7295 elderly hospitalized patients with catheter-associated urinary tract infection: a case-control study.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) ranks second among nosocomial infections in elderly patients after lung infections. Improper treatment can lead to death. This study analysed the risk factors, pathogen distribution, clinical characteristics and outcomes of CAUTI in elderly inpatients with a large sample size to provide evidence for clinical prevention and control. METHODS: Based on the HIS and LIS, a case‒control study was conducted on all hospitalized patients with indwelling urinary catheters ≥ 60 years old from January 1, 2019, to December 31, 2022, and the patients were divided into the CAUTI group and the non-CAUTI group. RESULTS: CAUTI occurred in 182 of 7295 patients, and the infection rate was 3.4/per 1000 catheter days. Urine pH ≥ 6.5, moderate dependence or severe dependence in the classification of self-care ability, age ≥ 74 years, male sex, hospitalization ≥ 14 days, indwelling urinary catheter ≥ 10 days, diabetes and malnutrition were independent risk factors for CAUTI (P < 0.05). A total of 276 strains of pathogenic bacteria were detected in urine samples of 182 CAUTI patients at different times during hospitalization. The main pathogens were gram-negative bacteria (n = 132, 47.83%), followed by gram-positive bacteria (n = 91, 32.97%) and fungi (n = 53, 19.20%). Fever, abnormal procalcitonin, positive urinary nitrite and abnormal urination function were the clinical characteristics of elderly CAUTI patients (P < 0.001). Once CAUTI occurred in elderly patients, the hospitalization days were increased by 18 days, the total hospitalization cost increased by ¥18,000, and discharge all-cause mortality increased by 2.314 times (P<0.001). CONCLUSION: The situation of CAUTI in the elderly is not optimistic, it is easy to have a one-person multi-pathogen infection, and the proportion of fungi infection is not low. Urine pH ≥ 6.5, moderate or severe dependence on others and malnutrition were rare risk factors for elderly CAUTI in previous studies. Our study analysed the clinical characteristics of CAUTI in the elderly through a large sample size, which provided a reliable basis for its diagnosis and identified the adverse outcome of CAUTI.

Kaempferide ameliorates cisplatin-induced nephrotoxicity via inhibiting oxidative stress and inducing autophagy.

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

Epidemiological Investigation of 387 Individuals Over 65 Years Old With Osteoporotic Fractures.

Context: With the rapidly aging population globally, osteoporosis (OP) has become a major public health problem, and fracture is a common complication of OP. Older adults, especially postmenopausal women, have a higher incidence of OP. Objective: The study intended to analyze the clinical information, epidemiological characteristics, treatments, and follow-up results of patients with osteoporotic fractures (OPFs) in adults over 65 years old, to provide data support for the prevention, treatment, and use of OPF focus groups in clinical practice. Design: The research team performed a retrospective analysis using electronic medical records and related imaging data of patients. Setting: The study took place at Hebei General Hospital in Hebei, China. Participants: Participants were 387 patients over 65 years old with osteoporotic fractures who had been admitted to the hospital between July 2012 and July 2018. Outcome Measures: The research team recorded participants' ages, genders, fracture causes, and fracture sites. The team performed a follow-up analysis on refractures, treatment with anti-osteoporotic drugs, exercise, and survival status within the 3 years after surgery. Results: The study's male-to-female ratio was 1:3.1, and the rate of osteoporotic fracture for females was significantly higher than that of males. The mean age of participants with fractures was 75.6 ± 8.5 years, and most fractures occurred in participants 78 to 85 years old. Of the 387 participants, 169 participants had hip fractures (43.67%); 98 had vertebral compression fractures (25.32%); 51 had distal radius and ulna fractures (13.18%); 42 had proximal humerus fractures (10.85%); and 27 had other fractures (6.98%). The number of women with fractures at each site was greater than the number of men, but the differences weren't statistically significant (P > .05). The main causes of injury were falls (71.58%), and the main place of the occurrence of injury was at home (65.6%). Of the 387 participants, 346 had surgical treatment (89.41%), and the effective rate of surgical treatment was 99.42%. Three years after surgery, the research team followed up with 235 participants, for a follow-up rate of 60.72%. Within the 3 years of the follow-up period, 61 participants had refractures (25.63%), 29 received treatment with regular anti-osteoporotic drugs (12.34%), 36 exercised twice or more a week (15.32%), and 32 had died for various reasons (13.62%). Conclusions: The study preliminarily described the epidemiological characteristics of 387 osteoporotic fractures in adults over 65 years old. More women had fractures than men; the hip was the most common fracture site, and falls were the main cause of injury. Most of the fractures occurred in the place of residence, and the refracture rate was 25.96% at three years after surgery.

