Identifying central symptom clusters and correlates in patients with lung cancer post-chemotherapy: A network analysis.

Objective: This study aims to investigate the network structures of symptoms and symptom clusters in patients with lung cancer post-chemotherapy, with a focus on identifying the central symptom cluster. Understanding the central cluster is crucial for targeted and effective symptom management. Methods: Symptom occurrence and severity were assessed using the Memorial Symptom Assessment Scale (MSAS). Principal component analysis (PCA) was employed to explore symptom clusters, while network analysis unveiled the network structure and pinpointed the central symptom cluster. Results: The study included 512 patients with lung cancer. Four distinct symptom clusters emerged: sickness behavior, psychological, lung cancer-specific, and epithelial. The sickness behavior symptom cluster was identified as the central symptom cluster. Conclusions: This research designates the sickness behavior symptom cluster as central in post-chemotherapy patients with lung cancer, offering valuable insights for clinical nurses in devising more effective symptom management strategies. Trial registration: ChiCTR2300070944 (Chinese Clinical Trial Register).

Exploring the effectiveness of endometrial receptivity array and immune profiling in patients with multiple implantation failure：A retrospective cohort study based on propensity score matching.

This study aimed to evaluate the effectiveness of the endometrial receptivity array (ERA), endometrial immune profiling, and a combination of both in improving the pregnancy outcomes for multiple implantation failure patients. According to patients' willingness, 1429 women who incurred at least two or more consecutive implantation failures in IVF/ICSI treatment opted for frozen embryo transfer and were divided into four groups: 'No test', 'Immune Profiling', 'ERA' and 'ERA+ Immune Profiling'. Women in three test groups underwent timed endometrial biopsy for ERA, immune profiling, a combination of both. We observed the overall incidence rates of the displaced window of implantation (WOI) and endometrial immune dysregulation were 75.14% and 79.29%, respectively. After 1:1 propensity score matching (PSM), our data revealed that the 'ERA' and 'ERA + Immune Profiling' groups demonstrated significantly higher rates of biochemical, clinical, ongoing pregnancy, and implantation compared to the 'No test' group (p < 0.01). The 'Immune Profiling' group showed a higher implantation rate compared to 'No test' group (p < 0.05). Furthermore, when comparing three test groups, the 'ERA + Immune Profiling' group exhibited notably higher rates of clinical and ongoing pregnancy compared to the 'Immune Profiling' group (p < 0.017). However, there was no association between endometrial immune profiling and ERA phases, and their results did not differ between embryo implantation and non-implantation in these patients. Our findings underline the increased implantation rates by use of ERA and endometrial immune profiling in patients with multiple implantation failure, either individually or corporately. Moreover, a combination of both could improve their pregnancy outcomes significantly.

The association between inflammation-related biomarkers and the subtypes of cancer-related cognitive impairment in colorectal cancer patients: A latent profile analysis.

PURPOSE: Cancer-related cognitive impairment (CRCI) has garnered considerable attention, yet limited research has delved into nuanced distinctions among varying degrees of CRCI in colorectal cancer survivors. This study aimed to identify distinct subgroups based on the patterns of CRCI, assess the heterogeneity among different subgroups, and investigate the potential correlations between the subgroups of CRCI and inflammation-related biomarkers. METHODS: 268 colorectal cancer patients were enrolled in this cross-sectional study, followed by the Functional Assessment of Cancer Therapy-Cognitive Function. The determination of CRCI subgroups was accomplished by the latent profile analysis (LPA). The effects of inflammation-related biomarkers on CRCI were examined using the binary logistic regression analysis. The receiver operating characteristic (ROC) curves assessed the diagnostic efficacy of inflammation-related biomarkers. RESULTS: Two latent profiles were identified: CRCI (n = 64, 23.88%) and non-CRCI (n = 204, 76.12%). Independent factors for CRCI in colorectal cancer patients were SIRI (OR = 3.248, 95%CI [1.197-8.807], P = 0.021) and ALI (OR = 0.962, 95%CI [0.937-0.989], P = 0.005). The areas under the curve (AUCs) for SIRI and ALI in predicting CRCI were 0.781 and 0.774, with the optimal cut-off values being 0.70 and 37.04, respectively. CONCLUSIONS: Colorectal cancer patients exhibited divergent cognitive performance profiles, categorized into two subgroups based on LPA. SIRI and ALI were identified as independent factors for CRCI, demonstrating strong diagnostic accuracy. These two inflammation-related biomarkers may potentially be novel indicators to identify and manage the development of CRCI among colorectal cancer patients.

