Regulatory T Cell and T Helper 17 Cell Imbalance in Patients with Unexplained Infertility.

Purpose: Female infertility is a global health concern. The aim of this study was to investigate the relationship between regulatory T (Treg) cells and helper T cells 17 (Th17) in peripheral blood and unexplained infertility (UI). In addition, we explored potential valuable diagnostic biomarkers for patients with UI and ascertained whether Treg and Th17 cells are associated with primary and secondary UI. Patients and Methods: The patients underwent standard fertility evaluation test, including blood tests, ultrasound examination, fallopian tube tests, ovulation assessment, and male partner's semen analysis. According to the inclusion and exclusion criteria, this study enrolled 37 patients with UI (30 with primary UI and 7 with secondary UI) and 26 age-matched healthy volunteers as the control group. Flow cytometry was used to detect the frequency of Treg and Th17 cells. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was used to assess the diagnostic performance. An AUC > 0.800 indicated good diagnostic performance. Results: The percentage of Treg decreased significantly, whereas the percentage and absolute count of Th17 cells increased. Moreover, the Th17/Treg ratio in patients with UI increased significantly. As a diagnostic biomarker for UI, the Th17/Treg ratio exhibited remarkable diagnostic performance (AUC: 0.813 (95% CI = 0.709-0.917)). However, the percentages and absolute counts of Treg and Th17 cells in the peripheral blood of women with primary and secondary UI, as well as their Th17/Treg ratios, did not differ significantly. Conclusion: The distribution of Treg and Th17 cells is imbalanced in patients with UI. Therefore, the Th17/Treg ratio may be a promising indicator of UI. However, there were no significant differences in the distribution of Treg and Th17 cells between women with primary and secondary UI.

High average output power, dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2†nm.

A dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2 nm was demonstrated. The maximum average output power was as high as 2.6 W with a pulse repetition frequency of 3.03 GHz. Meanwhile, the output power ratio of the dual-wavelength lasers can be effectively controlled by varying the incident pump power. To the best of our knowledge, this is the first dual-wavelength synchronously self-mode-locked Ho-doped fluoride solid state laser; moreover, our current experimental results represent the highest average output power from a GHz self-mode-locked oscillator in the 2 µm wave band.

Changes in subset distribution and impaired function of circulating natural killer cells in patients with colorectal cancer.

Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.

CD4 expression on monocytes correlates with recovery from multiple organ dysfunction syndrome and mortality in patients with septic shock.

Background: To date, the correlation between CD4 on the monocytes (mCD4) expression and the prognosis of patients with septic shock remains unclear. The purpose of this study was to analyze the expression of mCD4 in these patients and further evaluate whether mCD4 expression correlates with either the recovery from multiple organ dysfunction syndrome (MODS) or mortality. Methods: The study participants were recruited from a tertiary general hospital in China (Affiliated Dongyang Hospital of Wenzhou Medical University). Sepsis and septic shock were diagnosed based on the diagnostic criteria of Sepsis-3. MODS was defined as a Sequential Organ Failure Assessment score of at least two organ systems ≥2. Persistent MODS was defined as the continual meeting of the MODS criteria when re-evaluated one week after admission (day 7). A logistic regression model was used to test whether mCD4 was an independent prognostic factor for mortality in patients with septic shock. A paired sample rank sum test was used to examine the correlation between mCD4 expression and MODS recovery. Result: The study recruited 79 patients with septic shock as the study group, 74 patients with sepsis as the disease control group, and 56 volunteers as healthy controls. In the first 24 h after admission (day 1), mCD4 expression was significantly reduced in patients with septic shock compared to healthy controls and patients with sepsis. Moreover, mCD4 expression was an independent prognostic factor for in-hospital and 28 day mortality in patients with septic shock. mCD4 expression did not show significant differences in patients with persistent MODS on day 7 compared to day 1. However, mCD4 expression was significantly higher in patients without persistent MODS on day 7 than on day 1. Conclusion: mCD4 expression is significantly reduced in patients with septic shock, which is an independent prognostic factor for mortality and closely related to recovery from MODS.

The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

Watt-level output power and near-diffraction-limit beam quality mid-infrared Ho:GdVO4 self-Raman laser at 2.5†µm.