Risk factors for ventilator-associated pneumonia due to multi-drug resistant organisms after cardiac surgery in adults.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common intensive care unit (ICU)-acquired infections, which can cause multiple adverse events. Due to bacterial mutation and overuse of antimicrobial drugs, multidrug-resistant organisms (MDRO) has become one of the major causes of postoperative VAP infections in cardiac patients. Therefore, this study aims to explore the risk factors for VAP with MDRO following cardiac surgery in adults. METHODS: The clinical data of adult VAP patients following cardiac surgery in the hospital from Jan 2017 to May 2021 were analyzed retrospectively, and the patients were divided into the MDRO VAP group and the non-MDRO VAP group. Univariable and multivariable logistic regression analyses were performed on risk factors in patients with MDRO VAP. The species and drug sensitivity of pathogens isolated from the VAP patients were also analyzed. RESULTS: A total of 61 VAP cases were involved in this study, with 34 cases in the MDRO VAP group (55.7%) and 27 cases in the non-MDRO VAP group (44.3%). Multivariable logistic regression analysis showed that independent risk factors for MDRO VAP included preoperative creatinine clearance rate (CCR) ≥ 86.6ml, intraoperative cardiopulmonary bypass (CPB) time ≥ 151 min, postoperative acute kidney injury (AKI) and nasal feeding. Gram-negative bacilli were the main pathogens in VAP patients (n = 54, 90.0%), with the highest rate of Acinetobacter baumannii (n = 24, 40.0%). Additionally, patients with MDRO VAP had a significantly longer postoperative intensive care unit (ICU) duration and higher hospitalization costs than non-MDRO VAP patients, but there was no notable difference in the 28-day mortality rate between the two groups. CONCLUSION: Based on implementing measures to prevent VAP, clinicians should pay more attention to patients with kidney disease, longer intraoperative CPB time, and postoperative nasal feeding to avoid MDRO infections.

Research on High Sensitivity Oil Debris Detection Sensor Using High Magnetic Permeability Material and Coil Mutual Inductance.

Metallic contaminants (solid) are generated by friction pair, causing wear of equipment by enters the lubricating system. This poses a great potential threat to the normal operation of such machines. The timely analysis and detection of debris can lead to the avoidance of mechanical failures. Abnormal wear in machinery may produce debris exceeding 10 µm. The traditional inductance detection method has low sensitivity and cannot meet the actual detection requirements. To boost the sensitivity of the inductance sensor, the mutual inductance of coils and the strong magnetic conductivity of permalloy was utilized to design a high sensitivity inductance sensor for the detection of debris in lubricating oil. This design was able to detect 10-15 µm iron particles and 65-70 µm copper particles in the oil. The experimental results illustrate that low-frequency excitation is the best for detecting ferromagnetic particles, while high-frequency excitation has the best effect for detecting non-ferromagnetic particles. This paper demonstrates the significant advantages of coil mutual inductance, and strong magnetic conductivity of permalloy in improving the detection sensitivity of oil debris sensors. This will provide technical support for wear detection in mechanical equipment and fault diagnosis.

An Efficient UPLC-MS/MS Method for the Determination of Pyrroloquinoline Quinone in Rat Plasma and Its Application to a Toxicokinetic Study.

Pyrroloquinoline quinone (PQQ) is a powerful antioxidant coenzyme existing in diet, benefiting growth, development, cognition function, and the repair of damaged organs. However, a method for detecting PQQ in vivo was rarely described, limiting the research on the bioanalysis and metabolic properties of PQQ. In this study, a novel, simple, and efficient ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to quantify the concentration of PQQ in rat plasma. Detection through mass spectrometry was operated by multiple reaction monitoring (MRM) in negative electrospray ionization mode with ion transitions m/z 328.99→197.05 for PQQ and m/z 280.04→195.04 for the internal standard. The calibration curves were linear up to 10,000 ng/mL, with a lower limit of quantitation of 10 ng/mL. Inter-run and intra-run precision ranged from 1.79% to 10.73% and accuracy ranged from -7.73% to 7.30%. The method was successfully applied to a toxicokinetic study in Sprague-Dawley rats after the oral administration of PQQ disodium salt at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg. The toxicokinetic parameters were subsequently analyzed, which may provide valuable references for the toxicokinetic properties and safety evaluation of PQQ.

