Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.

Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.

Finite element analysis of changes in tensile strain and deformation by airbag impact in eyes of various axial lengths.

PURPOSE: Airbags have substantially reduced mortality and morbidity, while ocular injuries caused by airbags have been reported. We applied a three-dimensional finite element analysis (FEA) model we have established for evaluation of the deformation of an intact eyeball of various axial lengths induced by an airbag impact at various impact velocities. METHODS: A model human eye we have created was used in simulations with an FEA program, PAM-GENERIS™ (Nihon ESI, Tokyo, Japan). The airbag was set to impact eyes with various axial lengths of 21.85 mm (hyperopia), 23.85 mm (emmetropia) and 25.85 mm (myopia), at initial velocities of 30, 40, 50 and 60 m/s. Changes in the shape of the eye and the strain induced were calculated. Deformation of the eye in a cross-sectional view was displayed sequentially in slow motion. RESULTS: We found that considerable damage, such as corneal or scleral lacerations, was observed especially at higher impact velocities, such as 50 or 60 m/s, in eyes with any axial length. Deformation was most evident in the anterior segment. The decrease rate of axial length was greatest in the hyperopic eye, followed by the myopic eye, and the emmetropic eye. CONCLUSIONS: It was shown that hyperopic eyes are most susceptible to deformation by an airbag impact in this simulation. The considerable deformation by an airbag impact on the eye during a traffic accident shown in this study might indicate the necessity of ocular protection to avoid permanent eye damage.

The effects of intensive oral care before surgery for gastric cancer patients.

OBJECTIVES: Oral function management has been recognized as important strategy for preventing postoperative complications. In this historical cohort study, we focused on the patients who planed gastrectomy, and investigated the appropriate duration and frequency of preoperative oral care to prevent complications after surgery. METHODS: Patients who planed surgery for gastric cancer between 2012 and 2018 were enrolled. We defined intensive oral care (IOC) as initial intervention at least three weeks before surgery and follow-up intervention within a week before surgery. As the primary outcome, the incidence of postoperative infectious complications was compared between the IOC and non-intensive oral care groups. RESULTS: A total of 576 patients were enrolled, including 66 with IOC. The incidence of infectious complications was 2/66 (3.0%) in the IOC group and 64/510 (12.5%) in the non-intensive oral care group. After adjusting for confounding factors, patients with IOC exposure had a lower chance of developing postoperative infectious complications (odds ratio; 0.217, 0.051-0.927). CONCLUSIONS: Intensive oral care can help prevent postoperative infectious complications after gastrectomy. These findings suggest that appropriate preoperative oral care includes at least two interventions: three weeks or more before and within one week before surgery.

Development of Morin-Loaded Nanoemulsions Containing Various Polymers; Role of Polymers in Formulation Properties and Bioavailability.

Emulsions for oral delivery are not suitable for sustained drug absorption because such preparations diffuse rapidly in the gastrointestinal (GI) tract after oral administration. In order to generate sustained drug absorption and increase oral bioavailability, various polymers were added to a morin (MO) nanoemulsion to improve retention in the GI tract and alter the surface properties of oil droplets in the nanoemulsion. The influence of these polymers on the formulation properties was investigated. The area under the blood concentration-time curve (AUC) and the mean residence time (MRT) after oral administration of the nanoemulsions were measured, and the influence of the polymers on bioavailability was investigated. Chitosan (Chi) addition MO nanoemulsion (MO-Chi nanoemulsion) showed the highest AUC and MRT. MO-Chi nanoemulsion increased retention in the GI tract because of the relatively higher viscosity and high affinity between mucin and Chi covering the oil droplets. Furthermore, MO-Chi nanoemulsion could maintain the drug in oil droplets by suppression of drug release through the polymer hydration layer, and sustained drug release achieved continuous drug absorption. Nanoemulsions with sodium carboxymethylcellulose and poly-γ-glutamic acid potassium salt showed the next highest AUC and MRT after MO-Chi nanoemulsion. From these results, it was suggested that by increasing the viscosity of the nanoemulsion, there was high affinity between the added polymer and mucin, and sustained drug release was useful for enhancing the bioavailability of the polymer-containing nanoemulsions.

[Bendamustine and rituximab combination therapy for recurrent indolent B-cell lymphomas: a retrospective single-institution study].

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

Clinical impact of periodontal disease on postoperative complications in gastrointestinal cancer patients.

