Localized in vivo prodrug activation using radionuclides.

Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof-of-principle, we tested whether this strategy of " RA dionuclide i nduced D rug E ngagement for R elease" ( RAiDER ) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing exposure to activated chemotherapy in off-target sites. Methods: We screened the ability of radionuclides to chemically activate a model radiation-activated prodrug consisting of the microtubule destabilizing monomethyl auristatin E caged by a radiation-responsive phenyl azide ("caged-MMAE") and interpreted experimental results using the radiobiology computational simulation suite TOPAS-nBio. RAiDER was evaluated in syngeneic mouse models of cancer using fibroblast activation protein inhibitor (FAPI) agents 99m Tc-FAPI-34 and 177 Lu-FAPI-04, the prostate-specific membrane antigen (PSMA) agent 177 Lu-PSMA-617, combined with caged-MMAE or caged-exatecan. Biodistribution in mice, combined with clinical dosimetry, estimated the relationship between radiopharmaceutical uptake in patients and anticipated concentrations of activated prodrug using RAiDER. Results: RAiDER efficiency varied by 250-fold across radionuclides ( 99m Tc> 177 Lu> 64 Cu> 68 Ga> 223 Ra> 18 F), yielding up to 1.22µM prodrug activation per Gy of exposure from 99m Tc. Computational simulations implicated low-energy electron-mediated free radical formation as driving prodrug activation. Clinically relevant radionuclide concentrations chemically activated caged-MMAE restored its ability to destabilize microtubules and increased its cytotoxicity by up to 600-fold compared to non-irradiated prodrug. Mice treated with 99m Tc-FAPI-34 and caged-MMAE accumulated up to 3000× greater concentrations of activated MMAE in tumors compared to other tissues. RAiDER with 99m Tc-FAPI-34 or 177 Lu-FAPI-04 delayed tumor growth, while monotherapies did not ( P <0.03). Clinically-guided dosimetry suggests sufficient radiation doses can be delivered to activate therapeutically meaningful levels of prodrug. Conclusion: This proof-of-concept study shows that RAiDER is compatible with multiple radionuclides commonly used in nuclear medicine and has the potential to improve the efficacy of radiopharmaceutical therapies to treat cancer safely. RAiDER thus shows promise as an effective strategy to treat disseminated malignancies and broadens the capability of radiopharmaceuticals to trigger diverse biological and therapeutic responses.

Mediating effects of carbon monoxide on the development of hypertension in China.

OBJECTIVES: Understanding the relationship between ambient carbon monoxide (CO) exposure and hypertension is crucial for advancing public health research. We investigated the association between air pollution CO exposure and hypertension and determined whether various health indicators played a mediating role. STUDY DESIGN: Cross-sectional population-based study. METHODS: Our study examined the data of 13,240 participants in the China Health and Aging Longitudinal Study (CHARLS) conducted in 2015. A logistic regression approach was used to investigate the association between CO concentration and hypertension. The mediating effects (MEs) of health indicators on the association between carbon monoxide and hypertension prevalence were explored using mediation models. RESULTS: Hypertension was diagnosed in 2953 of the participants. A significantly increased prevalence of hypertension was associated with higher concentrations of air pollutant CO after adjusting for all covariates (OR: 1.19, 95% CI: 1.04-1.37) in the matched group (OR: 1.21, 95% CI: 1.03-1.42). The study also showed that proportional mediation was 3.7% by TG, -5.3% by TC, -2.9% by LDL-C and 19.0% by HDL-C for blood lipid; 4.6% by FPG and 12.2% by HbA1c for blood glucose; -2.0% by grip strength and 16.2% by chair rising time for muscle strength; 59.6% by WC and 1.8% by BMI for obesity indicator and -2.3% by nighttime sleep and 7.8% by daytime nap for sleep duration. CONCLUSIONS: A significant positive association has been found between environmental CO exposure and hypertension, and obesity, muscle strength, sleep duration, and metabolic factors may play a significant role in mediating this association.

Spiritual needs and influencing factors among people with stroke in China: a cross-sectional study.

