Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project-14.

PURPOSE: Various studies have demonstrated the causal relationship between gut microbiota and efficacy of chemotherapy; however, the impact of gut microbiota on breast cancer has not been fully elucidated. This study aimed to evaluate the associations between the gut microbiota before neoadjuvant chemotherapy and its consequent efficacy in breast cancer. METHODS: This prospective observational study included patients who received neoadjuvant chemotherapy for primary early breast cancer at eight institutions between October 1, 2019, and March 31, 2022. We performed 16S rRNA analysis of fecal samples and α and ß diversity analyses of the gut microbiota. The primary endpoint was the association between the gut microbiota and pathological complete response (pCR) to neoadjuvant chemotherapy. RESULTS: Among the 183 patients, the pCR rate after neoadjuvant chemotherapy was 36.1% in all patients and 12.9% (9/70), 69.5% (41/59), and 29.6% (16/54) in those with the luminal, human epidermal growth factor receptor 2, and triple-negative types, respectively. The α diversity of the gut microbiota did not significantly differ between patients with pCR and those without pCR. Among the gut microbiota, two species (Victivallales, P = 0.001 and Anaerolineales, P = 0.001) were associated with pCR, and one (Gemellales, P = 0.002) was associated with non-pCR. CONCLUSION: Three species in the gut microbiota had potential associations with neoadjuvant chemotherapy efficacy, but the diversity of the gut microbiota was not associated with response to chemotherapy. Further research is needed to validate our findings.

Nine-year seroepidemiological study of severe fever with thrombocytopenia syndrome virus infection in feral horses in Cape Toi, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal zoonosis caused by ticks in East Asia. As SFTS virus (SFTSV) is maintained between wildlife and ticks, seroepidemiological studies in wildlife are important to understand the behavior of SFTSV in the environment. Miyazaki Prefecture, Japan, is an SFTS-endemic area, and approximately 100 feral horses, called Misaki horses (Equus caballus), inhabit Cape Toi in Miyazaki Prefecture. While these animals are managed in a wild-like manner, their ages are ascertainable due to individual identification. In the present study, we conducted a seroepidemiological survey of SFTSV in Misaki horses between 2015 and 2023. This study aimed to understand SFTSV infection in horses and its transmission to wildlife. A total of 707 samples from 180 feral horses were used to determine the seroprevalence of SFTSV using enzyme-linked immunosorbent assay (ELISA). Neutralization testing was performed on 118 samples. In addition, SFTS viral RNA was detected in ticks from Cape Toi and feral horses. The overall seroprevalence between 2015 and 2023 was 78.5% (555/707). The lowest seroprevalence was 55% (44/80) in 2016 and the highest was 92% (76/83) in 2018. Seroprevalence was significantly affected by age, with 11% (8/71) in those less than one year of age and 96.7% (435/450) in those four years of age and older (p < 0.0001). The concordance between ELISA and neutralization test results was 88.9% (105/118). SFTS viral RNA was not detected in ticks (n = 516) or feral horses. This study demonstrated that horses can be infected with SFTSV and that age is a significant factor in seroprevalence in wildlife. This study provides insights into SFTSV infection not only in horses but also in wildlife in SFTS-endemic areas.

Prognostic improvement and treatment of COVID-19 in patients with rheumatic diseases until December 2022: Analysis of the JCR COVID-19 registry in Japan.

OBJECTIVES: The aim is to evaluate the treatment and prognosis of coronavirus disease 2019 (COVID-19) according to the time of onset and dominant strain in patients with rheumatic diseases. METHODS: This study analysed a nationwide COVID-19 registry of Japanese patients with rheumatic diseases compiled between June 2020 and December 2022. The primary endpoints of the study were hypoxaemia incidence and mortality. Multivariate logistic regression analysis was performed to assess differences according to the period of onset. RESULTS: A total of 760 patients were compared across four periods. Hypoxaemia rates were 34.9, 27.2, 13.8, and 6.1% and mortality rates were 5.6, 3.5, 1.8, and 0% until June 2021, between July and December 2021, January and June 2022, and July and December 2022, respectively. History of vaccination (odds ratio, 0.39; 95% confidence interval, 0.18-0.84) and onset during the July to December 2022 Omicron BA.5-dominant period (odds ratio, 0.17; 95% confidence interval, 0.07-0.41) were negatively associated with hypoxaemia in the multivariate model, adjusting for age, sex, obesity, glucocorticoid dose, and comorbidities. Over the Omicron-dominant period, antiviral treatment was administered in 30.5% of patients with a low probability of hypoxaemia. CONCLUSIONS: COVID-19 prognosis improved over time in patients with rheumatic diseases, especially in the Omicron BA.5-dominant period. In the future, treatment of mild cases should be optimised.

