Cordyceps sinensis accelerates stem cell recruitment to human skeletal muscle after exercise.

Cordyceps sinensis is a parasitic fungus known to induce immune responses. The impact of Cordyceps supplementation on stem cell homing and expansion to human skeletal muscle after exercise remains unexplored. In this study, we examined how pre-exercise Cordyceps supplementation influences cell infiltration, CD34+ cell recruitment, and Pax7+ cell expansion in human skeletal muscle after high-intensity interval exercise (HIIE) on a cycloergometer. A randomized, double-blind, placebo-controlled crossover study was conducted with 14 young adults (age: 24 ± 0.8 years). A placebo (1 g cornstarch) and Cordyceps (1 g Cordyceps sinensis) were administered before exercise (at 120% maximal aerobic power). Multiple biopsies were taken from the vastus lateralis for muscle tissue analysis before and after HIIE. This exercise regimen doubled the VEGF mRNA in the muscle at 3 h post-exercise (P = 0.006). A significant necrotic cell infiltration (+284%, P = 0.05) was observed 3 h after HIIE and resolved within 24 h. This response was substantially attenuated by Cordyceps supplementation. Moreover, we observed increases in CD34+ cells at 24 h post-exercise, notably accelerated by Cordyceps supplementation to 3 h (+51%, P = 0.002). This earlier response contributed to a four-fold expansion in Pax7+ cell count, as demonstrated by immunofluorescence double staining (CD34+/Pax7+) (P = 0.01). In conclusion, our results provide the first human evidence demonstrating the accelerated resolution of exercise-induced muscle damage by Cordyceps supplementation. This effect is associated with earlier stem cell recruitment into the damaged sites for muscle regeneration.

Altered PBP4 and GdpP functions synergistically mediate MRSA-like high-level, broad-spectrum ß-lactam resistance in Staphylococcus aureus.

Infections caused by Staphylococcus aureus are a leading cause of mortality worldwide. S. aureus infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are particularly difficult to treat due to their resistance to next-generation ß-lactams (NGBs) such as methicillin, nafcillin, and oxacillin. Resistance to NGBs, which is alternatively known as broad-spectrum ß-lactam resistance, is classically mediated by PBP2a, a penicillin-binding protein encoded by mecA (or mecC) in MRSA. Thus, presence of mec genes among S. aureus spp. serves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated, mecA-deficient S. aureus strains can also exhibit NGB resistance. These strains, which are collectively termed as methicillin-resistant lacking mec (MRLM), are currently being identified in increasing numbers among natural resistant isolates of S. aureus. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs, can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance toward NGBs at levels comparable to those of MRSAs. Our study provides a fresh new perspective about alternative mechanisms of NGB resistance, challenging our current overall understanding of high-level, broad-spectrum ß-lactam resistance in S. aureus. It thus suggests reconsideration of the current approach toward diagnosis and treatment of ß-lactam-resistant S. aureus infections. IMPORTANCE: In Staphylococcus aureus, high-level, broad-spectrum resistance to ß-lactams such as methicillin, also referred to as methicillin resistance, is largely attributed to mecA. This study demonstrates that S. aureus strains that lack mecA but contain mutations that functionally alter PBP4 and GdpP can also mediate high-level, broad-spectrum resistance to ß-lactams. Resistance brought about by the synergistic action of functionally altered PBP4 and GdpP was phenotypically comparable to that displayed by mecA, as seen by increased bacterial survival in the presence of ß-lactams. An analysis of mutations detected in naturally isolated strains of S. aureus revealed that a significant proportion of them had similar pbp4 and GGDEF domain protein containing phosphodiesterase (gdpP) mutations, making this study clinically significant. This study not only identifies important players of non-classical mechanisms of ß-lactam resistance but also indicates reconsideration of current clinical diagnosis and treatment protocols of S. aureus infections.

Long-term exposure to cadmium disrupts neurodevelopment in mature cerebral organoids.

