CD4⁺ T lymphocytes play an essential role in adaptive immune responses and comprise naïve, effector, and memory compartments. In pathogen infection, foreign antigen (Ag)-specific naïve T lymphocytes are activated to give rise to effector and memory cells to contribute to host protection from the pathogen. In addition to the conventional activation pathway, accumulating evidence suggests that some naïve cells can weakly respond to self-Ags to convert to “memory-phenotype (MP) cells” in steady state. Whereas newly generated MP cells adopt a rapidly proliferating, undifferentiated feature, they cease to divide with time while differentiating into distinct subsets including T helper type 1 (Th1)-like “MP1,” T helper type 17 (Th17)-like “MP17,” follicular helper T (Tfh)-like “MPfh,” and regulatory T cells. Functionally, these MP subsets can exert innate and adaptive immune responses to contribute to infectious and anti-tumor immunity as well as autoimmunity, demonstrating both physiological and pathological aspects of MP T lymphocytes. Furthermore, recent reports suggest that self-reactive MP cells are also existent in humans. In this article, I will review our current understanding on generation, maintenance, differentiation, and immunological functions of MP CD4⁺ T lymphocytes and discuss their potential as a new therapeutic target in several disease contexts.

To investigate the cataract-detecting ability of MEOCHECK, a novel, simple visual field measurement device, we undertook cataract examinations in 90 eyes of 45 male taxi drivers (chosen because their occupation requires a high degree of visual function) using conventional ophthalmological techniques (refraction, intraocular pressure, logMAR visual acuity, central foveal threshold, and Humphrey Field Analyzer 24-2-measured mean deviation) and MEOCHECK. Cataracts were graded according to the WHO Simplified Cataract Grading System (WHOSCGS) criteria. After the exclusion of 17 eyes with inserted intraocular lenses, a history of ocular disease, and missing both logMAR and IOP value, 72 eyes were enrolled in the present study. According to the WHOSCGS criteria, 17 eyes had nuclear cataract grade 0 (NUC0), 43 eyes had nuclear cataract grade 1 (NUC1), and 12 eyes had nuclear cataract grade 2 (NUC2). To evaluate the diagnostic power of each measurement factor, receiver operating characteristic (ROC) curves were plotted using sensitivity and specificity and the area under the curve (AUC) was measured as an indicator of the performance of a binary classifier. In discrimination between NUC0/1 and NUC2, the AUCs for age and MEOCHECK score were calculated to be 0.857 and 0.914, respectively. Comparing NUC0/1 with NUC2 in the 70-79-year age group showed that there was no significant difference in age, but was a significant difference in MEOCHECK score. Based on these findings, MEOCHECK, based on retinal projection technology, efficiently discriminated NUC2 from NUC0/1 in taxi drivers, indicating that MEOCHECK has the potential to detect cataracts.

We present the treatment by facelift procedure of three cases of dermoid cyst with oral and submental components, illustrated by the case of a 15-year-old girl with a mass in the oral cavity who had had difficulty in chewing and swallowing solid foods for 2 years. Our experience shows that treatment by facelift procedure provides adequate visualization, a good workspace, and excellent cosmetic results in suitably selected cases of dermoid cyst.

Strong coughing cleans the airways and prevents respiratory diseases. Cough intensity is regulated by respiratory muscle strength, which is improved by high- rather than low-intensity respiratory muscle training. Body trunk angles affect respiratory muscle force and function in healthy adults. Tetraplegic patients generally exhibit respiratory muscle weakness, leading to weak coughing and dyspnea, improved by 6-9 weeks of respiratory muscle exercise. However, the effects of semi-recumbent positions and long-term high-intensity respiratory muscle exercise on respiratory muscle strength and dyspnea in tetraplegic patients remain unclear. A male patient with a C4 spinal cord injury underwent high-intensity inspiratory muscle exercise for one year. We evaluated the abovementioned symptoms and explored the optimal trunk angle and exercise duration. We measured maximal inspiratory and expiratory pressures, respiratory functions such as vital capacity, and dyspnea at 45-degree, 30-degree, and 0-degree (supine) body trunk angles for one year. The inspiratory muscle force was generally stronger at the 45-degree position than in the supine position. In contrast, the supine position showed a trend toward greater respiratory functions and improved dyspnea than the 45-degree position. Inspiratory muscle force tended to strengthen until 6 months and then became stable. Expiratory pressures tended to be greater after 8 months. Vital capacity showed a trend greater at 12 months than at 0 months. Post-activity dyspnea continuously improved for up to 12 months. Thus, maintaining long-term high-intensity exercise and a 45-degree body trunk angle may be beneficial in strengthening inspiratory muscle force and alleviating dyspnea in tetraplegia.