We demonstrate an efficient active Q-switched Ho:GdVO4 self-Raman laser at 2500 nm for the first time, to our knowledge. Using Ho:GdVO4 crystal as the gain medium for both the 2048nm fundamental laser and the 2500 nm Raman laser, the output performances of a new mid-infrared self-Raman laser were investigated. The maximum average output power of 1.45 W was achieved at an incident pump power of 22.5 W, with a slope efficiency of 25.8%, for an output transmittance of 30% and a pulse repetition frequency of 15 kHz. The maximum single pulse energy of 96.7 µJ with a pulse width of 11.35 ns was obtained, corresponding to the peak power of 8.5 kW. The beam quality was near diffraction limited with the M2 factors of 1.15 and 1.06 along the x and y directions. Moreover, adopting the two-end output way of the fundamental laser and the Raman laser, the Raman gain coefficient of Ho:GdVO4 crystal was estimated to be 1.14 cm/GW at 2048nm. This work shows that Ho:GdVO4 is an excellent self-Raman laser crystal for the generation of high power Raman laser at 2.5 µm.

Distribution characteristics of circulating B cell subpopulations in patients with chronic kidney disease.

This study compared the levels of circulating B cell subpopulations in patients with different stages of chronic kidney disease (CKD), investigated the effects of haemodialysis (HD) on the B cell-related immune spectrum in patients with end-stage renal disease, and evaluated the link between renal function and immune homeostasis. Overall, 197 patients with CKD (158 non-dialysis patients with CKD stages I-V and 39 end-stage patients undergoing maintenance HD) and 77 healthy controls were included. Compared to healthy controls, patients with CKD stages I-II showed no significant differences except for the proportion of transitional B cells; patients with CKD stage V showed a significant decrease in the proportions of transitional B cells and CD5+ B cells and a significant increase in double-negative (DN) B cells. Compared with early-stage patients with CKD, the absolute count of various B cell subpopulations in advanced-stage patients with CKD showed a significant decrease. The distribution of circulating B cell subpopulations in patients with CKD was significantly altered and was associated with CKD progression. Furthermore, the proportion of DN B cells and CD5+ B cells was inconsistent pre- and post-HD. This in-depth study of the immune status of patients with CKD may have important clinical value.

CD36 relative mean fluorescence intensity of CD105+ nucleated erythroid cells can be used to differentiate myelodysplastic syndrome from megaloblastic anemia.

This study aims to evaluate the differences in CD105+ nucleated erythroid cell (NEC) immunophenotypes between myelodysplastic syndrome (MDS) and megaloblastic anemia (MA) using multiparameter flow cytometry and to screen potential markers. We analyzed bone marrow sample data from 37 patients with MDS, 35 with MA, 53 with iron-deficiency anemia (anemic controls), and 35 without anemia (normal controls). Compared with normal controls, the MDS and MA groups showed a decrease in the proportion of CD117+CD105+NEC and the relative mean fluorescence intensity (RMFI) of CD71 in CD105+NEC, accompanied by an increase in the coefficient of variation (CV) of CD71 and CD36. Additionally, CD36 RMFI of CD105+NEC increased in the MA group. Compared with anemia controls, the MDS and MA groups showed a significant increase in CD36 CV of CD105+NEC, and the CD36 RMFI in the MA group increased while that in the MDS group decreased. The proportions of CD117+CD105+NEC, CD36 CV, and CD36 RMFI in CD105+NEC differed significantly between MDS and MA groups. Among them, CD36 RMFI had good diagnostic performance (area under the curve: 0.844, 95% confidence interval: 0.753-0.935). CD36 RMFI of CD105+NEC may be a helpful marker in differentiating MDS and MA using multiparameter flow cytometry.

Characteristics and postoperative dynamic changes in circulating CD4+ helper T lymphocytes in patients with breast cancer.

Introduction: Circulating CD4+ helper T cell (Th) subsets provide potentially important information on disease progression in several cancers. In this study, we explored the characteristics and postoperative dynamic changes in circulating CD4+Th subsets in patients with breast cancer. Methods: Circulating CD4+Th subsets, including CD4+ naive T cells (Tn), CD4+ central memory T cells (Tcm), CD4+ effector memory T cells (Tem), CD4+CD57+T, and CD4+PD-1+T, were detected with multiparameter flow cytometry. T-test and Wilcoxon rank-sum test were used to compare differences between groups for normally and non-normally distributed continuous variables, respectively. Postoperative dynamic changes in CD4+Th subsets were assessed using the paired-sample rank-sum test. Results: Seventy-five patients with invasive breast cancer and fifty-three patients with benign breast tumors were enrolled. Compared with that in patients with benign tumors, the proportion of CD4+Tn in patients with breast cancer patients decreased, whereas the proportion and absolute number of CD4+CD57+T and CD4+PD-1+T increased. Moreover, the proportion of CD4+PD-1+T was correlated with the clinicopathology of breast cancer. After tumor resection, the proportion and absolute number of CD4+Tcm significantly decreased, while those of CD4+Tem significantly increased, compared with preoperative values. Tumor resection caused significant changes in the proportion and absolute number of CD4+CD57+T and CD4+PD-1+ T, both of which showed significant decreases. Discussion: We found significant changes in circulating CD4+Th subsets in patients with breast cancer. Additionally, complete tumor resection can benefit the patient as it balances the patient's immunosuppression and immune stress and improves the immune exhaustion and immunosenescence states.