Cadmium (Cd) is a pervasive environmental pollutant. Increasing evidence suggests that Cd exposure during pregnancy can induce adverse neurodevelopmental outcomes. However, due to the limitations of neural cell and animal models, it is challenging to study the developmental neurotoxicity and underlying toxicity mechanism of long-term exposure to environmental pollutants during human brain development. In this study, chronic Cd exposure was performed in human mature cerebral organoids for 49 or 77 days. Our study found that prolonged exposure to Cd resulted in the inhibition of cerebral organoid growth and the disruption of neural differentiation and cortical layer organization. These potential consequences of chronic Cd exposure may include impaired GFAP expression, a reduction in SOX2+ neuronal progenitor cells, an increase in TUJ1+ immature neurons, as well as an initial increase and a subsequent decrease in both TBR2+ intermediate progenitors and CTIP2+ deep layer cortical neurons. Transcriptomic analyses revealed that long-term exposure to Cd disrupted zinc and copper ion homeostasis through excessive synthesis of metallothionein and disturbed synaptogenesis, as evidenced by inhibited postsynaptic protein. Our study employed mature cerebral organoids to evaluate the developmental neurotoxicity induced by long-term Cd exposure.

Glycogen for lysosome-targeted CpG ODNs delivery and enhanced cancer immunotherapy.

CpG oligodeoxynucleotides (ODNs) strongly activate the immune system after binding to toll-like receptor 9 (TLR9) in lysosome, which demonstrated significant potential in cancer immunotherapy. However, their therapeutic efficacy is limited by drawbacks such as rapid degradation and poor cellular uptake. Although encouraging progress have been made on developing various delivery systems for CpG ODNs, safety risks of the synthetic nanocarriers as well as the deficient CpG ODNs release within lysosome remain big obstacles. Herein, we developed a novel nanovector for lysosome-targeted CpG ODNs delivery and enhanced cancer immunotherapy. Natural glycogen was simply aminated (NH2-Gly) through grafting with diethylenetriamine (DETA), which was spherical in shape with diameter of approximately 40 nm. NH2-Gly possessed good biocompatibility. Cationic NH2-Gly complexed CpG ODNs well and protected them from nuclease digestion. NH2-Gly significantly enhanced the cellular uptake of CpG ODNs. Efficient CpG ODNs release was observed in the presence of α-glucosidase that mimicking the environment of lysosome. Consequently, NH2-Gly/CpG complexes triggered potent antitumor immunity and effectively inhibit the tumor growth without causing any toxic effect or tissue damages. This work highlights the promise of glycogen for lysosome-targeted on-command delivery of CpG ODNs, which brings new hope for precision cancer immunotherapy.

The Influence of Hyperglycemia on Liver Triglyceride Deposition in Partially Pancreatectomized Rats.

Nonalcoholic fatty liver disease and diabetes always coexist. The relationship of fatty liver and hyperglycemia is not clear. We studied the influence of hyperglycemia on triglyceride (TG) accumulation in the liver and explored its possible mechanisms. SD rats were divided into three groups: Group A (sham operation control), Group B (partially pancreatectomized rats), and Group C (partially pancreatectomized rats treated with insulin). At 4 weeks after surgery, pancreatic weights and liver TG contents were measured. Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed. The gene expression of sterol regulatory element-binding protein1c (SREBP-1c), carbohydrate regulatory element-binding protein (ChREBP), fatty acid synthase(FAS), carnitine palmitoyltransferase 1 (CPT-1), and fibroblast growth factor 21 (FGF21) was determined by real-time PCR. Compared with Group A, postprandial glucose increased significantly; the concentrations of insulin and C-peptides, pancreatic weights and serum FGF21 levels were decreased, liver TG was increased significantly in Group B, and insulin treatment improved these changes. Compared with Group A, the gene expressions of FGF21, CPT-1 and FAS in the liver were decreased in Group B (all p<0.05). Compared with Group B, the gene expressions of FGF21, FAS, ChREBP, SREBP-1c and CPT-1 in the liver in Group C were all increased significantly (p<0.05, respectively). Hyperglycemia induced by partial pancreatectomy could lead to increased liver TG. Insulin treatment could decrease glucose levels and improve fatty liver, and genes related to lipid metabolism may play a role in this process.

Microarray Expression Profile of Exosomal circRNAs from High Glucose Stimulated Human Renal Tubular Epithelial Cells.

Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma.

Purpose: Uterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma. Materials and methods: This is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen. Results: Fifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events. Conclusion: Use of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.