BACKGROUND: The effectiveness of perioperative oral management in gastrointestinal surgery remains unclear. To elucidate the clinical significance of oral care, we investigated the relationship between the oral environment and postoperative infectious complications (POICs) in patients undergoing gastrointestinal surgery. METHODS: This was a single-institute and historical cohort study of 341 patients. The participants were isolated from consecutive patients undergoing planned radical resection for gastrointestinal carcinoma from January 2016 to June 2017. Dentists assessed the oral environment for periodontal disease, hygiene status, dry mouth, fur on tongue, and tooth stumps. All patients received scaling and tooth brushing instructions. A stepwise logistic regression analysis was conducted to identify risk factors for POICs among the different oral statuses. RESULTS: The surgical procedures performed were gastrectomy in 123 (36.1%), colorectal resection in 185 (54.2%), and pancreatoduodenectomy or others in 38 (11.1%). POICs occurred in 48 patients (14.1%), including deep organ space infection in 20, surgical site infection in 11, anastomotic leakage in 5, urinary tract infection in 4, pneumonia in 2, and others in 6. After adjusting for confounding factors, periodontal disease was isolated as an independent risk factor for POICs (odds ratio 2.091, p = 0.037, 95% confidence interval 1.045-4.183). Other variables of oral environment such as hygiene status, dry mouth, fur on tongue, and tooth stumps did not have a significant impact on POICs. CONCLUSIONS: Periodontal disease is a risk factor for infectious complications after gastrointestinal surgery.

Influence of Polysorbate 60 on Formulation Properties and Bioavailability of Morin-Loaded Nanoemulsions with and without Low-Saponification-Degree Polyvinyl Alcohol.

The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets. MCT-LL810 nanoemulsion containing LL-810 was prepared with a reduced amount of Tween 60. However, the area under the blood concentration-time curve (AUC) of MCT-LL810 (0.18) nanoemulsion containing a small amount of Tween 60 did not increase because the absorption of morin was limited by P-glycoprotein (P-gp)-mediated efflux. MCT-LL810 (0.24) nanoemulsion containing a large amount of Tween 60 showed the highest AUC, dispersed droplets containing Tween 60 may have been transported into epithelial cells in the small intestine, and P-gp transport activity appeared to be suppressed by permeated Tween 60. Based on the plasma concentration profile, dispersed droplets in MCT-LL810 (0.24) nanoemulsion permeated more rapidly through the mucus layer and the intestinal membrane than MCT (0.24) nanoemulsion without LL-810. In conclusion, a novel feature of Tween 60 incorporated into the dispersed droplets of a nanoemulsion interacting with P-gp was demonstrated herein. Dispersed droplets in MCT-LL810 (0.24) nanoemulsion containing LL-810 permeated rapidly through the mucus layer and intestinal membrane, and Tween 60 incorporated in dispersed droplets interacted with P-gp-mediated efflux, increasing the bioavailability of morin.

Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets using PEG and hard fat showed sufficient adhesiveness and sustained drug release, those using PEG as the base did not. Drug release was controlled by the amount of hard fat and the saponification degree of PVA. The drug release rate was most increased in a tablet containing PVA with an intermediate degree of saponification, PEG and hard fat. From differential scanning calorimetry and powder X-ray diffraction, IM was considered to exist in the molecular phase. From the results of buccal administration of tablets to rats, highest tissue concentrations were observed in the tablet containing PVA with the intermediate degree of saponification using PEG and hard fat, and the plasma concentrations were sufficiently low in comparison.

Uncoupling endocardial bundles coupled by an epicardial bundle in the left atrium and pulmonary veins.

Uncoupling of the endocardial bundles in the left atrium was suggested during modified posterior wall isolation. Although this fact may not be observed because of the possible bridging conduction by epicardial bundles in humans, partially failed transmural ablation in the atrial roof may have iatrogenically unveiled this fact.

Epidemiological shifts in and impact of COVID-19 on streptococcal toxic shock syndrome in Japan: A genotypic analysis of group A Streptococcus isolates.

OBJECTIVES: Streptococcal toxic shock syndrome (STSS) is caused by group A Streptococcus (GAS; Streptococcus pyogenes) strains. In Japan, the number of STSS cases has decreased; however, the underlying reason remains unclear. Moreover, information on distribution and prevalence of specific emm types in STSS cases is scarce. Hence, we investigated the reason for the decreased number of STSS cases in Japan. METHODS: We genotyped emm of 526 GAS isolates obtained from 526 patients with STSS between 2019 and 2022. The distributions of emm types in each year were compared. RESULTS: The emm1 type was predominant, with the highest proportion in 2019, which decreased after 2020 following the onset of the coronavirus disease 2019 (COVID-19) pandemic. Strains isolated during the pandemic correlated with strains associated with skin infection, whereas those isolated during the prepandemic period correlated with strains associated with both throat and skin infections. The decrease in the annual number of STSS cases during the COVID-19 pandemic could be due to a decreased proportion of strains associated with pharyngeal infections. CONCLUSIONS: Potential associations between pandemic and STSS numbers with respect to public health measures, such as wearing masks and changes in healthcare-seeking behavior, may have affected the number of GAS-induced infections.