Characteristics of circulating adaptive immune cells in patients with colorectal cancer.

Adaptive immune cells prevent solid tumor progression by targeting and killing tumor cells. However, there are no comprehensive studies on peripheral circulating adaptive immune cell characterization in colorectal cancer (CRC) patients or the effect of tumor-node-metastasis (TNM) stages on these cells. In this study, the number, phenotype, and function of different subsets of circulating adaptive immune cells in peripheral blood of CRC patients were analyzed. We found remarkable differences in CRC patients compared with those in healthy controls, including reduced absolute counts of total T cells, helper T lymphocytes (Th), cytotoxic T lymphocytes (Tc), and double-negative T lymphocytes, a decreased proportion of INF-γ+ cells in total T cells and Th, and increased percentages of B cells, plasmablasts, and activated T cells. Compared with early-stage CRC patients, advanced-stage CRC patients showed more severe immunosenescence, which manifested as decreased proportions of CD8+ naive T cells with strong proliferative ability and CD8+ central memory T cells with immune surveillance function. Proportions and absolute counts of CD8+ and CD4+ terminally differentiated effector memory T cells were increased, indicating immunosenescence. The immune cell characteristics analyzed in this study serve as a starting point for further research to determine potential clinical implications.

CD4+ Memory Stem T Cell in Peripheral Blood: A Promising Immune Index for Early Screening and Auxiliary Diagnosis of Colorectal Cancer.

BACKGROUND AND AIMS: Colorectal cancer (CRC) lacks obvious symptoms in the early stage of the disease, making it is easy to be misdiagnosed and remain undetected. Here, we explored the role of CD4+ memory stem T cells (TSCM) in peripheral blood in the early screening and auxiliary diagnosis of CRC. MATERIALS AND METHODS: Patients diagnosed with a "colorectal mass" by colonoscopy, at the Dongyang People's Hospital (Zhejiang, China), between November 2020 and June 2021, were included in this prospective study. Using histopathological results as the gold standard for diagnosis, patients were divided into "CRC group" and "benign tumor group". Healthy volunteers were recruited as "healthy controls." Ten-color flow cytometry was used to detect CD4+ T cell subsets, and the results were analyzed using the Kaluza software. Carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were detected by the Roche Cobas e 602 electrochemiluminescence immunoassay analyzer. RESULTS: This study involved 33 patients with CRC, 41 patients with colorectal benign tumors, and 49 healthy volunteers. The absolute value and frequency of CD4+ TSCM can clearly distinguish colorectal cancer, benign tumors, and healthy controls. According to the area under the receiver operating characteristic curve (AUC), the absolute value of CD4+ TSCM used to assist in the diagnosis of CRC was 0.758 (sensitivity: 0.612; specificity: 0.788), which is higher than the values for CEA (AUC: 0.707) and CA199 (AUC: 0.552). In early screening, the sensitivity of the absolute value of CD4+ TSCM (sensitivity: 0.612) was significantly higher than that of CEA (sensitivity: 0.333) and CA199 (sensitivity: 0.259). CONCLUSION: CD4+ TSCM in peripheral blood may be a promising immune index for the early screening and auxiliary diagnosis of CRC.

NCEH1 may be a prognostic biomarker for pancreatic cancer.

Neutral Cholesterol Ester Hydrolase 1 (NCEH1) is an enzyme involved in ether lipid metabolism, and the NCEH1 gene is overexpressed in a variety of tumors. However, its role in pancreatic cancer remains unknown. Therefore, we compared the gene transcription data of healthy and pancreatic cancer tissues using the Cancer Genome Atlas and Genotype-Tissue Expression databases. R software (v3.6.1) was used for the differential, clinicopathological correlation, and survival analyses. We found that NCEH1 was overexpressed in pancreatic cancer tissues compared with that in healthy tissues (P = 1.732 e-50), and that its expression level was related to lymph node metastasis. High NCEH1 expression was associated with poor overall survival (P = 0.002). Using univariate and multivariate Cox regression analyses, we determined that NCEH1 is an independent risk factor for pancreatic cancer. Gene set enrichment analysis identified that NCEH1 overexpression is prominent in cell-cell adhesion junctions, pancreatic cancer, cancer-associated pathways, prostate cancer, and chronic myeloid leukemia. In contrast, low NCEH1 expression correlated to high oxidative phosphorylation. Thus, we conclude that NCEH1 may be a prognostic biomarker for pancreatic cancer.