Epigenetic Regulation of Angiogenesis in Peripheral Artery Disease.

Peripheral arterial disease (PAD) represents a global health concern with a rising prevalence attributed to factors such as obesity, diabetes, aging, and smoking. Among patients with PAD, chronic limb-threatening ischemia (CLTI) is the most severe manifestation, associated with substantial morbidity and mortality. While revascularization remains the primary therapy for CLTI, not all patients are candidates for such interventions, highlighting the need for alternative approaches. Impaired angiogenesis, the growth of new blood vessels, is a central feature of PAD, and despite decades of research, effective clinical treatments remain elusive. Epigenetics, the study of heritable changes in gene expression, has gained prominence in understanding PAD pathogenesis. Here, we explore the role of epigenetic regulation in angiogenesis within the context of PAD, with a focus on long non-coding RNAs and fibroblast-endothelial cell transdifferentiation. Additionally, we discuss the interplay between metabolic control and epigenetic regulation, providing insights into potential novel therapeutic avenues for improving PAD treatments. This review aims to offer a concise update on the application of epigenetics in angiogenesis and PAD research, inspiring further investigations in this promising field.

Altered PBP4 and GdpP functions synergistically mediate MRSA-like high-level, broad-spectrum ß-lactam resistance in Staphylococcus aureus.

Infections caused by Staphylococcus aureus are a leading cause of mortality worldwide. S. aureus infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA) are particularly difficult to treat due to their resistance to Next Generation ß-lactams (NGB) such as Methicillin, Nafcillin, Oxacillin etc. Resistance to NGBs, which is alternatively known as broad-spectrum ß-lactam resistance is classically mediated by PBP2a, a Penicillin-Binding Protein encoded by mecA (or mecC) in MRSA. Thus, presence of mec genes among S. aureus serves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated, mecA deficient S. aureus strains can also exhibit NGB resistance. These strains, which are collectively termed as Methicillin-Resistant Lacking mec (MRLM) are currently being identified in increasing numbers among natural resistant isolates of S. aureus. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance towards NGBs at levels comparable to that of MRSAs. Our study, provides a fresh new perspective about alternative mechanisms of NGBs resistance, challenging our current overall understanding of high-level, broad-spectrum ß-lactam resistance in S. aureus. It thus suggests reconsideration of the current approach towards diagnosis and treatment of ß-lactam resistant S. aureus infections.

Transflammation in tissue regeneration and response to injury: How cell-autonomous inflammatory signaling mediates cell plasticity.

Inflammation is a first responder against injury and infection and is also critical for the regeneration and repair of tissue after injury. The role of professional immune cells in tissue healing is well characterized. Professional immune cells respond to pathogens with humoral and cytotoxic responses; remove cellular debris through efferocytosis; secrete angiogenic cytokines and growth factors to repair the microvasculature and parenchyma. However, non-immune cells are also capable of responding to damage or pathogens. Non-immune somatic cells express pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The PRRs activation leads to the release of inflammatory cytokines required for tissue defense and repair. Notably, the activation of PRRs also triggers epigenetic changes that promote DNA accessibility and cellular plasticity. Thus, non-immune cells directly respond to the local inflammatory cues and can undergo phenotypic modifications or even cell lineage transitions to facilitate tissue regeneration. This review will focus on the novel role of cell-autonomous inflammatory signaling in mediating cell plasticity, a process which is termed transflammation. We will discuss the regulation of this process by changes in the functions and expression levels of epigenetic modifiers, as well as metabolic and ROS/RNS-mediated epigenetic modulation of DNA accessibility during cell fate transition. We will highlight the recent technological developments in detecting cell plasticity and potential therapeutic applications of transflammation in tissue regeneration.

[The Influence of Confinement Location on Maternal Psychological and Role Adaptation: A Six-Month Follow-Up Study].