Three layers in spinal canal.

Contrast-enhanced computed tomography revealed spontaneous spinal epidural hematoma, which mimicked aortic dissection.

Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes.

This study aimed to identify the serum metabolites associated with sarcopenic risk in Japanese patients with type 2 diabetes, determine the effect of dietary protein intake on the serum metabolic profile, and examine its association with sarcopenia. Ninety-nine Japanese patients with type 2 diabetes were included, and sarcopenic risk was defined as low muscle mass or strength. Seventeen serum metabolites were quantified after gas chromatography-mass spectrometry analysis. The relationship between dietary protein intake and the metabolites concerning sarcopenia was analyzed, and the factors affecting sarcopenic risk were clarified. Twenty-seven patients were classified as being at risk of sarcopenia, the same as the general risk, which was associated with older age, a longer duration of the disease, and a lower body mass index. Low levels of leucine and glutamic acid were significantly associated with low muscle strength (p = 0.002 and p < 0.001, respectively), and leucine was also associated with muscle mass (p = 0.001). Lower levels of glutamic acid had higher odds of sarcopenic risk after being adjusted for age and HbA1c (adjusted OR 4.27, 95% CI 1.07-17.11, p = 0.041), but not for leucine. Leucine and glutamic acid can serve as useful biomarkers for sarcopenia, highlighting potential targets for its prevention.

Serotype Distribution and Antimicrobial Resistance of Streptococcus agalactiae Isolates in Nonpregnant Adults with Streptococcal Toxic Shock Syndrome in Japan in 2014 to 2021.

The incidence of streptococcal toxic shock syndrome (STSS) due to group B Streptococcus (GBS) has been increasing annually in Japan and is becoming a serious challenge. Furthermore, in recent years, penicillin- or clindamycin-resistant strains used in treating streptococcal toxic shock syndrome have been reported. However, no report analyzed >100 isolates of group B Streptococcus causing streptococcal toxic shock syndrome. Therefore, we aimed to perform serotyping and antimicrobial susceptibility testing of 268 isolated group B Streptococcus strains from streptococcal toxic shock syndrome cases involving nonpregnant adult patients in Japan between 2014 and 2021. The most prevalent serotype was Ib, followed by serotypes V, III, and Ia. Seven isolates were resistant to penicillin G, and 17.9% (48 isolates) were resistant to clindamycin. Of the penicillin-resistant group B Streptococcus isolates, 71.4% (5 isolates) were clindamycin resistant. In addition, group B Streptococcus strains resistant to penicillin and clindamycin were isolated from patients with streptococcal toxic shock syndrome. Therefore, before these strains become prevalent, introduction of the group B Streptococcus vaccine is essential for disease prevention. IMPORTANCE Group B Streptococcus (GBS) has been increasingly associated with invasive disease in nonpregnant adults. Such infections are responsible for substantial morbidity and mortality, particularly in individuals with underlying chronic conditions. Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. In this study, we assessed 268 GBS-related STSS cases in nonpregnant adults in Japan between 2014 and 2021. Serotype Ib was the most prevalent, followed by serotypes V, III, and Ia, which were identified in more than 80% of STSS isolates. We found that 48 clindamycin-resistant strains and 7 penicillin G-resistant strains were isolated between 2014 and 2021. We believe that our study makes a significant contribution to the literature because we show that the GBS vaccine, particularly the hexavalent conjugate vaccine, is important to reduce the number of patients with STSS.

Metabolic phenotypes and incident type 2 diabetes: Population-based Panasonic cohort study 6.