Risk factors for hospitalization or mortality for COVID-19 in patients with rheumatic diseases: Results of a nationwide JCR COVID-19 registry in Japan.

OBJECTIVES: The incidence and prognosis of Coronavirus Disease 2019 (COVID-19) and rheumatic disease vary among ethnicities and regions. COVID-19 outcomes in rheumatic disease patients remain unclear, especially in the Asia-Pacific region. This study aimed to clarify the demographic and clinical factors that may influence COVID-19 prognosis in rheumatic disease patients. METHODS: This was a case series of patients registered with the COVID-19 national registry of Japan College of Rheumatology between 3 June 2020 and 30 June 2021. Multivariable logistic regression was used to estimate the risk of hospitalization or death. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities, and rheumatic disease medications are taken immediately before infection was analysed. RESULTS: A total of 220 patients from 55 institutions in Japan were included in the study, among whom 186 (84.5%) were hospitalized and 11 (5.0%) died. COVID-19 treatments were provided to 126 patients (57.3%) and mainly comprised glucocorticoids, favipiravir, remdesivir, and tocilizumab.In the multiple logistic regression model, older age and a history of hypertension were associated with hospitalization, while older age was associated with mortality. No specific treatment was correlated with mortality or hospitalization by the multivariate analysis. CONCLUSIONS: Older age and hypertension were associated with a poor prognosis in Japanese COVID-19 patients with connective tissue disease. Factors not directly related to connective tissue disease were closely associated with the prognosis.

Single-cell profiling of transcriptomic changes during in vitro maturation of human oocytes.

Purpose: In vitro maturation (IVM) of human oocytes offers an invaluable opportunity for infertility treatment. However, in vitro matured oocytes often show lower developmental abilities than their in vivo counterparts, and molecular mechanisms underlying successful maturation remain unclear. In this study, we investigated gene expression profiles of in vitro matured oocytes at the single-cell level to gain mechanistic insight into IVM of human oocytes. Methods: Human oocytes were retrieved by follicular puncture and in vitro matured. In total, 19 oocytes from 11 patients were collected and subjected to single-cell RNA-seq analyses. Results: Global gene expression profiles were similar among oocytes at the same maturation stage, while a small number of oocytes showed distinct transcriptomes from those at the corresponding maturation stage. Differential gene expression analysis identified hundreds of transcripts that dynamically altered their expression during IVM, and we revealed molecular pathways and upstream regulators that may govern oocyte maturation. Furthermore, oocytes that were delayed in their maturation showed distinct transcriptomes. Finally, we identified genes whose transcripts were enriched in each stage of oocyte maturation. Conclusions: Our work uncovers transcriptomic changes during human oocyte IVM and the differential gene expression profile of each oocyte.

[A literature review on the relationship between questionnaires for assessing minor health complaints and health status indices among Japanese people].