BACKGROUND: Approximately 70% of postpartum women in Taiwan choose postpartum care institutions for their postpartum confinement. However, few studies have explored the follow-up relationship between confinement location and, respectively, maternal psychological and role adaptation. PURPOSE: To explore the differences in psychology and maternal role adaptation between postpartum women in two different confinement locations and to analyze the predictors of maternal confidence and maternal competence at six-months postpartum. METHODS: A comparative and follow-up research design was adopted. We recruited a convenience sample of two groups of women confined, respectively, at postpartum nursing centers and at home. One hundred fifty-seven mothers recruited after G-power estimation were enrolled as participants and completed demographic data and six scales at one-week, one-month, and six-months postpartum. The statistical analysis was performed mainly using generalized estimating equations. RESULTS: For all participants, maternal confidence was positively associated with time, being multipara, having religious beliefs, and having better mother-infant bonding (p < .05). In addition, being confined at home, being unemployed, having religious beliefs, perceiving lower levels of stress and depression, having better sleep quality, and having better mother-infant bonding were associated with higher maternal competence (p < .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Based on the findings of this study, postpartum nursing institutions should actively promote strategies to improve maternal competence to help mothers staying in postpartum nursing centers strike an optimal balance between recuperation and parenting preparation. Furthermore, obstetric health professionals should implement policies related to mother-infant bonding to increase maternal confidence and competence and, subsequently, facilitate maternal role adjustment.

H-NMR-based metabolomics study on the effects of raw and processed radix Wikstroemia indica on endogenous metabolites in rat plasma.

Based on metabolomics, to study the mechanism of Radix Wikstroemia indica (RWI) "Sweat soaking method" processing detoxification. The raw drug group and processed products was given raw RWI and processed RWI respectively by gavage. The control group was given the same amount of 1% sodium carboxy methyl cellulose distilled water by gavage. After 7 days of continuous gavage, blood samples were collected. The blood samples of rats in each group were analyzed by 1H-NMR technology to explore the changes of endogenous metabolism and the possible metabolic pathways to rats before and after processing. Compared with the control group, the raw RWI could significantly reduce 16 metabolites and increase 10 metabolites. The processed RWI can increase the levels of most metabolites that decrease to the raw RWI, such as 13 metabolites such as alanine, L-glutamine, L-valine, L-serine, betaine and glutamic acid; At the same time, the metabolites that increased in the level of crude products were down-regulated, such as asparagine, lactic acid, 2-hydroxyisobutyric acid, sucrose, glucose and D-glucose. Compared with raw products, RWI treated with "Sweat soaking method" can reversely regulate or reduce amino acid, choline metabolism, energy and carbohydrate metabolism, thereby reducing hepatotoxicity and nephrotoxicity.

Parental Postoperative Pain Management Perceptions, Attitudes, and Practices in Pediatric Limb Fractures.

BACKGROUND: Post-surgical pain in children is common, severe, and inadequately controlled. An effective model should involve the participation of parents. AIMS: To investigate parental perceptions, attitudes, and practices in postoperative pain management in children with limb fractures and analyze the factors affecting parental practices. DESIGN: This was a descriptive cross-sectional study. SETTINGS: Research was conducted at a tertiary Children's Hospital Affiliated with Soochow University. PARTICIPANTS: Parents whose children (age, 6-18 years) underwent orthopedic fracture surgery between January 1, 2020, and August 31, 2020, were recruited using purposive sampling. METHODS: The parents were asked to complete self-report questionnaires: "Pain Management Knowledge and Attitudes Questionnaire" and "Parents' Use of Pain Relief Strategies Questionnaire." The Wong-Baker Faces Scale was used to measure pain intensity in children. The Mann-Whitney U test, Kruskal-Wallis H test, and correlation and regression analyses were used for statistical analyses. RESULTS: Data of 180 parents were collected. Of the participants, 80.6%, 78.3%, and 71.7% had low-to-moderate scores for knowledge, general attitudes, and use of pain relief strategies, respectively. Moreover, 93.9% of parents had moderate-to-high scores for negative attitudes toward medication, despite 89.5% of them reporting moderate-to-high pain intensities in their children (median proxy-report of pain intensity, 7.0 [3.00]). Multivariate linear stepwise regression showed that parents' use of pain-relief strategies was related to their general attitudes, knowledge, and sex. CONCLUSIONS: Most parents had low-to-moderate scores for perceptions and general attitudes toward children's postoperative pain management, and use of pain relief strategies. Moreover, they lacked knowledge of and had negative attitudes toward pain assessment and analgesics, which significantly impacted their practices. CLINICAL IMPLICATIONS: Clinical pediatric nurses should provide appropriate support for the entire family of the child. Moreover, to enhance parental practices, they should develop targeted parental education programs for pain management, particularly regarding pain assessment tools and pain medications.

