signaling by calmodulin.

Unlocking fertilization potential of anaerobically digested sewage sludge centrate for protein-rich rice cultivation with composted sludge amendment.

The use of composted sewage sludge (CSS) and centrate as alternatives to synthetic fertilizers in rice cultivation holds great promise. This study aims to determine the effects of varying doses and timings of centrate derived from anaerobically digested sewage sludge on rice yield, nutrient quality, and soil fertility when applied as a topdressing to rice fields fertilized with CSS. At the panicle initiation (PI) stage, 100, 300, and 500 kg N ha-1 of centrate topdressing (CT100, CT300, and CT500, respectively) was applied. In addition, different topdressing timings at a total dose of 500 kg N ha-1 were evaluated, including a two-split application (40% at active tillering (AT) and 60% at PI; CT500S2) and a three-split application (40% at AT + 40% at PI + 20% at heading; CT500S3). At a rate of 160 kg N ha-1, CSS was used as a base fertilizer in all treatments. A control treatment received synthetic fertilizers at a rate of 160 kg N ha-1 as a base application and 100 kg N ha-1 as a topdressing. Results showed that CSS-treated rice plants exhibited a lower N status and leaf chlorophyll content during the vegetative growth stage; however, the split application of centrate topdressing improved plant N status, resulting in an increase in biomass and grain yield. Centrate and CSS tended to increase the mineral content of rice; nevertheless, a significant accumulation of As in grains raised concerns about food safety. Combining CSS and centrate has the potential to increase rice production, improve grain nutritional value, and decrease reliance on synthetic fertilizers. However, it is essential to optimize this fertilization, mitigate environmental risks, and ensure food safety by employing appropriate fertilization dosing and timing as well as appropriate field management strategies.

SMARCB1/INI1-deficient intrathoracic neoplasm with rhabdoid/plasmacytoid cytomorphology in a patient with plasma cell myeloma: A case report.

SMARCB1 (INI1) is one of the switch/sucrose nonfermentable (SWI/SNF) complexes whose loss is associated with several tumors. SMARCB1 (INI1)-deficient intrathoracic neoplasms are extremely rare and known to be highly malignant and lethal. This report presents the case of a patient diagnosed with SMARCB1 (INI1)-deficient intrathoracic neoplasm during chemotherapy for plasma cell myeloma. A 77-year-old male patient complained of cough, bloody sputum, and fever with an enlarged right lung mass and pleural effusion. His cytological examination revealed undifferentiated epithelioid and rhabdoid/plasmacytoid cells with bi- or multinucleation, vacuolization, mitosis, and pleomorphism. However, it was difficult to distinguish the relapse of plasma cell myeloma as atypical plasmacytoid cells were detected. Immunohistochemically, the neoplastic cells showed a loss of SMARCB1 (INI1) expression in the cell block of pleural fluid and in the right lung of the autopsy specimen. Further, the patient was diagnosed with SMARCB1 (INI1)-deficient intrathoracic neoplasm of the right lung based on histological and autopsy findings. To the best of our knowledge, this is the first report of cytomorphology in a SMARCB1 (INI1)-deficient intrathoracic neoplasm.

Exploration of an efficient method for removing antibiotics from water and digested sewage sludge using Fe(VI): Kinetics and P phytoavailability and compostability in treated sludge.

Potassium ferrate (K2FeO4) containing hexavalent iron [Fe(VI)] is an environmentally friendly oxidant, which possesses strong oxidizing power to treat wastewater and sludge. Therefore, the present study investigated degradation of selected antibiotics, namely levofloxacin (LEV), ciprofloxacin (CIP), oxytetracycline (OTC), and azithromycin (AZI), in water and anaerobically digested sewage sludge samples using Fe(VI). The effects of different Fe(VI) concentrations and initial pH values on antibiotic removal efficiency were evaluated. Under the studied conditions, LEV and CIP were almost completely removed from water samples, following second-order kinetics. In addition, over 60% of the four selected antibiotics were removed from sludge samples using 1 g L-1 Fe(VI). Furthermore, P phytoavailability and compostability of Fe(VI)-treated sludge were evaluated using different extraction reagents and a small composting unit. The extraction efficiency of phytoavailable P using 2% citric acid and neutral ammonium citrate was approximately 40% and 70%, respectively. The mixture of Fe(VI)-treated sludge and rice husk was self-heated in a closed composting reactor through the biodegradation of organic matter derived from the treated sludge. Therefore, Fe(VI)-treated sludge may be used as an organic material containing phytoavailable P for compost.

LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been identified as the sixth most common disease in the world, and its prognosis remains poor. The basic treatment of HNSCC includes a combination of chemoradiation and surgery. With the advent of immune checkpoint inhibitors, the prognosis has improved; however, the efficacy of checkpoint inhibitors is limited. L-type amino acid transporter 1 (LAT1), an amino acid transporter, is highly expressed in a cancer-specific manner. However, to the best of our knowledge, LAT1 expression in HNSCC has not been determined. Therefore, the present study aimed to examine the role of LAT1 expression in HNSCC. A total of three HNSCC cell lines (Sa3, HSC2 and HSC4) were used to investigate the characteristics of LAT1-positive cells, including their ability to form spheroids, and their invasion and migration. The present study also examined LAT1 by immunostaining of biopsy specimens from 174 patients diagnosed, treated and followed-up at Akita University (Akita, Japan) between January 2010 and December 2019, and overall survival, progression-free survival and multivariate analyses were performed. The results demonstrated that LAT1-positive cells in HNSCC were an independent prognostic factor for overall survival and progression-free survival, and were resistant to chemoradiation. Therefore, JPH203, a LAT1 inhibitor, may be effective in treating chemoradiotherapy-resistant HNSCC and may improve the prognosis of patients with HNSCC.

Degradation of sulfamonomethoxine in solution using pulsed plasma discharge - identification of by-products and toxicity of treated solution to green algae.

This study investigated the degradation of sulfamonomethoxine (SMM) by pulsed plasma discharge. SMM was successfully degraded following the first-order kinetics model. The percentage removal of SMM was estimated by the total input energy of plasma discharge, which was dependent on the initial SMM concentration. In addition, three types of by-products were observed at an early reaction time, which were then degraded. In contrast, the ecotoxicity of the treated solution by plasma discharge was assessed by an acute toxicity test using the green alga Raphidocelis subcapitata. The plasma discharge in water generated hydrogen peroxide with a concentration higher than the EC50 for R. subcapitata. It is therefore necessary to remove H2O2 or prevent the generation of H2O2 for the degradation of antibiotics in solutions using plasma discharge.

Study into the chemical changes of tea leaf polyphenols during japanese black tea processing.

During the processing of black tea, enzymatic oxidation converts tea catechins into a complex mixture of oxidative products, including theaflavins, and thearubigins. In this study, ultra-performance liquid chromatography was carried out to analyze the tea extracts collected after each processing stage to clarify the quantitative changes in these compounds during black tea processing. It was found that the catechin content was significantly reduced during processing, and in particular between the later rolling and fermentation periods. In contrast, the variation in the theaflavin content was negatively correlated with the catechin content. Twenty-three compounds containing the known catechins dimers and flavonol glycosides were identified by liquid chromatography-mass spectrometry (LC-MS). In addition, 45 components whose contents increased significantly between the late rolling and late fermentation stages were extracted using principal components analysis by LC-MS. It was considered that due to the catechin-like units present in these components, they likely contribute to thearubigin production during black tea processing.

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma-Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis.

Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens. Methods: We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival. Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor. Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.

A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells.

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

Tumor Infiltrating Lymphocytes are Prognostic Factors and Can Be Markers of Sensitivity to Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are assessed by the ratio of the area of lymphocytes infiltrating the stroma. TILs are important in breast cancer and malignant melanoma and are being established as a marker of prognosis and sensitivity to chemotherapy. This has resulted in various therapies being developed in fields such as breast cancer. However, the evaluation of TILs in head and neck squamous cell carcinoma (HNSCC) is not progressing, and the prognosis is still poor. Thus, investigating whether or not the evaluation of TILs is also effective in HNSCC and prognoses can be predicted with just biopsy samples alone is required. METHODS: This study included 153 patients who were diagnosed with HNSCC between January 2010 and December 2019, underwent treatment, and could be followed up thereafter at our institution. RESULTS: TILs, overall survival (OS), and progression-free survival (PFS) were evaluated in all patients, the chemoradiotherapy arm, and the surgery arm. The cut-off value for TILs was 50%. In all patients, OS was 69.8% and 40.2% (P = 0.01) and PFS was 58.4% and 31.6% (P = 0.003) in the high and low TIL groups, respectively. Multivariate analyses revealed that TILs independently predicted prognosis. In the chemoradiotherapy arm, OS was 70.8% and 31.6% (P = 0.012) and PFS was 63.4% and 20.3% (P = 0.001) in the high and low TIL groups, respectively. No significant differences were noted in the surgery arm. CONCLUSIONS: In HNSCC, TILs can be used as a prognosis predictor and chemoradiotherapy biomarker. Assessments can be performed just with hematoxylin-eosin staining and is very simple. This will greatly contribute to report personalized therapy progress. Further evaluations and, thus, prospective clinical multicenter trials are needed to use TILs in clinical practice for HNSCC.