OBJECTIVE: This study aimed to assess the association between changes in metabolic phenotypes and incident type 2 diabetes. METHODS: This retrospective cohort study included participants from a medical health checkup program conducted by the Panasonic Corporation, Japan, between 2008 and 2018. The metabolic phenotypes of the participants in 2008 and 2013 were assessed. The association between changes in metabolic phenotypes from 2008 to 2013 and incident type 2 diabetes (n = 58,638) were evaluated for a 5-year follow-up using Cox regression analyses. RESULTS: The stable, metabolically healthy obesity group was associated with a higher risk of incident type 2 diabetes than the stable, metabolically healthy nonobesity (MHNO) group (hazard ratio [HR] 3.22, 95% CI: 2.71-3.83). When participants with metabolically healthy obesity experienced a change to MHNO, their risk of incident type 2 diabetes was similar to that of participants in the stable MHNO group (HR 1.28, 95% CI: 0.78-1.90). Once the participants had metabolic abnormalities, the risk of incident type 2 diabetes was higher than that in the stable MHNO group, even after undergoing a change to MHNO. CONCLUSIONS: This study demonstrates that it is important to pay attention to the changes in metabolic phenotypes to prevent incident type 2 diabetes in Japanese populations.

Analysis of Cytokine Production Profiles of Local and Systemic Lymphocytes in Sick Building Syndrome Compared with Ocular Allergy.

Purpose: We have previously studied clinical and allergological aspects of sick building syndrome (SBS) cases with ocular disorders and found that SBS is suggested to be partially induced by an allergic response. We analyzed the cytokine production profiles of conjunctival and peripheral blood lymphocytes in patients with SBS with ocular manifestations to further evaluate the pathophysiology of SBS from an immunological standpoint. Methods: We obtained conjunctival samples and peripheral blood mononuclear cells (PBMC) from 15 cases of SBS with ocular findings, 49 cases of allergic conjunctival diseases (ACD) (allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC)), and normal controls. Frequencies of cytokine-producing T cells were analyzed by flow cytometry based on an intracellular cytokine staining method. Results: Although no significant difference was observed in the percentage of interferon (IFN)-γ-producing CD4+ T cells in PBMC between patients with SBS and controls, the percentage of interleukin (IL)-4-producing PBMC CD4+ T cells in patients with SBS was significantly higher than that in controls. The percentage of IL-4-producing CD4+ T cells in the conjunctiva in patients with SBS was significantly higher than that in controls, whereas it was significantly lower than that in AKC and VKC. A significant correlation was observed between the percentage of IL-4-producing CD4+ T cells in the conjunctiva and clinical score. Conclusion: These results suggest that SBS may be a kind of allergic disorder and that IL-4 plays a role in the development of allergic disorders in SBS ocular lesions.

Gut Microbiota Changes by an SGLT2 Inhibitor, Luseogliflozin, Alters Metabolites Compared with Those in a Low Carbohydrate Diet in db/db Mice.

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

A case of fungal conjunctivitis with giant papillae treated surgically.

Fungal conjunctivitis is a rare disorder, with low incidence and difficulty in diagnosis due to a lack of specific clinical findings. We report a case of fungal conjunctivitis which exhibited a specific clinical feature of giant papilla formation, and its diagnosis was a complex process. A 19-year-old woman with a history of atopic dermatitis and hard contact lens use was referred to us with a 3-month history of giant papillary conjunctivitis of the right eye in spite of treatment with antiallergic and corticosteroid eye drops, complicated by intraocular pressure elevation. The left eye showed no symptom of ocular surface disorder throughout the clinical course. The right eye did not respond to oral corticosteroid. Polymerase chain reaction of conjunctival scrapings against Chlamydia trachomatis was negative, and she was treated surgically by total papilla resection. Conjunctival giant papilla recurrence was not observed after surgery. Although the primary histopathological diagnosis was chronic inflammation due to atopic keratoconjunctivitis, repeated histopathological survey of excised conjunctival tissue including immunohistochemical staining revealed histiocytes, yeast type spores and hyphae, and phagocytosed spores and hyphae in macrophages. The causative organism was identified morphologically as a Candida species. Later, histopathological examination of a cervical swab revealed the presence of Candida sp. This rare case indicates that a fungal organism may underlie refractory conjunctivitis with specific giant papillary hypertrophy mimicking vernal keratoconjunctivitis.

Factors affecting psychosocial development of very low birth weight infants at 18 and 36 months of age.

AIM: To identify relationships between neonatal factors including conditions and treatments, nurturing environment, and psychosocial development of children born at very low birth weight (VLBW). METHODS: In this longitudinal study, the medical records of 113 VLBW infants were examined, and the children were then followed up at 18 and 36 months of age. Their developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development (KSPD), and their parents were asked about their own health, financial situation, education, and family support. Pearson's correlation and stepwise multiple regression analyses were used to explore relationships between DQ, potentially significant predictors on the KSPD, and nurturing environment. RESULTS: DQ at 18 months was associated with the following neonatal factors: mechanical ventilation days (ß = -.241, p = .020), Apgar score at 5 min (ß = .278, p = .005), periventricular leukomalacia (ß = -.218, p = .006), and treatment for retinopathy of prematurity (ß = -.171, p = .048) (adjusted R2 = .32). DQ at 36 months was associated with the following neonatal and parenting factors: mechanical ventilation days (ß = -.354, p < .001), periventricular leukomalacia (ß = -.207, p = .009), sex (ß = -.199, p = .011), mother's educational background (ß = -.304, p < .001), mother's health status (ß = -.159, p = .042) (adjusted R2 = .35). CONCLUSIONS: These findings suggest that in addition to neonatal clinical parameters including conditions and treatments, the nurturing environment after discharge from the neonatal intensive care unit influences the psychosocial development of VLBW infants.