Curative effect of medicine cake sticking ultrasound drug penetration combined with body training on hemiplegia after stroke: An in vitro ultrasound targeted drug controlled release technology.

To explore the efficacy of ultrasound drugs in the treatment of hemiplegia after stroke. The evaluation included clinical symptoms and signs, the Stroke Scale, activities of daily living, sensory disorder Fugl-Meyer and Lindmark, electromyography sensory nerve amplitude, and conduction velocity indexes in both groups. There was no significant difference in the improved Fugl-Meyer and Lindmark score between treatment (26.97 ± 2.78) and the control group (27.45 ± 3.1) (t = 14.528, P = 0.593). After treatment, the observation group (37.10 ± 4.2) was significantly different from the control group (34.76 ± 4.36) (t = 11.259, P = 0.005) and (t = 10.15 ± 1.69), (40.87 ± 6.58) (t = 7.943,9.538, P = 0.564,0.826). After treatment, the observation group the Stroke Scale (4.27 ± 0.57), activities of daily living score (76.15 ± 12.38) and the control group (5.36 ± 0.89), (58.41 ± 9.69) (t = 16.274,5.379, P = 0.035,0.000) after treatment and F wave and M wave. The cure rate of the observation group was 77.50% (31/40), which was significantly better than that of the control group, 47.50% (19/40), with a significant difference (χ2 = 11.724,P = 0.000). After comparison, the total response rate of the observed group reached 92.500% (37 / 40), which was significantly higher than the 80.00% (32 / 40) of the control group. This difference was statistically significant (χ 2 = 9.458, P = 0.015). This therapy closely links the theoretical knowledge of modern medicine with the theoretical knowledge of traditional Chinese medicine, and uses the meridian theory to give full play to the unique advantages of traditional Chinese medicine.

Oral and inhalation bioaccessibility of mercury in contaminated soils and potential health risk to the kidneys and neurodevelopment of children in Taiwan.

Health risk assessments of exposure to mercury (Hg) from soils via ingestion and inhalation are indispensable for Taiwanese people living in the vicinity of Hg-contaminated sites. In this study, anthropogenic soils were collected from various polluted sources in Taiwan. In vitro oral and inhalation bioaccessible fractions of Hg were analyzed to avoid from overestimating the exposure risk. Discrepancies in oral and inhalation bioaccessible levels of Hg in soils were found using different in vitro assays with different pH levels and chemical compositions. The freshly contaminated soil (soil S7) polluted by chlor-alkali production activity sampled before the site was remediated had the highest total Hg concentration of 1346 mg/kg, with the highest oral bioaccessibility of 26.2% as analyzed by SW-846 Method 1340 and inhalation bioaccessibility of 30.5% as analyzed by modified Gamble's solution. The lesser extent of aging of Hg in soil S7 increased the Hg availability for humans, which was also found based on results of a sequential extraction procedure. Results of the hazard quotient showed that soil ingestion was the main pathway causing non-carcinogenic risks for children and adults. Children were also exposed to higher risks than were adults due to higher frequencies of hand-to-mouth behaviors and lower body weights. Furthermore, hazard index results adjusted for oral and inhalation bioaccessible Hg were lower than those obtained based on the total Hg content; however, an unacceptable value of the non-carcinogenic risk (> 1) for children living near soil S7 was still observed. This study suggests that children living near sites polluted for a short period of time may suffer potential renal effects regardless of the bioaccessibility. Our findings provide suggestions for decision makers on setting new strategies for managing risks of Hg-contaminated soils in Taiwan.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy.