BACKGROUND: Stroke is one of the primary causes of disability in China and around the world, having an impact on the health and well-being of stroke patients. The importance of spiritual needs for stroke patients has always been a controversial topic internationally, partly because related research was mostly qualitative and may not directly reflect the degree of spiritual needs. In addition, most studies focus on the same cultural background, there is a lack of research that delves into the nuances of Chinese culture and background. The goal of this study is to evaluate the level of spiritual needs and influencing factors in Chinese stroke patients and to explore the mediating role and pathways of these variables on spiritual needs. METHODS: From August 2022 to January 2023, we conducted a cross-sectional questionnaire survey of 422 stroke patients in the affiliated hospitals of Hunan University of Chinese Medicine in Changsha Province by cluster sampling. We measured the patient's spiritual needs, quality of life, anxiety and depression levels, and family support using the Spiritual Needs Questionnaire (SPNQ), the MOS36 item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Family Support Self Rating Scale (PSS-Fa). We used the General Information Questionnaire to gain insight into the sociodemographic characteristics of the patients. Nonparametric tests and multiple linear regression models were used to analyze the independent relationship between spiritual needs and quality of life, anxiety, depression, and family support. The mediation model in AMOS 24.0 software was used to analyze the mediating role among the five variables. RESULTS: The score of spiritual needs of people with stroke included in this study was 37 points [IQR 33 to 40)]. The influencing factors of spiritual needs included primary economic sources for disease-related expenditures (p = 0.044), number of stroke occurrences (p = 0.001), duration of illness (p = 0.023), activities of daily living (p = 0.006), depression scores(p = 0.034), and family support scores(p = 0.008). Anxiety (ß = 0.347, p = 0.004), depression (ß = 0.368, p = 0.005), and family support (ß = 0.167, p = 0.023) had directly or indirectly affected the spiritual needs of people with stroke. Quality of life (ß=-0.202, p = 0.017) had a direct effect on spiritual needs. CONCLUSIONS: The spiritual needs of people with stroke were at an intermediate level. Our findings highlight that the SPNQ score is associated with anxiety, depression, quality of life, and family support. Therefore, nurses should identify the spiritual needs of patients and provide them with effective and comprehensive spiritual care by reducing negative emotions and enhancing social support, promoting the development and progress of spiritual care in China. This study offers a theoretical basis for the spiritual care of clinical people with stroke and constructing a stroke spiritual care model.

[Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways].

OBJECTIVE: To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang (SC) root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments. METHODS: The targets of SC and pancreatic cancer were predicted using the network pharmacological database, the protein-protein interaction network was constructed, and pathways, functional enrichment and molecular docking analyses were performed. CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines, and its effects on invasion, migration, proliferation, and apoptosis of pancreatic cancer cells were evaluated. Western blotting was performed to verify the results of network pharmacology analysis. RESULTS: We identified a total of 18 active components in SC, which regulated 21 potential key targets in pancreatic cancer. GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation, signal transduction, and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways. Among the 8 cancer cell lines, The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells, and significantly inhibited the invasion, migration, and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells (P < 0.05). Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells (P < 0.001). CONCLUSION: The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Oral health education strategies for patients living with cardiovascular disease within hospital settings: a scoping review.

Objective: To identify and describe the impact of current oral health education programmes provided to patients in cardiology hospital wards and outpatient clinics. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews statement. Searches were conducted using electronic databases: Cochrane, Medline, and Scopus, as well as grey literature searching. Results: Three eligible studies were identified. All included studies reported generalised poor oral health in their participants at baseline, with significant improvement at follow-up. They all reported significant reductions in plaque deposits and gingival bleeding. One study reported significantly less bacteria on participant tongues, as well as fewer days with post-operative atrial fibrillation in the intervention group. Furthermore, in this study, one patient in the intervention group developed pneumonia, whilst four patients in the control group did. Conclusion: Oral health education for patients with cardiovascular disease is limited and many have poor oral health. Educational programmes to improve oral health behaviours in patients with cardiovascular disease can improve both oral and general health outcomes. Implications for public health: Oral disease is a modifiable risk factor for cardiovascular disease. Integrating oral health education into cardiology hospital settings is a simple strategy to improve access to oral health information and improve both oral and cardiovascular outcomes.

[Molecular mechanism analysis of a family with hereditary coagulation F â ª deficiency caused by compound heterozygous mutations].

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

UiO-66/AgNPs Coating for Dental Implants in Preventing Bacterial Infections.

Titanium (Ti)-based biomaterials lack inherent antimicrobial activities, and the dental plaque formed on the implant surface is one of the main risk factors for implant infections. Construction of an antibacterial surface can effectively prevent implant infections and enhance implant success. Silver nanoparticles (AgNPs) exhibit broad antibacterial activity and a low tendency to induce drug resistance, but AgNPs easily self-aggregate in the aqueous environment, which significantly impairs their antibacterial activity. In this study, UiO-66/AgNP (U/A) nanocomposite was prepared, where zirconium metal-organic frameworks (UiO-66) were employed as the confinement matrix to control the particle size and prevent aggregation of AgNPs. The bactericidal activity of U/A against methicillin-resistant Staphylococcus aureus and Escherichia coli increased nearly 75.51 and 484.50 times compared with individually synthesized Ag. The antibacterial mechanism can be attributed to the enhanced membrane rupture caused by the ultrafine AgNPs on UiO-66, leading to protein leakage and generation of intracellular reactive oxygen species. Then, U/A was loaded onto Ti substrates (Ti-U/A) by using self-assembly deposition methods to construct an antibacterial surface coating. Ti-U/A exhibited excellent antibacterial activities and desired biocompatibility both in vitro and in vivo. The U/A nanocomposite coating technique is thus expected to be used as a promising surface modification strategy for Ti-based dental implants for preventing dental implant infections.