[Functional analysis of functional membrane microdomains in the biosynthesis of menaquinone-7].

Functional membrane microdomains (FMMs) that are mainly composed of scaffold proteins and polyisoprenoids play important roles in diverse cellular physiological processes in bacteria. The aim of this study was to identify the correlation between MK-7 and FMMs and then regulate the MK-7 biosynthesis through FMMs. Firstly, the relationship between FMMs and MK-7 on the cell membrane was determined by fluorescent labeling. Secondly, we demonstrated that MK-7 is a key polyisoprenoid component of FMMs by analyzing the changes in the content of MK-7 on cell membrane and the changes in the membrane order before and after destroying the integrity of FMMs. Subsequently, the subcellular localization of some key enzymes in MK-7 synthesis was explored by visual analysis, and the intracellular free pathway enzymes Fni, IspA, HepT and YuxO were localized to FMMs through FloA to achieve the compartmentalization of MK-7 synthesis pathway. Finally, a high MK-7 production strain BS3AT was successfully obtained. The production of MK-7 reached 300.3 mg/L in shake flask and 464.2 mg/L in 3 L fermenter.

Dysregulated low-density granulocyte contributes to early spontaneous abortion.

Spontaneous abortion (SA) is a common adverse pregnancy event with unclarified pathogenesis and limited therapeutic efficiency. Although most SA cases with the euploid embryo(s) are associated with immunological factors, the contribution of low-density granulocyte (LDG) in SA pathogenesis is rarely reported. This study aimed to investigate the serial characteristics and possible contribution of LDG and their subpopulations in early pregnancy, especially in early SA. Unpregnant (UP), normally pregnant (NP), and SA women were recruited, and the peripheral blood and endometrium/decidua were collected for LDG isolation and histological observation. The percentage, phenotype, and subpopulations of LDG were analyzed via flow cytometric analysis, and the ability of Nets formation was assessed by immunofluorescent and immunohistochemical assays. As a result, 43 participants were enrolled, including 10 UP, 15 NP, and 18 SA women. Compared with the UP group, the LDG percentage in peripheral blood mononuclear cells (PBMCs) and decidual immune cells (DICs) increased in the NP group, while the loss of this increase was observed in the SA group. Meanwhile, CD16int/- cell percentage in peripheral blood LDG (PB-LDG) increased in the NP and SA groups, and insufficient activation of CD16hi PB-LDG characterized by reduced CD11b expression was discovered in the SA group. Moreover, the LDG percentage in DICs was higher than that in PBMCs, and the decidual LDG (D-LDG) showed a surface marker expression profile that is easier to be activated in the pregnant cohort (NP + SA women). Finally, increased decidual Nets formation was observed in the SA group compared with the NP group, and more Nets formation was detected in D-LDG of NP and SA women following PMA stimulation. Overall, LDG participates in the maintenance of early pregnancy, while dysregulated LDG is responsible for early SA, providing novel potential targets for further exploration of SA pathogenesis and therapeutics.

miR-146a-5p enhances embryo survival in unexplained recurrent spontaneous abortion by promoting M2 polarization of decidual macrophages.

Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions in the reproductive field, and macrophage M1/M2 polarization disorder is involved in URSA pathogenesis, although the relevant mechanisms are undefined. miR-146a-5p possesses an immunoregulatory role and is expressed in decidual immune cells, and this study aims to investigate its effect on decidual macrophage polarization and therapeutic prospects in URSA, which has never been reported. The levels of M1/M2 markers in the deciduae and the miR-146a-5p expression in the decidual macrophages of URSA and healthy pregnant women were first detected and analyzed. Then, the in vitro effect of miR-146a-5p on the M1/M2 polarization and the secretion of inflammatory cytokines was investigated in Tamm-Horsfall protein-1 (THP-1)-induced macrophages. Finally, the in vivo immunotherapeutic effect of miR-146a-5p on embryo survival and the potential mechanisms were evaluated in a murine model of immune-based URSA. As a result, the abnormal M1/M2 polarization, which showed a shift towards the M1 phenotype and correlated with the decreased expression of miR-146a-5p, was verified in human URSA decidual macrophages. miR-146a-5p could inhibit M1 polarization, promote M2 polarization, and result in an anti-inflammatory microenvironment in THP-1-induced macrophages. The intravenous injection of exogenous miR-146a-5p in the first trimester of pregnant URSA mice significantly reduced the embryo resorption rate and promoted the M2 polarization of decidual macrophages. In conclusion, miR-146a-5p enhances embryo survival in URSA by promoting decidual macrophage polarization toward an M2 phenotype, giving new ideas and potential targets for subsequent research on the pathogenesis and immunotherapeutic strategies of URSA.