Increased attentional network activity in premature ejaculation patients with anxiety revealed by resting-state functional magnetic resonance imaging.

Psychological account hypothesizes that premature ejaculation (PE) is a learned pattern of rapid ejaculation maintained by anxiety about sexual failure, whereas neuropsychological accounts hypothesizes that PE is the result of dysfunction of central nervous system regulating ejaculatory. However, the central neural mechanism underlying PE patients with anxiety remains unclear. Resting-state functional magnetic resonance imaging (fMRI) data were collected in 20 PE (diagnoses based on PE Guidelines drafted by the International Society for Sexual Medicine [ISSM]) patients with anxiety and 25 matched healthy controls (HCs) from January 2019 to December 2020. The values of fractional amplitude of low-frequency fluctuation (fALFF) were compared between groups. Moreover, the correlations between fALFF and the severity of PE and anxiety of patients were examined. PE patients with anxiety had increased fALFF values in the right inferior frontal gyrus (opercular part) and middle frontal gyrus. In addition, significant positive correlations were found between the scores of PE diagnostic tool (PEDT) and fALFF values of the right inferior frontal gyrus (opercular part), as well as the right middle frontal gyrus. Moreover, fALFF values of the right inferior frontal gyrus (opercular part) and middle frontal gyrus were positively correlated with the scores of self-rating anxiety scale (SAS). Our results suggested that increased attentional network activity might play a critical role in the neural basis of PE patients with anxiety.

[Cordyceps sinensis combined with Jujing Pills for male infertility].

OBJECTIVE: To observe the clinical effect and safety of Cordyceps sinensis (CS) combined with Jujing Pills (JJP) in the treatment of male infertility. METHODS: We randomly divided 90 male infertility patients into three groups of an equal number and treated them with JJP tid 5g once, CS bid 1g once and CS+JJP, respectively, all for 12 weeks. Before and after 4, 8 and 12 weeks of medication, we obtained the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) and sperm DNA fragmentation index (DFI), and compared them between the two groups of patients. RESULTS: The total therapeutic effectiveness rate was significantly higher in the CS+JJP than in the CS and JJP groups (96.42% vs 78.57% and 63.33%, P < 0.05), and so was PMS (ï¼»30.05 ± 10.24ï¼½% vs ï¼»24.74 ± 11.24ï¼½% and ï¼»22.71 ± 13.60ï¼½%, P < 0.01). The CS+JJP group also showed a higher percentage of MNS than the JJP group (ï¼»4.16 ± 2.86ï¼½% vs ï¼»2.73 ± 1.86ï¼½%, P < 0.01) but lower than the CS group (ï¼»5.03 ± 2.99ï¼½%) (P < 0.05). The sperm DFI was markedly lower in the CS+JJP than in the CS and JJP groups (ï¼»15.26 ± 6.93ï¼½% vs ï¼»15.90 ± 7.39ï¼½% and ï¼»16.85 ± 8.52ï¼½%, P < 0.05). CONCLUSIONS: Cordyceps sinensis combined with Jujing Pills can effectively improve sperm quality and reduce sperm DFI. Based on the TCM theory of "mutual generation between metal and water", Cordyceps sinensis can significantly enhance the effectiveness of the kidney-tonifying therapy.

[Associations between the efficiency of the brain white matter network and clinical symptoms in patients with type â ¢ B prostatitis].