Epicardial and pericoronary adipose tissue and coronary plaque burden in patients with Cushing's syndrome: a propensity score-matched study.

PURPOSE: To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing's syndrome (CS) based on coronary computed tomography angiography (CCTA). METHODS: This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded. RESULTS: The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (ß [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (ß [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (ß [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (ß [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients. CONCLUSIONS: Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.

[Study of the effects of dietary patterns on glycemic control in community type 2 diabetic mellitus patients].

Objective: To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients. Methods: Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control. Results: Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95%CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95%CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern (OR=0.71, 95%CI: 0.52-0.98) and fruit-aquatic products-potato patterns (OR=0.71, 95%CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns (OR=0.60, 95%CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern (OR=1.41, 95%CI: 1.03-1.94; OR=1.68, 95%CI: 1.13-2.51) and egg-milk-bean pattern (OR=1.75, 95%CI: 1.25-2.46; OR=1.56, 95%CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern (Q4 group), vegetable-grain pattern (Q2 group), egg-milk-bean pattern (Q3 group)" was higher (OR=6.79, 95%CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern (Q4 group), vegetable-grain pattern (Q3 group), egg-milk-bean pattern (Q2 group), oil-salt pattern (Q2 group)" had higher control rate of 2 h PBG (OR=12.78, 95%CI: 1.26-130.05, P=0.031). Conclusions: A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.

[Genetic characteristics of the first human infection with the G4 genotype eurasian avian-like H1N1 swine influenza virus in Shaanxi Province,China].

Objective: To analyze the genetic characteristics of the first human infection with the G4 genotype of Eurasian avian H1N1 swine influenza virus (EA H1N1 SIV) in Shaanxi Province. Methods: The patient's throat swab samples were collected, and MDCK cells were inoculated for virus isolation to obtain the virus strain. The whole genome deep sequencing method was used to obtain the eight gene segments of the isolated strain. The nucleotide homology analysis was conducted through the Blast program in the GenBank database, and a phylogenetic tree was constructed to analyze the genetic characteristics of the virus. Results: The throat swab specimens of the case were confirmed as EA H1N1 SIV in the laboratory, and the isolated strain was named A/Shaanxi-Weicheng/1351/2022(H1N1v). Homology analysis found that the PB2, NP, HA, NA, and M genes of this isolate had the highest nucleotide homology with A/swing/Beijing/0301/2018 (H1N1), about 98.29%, 98.73%, 97.41%, 97.52%, and 99.08%, respectively. The phylogenetic tree showed that the isolate belonged to G4 genotype EA H1N1 SIV, with PB2, PB1, PA, NP and M genes from pdm/09 H1N1, HA and NA genes from EA H1N1, and NS gene from Triple-reassortant H1N1. The cleavage site of the HA protein was IPSIQSR↓G, which was the molecular characteristic of the low pathogenic influenza virus. No amino acid mutations associated with neuraminidase inhibitors were found in the NA protein. PB2 protein 701N mutation, PA protein P224S mutation, NP protein Q357K mutation, M protein P41A mutation, and NS protein 92D all indicated its enhanced adaptability to mammals. Conclusion: The patient is the first human infection with G4 genotype EA H1N1 SIV in Shaanxi province. The virus is low pathogenic, but its adaptability to mammals is enhanced. Therefore, it is necessary to strengthen the monitoring of such SIVs.

Dynapenic Abdominal Obesity and Risk of Heart Disease among Middle-Aged and Older Adults: A Prospective Cohort Study.