Japan has the most aged population globally, and the number of older people requiring long-term care and deaths is increasing yearly. Therefore, it is essential to explore issues so that older patients can receive appropriate medical and long-term care in their respective living places. This study aimed to clarify the characteristics and death circumstances of older patients who are emergency admitted to a hospital for acute inpatient treatment based on the differences between their home and nursing home. The analysis was conducted using Japan’s nationwide administrative database. We collected discharge records of patients aged 65 or older who were emergency admitted. Those who had received home-visit medical care before admission and were admitted to a nursing home were selected and categorized into the home and nursing home groups. Patient characteristics were shown by group, and factors determining group differences were estimated using logistic regression analysis. 196,059 people in the home group and 354,864 in the nursing home group were selected. The nursing home group had significantly higher rates of long-term care needs level and dementia and was more likely to receive lifesaving treatment and confirmation of death at admission. It became clear that the nursing home group was more likely to be emergency admitted in a fatal condition. We recommend that medical professionals, care workers, and policymakers understand these trends so that older patients can receive appropriate medical and long-term care services in their places of living until the last days of their lives.

The relationship between Gestational Diabetes Mellitus (GDM) and Retinopathy of Prematurity (ROP) is not fully understood, but both conditions may share critical molecular biomarkers. This study integrated datasets to identify genes associated with GDM and ROP. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct networks and identify gene modules related to GDM and ROP. Three machine learning models were utilized to filter for core co-morbid genes. Immune infiltration analysis was performed to investigate the correlations of these genes with immune cells. Finally, a diagnostic nomogram model was constructed based on the expression levels of the three core co-morbid genes, and Receiver Operating Characteristic (ROC) curve analysis was conducted to assess its diagnostic capabilities. We identified 16 co-morbid genes associated with GDM and ROP. Through machine learning model filtering, chorionic gonadotropin beta subunit 7 (CGB7), MYCN upstream transcript (MYCNUTR), and G protein-coupled receptor 32 (GPR32) were confirmed as core genes. These genes exhibited significantly elevated expression levels in patients with GDM and ROP, positively correlating with activated cytotoxic T lymphocytes (CD8 T) cells and negatively correlating with central memory CD8 T cells. The diagnostic nomogram model achieved an Area Under the Curve (AUC) value of 0.913 in the GDM training set and 0.875 in the ROP training set. This study reveals a potential shared critical role for CGB7, MYCNUT, and GPR32 in the interplay between GDM and ROP. The constructed diagnostic nomogram model shows promising predictive capability.

Elevated histone lactylation is crucial in the initiation and progression of various cancers. Although its role in breast cancer remains unconfirmed, the increased lactate release from enhanced glycolysis in triple-negative breast cancer (TNBC) suggests a potential link. In order to investigate the effect of histone lactylation on TNBC, we detected the lactate production and histone lactylation levels. Chromatin immunoprecipitation (ChIP) assay was used to confirm that minichromosome maintenance complex component (MCM) 7 is a downstream target. A variety of experimental techniques including, cell viability, colony formation assay, apoptosis assay, and transwell assay were used to describe the cell proliferation and migration ability. Histone lactylation levels were increased in TNBC tissues. Inhibiting lactate production suppressed the proliferation and migration of TNBC cells and histone lactylation in TNBC cells. Histone lactylation modulated MCM7 expression and translation, and MCM7 participated in histone lactylation regulation of TNBC cell function. These data show that enhanced glycolysis in TNBC cells results in increased lactate production, directly contributing to histone lactylation and subsequent activation of MCM7 promoter. Our results highlight that targeting the feedback loop involving glycolysis, lactate production, histone lactylation, and MCM7 transcription could be a therapeutic strategy for TNBC by inhibiting cell proliferation and migration.