OBJECTIVE: To investigate the changes in the topological properties of the global and local nodal efficiencies of the brain white matter network in patients with type III B prostatitis, and to analyze the correlation between the information transmission efficiency of different brain regions and pelvic pain. METHODS: We enrolled 19 patients with type Ⅲ B prostatitis and 32 normal controls matched in general demographic data for this study. We assessed the pelvic pain of the patients based on the NIH-CPSI, obtained the structural and diffusion-weighted MR images of the brain, preprocessed the MRI data, constructed the brain structural networks and calculated the topological properties of the nodal local and global efficiencies using the FSL software package and brain connection toolbox. Finally, we compared the topological properties between the two groups by t-test with the SPSS 20 software, performed multiple correction of the values using the false discovery rate (FDR) method, and investigated the associations of the altered brain regions with the NIH-CPSI scores by Pearson correlation analysis. RESULTS: The global efficiency of the orbital part of the right median frontal gyrus in the patients with type Ⅲ B prostatitis, compared with that in the normal controls, was dramatically decreased (0.095 ± 0.046 vs 0.13 ± 0.015, P < 0.01) while that of the left median cingulate gyrus markedly increased (0.16 ± 0.027 vs 0.14 ± 0.019, P < 0.01), which were corrected by FDR. The local efficiency of the left median cingulate gyrus was also remarkably decreased in the patients as compared with that in the controls (0.25 ± 0.075 vs 0.19 ± 0.036, P < 0.01), and so was that of the left paracentral lobule (0.25 ± 0.088 vs 0.17 ± 0.065, P < 0.01), which were corrected by FDR. In the patients, the local efficiencies of the left precuneus (r = 0.46, P = 0.045), right supplementary motor area (r = 0.47, P = 0.043) and left median cingulate gyrus (r = 0.60, P = 0.0065) were positively correlated with the total score of NIH-CPSI, the scores of pain and discomfort symptoms, and the scores of the influence of the symptoms on the quality of life. CONCLUSIONS: The changes of the brain regions in the executive control network of the patient with type Ⅲ B prostatitis might be involved in enhancing his sensitivity to pain and discomfort, and consequently lead to pelvic pain and discomfort.

A review of pig liver xenotransplantation: Current problems and recent progress.

Pig liver xenotransplantation appears to be more perplexing when compared to heart or kidney xenotransplantation, even though great progress has been achieved. The relevant molecular mechanisms involved in xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia, are complex, and need to be systematically investigated. The deletion of expression of Gal antigens in the liver graft highlights the injurious impact of nonGal antigens, which continue to induce humoral rejection. Innate immunity, particularly mediated by macrophages and natural killer cells, interplays with inflammation and coagulation disorders. Kupffer cells and liver sinusoidal endothelial cells (LSECs) together mediate leukocyte, erythrocyte, and platelet sequestration and phagocytosis, which can be exacerbated by increased cytokine production, cell desialylation, and interspecies incompatibilities. The coagulation cascade is activated by release of tissue factor which can be dependent or independent of the xenoreactive immune response. Depletion of endothelial anticoagulants and anti-platelet capacity amplify coagulation activation, and interspecies incompatibilities of coagulation-regulatory proteins facilitate dysregulation. LSECs involved in platelet phagocytosis and transcytosis, coupled with hepatocyte-mediated degradation, are responsible for thrombocytopenia. Adaptive immunity could also be problematic in long-term liver graft survival. Currently, relevant evidence and study results of various genetic modifications to the pig donor need to be fully determined, with the aim of identifying the ideal transgene combination for pig liver xenotransplantation. We believe that clinical trials of pig liver xenotransplantation should initially be considered as a bridge to allotransplantation.

Cytokine profiles in Tibetan macaques following α-1,3-galactosyltransferase-knockout pig liver xenotransplantation.