OBJECTIVES: The vicious cycle of dynapenia and abdominal obesity may have synergistic detrimental impacts on health. We aim to investigate the prospective association between dynapenic abdominal obesity and the risk of heart disease among middle-aged and older adults. DESIGN: A prospective cohort study. SETTING: English Longitudinal Study of Ageing, 2002-2019. PARTICIPANTS: A total of 4734 participants aged 50 years and older were included. MEASUREMENTS: Individuals were divided into non-dynapenia/non-abdominal obesity (ND/NAO), non-dynapenia/abdominal obesity (ND/AO), dynapenia/non-abdominal obesity (D/NAO), and dynapenia/abdominal obesity (D/AO) according to grip strength and waist circumference at baseline. The Cox proportional hazards models were used to obtain the hazard ratios (HRs) of incident heart disease associated with dynapenia and abdominal obesity after adjusting for potential confounding factors. RESULTS: During a median follow-up of 9.5 years, 1040 cases of heart disease were recorded. Compared with ND/NAO group, the multivariable HRs were 1.05 (0.92, 1.21) for ND/AO group, 1.31 (0.96, 1.81) for D/NAO group, and 1.39 (1.03, 1.88) for D/AO group. The significant association of D/AO with incident heart disease was detected in women but not in men [HR = 1.55 (1.07, 2.24) and 1.06 (0.60, 1.88), respectively]. Among middle-aged adults, significant associations of D/NAO and D/AO with incident heart disease were observed [HR = 2.46 (1.42, 4.29) and 1.74 (1.02, 2.97), respectively]. CONCLUSION: Both D/NAO and D/AO might increase the risk of developing heart disease, highlighting the importance of dynapenia and obesity early screening for heart disease prevention.

[Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm].

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN). METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, ß-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, ß-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN. RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. ß-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. ß-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05). CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

[Erythrocytosis after hematopoietic stem cell transplantation: report of 3 cases and literature review].

This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.

The identification of sex-specific biomarkers in peripheral blood mononuclear cells from elderly individuals with ischemic stroke.

OBJECTIVE: The aim of this study was to identify sex-specific biomarkers for ischemic stroke (IS) prophylaxis in elderly individuals. MATERIALS AND METHODS: The GSE22255 dataset for elderly individuals with IS was retrieved from the gene expression omnibus database. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, as well as gene set enrichment analysis (GSEA). Furthermore, protein-protein interactions (PPIs) were explored using the STRING database, and to screen central genes from the Cytoscape PPI network, corresponding to peripheral blood samples from elderly individuals, we used the molecular complex detection plug-in and cytoHubba. Moreover, a Venn diagram was used to visualize the key genes common among elderly women and men with IS. Statistical analysis was also performed, and receiver operating characteristic (ROC) curves were constructed to evaluate the specificity and sensitivity of the prediction of IS in the elderly. RESULTS: Compared with the healthy controls, in elderly women with IS, 511 biological process (BP) terms, 16 molecular function (MF) terms, and 34 KEGG terms were significantly enriched, whereas in the elderly men with IS, 681 BP terms, 12 MF terms, and 44 KEGG terms were enriched. The GSEA revealed 99 and 140 significantly enriched gene sets in elderly women and men with IS, respectively. Furthermore, in the PPI network, 10 hub genes for each sex with high specificity and sensitivity were identified using ROC curves. CONCLUSIONS: Ten genes for each sex with significant differential expression were also identified in individuals with IS. The novel sex-specific gene targets may be promising diagnostic or prognostic markers and potential therapeutic targets for IS in the elderly.

[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Inhibitory effect and mechanism of Lactobacillus crispatus on cervical precancerous cells Ect1/E6E7 and screening of early warning factors.

OBJECTIVE: To study the potential mechanism of Lactobacillus crispatus inhibiting cervical squamous intraepithelial lesion (SIL) and screen the early warning factors of SIL. METHODS: The effects of Lactobacillus crispatus on the proliferation, apoptosis, cross pore migration and invasion and cytokines of cervical precancerous cells Ect1/E6E7 were detected respectively. The effect of Lactobacillus crispatus on the expression of differential proteins screened in Ect1/E6E7 cells were detected by Western blot. RESULTS: Lactobacillus crispatus significantly inhibited the proliferation, induced apoptosis and inhibited cell migration of Ect1/E6E7 cells in a time-dependent manner (P < 0.05), but had no significant effect on cell invasion. Lactobacillus crispatus significantly promoted the secretion of Th1 cytokines and inhibited the secretion of Th2 cytokines by Ect1/E6E7 cells (P < 0.05). In addition, compared with SiHa cells in the control group, the expression of differential proteins PCNA, ATM, LIG1 and HMGB1 in Ect1/E6E7cells decreased significantly, while the expression of TDG and OGG1 proteins increased significantly (P < 0.05). ABCG2 protein in Ect1/E6E7 cells was slightly higher than that in SiHa cells, but the difference was not statistically significant. What is interesting is that Lactobacillus crispatus significantly inhibited the expression of ABCG2, PCNA, ATM, LIG1, OGG1 and HMGB1 proteins in Ect1/E6E7 cells, and promoted the expression of TDG protein. CONCLUSIONS: Lactobacillus crispatus may inhibit the function of Ect1/E6E7 cells through multiple pathways and exert the potential to reverse the progression of SIL.