BACKGROUND: The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC) is a common clinical concern. AIM: To analyse the prognostic factors of overall survival (OS) in patients with unresectable HCC who received conversion therapy. METHODS: One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort (n = 120) and a validation cohort (n = 30). Using the independent risk factors in the training cohort, a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection. The nomogram was internally validated with the bootstrapping method. The predictive performance of nomogram was assessed by Harrell's concordance index (C-index), calibration plot and time-dependent receiver operating characteristic curves and compared with six other conventional HCC staging systems. RESULTS: Multivariate Cox analysis identified that albumin, blood urea nitrogen, gamma-glutamyl transpeptidase to platelet ratio, platelet to lymphocyte ratio, macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model. The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS, which were higher than those of the six conventional HCC staging systems (0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort). The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS. Decision curve analyses indicated satisfactory clinical utility. With a total nomogram score of 196, patients were accurately classified into low-risk and high-risk groups. Furthermore, we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/. CONCLUSION: The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy, which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Erectile dysfunction, depression, and anxiety in patients with functional anorectal pain: a case-control study.

BACKGROUND: Men with functional anorectal pain (FARP) report having erectile dysfunction (ED) and significant changes in psychological status. AIM: The study sought to investigate the risk factors associated with FARP among male Chinese outpatients, alongside the impact of FARP on patients' ED, depression, and anxiety. METHODS: This case-control study included 406 male participants, divided into FARP (n = 323) and healthy control (n = 73) groups. Demographic and disease characteristics were collected from the patients, and the 5-item International Index of Erectile Function, Patient Health Questionnaire-9, and Generalized Anxiety Disorder 7 were used to assess erectile function, depression, and anxiety symptoms. Baseline characteristics were described using descriptive statistics, logistic regression analysis identified factors influencing FARP, and its association with ED, depression, and anxiety were analyzed using linear and ordinal logistic regression analyses. Validity was ensured through subgroup and sensitivity analyses. OUTCOMES: The primary outcome was the association between FARP and ED, depression, and anxiety; the secondary outcome was the influencing factors of FARP such as lifestyle and work habits. RESULTS: Men with FARP were likely to have more serious ED (59.8% vs 32.9%), depression (20.7% vs 4.1%), and anxiety(31.5% vs 12.3%); have lower 5-item International Index of Erectile Function scores; or have higher Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7 scores compared with unaffected participants. Alcohol intake, family relationship, high work pressure, and prolonged bowel movements were significantly associated with FARP severity. The association between FARP with ED, depression, and anxiety was statistically significant in both crude and adjusted models. FARP was associated with 2.47, 2.73, and 2.67 times higher risk for ED, depression, and anxiety, respectively. An increase pain severity increased the incidence of ED (moderate pain: 4.80 times, P < .000; severe pain: 3.49 times, P < .004), depression (moderate pain: 1.85 times, P < .017; severe pain: 2.04 times, P < .037), and anxiety (moderate pain: 1.86 times, P < .014).Clinical Implications: Changes in lifestyle and work habits can help prevent pain symptom exacerbation. Attention to erection and psychological issues in patients with FARP and interdisciplinary comprehensive treatment may improve the efficacy. STRENGTHS AND LIMITATIONS: The study highlights a correlation between FARP and ED, depression, and anxiety, with pain severity being a contributing factor. However, the study's limitations include a small sample size and potential recall bias, and other sexual functions were not thoroughly explored. CONCLUSION: Patients with FARP have a higher prevalence of ED, depression, and anxiety, which increase with pain severity. Factors such as alcohol intake, work pressure, prolonged sitting, and longer defecation times are significantly correlated with FARP pain severity.

QR code technology in individual identification training provides an introduction in hands-on forensic DNA genotyping to medical students.