Potential effects of umami ingredients on human health: Pros and cons.

Umami taste is the most recent confirmed basic taste in addition to sour, sweet, bitter, and salty. It has been controversial because of its effects on human nutritional benefit. Based on the available literatures, this review categorized 13 positive and negative effects of umami taste on human health. On the positive side, umami taste can improve food flavor and consumption, improve nutrition intake of the elderly and patients, protect against duodenal cancer, reduce ingestion of sodium chloride, decrease consumption of fat, and improve oral functions. On the other hand, umami taste can also induce hepatotoxicity, cause asthma, induce migraine headaches, damage the nervous system, and promote obesity. Due to its novelty, there are many functions and effects of umami taste waiting to be discovered. With further investigation, more information regarding the effects of umami taste on human health will be discerned.

Room-temperature quantum interference in single perovskite quantum dot junctions.

The studies of quantum interference effects through bulk perovskite materials at the Ångstrom scale still remain as a major challenge. Herein, we provide the observation of room-temperature quantum interference effects in metal halide perovskite quantum dots (QDs) using the mechanically controllable break junction technique. Single-QD conductance measurements reveal that there are multiple conductance peaks for the CH3NH3PbBr3 and CH3NH3PbBr2.15Cl0.85 QDs, whose displacement distributions match the lattice constant of QDs, suggesting that the gold electrodes slide through different lattice sites of the QD via Au-halogen coupling. We also observe a distinct conductance 'jump' at the end of the sliding process, which is further evidence that quantum interference effects dominate charge transport in these single-QD junctions. This conductance 'jump' is also confirmed by our theoretical calculations utilizing density functional theory combined with quantum transport theory. Our measurements and theory create a pathway to exploit quantum interference effects in quantum-controlled perovskite materials.

The association of D-dimer with clinicopathological features of breast cancer and its usefulness in differential diagnosis: A systematic review and meta-analysis.

BACKGROUND: Studies have shown that D-dimer levels are significantly correlated with the differential diagnosis and clinicopathological features of breast cancer. However, the results are currently limited and controversial. Therefore, we performed this meta-analysis to evaluate the relationship between D-dimer levels and breast cancer. MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases were searched to find studies that assessed the association of D-dimer with clinicopathological features of breast cancer and its usefulness in aiding with differential diagnosis. The standardized mean difference (SMD) was applied as the correlation measure. RESULTS: A total of 1244 patients with breast cancer from 15 eligible studies were included in the meta-analysis. D-dimer levels were higher in the breast cancer group than in the benign (SMD = 1.02; 95% confidence interval [CI] = 0.53-1.52) and healthy (SMD = 1.27; 95% CI = 0.85-1.68) control groups. In addition, elevated D-dimer levels were associated with progesterone receptor-negative tumors (SMD = -0.25; 95% CI = -0.44--0.05). Similarly, there was a significant correlation between D-dimer levels and tumor node metastasis staging (n = 11, SMD = 0.82; 95% CI = 0.57-1.06) and lymph node involvement (n = 8, SMD = 0.79; 95% CI = 0.50-1.09). In contrast, other clinicopathological factors, including estrogen receptor expression and human epidermal growth factor receptor 2 expression, were not associated with D-dimer levels. CONCLUSION: The results of this meta-analysis indicate that plasma D-dimer levels can be used as an important reference for the early identification and staging of breast cancer.

Multicenter-Bond-Based Quantum Interference in Charge Transport Through Single-Molecule Carborane Junctions.

Molecular components are vital to introduce and manipulate quantum interference (QI) in charge transport through molecular electronic devices. Up to now, the functional molecular units that show QI are mostly found in conventional π- and σ-bond-based systems; it is thus intriguing to study QI in multicenter bonding systems without both π- and σ-conjugations. Now the presence of QI in multicenter-bond-based systems is demonstrated for the first time, through the single-molecule conductance investigation of carborane junctions. We find that all the three connectivities in carborane frameworks show different levels of destructive QI, which leads to highly suppressed single-molecule conductance in para- and meta-connected carboranes. The investigation of QI into carboranes provides a promising platform to fabricate molecular electronic devices based on multicenter bonds.

Preparation of umami octopeptide with recombined Escherichia coli: Feasibility and challenges.

The taste of umami peptide H-Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala-OH (LGAGGSLA) is controversial. One possible reason for this controversy is the use of chemically synthesized LGAGGSLA to confirm its taste. To explore other ways to further confirm the flavor of LGAGGSLA, we developed a new strategy to prepare a bio-source peptide by adopting a gene engineering method to express LGAGGSLA in recombinant Escherichia coli. In our previous work, we structured the LGAGGSLA recombinant expression system and optimized the culturing conditions for preparing a fusion protein. However, the fusion protein was not cleaved by enterokinase to obtain LGAGGSLA. Because the cleavage conditions of commercial enterokinase were not specific and recombinant engineered bacteria had the potential to be used in industrial processes, in this addendum, we calculated the mass and volume yields of key processing steps in the preparation of LGAGGSLA, and established a model of cleavage conditions with the cleavage ratio of LGAGGSLA. When the LGAGGSLA was confirmed to show umami taste, it is considered as a new umami or umami enhancer. The gene information of LGAGGSLA should have a great potential in the development of new flavor product and food product containing high umami flavor.

RAD52 gene polymorphisms are associated with risk of colorectal cancer in a Chinese Han population.

Upward trends in the incidence and mortality rates of colorectal cancer (CRC) in China over the past decade mean that it is critical to improve survival outcomes for patients with this malignancy. Analysis of genetic variants may identify biomarkers that have a role in CRC susceptibility and clinical outcomes in Chinese patients with CRC. RAD52 is a key mediator during DNA strand exchange and homologous recombination within mammalian cells. In this study, we explored the effects of RAD52 single nucleotide polymorphisms (SNPs) in the susceptibility and clinicopathological characteristics of Chinese Han patients with CRC. Five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs6489769, and rs7963551) were analyzed using TaqMan SNP genotyping in 281 patients with CRC and 309 healthy controls. Among those aged over 60 years in the total population, carriers of the variant C allele or at least one T allele of the rs1051669 SNP were at a lower risk of CRC than carriers of the wild-type CC variant of rs1051669, while in those carrying the rs7963551 SNP, the GT or GT+GG alleles were associated with an increased risk of CRC compared with patients carrying TT alleles. We indicated a significant correlation between RAD52 rs7963551 polymorphism and lymph node metastasis in CRC patients. In all patients, the T-T-T-T-T, C-T-T-T-T, and C-T-A-C-T haplotypes were associated with an increasing risk of CRC. Our findings suggest that 4 RAD52 SNPs (rs1051669, rs10774474, rs11571378, and rs6489769) might contribute to the prediction of CRC susceptibility. In conclusion, our study demonstrated that RAD52 polymorphisms were associated with CRC in a Chinese Han cohort.

[Investigation of a family with Kennedy disease by genetic analysis].

OBJECTIVE: To report on a Chinese family from Wenzhou with genetically confirmed Kennedy disease and describe its clinical and genetic features. METHODS: The clinical phenotype and the level of relevant biochemical markers were assessed. To determine the number of CAG repeats in the exon 1 of androgen receptor (AR) gene, genomic DNA was extracted from peripheral blood samples of the family members, amplified by PCR and identified by DNA sequencing. RESULTS: The proband showed predominantly proximal limb weakness, fasciculation, muscle atrophy, gynecomastia, sexual dysfunction and increased serum creatine kinase. Myopathy and neuropathy were identified by electromyography. Two other affected males and 2 affected female carriers were identified to carry an expanded CAG repeat in the AR gene. The numbers of CAG repeats were found to be 43 in the proband, 43 and 42 in the other two affected males, one of which had similar clinical symptoms to the proband. CONCLUSION: The family was diagnosed with Kennedy disease by analysis of the AR gene.

The polymorphism in the let-7 targeted region of the Lin28 gene is associated with increased risk of type 2 diabetes mellitus.

Genetic polymorphisms in the miRNAs pathway of the pathogenesis of disease might contribute to the risk of disease. However, it is unclear whether these polymorphisms about miRNAs are associated with the risk of type 2 diabetes mellitus (T2DM). We performed a case-control study to investigate two polymorphisms in the let-7/Lin28 pathway based on 588 T2DM patients and 588 age and sex matched controls. The results showed that the rs3811463 polymorphism was associated with increased risk of T2DM (odds ratio (OR)=1.47, 95% confidence inference (95%CI)=1.13-1.93, P=0.005), while the rs3811464 not (OR=1.04, 95%CI=0.79-1.36, P=0.78). For the rs3811463 polymorphism, the variant genotypes were associated with increased risk of disease in females; statistically differences were observed in the clinical features of age at diagnosis, hypertension and peripheral neuropathy for the variant and wild genotype of the rs3811463 in T2DM. In summary, the results indicated that the rs3811463 polymorphism in the let-7/Lin28 pathway could significantly increase the risk of T2DM.