[Homeostatic medicine: new strategy and concept of health maintenance as well as diagnosis and treatment of diseases].

Homeostasis is a dynamic balance process of self-regulating. Biological systems remain stable through adapting to changing external conditions to maintain normal life activities. Homeostatic medicine is the science of studying homeostasis of human molecules, cells, organs and the whole body. It is a comprehensive discipline based on maintaining homeostasis to keep human health and assist for diseases prevention and diagnoses. Homeostatic medicine focuses on the whole body and on the role of homeostasis in health and disease, which is expected to provide new ideas and strategies for maintaining health as well as diagnosing and treating diseases. Nitric oxide (NO) plays an important role in the control of multisystem homeostasis. Nitrate is an important substance in regulating NO homeostasis through the nitrate-nitrite-NO pathway. Sialin, nitrate transporter which is located in the cell membrane and cytoplasm, mediates multiple cellular biological functions. The nitrate-nitrite-NO pathway and sialin-mediated biological functions play an important role in the regulation of body homeostasis.

[The prevalence and risk factors of diabetic peripheral artery disease in Chinese communities].

Objective: To investigate the prevalence and risk factors of diabetic peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) managed in primary health care in China. Methods: A total of 2 528 T2DM patients were selected using a two-stage cluster random sampling method based on the baseline survey of the "China Diabetic Foot Prevention Model Project." The study was conducted in 2015 among T2DM patients in 8 primary healthcare centers in Changshu county and Jiang'an district of Wuhan, China. Data collection methods included a questionnaire, body measurement, and blood glucose detection. The Ankle-Brachial Index (ABI) is the most widely used noninvasive vascular test. A binary logistic regression model was used to analyze the influence factors. Results: The prevalence of PAD was 11.2% among the diabetic patients managed in primary health care in the two cities. The prevalence of PAD under 55 years old, 55- years old, 65- years old, and ≥75 years old were 7.8%, 6.0%, 12.9% and 22.5%, respectively. Multivariate stepwise logistic regression identified influence factors included older age, higher education level, smoking, drinking, postprandial glucose uncontrol, and prior myocardial infarction or angina. Compared to age <55 years, the odds ratio for PAD were 0.74 for 55- years (95%CI: 0.43-1.28), 1.72 for 65- years (95%CI: 1.05-2.81), 3.56 for 75 years and above (95%CI: 2.07-6.11), respectively. Compared to patients with education in primary school and below, the odds ratio was 1.37 (95%CI: 0.97-1.94), 2.48 (95%CI: 1.73-3.55), 1.99 (95%CI: 1.26-3.13) for those with education levels of junior high school, senior high school, and college, respectively. Current smoking (OR=1.49, 95%CI: 1.02-2.17), current drinking (OR=0.45, 95%CI: 0.28-0.71), postprandial glucose uncontrol (2 h postprandial plasma glucose >10.0 mmol/L: OR=1.72, 95%CI: 1.22-2.43), and prior myocardial infarction or angina (OR=2.32, 95%CI: 1.50-3.61) were influencing factors of PAD. Conclusions: Despite the high prevalence of PAD in diabetes managed in primary health care; multiple risk factors are not effectively aware of and under control. It is urgent to promote ABI screening and standardized management for diabetes, especially in primary health care.

Molecular mechanism of Tongmai Yangxin Pill intervention in elderly patients with coronary heart disease.

OBJECTIVE: The Tongmai Yangxin Pill (TMYX) is considered an effective treatment for coronary heart disease (CHD). However, its mechanism is unclear. This study aimed at exploring the molecular mechanisms and key genes of the TMYX in the treatment of CHD. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in the GSE142008 dataset were screened with the R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Then, protein-protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes database. The correlation analysis between key genes was conducted, and gene expression was verified. RESULTS: A total of 1,614 DEGs were identified, including 1,591 upregulated and 23 downregulated genes. GO enrichment analysis revealed that 240 biological processes, 44 cellular components, and 23 molecular functions were significantly enriched for DEGs in elderly patients with CHD. Similarly, 36 KEGG terms were significantly enriched for DEGs. Ten key genes were screened, and after verification and analysis, seven key genes (RSL24D1, NMD3, DCAF13, WDR36, SDAD1, KRR1, and RPF1) were identified as significantly overexpressed. CONCLUSIONS: We identified seven key genes as candidate biomarkers for TMYX in the treatment of elderly patients with CHD; these results can serve as a theoretical basis for targeted therapy.