BACKGROUND: Forensic biology is a subject in the field of forensic science that stresses practical teaching and training in laboratory skills. Visualization of deoxyribonucleic acid (DNA) profiles is important in individual identification and is easily performed by well-trained examiners. Therefore, developing a novel training project for obtaining individual DNA profiles can improve the quality of teaching for medical students or trainees. DNA profiles based on quick response (QR) codes can also be applied to practical teaching and operation training for individual identification. METHODS: A novel training project was developed through an experimental course in forensic biology. Blood samples and buccal swabs with oral epithelial cells, as used in the forensic DNA laboratory, were obtained from medical students at Fujian Medical University. DNA was isolated, and a number of short tandem repeat (STR) loci were used as genetic markers to generate DNA profiles. The students converted DNA profiles and individual information into a QR code. The QR code could then be scanned by a mobile phone for consulting and retrieval. Gene identity cards with QR codes were produced and provided to every student. The participation rate and passing rate of students who participated in the novel training project were calculated and compared with those of students in the traditional experimental course, and a chi-square test was carried out by SPSS 23.0 software to evaluate the teaching effectiveness. p < 0.05 indicated significant differences. In addition, a survey was conducted to investigate the likelihood of using of gene identity cards with QR codes in the future. RESULTS: A total of 54 of 91 medical students who studied forensic biology participated in the novel training project in 2021. Only 31 of 78 students who studied forensic biology participated in the traditional experimental course in 2020. The participation rate in the novel training project was 24% higher than that of the traditional experimental course. The participants in the novel training project showed better performance in forensic biological handling techniques. The passing rate of the students in the forensic biology course with the novel training project was approximately 17% higher than that of the students in the former course. The participation rates and passing rates of the two groups were significantly different (χ = 6.452, p = 0.008 and χ = 11.043, p = 0.001). In the novel training project, all participants made 54 gene identity cards with QR codes. Furthermore, in the DNA profiles of four African students who participated, we found two rare alleles that were not discovered in Asians. The survey showed that the use of gene identity cards with QR codes was accepted by most participants, and the likelihood of future utilization was 78%. CONCLUSION: We established a novel training project to promote the learning activities of medical students in experimental forensic biology courses. The participants showed great interest in using gene identity cards with QR codes to store general individual identity information and DNA profiles. They also examined the genetic population differences between different races based on DNA profiles. Hence, the novel training project could be useful for training workshops, forensic experimental courses, and medical big data research.

Role of angiogenic transdifferentiation in vascular recovery.

Tissue repair requires the orchestration of multiple processes involving a multiplicity of cellular effectors, signaling pathways, and cell-cell communication. The regeneration of the vasculature is a critical process for tissue repair and involves angiogenesis, adult vasculogenesis, and often arteriogenesis, which processes enable recovery of perfusion to deliver oxygen and nutrients to the repair or rebuild of the tissue. Endothelial cells play a major role in angiogenesis, whereas circulating angiogenic cells (primarily of hematopoietic origin) participate in adult vasculogenesis, and monocytes/macrophages have a defining role in the vascular remodeling that is necessary for arteriogenesis. Tissue fibroblasts participate in tissue repair by proliferating and generating the extracellular matrix as the structural scaffold for tissue regeneration. Heretofore, fibroblasts were not generally believed to be involved in vascular regeneration. However, we provide new data indicating that fibroblasts may undergo angiogenic transdifferentiation, to directly expand the microvasculature. Transdifferentiation of fibroblasts to endothelial cells is initiated by inflammatory signaling which increases DNA accessibility and cellular plasticity. In the environment of under-perfused tissue, the activated fibroblasts with increased DNA accessibility can now respond to angiogenic cytokines, which provide the transcriptional direction to induce fibroblasts to become endothelial cells. Periphery artery disease (PAD) involves the dysregulation of vascular repair and inflammation. Understanding the relationship between inflammation, transdifferentiation, and vascular regeneration may lead to a new therapeutic approach to PAD.

Analysis of a Yp11.2 region deletion in a Chinese female with Turner syndrome: A case report.

In recent years, an increasing number of abnormal DNA genotypes caused by chromosomal abnormalities have been revealed in cases of individual identification and sex-typing analysis, especially analyses of the amelogenin and short tandem repeat (STR) loci on the sex chromosomes. Here, we report a 17-year-old female with Turner syndrome typed as male due to the presence of the amelogenin Y allele. The Y-STR haplotype showed allele dropout of three Y-STR loci (DYS549, DYS392 and DYS448). Further examination showed that the proband's karyotype was 45,X/46,X,del(Y) (q11.23), and the deletion of the Yp11.2 region was confirmed to encompass the observed microdeletion of the azoospermia factor (AZF)b + c region. One challenge in forensics is inaccurate sex typing of individuals at the molecular level, particularly for individuals with chromosomal abnormalities. This case suggests that various medical evaluations, including the examination of sex-related manifestations, karyotypes, and clinical phenotypes of individuals, along with the detection of sex-typing gene markers will be beneficial to overcome the issues caused by cytogenetic disorders of the sex chromosomes.