The growth of cancer is one of the many physiological and pathological processes that depend on ferroptosis, an iron-dependent kind of programmed cell death. This study examines how ferroptosis is regulated and how it affects the development of hepatocellular carcinoma (HCC) by means of the sterol carrier protein 2 (SCP2)/heat shock protein family B (small) member 1 (HSPB1) axis. The effects of SCP2 overexpression and the ferroptosis inhibitor Ferrostain-1 on cell viability, proliferation, invasion, and the expression of HSPB1 and ferroptosis-related genes were evaluated using cell counting kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) assays, transwell assays, and protein expression analysis. Overexpression experiments were conducted to further explore the impact of HSPB1 and SCP2 on HCC cell function and ferroptosis. In HCC cell lines, overexpression of SCP2 significantly inhibited cell proliferation and invasion, while enhancing ferroptosis through the upregulation of malondialdehyde (MDA) and downregulation of antioxidant proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) and nuclear factor erythroid 2-related factor 2 (Nrf2). Notably, overexpression of HSPB1 reversed the effects of SCP2 on the viability, proliferation, invasion and ferroptosis of HCC cells. The SCP2/HSPB1 axis plays a crucial role in HCC progression, SCP2 inhibits the progression of HCC by suppressing the expression of HSPB1 to inducing ferroptosis. According to our results, focusing on the SCP2/HSPB1 axis may offer a unique treatment strategy to manage the evolution of HCC and get past ferroptosis-related resistance.

Lymph node (LN) metastasis is one of the most common mechanisms underlying the spread of solid cancers. Mouse models of orthotopic tumor transplantation have been used to elucidate the metastatic mechanisms. Previous studies have mainly focused on metastasis in orthotopic models, and the correlation between histological findings of infiltrated cancer cells and tumor microenvironment has not been fully explored. Cancer-associated fibroblasts (CAFs) play a key role in metastasis, especially via secreting Wnt2, which plays a functional role in cancer progression. Here, we investigated the correlation between the incidence of LN metastases and histological findings in an orthotopic mouse model using 22 colorectal cancer cell lines. Lymphatic invasion was significantly associated with LN metastasis. Immunohistochemistry revealed that podoplanin and αSMA were highly expressed in the cancer stroma, thus suggesting that CAFs were also induced in the orthotopic implantation mouse model. Furthermore, Wnt2 positivity was mainly observed in the cancer stroma, and Wnt2 expression was significantly associated with the incidence of LN metastasis. Our results indicate that the orthotopic mouse model recapitulates cancer infiltration and the tumor microenvironment, including CAFs. The contribution of Wnt2 toward LN metastasis was also validated in an in vivo model. Thus, our findings provide new insights into the functional roles of CAFs and Wnt2 in metastasis.

Japan has a national financial assistance program called the “Specified Chronic Pediatric Diseases of Japan” (SCPDJ; also called “Shouman” in Japanese) for children with chronic diseases designated by the Japanese Ministry of Health, Labour and Welfare. The information of registrants in the system is digitized for research. We utilized the database to clarify the characteristics of children with diseases designated by the SCPDJ program. Analysis was performed with a particular focus on patients aged 12-19 years, which are considered the important ages for transition support from pediatric to adult medical care. The data included 69,061 cases aged 0 to 19 years from April 2016 to March 2017. The number of registrants showed a cumulative increase from 2 years toward adulthood. There were four distribution patterns for registered age and age at onset by disease category: 1) both age and age of onset peaked at age 0; 2) age distribution was mostly flat, while the most common age of onset was age 0; 3) age distribution peaked in older age groups, while age of onset of 0 was most common; and 4) both age and age of onset peaked at older ages. Approximately half of the patients aged 12-19 years were diagnosed after reaching school age. Although the disease condition of most patients remained good, some aged 12-19 years experienced exacerbation. The database was analyzed to provide an overview of children with diseases designated by the SCPDJ program and issues related to transition to adult care systems.