PD-1 gene polymorphisms and thyroid expression of PD-1 ligands differ between Graves' and Hashimoto's diseases.

The programmed cell death-1 (PD-1)/PD ligand pathway plays a key role in the maintenance of peripheral tolerance by enhancing the suppressive activity of regulatory T (Treg) cells. The promoter activity of the A allele of PD1 rs36084323 G/A polymorphism is lower than that of the G allele. We examined the association of PD1 gene polymorphisms, PD-1 expression on Treg cells, and thyroid PD-1/PD-1 ligand (PD-L1) expression with the pathogenesis of autoimmune thyroid disease (AITD). We classified patients and genotyped PD-1 polymorphisms by using the PCR-RFLP method in a total of 176 Graves' disease (GD) patients, 150 Hashimoto's disease (HD) patients with different disease severities and 99 healthy controls. PD-1 expression on Treg cells was analysed by flow cytometry. Indirect immunofluorescence staining was performed in thyroid tissue to detect PD-1, PD-L1, and PD-L2. The frequencies of the A allele and the AA + AG genotypes of the PD1 rs36084323 polymorphism were lower in HD patients than in GD patients, and the frequencies of the AA genotype of the PD1 rs36084323 and of the TT genotype of the PD1 rs2227982 were lower in mild HD patients than in severe HD patients. In patients with severe HD, the titres of TgAb at the onset were higher in patients with the PD1 rs36084323 AA genotype than in patients with the GG genotype. Peripheral PD1+ Treg cells tended to decrease in individuals with the PD1 rs36084323 AA genotype than with the G carrier genotype. Peripheral PD-1+ Treg cells were increased in HD, especially in mild HD. PD-1, PD-L1, and PD-L2 were expressed in thyroid-infiltrating mononuclear cells (TIMCs), and PD-L1 and PD-L2 were expressed in thyroid epithelial cells (TECs) in AITD patients but not in normal controls. Expression of PD-L1 in TIMCs and expression of PD-L2 in TECs were predominant in HD and GD patients, respectively. In conclusion, the functional PD1 rs36084323 polymorphism and the thyroid PD-1/ PD-L1s expression which may enhance the suppressive activity of Treg cells differ between GD and HD, and the PD1 rs36084323 and rs2227982 polymorphisms and PD1+ Treg cells are related to the severity of HD.

The expression of trefoil factor 3 is related to histologic subtypes and invasiveness in lung adenocarcinoma.

Adenocarcinoma is the most common histological type of lung cancer and has various histologic subtypes, including lepidic, papillary, acinar and invasive mucinous adenocarcinoma. Histologic subtypes are associated with tumor invasiveness. For example, the lepidic subtype is less invasive than the papillary/acinar subtype. Trefoil factor 3 (TFF3) is a small secreting protein that is a member of the trefoil factor family, which is involved in mucosal stabilization and repair through its mitogenic and antiapoptotic activities. TFF3 overexpression is associated with various types of cancer. In lung cancer, TFF3 is expressed significantly in adenocarcinoma. However, the relationship between TFF3 expression and histologic subtypes in lung adenocarcinoma is unclear. The current study immunohistochemically revealed that, beside invasive mucinous carcinoma, the expression of TFF3 in papillary and acinar adenocarcinoma was significantly higher than that in lepidic adenocarcinoma. To further confirm these results, the expression of TFF3 in cases with both lepidic and papillary/acinar areas were examined. The expression of TFF3 in papillary/acinar areas was significantly higher when compared with lepidic areas in a single sample. Furthermore, using the lung adenocarcinoma cell line A549, TFF3-knockdown cells were generated. The results revealed that knockdown of TFF3 attenuated invasion. In vitro and immunohistochemical assays using clinical samples demonstrated that TFF3 expression was associated with lung adenocarcinoma invasiveness. To the best of our knowledge, the current study is the first to report that TFF3 expression was associated with the histologic subtypes of lung adenocarcinoma.