Da Vinci Robot-Assisted Video Image Processing under Artificial Intelligence Vision Processing Technology.

This research was aimed to explore the application value of intelligent algorithm-based digital images in Da Vinci robot-assisted treatment of patients with gastric cancer surgery. 154 patients were included as the research objects, with 89 cases in the control group underwent laparoscopic surgery, and 65 cases in the experimental group underwent robotic surgery. According to the propensity score, the patients in two groups were pair matched (1: 1), of which 104 cases (52 cases in each group) were successfully matched. The general data of patients, the changes in the images before and after the algorithm processing, the intraoperative and postoperative conditions, the pathological examination results, and the follow-up information were observed after matching. Compared with the original images, the images processed by the thread image edge detection algorithm had the significantly improved clarity, as well as highly reduced artifacts and noises. The sensitivity, specificity, and accuracy of image-assisted diagnosis were improved remarkably, showing the differences of statistical significance (P < 0.05). The total time of surgery, intraoperative bleeding, CRP (1d and 3d after surgery), and postoperative total abdominal drainage showed the significant differences as well (P < 0.05). The surgeries of patients in both groups met R0 resection (no tumor infiltration within 1 mm of the surgical margin), but there was a significant difference in the number of lymph node dissections (P < 0.05). The overall survival rates of patients in the experimental group and the control group were 83.0% and 76.1%, respectively, 2 years after surgery, with no significant difference (P > 0.05). The thread image edge detection algorithm produced a better processing effect on the images, which greatly improved the diagnostic sensitivity, specificity, and accuracy. Compared with endoscopic surgery, robotic surgery has better postoperative recovery, safety and reliability, and obvious advantages of minimally invasive surgery.

Comparison of the Effectiveness of Endometrial Receptivity Analysis (ERA) to Guide Personalized Embryo Transfer with Conventional Frozen Embryo Transfer in 281 Chinese Women with Recurrent Implantation Failure.

BACKGROUND This study aimed to compare the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) with conventional frozen embryo transfer (FET) in 281 Chinese women with recurrent implantation failure (RIF). MATERIAL AND METHODS A total of 281 eligible patients with RIF were recruited and assigned to ERA (ERA followed by pET) and FET groups. The clinical pregnancy outcomes were compared between the 2 groups. RESULTS There were no significant differences between the ERA and FET groups in terms of endometrial thickness on the day of embryo transfer, mean attempts of assisted reproductive technology (ART) treatment, anti-Mullerian hormone, follicle-stimulating hormone, or antral follicle count in the fresh cycle (P>0.05). The ERA test identified 35% of samples as receptive and 65% as nonreceptive, and comparable pregnancy outcomes were observed between receptive and nonreceptive patients (P>0.05). Higher pregnancy and implantation rates were found in the ERA group than in the FET group (P<0.01), while no significant differences were detected between the 2 groups in terms of miscarriage rates (P>0.05). CONCLUSIONS In this study of Chinese women with RIF undergoing in vitro fertilization and embryo transfer, ERA-guided pET resulted in a significant improvement in pregnancy and implantation rates when compared with FET.

Effectiveness comparison between endometrial receptivity array, immune profiling and the combination in treating patients with multiple implantation failure.