Ligustilide is a natural benzoquinone derivative with many pharmacological properties, including anticancer and anti-inflammatory activities. Here, we investigated the antitumor efficacy of ligustilide in gastric cancer. MKN74 and AGS cells were treated with 20, 60, and 100 µM ligustilide. The antitumor efficacy of ligustilide was studied with MTT assays, colony formation assays, and flow cytometry. Apoptosis-, endoplasmic reticulum stress-, and autophagy-associated proteins were examined by immunoblotting and immunofluorescence. JC-1 staining was used to detect mitochondrial membrane potential in cancer cells. Tumor-bearing mice were intraperitoneally injected with 5 mg/kg ligustilide. Tumor weight and tumor volume were measured after 20 days of administration. We demonstrated that ligustilide suppressed gastric cancer cell proliferation by inducing cell cycle arrest and apoptosis. Mechanistically, ligustilide disrupted mitochondrial function by increasing the Bax/Bcl-2 ratio, triggering cytochrome c release into the cytoplasm, and activating caspase-3 and PARP cleavage, ultimately leading to mitochondrial membrane potential loss. Furthermore, ligustilide enhanced autophagy, as evidenced by elevated LC3-II/LC3-I ratio and ATG5 expression, accompanied by reduced p62 levels. This autophagic response was mediated through endoplasmic reticulum stress via the PERK-eIF2α-CHOP pathway. Notably, the proapoptotic effects of ligustilide were attenuated by 4-phenylbutyric acid (an ER stress inhibitor) or 3-methyladenine (an autophagy inhibitor). Consistent with in vitro findings, 4-phenylbutyric acid also abrogated the antitumor efficacy of ligustilidein vivo by concurrently suppressing apoptosis and autophagy.Overall, ligustilide triggers mitochondrial dysfunction, autophagy, and endoplasmic reticulum stress, collectively promoting gastric cancer cell death and suppressing survival.

Immunity and inflammation contribute to the development of recurrent spontaneous abortion (RSA); tumor necrosis factor inhibitor (TNFi) is a well-known anti-inflammation treatment for immune diseases. This study aimed to investigate the effect of TNFi on pregnancy outcomes and tolerance in RSA patients. This retrospective, observational study analyzed 115 RSA patients. Forty-three patients received TNFi plus intravenous immunoglobin (IVIG) and low molecular weight heparin (LMWH) treatment (the TNFi group), whereas another 72 patients received IVIG plus LMWH or LMWH alone treatment (the Control group). TNFi agents included certolizumab, etanercept, and adalimumab. The live birth rate was greater in the TNFi group than in the Control group (72.1% vs. 45.8%, P = 0.006), whereas the premature delivery rate tended to be lower in the TNFi group vs. the Control group but did not reach statistical significance (9.7% vs. 24.2%, P = 0.123). Multivariable logistic regression revealed that treatment (TNFi vs. Control) was independently correlated with greater live birth achievement (P = 0.001, odds ratio = 5.470); furthermore, treatment (TNFi vs. Control) tended to be independently associated with a reduced premature delivery risk (P = 0.055, odds ratio = 0.178). The type of labor (P = 0.321), neonatal birth weight (P = 0.159), and newborn Apgar score (P = 0.233) did not differ between the TNFi group and the Control group. Furthermore, adverse events, including rash, gestational hypertension, abnormal liver function index, ecchymosis, fever, and abnormal renal function index were not different between the TNFi and Control groups (all P > 0.05). TNFi improves live birth rate and tends to reduce premature delivery risk in RSA patients, providing a potential treatment option.