Objectives　Minor health complaints related to stress, mental health, sleep, and fatigue are closely associated with each other, and their deterioration may cause lifestyle diseases. The health status of people can be predicted through a questionnaire by exploring the relationship between their state of minor health complaints and objective health status indices. Therefore, we conducted a systematic review of the relationship between a questionnaire on the state of minor health complaints and health status indices among Japanese people who have a high level of stress, which they experience on a daily basis, using epidemiological literature. Additionally, we considered items for the questionnaire which were necessary for an index development.Methods　The PubMed database was searched for papers on "autonomic nervous system," "sleep disorders," "mental health and stress," and "fatigue," using keywords mentioned in previous studies on minor health complaints.　The extracted research papers were screened according to the following inclusion criteria: 1) the participants were healthy Japanese people; 2) descriptions included characteristics of the target population; 3) use of analytic epidemiological study design, intervention studies, and systematic reviews; 4) minor health complaints assessed by a questionnaire; 5) evaluation of the relationship between the questionnaires for minor health complaints and the health index; and 6) written in Japanese or English. Based on this, ten papers were adopted.Results　Of the 10 papers collected, one was a cohort study, three were case-control studies, and six were cross-sectional studies. The participants in five of them were working adults. Reports on three out of six questionnaires on stress, four out of seven on sleep, and all two on comprehensive health status showed significant associations between minor health complaints assessed by the questionnaires and the index for health status. The increase in responses about work-related stress from the questionnaire was associated with an increase in the "risk of developing depression" [odds ratio 2.96 (confidence interval: 1.04-8.42)]. Poor sleep quality was associated with an increase in "changes in autonomic index," "number of comorbidities and the rate of depression," and the "risk of work-related injuries." Moreover, the health score was associated with the "autonomic nervous system index".Conclusion　These results suggest that a questionnaire evaluating minor health complaints should include questions about "stress," "sleep quality," and "comprehensive health status." Since studies that appropriately adopted for risk of bias were limited, it is necessary to further examine these relationships by applying prospective studies such as cohort studies and intervention studies.

Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer.

Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT.

Phospholipase C-ß3 regulates FcɛRI-mediated mast cell activation by recruiting the protein phosphatase SHP-1.

Mast cells are major effectors in high-affinity IgE receptor (FcɛRI)-dependent allergic reactions. Here we show that phospholipase C (PLC)-ß3 is crucial for FcɛRI-mediated mast cell activation. Plcb3(-/-) mice showed blunted FcɛRI-dependent late-phase, but not acute, anaphylactic responses and airway inflammation. Accordingly, FcɛRI stimulation of Plcb3(-/-) mast cells exhibited reduced cytokine production but normal degranulation. Reduced cytokine production in Plcb3(-/-) cells could be accounted for by increased activity of the negative regulatory Src family kinase Lyn and reduced activities of the positive regulatory protein kinases MAPKs. Mechanistically, PLC-ß3 constitutively interacts with FcɛRI, Lyn, and SHP-1 (protein phosphatase). SHP-1 probably recognizes its substrates Lyn and MAPKs via the recently described kinase tyrosine-based inhibitory motif, KTIM. Consistent with PLC-ß3- and SHP-1-mediated repression of Lyn activity by dephosphorylation at Tyr396, FcɛRI-mediated phenotypes were similar in Plcb3(-/-) and SHP-1 mutant mast cells. Thus, we have defined a PLC-ß3- and SHP-1-mediated signaling pathway for FcɛRI-mediated cytokine production.

Development of functional agricultural products utilizing the new health claim labeling system in Japan.

In April 2015, Consumer Affairs Agency of Japan launched a new food labeling system known as "Foods with Function Claims (FFC)." Under this system, the food industry independently evaluates scientific evidence on foods and describes their functional properties. As of May 23, 2017, 1023 FFC containing 8 fresh foods have been launched. Meanwhile, to clarify the health-promoting effects of agricultural products, National Agriculture and Food Research Organization (NARO) implemented the "Research Project on Development of Agricultural Products" and demonstrated the risk reduction of osteoporosis of ß-cryptoxanthin rich Satsuma mandarins and the anti-allergic effect of the O-methylated catechin rich tea cultivar Benifuuki. These foods were subsequently released as FFC. Moreover, NARO elucidated the health-promoting effects of various functional agricultural products (ß-glucan rich barley, ß-conglycinin rich soybean, quercetin rich onion, etc.) and a healthy boxed lunch. This review focuses on new food labeling system or research examining functional aspects of agricultural products.

Effects of flavonol-rich green tea cultivar (Camellia sinensis L.) on plasma oxidized LDL levels in hypercholesterolemic mice.