BACKGROUND: Pig-to-nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno-immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation. METHODS: Appropriate donor and recipient matches were screened using complement-dependent cytotoxicity assays. Donor liver grafts from α1,3-galactosyltransferase gene-knockout (GTKO) pigs or GTKO pigs additionally transgenic for human CD47 (GTKO/CD47) were transplanted into Tibetan macaques via two different heterotrophic auxiliary liver xenotransplantation procedures. The cytokine profiles, hepatic function, and coagulation parameters were monitored during the clinical course of xenotransplantation. RESULTS: Xenograft blood flow was stable in recipients after heterotopic auxiliary transplantation. A Doppler examination indicated that the blood flow speed was faster in the hepatic artery (HA) and hepatic vein (HV) of xenografts subjected to the modified Sur II (HA-abdominal aorta+HV-inferior vena cava) procedure than in those subjected to our previously reported Sur I (HA-splenic artery+HV-left renal vein) procedure. Tibetan macaques receiving liver xenografts did not exhibit severe coagulation disorders or immune rejection. Although the recipients did suffer from a rapid loss of platelets, this loss was mild. In blood samples dynamically collected after xenotransplantation (post-Tx), dramatic increases in the levels of monocyte chemoattractant protein 1, interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor, IL-6, and interferon gamma-induced protein 10 were observed at 1 hour post-Tx, even under immunosuppression. We further confirmed that the elevation in individual cytokine levels was correlated with the onset of graft damage. Finally, the release of cytokines might contribute to leukocyte infiltration in the xenografts. CONCLUSION: Here, we established a modified auxiliary liver xenotransplantation model resulting in near-normal hepatic function. Inflammatory cytokines might contribute to early damage in liver xenografts. Controlling the systemic inflammatory response of recipients might prevent early post-Tx graft dysfunction.

An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC).

Colorectal cancer (CRC) is the third most common malignant disease worldwide, and its incidence is increasing, but the molecular mechanisms of this disease are highly heterogeneous and still far from being fully understood. Increasing evidence suggests that fibrosis mediated by abnormal activation of fibroblasts based in the microenvironment is associated with a poor prognosis. However, the function and pathogenic mechanisms of fibroblasts in CRC remain unclear. Here, combining scrna-seq and clinical specimen data, DAZ Interacting Protein 1 (DZIP1) was found to be expressed on fibroblasts and cancer cells and positively correlated with stromal deposition. Importantly, pseudotime-series analysis showed that DZIP1 levels were up-regulated in malignant transformation of fibroblasts and experimentally confirmed that DZIP1 modulates activation of fibroblasts and promotes epithelial-mesenchymal transition (EMT) in tumor cells. Further studies showed that DZIP1 expressed by tumor cells also has a driving effect on EMT and contributes to the recruitment of more fibroblasts. A similar phenomenon was observed in xenografted nude mice. And it was confirmed in xenograft mice that downregulation of DZIP1 expression significantly delayed tumor formation and reduced tumor size in CRC cells. Taken together, our findings suggested that DZIP1 was a regulator of the CRC mesenchymal phenotype. The revelation of targeting DZIP1 provides a new avenue for CRC therapy.

Altered brain activity in diabetic patients with erectile dysfunction revealed by fractional amplitude of low-frequency fluctuation: A resting-state fMRI study.

INTRODUCTION: Diabetes mellitus is one of the major chronic diseases, which enhances the risk of erectile dysfunction. However, the central pathological mechanisms of erectile dysfunction in diabetes mellitus patients are still unclear. METHODS: Resting-state functional magnetic resonance imaging data were acquired in 30 type-2 diabetes mellitus, 31 type-2 diabetes mellitus with erectile dysfunction patients, and 31 healthy controls. The measure of fractional amplitude of low-frequency fluctuation was calculated and compared among groups. RESULTS: Differences of fractional amplitude of low-frequency fluctuation values were found in the left superior frontal gyrus (medial) and middle temporal gyrus among three groups. Compared with healthy controls group, type-2 diabetes mellitus group exhibited lower fractional amplitude of low-frequency fluctuation values in the left superior frontal gyrus (dorsolateral), anterior cingulate gyrus, calcarine fissure, and increased fractional amplitude of low-frequency fluctuation values in the left post-central gyrus. Compared with healthy controls group, erectile dysfunction with type-2 diabetes mellitus group exhibited lower fractional amplitude of low-frequency fluctuation values in the left superior frontal gyrus (medial), middle temporal gyrus, temporal middle (pole), and increased fractional amplitude of low-frequency fluctuation values in the right post-central gyrus. Compared with type-2 diabetes mellitus group, erectile dysfunction with type-2 diabetes mellitus group exhibited increased fractional amplitude of low-frequency fluctuation values in the right median cingulum gyrus and left calcarine fissure. CONCLUSION: Erectile dysfunction with type-2 diabetes mellitus patients showed functional changes in brain regions that were closely correlated with sexual dysfunction, which suggested that altered regional brain activity might be related to the pathophysiology of erectile dysfunction with type-2 diabetes mellitus.

Single-cell RNA sequencing reveals cell-cell communication and potential biomarker in sepsis and septic shock patients.