Complications and pelvic floor dysfunction (PFD) in women after cesarean section have attracted attention. The objective was to identify novel biomarkers that would facilitate more accurate prediction of postpartum complications and PFD, thereby offering new insights into clinical prevention and management strategies. The study population consisted of 120 primigravid women who underwent cesarean section at the hospital. Serum miR-19-3p and miR-124-3p expression was determined by quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miR-19-3p and miR-124-3p for the occurrence of complications and PFD in women undergoing cesarean section. Multivariate logistic regression was utilized to analyze the risk factors associated with PFD. Fifteen out of 120 women who underwent cesarean section suffered from postpartum complications, and 28 suffered from PFD. miR-19-3p expression was upregulated, and miR-124-3p was downregulated in women presenting with complications and PFD. miR-19-3p and miR-124-3p had a predictive value for both postpartum complications and PFD. miR-19-3p combined with miR-124-3p predicted complications and PFD with an AUC of 0.814 and 0.843, respectively. In addition, miR-19-3p and miR-124-3p were risk factors for PFD in women undergoing cesarean section. In conclusion, the potential exists for the use of miR-19-3p and miR-124-3p as molecular markers to predict postoperative complications and PFD, which may prove beneficial in the management of cesarean section patients.

The expression of microRNA is likely to be closely associated with intrahepatic cholestasis of pregnancy (ICP). This study aimed to investigate the potential mechanisms underlying miR-940/RhoA-induced apoptosis in HTR8-S/Vneo cells in ICP. In this study, 80 pregnant women diagnosed with ICP were recruited, with healthy pregnant women as controls. RT-qPCR was utilized to quantify the expression levels of miR-940 and RhoA. Cell proliferation was evaluated using the CCK-8 assay, while flow cytometry was employed to assess cell apoptosis. The dual-luciferase reporter assay confirmed the targeting relationship between miR-940 and RhoA. miR-940 expression was significantly elevated in the ICP group. ROC curve analysis demonstrated that miR-940 exhibited high diagnostic accuracy for ICP. Cell proliferation assays indicated that miR-940 negatively regulates cell proliferation. Apoptosis experiments revealed that low levels of miR-940 inhibited apoptosis. The dual-luciferase reporter assay confirmed that miR-940 targeted RhoA, establishing a negative correlation between them. The reversed experiment demonstrated that while the downregulation of miR-940 promoted cell proliferation and inhibited apoptosis, these effects were partially reversed when RhoA expression was suppressed. In conclusion, miR-940 played a crucial role in regulating cell proliferation and apoptosis, and it held potential as a therapeutic target for inhibiting the apoptosis of HTR8-S/Vneo cells in ICP.

Labor analgesia is commonly used in parturient women and its variable effect has been proven to be related to genetic factors. The P2RX7 rs7958311 polymorphism is closely associated with the occurrence and sensitivity of pain. This study focused on the correlation between the P2RX7 rs7958311 polymorphism and labor analgesia in primiparas. Two hundred full-term hospitalized primiparas who voluntarily requested labor analgesia were recruited in this study. P2RX7 rs7958311 genotyping was performed on all participants after genomic DNA extraction from blood samples. Ropivacaine combined with sufentanil was employed for labor analgesia. Evaluation was performed on pain scores, labor duration, and maternal and infant outcomes. Potential factors affected by rs7958311 polymorphism were assessed by logistic regression analysis. Obviously, reduced visual analog scale (VAS) scores were shown within 1 h after labor analgesia and at 2 h postpartum in GA and AA groups (P < 0.05) with lower VAS scores in the AA group than in the GA group (P < 0.01) at 2 h postpartum. The total and the first two stages of labor exhibited a shortened duration in the AA group (P < 0.05). Analysis of adverse reactions in primiparas and assessment of neonates identified a statistical difference in nausea/emesis (P = 0.005) among 3 groups. Logistic regression analysis demonstrated the effect of P2RX7 rs7958311 polymorphism on the VAS score at 2 h postpartum (OR = 0.386, 95% CI: 0.192-0.777, P = 0.008) and nausea/emesis (OR = 0.232, 95% CI: 0.071-0.762, P = 0.016) in primiparas. The P2RX7 rs7958311 polymorphism remarkably influenced the effect of labor analgesia in primiparas, especially the VAS score at 2 h postpartum and nausea/emesis.