PROBLEM: The clinical value of endometrial receptivity array (ERA), endometrial immune profiling, or a combination of both for multiple implantation failure patients is unclear. METHOD OF STUDY: One hundred and seventy-two women with a history of at least two or more consecutive implantation failures in IVF/ICSI treatment were included. According to patients' willingness, they were divided into four groups, 'no treatment', 'Immune Profiling', 'ERA' and 'ERA + Immune Profiling'. Endometrial biopsy was examined by ERA, immune profiling alone, or combination, and intention was adopted accordingly. Pregnancy outcomes were compared, and the association between ERA phases and endometrial immune profiling was also assessed. RESULTS: The overall incidence rate of the displaced window of implantation (WOI) and endometrial immune dysregulations were 84.9% and 75.3%, respectively. Implantation rate was significantly higher in the 'ERA + Immune Profiling' group than the 'no treatment' group (P = .007). Clinical pregnancy rate was somewhat improved in the three treatment groups but with a borderline significance (P = .071). After controlling for other confounders, 'ERA + Immune Profiling' treatment was associated with a higher pregnancy rate [aOR (95%CI)  = â€Š3.412 (1.387-8.395), P = .008]. There was no association between endometrial immune profiling and ERA phases. CONCLUSIONS: Our findings highlight the high incidence of displaced WOI and endometrial immune dysregulation in multiple implantation failure patients. The combination of ERA and endometrial immune profiling is more likely to have clinical value than ERA or immune profiling alone. These data suggested the unsubstitutability of ERA and endometrial immune profiling on the treatment outcome for multiple implantation failure patients.

miR-146a-5p improves the decidual cytokine microenvironment by regulating the toll-like receptor signaling pathway in unexplained spontaneous abortion.

Spontaneous abortion (SA) is a common pregnancy failure, but the cause of numerous cases remains unexplained. Decidual immune cells (DICs)-mediated cytokine microenvironment is involved in pregnancy and regulated by many microRNAs, but whether microRNA-146a-5p (miR-146a) regulate the decidual cytokine microenvironment and the potential mechanisms in unexplained SA pathogenesis have rarely been reported. In this study, the levels of cytokines and miR-146a in healthy and unexplained SA deciduae were first investigated, and the correlation between them was analyzed. Then, the effect of miR-146a inhibitor on cytokines was assessed in healthy deciduae-derived DICs. Third, the downstream targets and related molecular mechanisms of miR-146a were analyzed by bioinformatics, and the levels of the predicted targets in deciduae were assessed, followed by the correlation analysis between the levels of miR-146a and the targets. Finally, the effect of miR-146a on the predicted targets and inflammatory cytokines was validated in unexplained SA deciduae-derived DICs. As a result, decreased miR-146a correlated with the cytokine disorder in unexplained SA deciduae, and inhibition of miR-146a promoted pro-inflammatory response in healthy deciduae-derived DICs. One hundred four target genes and related molecular mechanisms of miR-146a were predicted, among which the toll-like receptor (TLR) pathway might be associated with the decidual cytokine regulation. Upregulation of miR-146a inhibited the expression of the predicted molecules enriched in the TLR pathway and improved the cytokine disorder in unexplained SA deciduae-derived DICs. Collectively, miR-146a improves the decidual cytokine microenvironment by regulating the TLR pathway in unexplained SA, providing novel potential targets for further therapeutic research.

[Effects of Artificial Destratification and Induced-natural Mixing on Water Quality Improvement in a Drinking Water Reservoir].

To explore the effects of water quality improvement by artificial destratification and artificially-induced mixing, as well as realize the conditions of artificial mixing and natural mixing, the Lijiahe Reservoir was selected to monitor the indexes of water quality and hydrometeorology from June 2017 to April 2019 and to analyze the characteristics of variations in water temperature, dissolved oxygen, and pollutants during the natural and induced-mixing processes. The results demonstrated that:① The natural process had the features of a long period of thermal stratification and only a short period of mixing of about 2.5 months. Through the operation of water-lifting aerators (WLAs) during the induced-mixing process, the water body was completely mixed and entered the cooling period at the end of September, achieving the conditions of induced-natural mixing. The surface water temperature and average air temperature were 20.17℃ and 16.5℃, respectively, and the water body continued to be naturally mixed after the WLA system was shut down, which led to a natural mixing cycle of 5.5 months. ② During the natural-mixing process, the concentration of pollutants was relatively high in the whole period, and the concentration of surface pollutants in the mixing stage presented a trend of increasing first and then decreasing. The oxycline appeared with thermal stratification, and the anaerobic cycle in the bottom of water column reached 6 months. ③ Compared with the natural-mixing process, the hypolimnetic anaerobic condition was eliminated and the control effects of pollutants dominated during the induced-mixing process. Simultaneously, the concentrations of NH4+-N, TP, Fe, and Mn in the bottom of the water column were cut by 76.2%, 75.5%, 82.2%, and 82.1%, respectively, during the same period from October to March of the following year, and met the "Environmental Quality Standards for Surface Water". This study shows that the artificially-induced mixing process contributes to water quality improvement and mixing-period prolongation.