To examine the possible benefits of tea flavonols, we compared anti-atherogenic effects between common and flavonol-rich tea cultivars. The tea infusion made from a flavonol-rich cultivar, but not a common cultivar, significantly decreased the plasma oxidized low-density lipoprotein level in mice fed a high-cholesterol diet. The result suggests that tea flavonols have the potential to protect against cardiovascular diseases.

Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans.

We conducted a systematic review of the literature for the ability of green tea epigallocatechin gallate (EGCG) to lower low-density lipoprotein cholesterol (LDL-C). Study subjects were limited to healthy individuals and randomized, controlled trials on human serum lipid levels, especially LDL-C, conducted. A total of 17 trials (n = 1356) met all of the inclusion criteria. According to weighted mean differences for changes from baseline with 95% confidence intervals (CI), 107-856 mg/d of EGCG for 4 to 14 weeks reduced LDL-C by -9.29 mg/dl (95% CI, -12.27 to -6.31). Sub-analysis was performed to compare the EGCG lowering effect on LDL-C between non-obese and obese subjects, EGCG dose, baseline of LDL-C levels, or BMI. We concluded that consumption of green tea EGCG resulted in a significant reduction of LDL-C at any baseline level and any dose between 107 and 856 mg/d, and the effect size was slightly dependent on the baseline lipid level of the subjects.

[Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells.

BACKGROUND: Stimulation with antigen and IgE is known to activate NF-κB in mast cells. In the present research, we studied the role of NF-κB on cellular migration in mast cell-like RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) using the NF-κB inhibitor (-)-DHMEQ. METHODS: A Matrigel invasion chamber was used to evaluate cell migration. A PCR array was used to screen the expression of 84 key genes involved in cell migration. RESULTS: (-)-DHMEQ inhibited antigen/IgE-induced NF-κB activation and expressions of its target genes such as IL-6 and TNF-α. (-)-DHMEQ was found to inhibit in vitro invasion toward the antigen without any toxicity. We then looked for NF-κB-dependent genes that would be important for mast cell invasion using the PCR array. (-)-DHMEQ was found to lower the expression of matrix metalloproteinase (MMP)-2. The MMP inhibitor GM6001 also inhibited cellular invasion toward the antigen. These effects of (-)-DHMEQ were obtained in both RBL-2H3 cells and BMMCs. CONCLUSIONS: These findings indicate that (-)-DHMEQ suppressed mast cell migration via the inhibition of NF-κB-regulated MMP-2 expression.

Cloning and characterization of a novel O-methyltransferase from Flammulina velutipes that catalyzes methylation of pyrocatechol and pyrogallol structures in polyphenols.

A novel O-methyltransferase gene was isolated from Flammulina velutipes. The isolated full-length cDNA was composed of a 690-nucleotide open reading frame encoding 230 amino acids. A database search revealed that the deduced amino acid sequence was similar to those of other O-methyltransferases; the highest identity was only 61.8% with Laccaria bicolor. The recombinant enzyme was expressed by Escherichia coli. BL21 (DE3) was assessed for its ability to methylate (-)-epigallocatechin-3-O-gallate (EGCG). LC-TOF-MS and NMR revealed that the enzyme produced five kinds of O-methylated EGCGs: (-)-epigallocatechin-3-O-(3-O-methyl)gallate, (-)-epigallocatechin-3-O-(4-O-methyl)gallate, (-)-epigallocatechin-3-O-(3,4-O-dimethyl)gallate, (-)-epigallocatechin-3-O-(3,5-O-dimethyl)gallate, and (-)-4'-O-methylepigallocatechin-3-O-(3,5-O-dimethyl)gallate. The substrate specificity of the enzyme for 20 kinds of polyphenols was assessed using the crude recombinant enzyme of O-methyltransferase. This enzyme introduced methyl group(s) into polyphenols with pyrocatechol and pyrogallol structures.

In vitro-in vivo correlation of the effect of supersaturation on the intestinal absorption of BCS Class 2 drugs.