BACKGROUND: Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock. METHODS: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data. RESULTS: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis. CONCLUSIONS: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease.

Gut microbiota composition may be an indicator of erectile dysfunction.

Erectile Dysfunction (ED) is considered a physical and mental illness. A variety of potential associations between gut microbiota and health or disease have been found. By comparing the gut microbiota of healthy controls and ED patients, our study investigated the relationship between ED and gut microbiota. The results revealed that the ED group exhibited a significantly higher relative abundance of Bacteroides, Fusobacterium, Lachnoclostridium, Escherichia-Shigella and Megamonas, while showing a significantly lower relative abundance of Bifidobacterium compared to the control group. The dysbiosis of gut microbiota played a role in the onset and progression of ED by influencing the gut barrier, cardiovascular system and mental health, which provided a novel perspective on understanding the pathophysiology of ED. What is more, we had identified several key gut microbiota. By combining 16S rRNA sequencing with machine learning techniques, we were able to uncover the significant value and impact of gut microbiota in the early detection of ED.

Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation.

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

A link between premenopausal iron deficiency and breast cancer malignancy.

BACKGROUND: Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. METHODS: One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. RESULTS: We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-ß and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). CONCLUSIONS: Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients.

RNA interference of GGTA1 physiological and immune functions in immortalized porcine aortic endothelial cells.

BACKGROUND: Pig organs are commonly used in xenotransplantation, and α-1,3-galactose has been shown to be the main cause of hyperacute rejection. The development of transgenic pigs that lack α-1,3-galactosyltransferase (GGTA1) has overcome this problem to a certain extent, but transgenic pigs are difficult to maintain, making their usefulness in basic research limited. For this reason, we propose to establish a cell model to study hyperacute rejection. METHODS: Immortalized primary porcine aortic endothelial cells were transfected with a short hairpin RNA targeted to GGTA1. Cell proliferation, apoptosis, complement C3 activation, and the binding of human immunoglobulins and components of the complement system, including IgM, IgG, C3, and C5b-9, were examined. RESULTS: After RNA interference, GGTA1 was found to be reduced at both the transcript and protein level as assessed by quantitative polymerase chain reaction and flow cytometry, respectively. When cultured in the presence of human serum, the proliferation rate of the transfected cells was higher than that of untransfected cells, and the apoptosis rate was lower. Additionally, activation of C3 and the binding of human immunoglobulins IgM and IgG and complement component C3 and C5b-9 to the transfected cells were lower than in the immortalized group but higher than in untransfected cells. CONCLUSIONS: RNA interference of GGTA1 in cultured porcine endothelial cells reduces the reaction of immunoglobulin and complement system with the cells. Therefore, this in vitro cell model could be useful for further study of xenotransplantation.

Lumican expression in pancreatic ductal adenocarcinoma.

BACKGROUND/AIMS: The present study was aimed to investigate lumican expression in and correlation with severity of pancreatic ductal adenocarcinoma (PDA). METHODOLOGY: We assessed mRNA expression and protein localization (using immunohistochemistry) in PDA samples collected from 260 patients. Additionally, we compared lumican expression with expression of Ki-67, VEGF and mutated p53 proteins, which are markers of cancer progression. RESULTS: Expression levels of lumican mRNA and protein in cancer tissue were significantly higher than those in tumor-adjacent tissue (t=5.69, p<0.05). The stromal expression of lumican in poorly differentiated cases was significantly higher at stage T4 than stage T2-3 (χ²=21.06, p<0.05); similarly, the stromal expression of lumican was significantly higher in TNM stage III-IV than in stage I-Il (χ²=17.01, p<0.05). Additionally, expression of Ki67 was higher in poorly differentiated cases than in highly-moderately differentiated cases (χ²=13.06, p<0.05). Finally, in highly-moderately differentiated samples, stromal expression of lumican was negatively correlated with expression of Ki-67, VEGF and mutated P53 (p<0.05). CONCLUSIONS: Lumican expression is higher in pancreatic ductal adenocarcinoma than in tumor-adjacent tissue, and the correlation of lumican expression with TNM stage in poorly differentiated samples, in contrast with its negative correlation with expression of Ki-67, VEGF and mutated P53 mutation in highly-moderately differentiated samples.