The role of regulatory T cells in thymectomy-induced autoimmune ovarian disease.

PROBLEM: To evaluate the role of regulatory T (Treg) cells in autoimmune ovarian disease (AOD). METHOD OF STUDY: AOD model was set up by thymectomy of BALB/C mice on day 3 (d3tx). The variation of T lymphocyte subsets, especially the Treg cells were analyzed in the peripheral blood, spleen, para-aortic, and inguinal lymph nodes in d3tx mice. The effect of Treg cells on AOD was further evaluated by adoptive transfer of Treg cells into d3tx mice (d3tx+Treg). RESULTS: In d3tx mice, the ratio of Treg/CD4+ was significantly increased rapidly from 1st to 2nd week, rapidly declined in 3rd week, then decreased slowly until the 9th week. The CD3+ /T lymphocytes and the ratio of CD4+ /CD3+ were significantly decreased in the para-aortic and inguinal lymph nodes of d3tx mice, but the ratio of Treg/CD4+ and CD8+ /CD3+ were increased simultaneously. In d3tx mice with adoptive transfer of Treg cells (0.5×104 ~5×105 ), there was a significant increase in the Treg/CD4+ ratios in the spleen and peripheral blood. AOD score, especially adoptive transferred treg cells from the ovarian lymph nodes was significantly decreased. Oocytes were successfully obtained from d3tx+Treg mice, which could fertilize and develop to embryos normally. CONCLUSION: Treg cells involved in the pathogenesis of AOD. Sufficient numbers of Treg cells can modify AOD in the early phase in d3tx mice.

Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines.

Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated ß-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR-containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH-sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen.

A highly selective and sensitive fluorescent probe for quantitative detection of Hg(2+) based on aggregation-induced emission features.

A π-conjugated cyanostilbene derivative of (Z)-2-(4-nitrophenyl)-3-(4-(vinyloxy)phenyl)acrylonitrile (CN-vinyl) had been designed, synthesized and confirmed by the standard spectroscopic analyses. CN-vinyl possesses an unusual high emissive aggregation-induced emission (AIE) feature in a tetrahydrofuran/water mixture (2:8, v/v). The fluorescence intensity of CN-vinyl can be quenched linearly with the addition of Hg(2+) in a range of 0-50 µM with a correlation coefficient of R(2)=0.9957. The detection limit of Hg(2+) is 37 nM. The mechanism for Hg(2+)-mediated optical properties of CN-vinyl is due to the selective cleavage of vinyl group by Hg(2+). Accuracy of the proposed methodology was evaluated by means of the recovery study in real samples and the analyzing certified reference material of the standard solution of Hg(2+). By this novel strategy, CN-vinyl can be used for quantitative detection of Hg(2+) as well as the presence of other physiological relevant metal ions.

Clinical evaluation of the recombinant 38 kDa protein of Mycobacterium tuberculosis.

The diagnosis of tuberculosis remains among public health concerns due to shortcomings of the purified protein derivative (PPD). Recombinant truncated 38 kDa protein (rTPA38) of Mycobacterium tuberculosis was evaluated to screen new tuberculosis-specific tuberculin. 539 patients, 1133 healthy controls, and 55 guinea pigs were recruited to assess their sensitivity and specificity to rTPA38; 221 healthy controls, with negative responses to rTPA38 and PPD, were vaccinated with M. bovis BCG to determine their cross-reactions with M. bovis BCG. The Mantoux technique was adopted to perform skin tests. No difference in the sensitivity of skin tests was detected between rTPA38 and PPD (78.2% vs 83.4%), but there was a significant difference in the specificity of skin tests between rTPA38 and PPD (75.2% vs 47.0%). Compared to PPD, rTPA38 elicited low positive responses for those recruitments vaccinated with M. bovis BCG. The rTPA38 had significant skin reactions in M. tuberculosis-sensitized guinea pigs, and the opposite was true for both M. fortuitum- and M. kansasii-sensitized guinea pigs. These findings indicate that rTPA38 may have potential as a tuberculosis-specific skin test antigen.