The aim of this study was to establish an in vitro method for evaluating the effect of supersaturation on oral absorption of poorly water-soluble drugs in vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model drugs. Supersaturation of each drug was induced by diluting its stock solution by fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then dissolution and precipitation profile of the drug was observed in vitro. The crystalline form of the precipitate was checked by differential scanning calorimetry (DSC). For comparison, control suspension was prepared by suspending a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal absorption of the drug was observed in rats by determined the plasma concentration after intraduodenal administration of drug suspensions. For all drugs, suspensions prepared by solvent-shift method showed significantly higher dissolved concentration in vitro than that prepared by powder-suspending method, clearly indicated the induction of supersaturation. DSC analysis revealed that crystalline form of the precipitate profoundly affects the extent and the duration of supersaturation. A rat in vivo study confirmed that the supersaturation of these drugs increased the fraction absorbed from the intestine, which corresponded well to the in vitro dissolution and precipitation profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption study was performed in rats pretreated with 1-aminobenzotriazole, a potent inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the high luminal concentration of ketoconazole caused by supersaturation saturated the metabolic enzymes and further increased the systemic exposure of the absorbed drug. The additional effects of supersaturation on the absorption of ketoconazole are consistent with previous studies in humans under differing gastric pH conditions. In conclusion, effects of supersaturation on the intestinal absorption of poorly water-soluble drugs could be predicted from in vitro dissolution and a precipitation study. However if supersaturation affects the pharmacokinetic profiles of drugs, such as a first-pass metabolism, a combination with in vivo study should be required to evaluate its impact on oral bioavailability.

Purification and characterization of a novel O-methyltransferase from Flammulina velutipes.

An enzyme catalyzing the methylation of phenolic hydroxyl groups in polyphenols was identified from mycelial cultures of edible mushrooms to synthesize O-methylated polyphenols. Enzyme activity was measured to assess whether methyl groups were introduced into (-)-epigallocatechin-3-O-gallate (EGCG) using SAM as a methyl donor, and (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me), (-)-epigallocatechin-3-O-(4-O-methyl)-gallate (EGCG4″Me), and (-)-epigallocatechin-3-O-(3,5-O-dimethyl)-gallate (EGCG3″,5″diMe) peaks were detected using crude enzyme preparations from mycelial cultures of Flammulina velutipes. The enzyme was purified using chromatographic and two-dimensional electrophoresis. The purified enzyme was subsequently analyzed on the basis of the partial amino acid sequence using LC-MS/MS. Partial amino acid sequencing identified the 17 and 12 amino acid sequences, VLEVGTLGGYSTTWLAR and TGGIIIVDNVVR. In database searches, these sequences showed high identity with O-methyltransferases from other mushroom species and completely matched 11 of 17 and 9 of 12 amino acids from five other mushroom O-methyltransferases.

Metabolic stability and inhibitory effect of O-methylated theaflavins on H2O2-induced oxidative damage in human HepG2 cells.

Seven new O-methylated theaflavins (TFs) were synthesized by using O-methyltransferase from an edible mushroom. Using TFs and O-methylated TFs, metabolic stability in pooled human liver S9 fractions and inhibitory effect on H(2)O(2)-induced oxidative damage in human HepG2 cells were investigated. In O-methylation of theaflavin 3'-O-gallate (TF3'G), metabolic stability was potentiated by an increase in the number of introduced methyl groups. O-methylation of TF3,3'G did not affect metabolic stability, which was likely because of a remaining 3-O-galloyl group. The inhibitory effect on oxidative damage was assessed by measuring the viability of H(2)O(2)-damaged HepG2 cells treated with TFs and O-methylated TFs. TF3,3'G and O-methylated TFs increased cell viabilities significantly compared with DMSO, which was the compound vehicle (p < 0.05), and improved to approximately 100%. Only TF3'G did not significantly increase cell viability. It was suggested that the inhibitory effect on H(2)O(2)-induced oxidative damage was potentiated by O-methylation or O-galloylation of TFs.

'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). METHODS: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. RESULTS: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. CONCLUSIONS: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

'Benifuuki' Green Tea Containing O-Methylated Catechin Reduces Symptoms of Japanese Cedar Pollinosis: A Randomized, Double- Blind, Placebo-Controlled Trial.

BACKGROUND: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). METHODS: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700 ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. RESULTS: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. CONCLUSIONS: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/µL for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC.