Feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in awake mice.

AIMS: Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness. METHODS: We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively. RESULTS: We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory. CONCLUSION: Our findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective.

Impact of web-based positive psychological intervention on emotions, psychological capital, and quality of life in gastric cancer patients on chemotherapy.

BACKGROUND: Gastric cancer is a malignant digestive tract tumor that originates from the epithelium of the gastric mucosa and occurs in the gastric antrum, particularly in the lower curvature of the stomach. AIM: To evaluate the impact of a positive web-based psychological intervention on emotions, psychological capital, and quality of survival in gastric cancer patients on chemotherapy. METHODS: From January 2020 to October 2023, 121 cases of gastric cancer patients on chemotherapy admitted to our hospital were collected and divided into a control group (n = 60) and an observation group (n = 61) according to the admission order. They were given either conventional nursing care alone and conventional nursing care combined with web-based positive psychological interventions, respectively. The two groups were compared in terms of negative emotions, psychological capital, degree of cancer-caused fatigue, and quality of survival. RESULTS: After intervention, the number of patients in the observation group who had negative feelings toward chemotherapy treatment was significantly lower than that of the control group (P < 0.05); the Positive Psychological Capital Questionnaire score was considerably higher than that of the control group (P < 0.05); the degree of cancer-caused fatigue was significantly lower than that of the control group (P < 0.05); and the Quality of Life Scale for Cancer Patients (QLQ-30) score was significantly higher than that of the control group (P < 0.05). CONCLUSION: Implementing a web-based positive psychological intervention for gastric cancer chemotherapy patients can effectively improve negative emotions, enhance psychological capital, and improve the quality of survival.

IL-33/ST2 enhances MMP-12 expression by macrophages to mediate inflammatory and immune response in IgG4-Related Ophthalmic Disease.

IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the LatY136F mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12+ cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.

Efficient CRISPR-mediated genome editing can be initiated by embryonic injection but not by ovarian delivery in the beetle Tribolium castaneum.

The clustered regularly interspaced small palindromic repeats (CRISPR) / CRISPR-associated nuclease 9 (Cas9)-mediated gene editing technology has revolutionized the study of fundamental biological questions in various insects. Diverse approaches have been developed to deliver the single-guide RNA (sgRNA) and Cas9 to the nucleus of insect embryos or oocytes to achieve gene editing, including the predominant embryonic injection methods and alternative protocols through parental ovary delivery. However, a systematic comparative study of these approaches is limited, especially within a given insect. Here, we focused on revealing the detailed differences in CRISPR/Cas9-mediated gene editing between the embryo and ovary delivery methods in the beetle Tribolium castaneum, using the cardinal and tyrosine hydroxylase (TH) as reporter genes. We demonstrated that both genes could be efficiently edited by delivering Cas9/sgRNA ribonucleoproteins to the embryos by microinjection, leading to the mutant phenotypes and indels in the target gene sites. Next, the Cas9/sgRNA complex, coupled with a nanocarrier called Branched Amphiphilic Peptide Capsules (BAPC), were delivered to the ovaries of parental females to examine the efficacy of BAPC-mediated gene editing. Although we observed that a small number of beetles' progeny targeting the cardinal exhibited the expected white-eye phenotype, unexpectedly, no target DNA indels were found following subsequent sequencing analysis. In addition, we adopted a novel approach termed "direct parental" CRISPR (DIPA-CRISPR). However, we still failed to find gene-editing events in the cardinal or TH gene-targeted insects. Our results indicate that the conventional embryonic injection of CRISPR is an effective method to initiate genome editing in T. castaneum. However, it is inefficient by the parental ovary delivery approach.

Clinical values of oblique lumbar interbody fusion on the treatment of single-level degenerative lumbar diseases.

Objectives: Minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) and oblique lumbar interbody fusion (OLIF) are increasingly replacing traditional approaches. This study aimed to compare the clinical outcomes of OLIF and Mis-TLIF in treating single-level degenerative lumbar diseases. Methods: Patients with single-level degenerative lumbar diseases underwent either OLIF (30 patients) or Mis-TLIF (30 patients). Surgical data, including operation time, blood loss, postoperative drainage, and postoperative bed rest duration, were collected. Clinical outcomes were assessed using the Oswestry disability index, the visual analog scale scores for low back pain and leg pain, and Japanese Orthopaedic Association scores for daily ability, along with monitoring of complications. Results: The OLIF group showed significantly shorter operative times, less blood loss, reduced postoperative drainage, and shorter bed rest durations than the Mis-TLIF group. At the 1-month follow-up, OLIF patients also demonstrated significantly better clinical outcome scores than Mis-TLIF patients. No significant differences were observed between OLIF and Mis-TLIF patients before surgery and after 3 months. Furthermore, lumbar lordosis and disc height were significantly greater in the OLIF group at the final follow-up. Conclusions: Both OLIF and Mis-TLIF achieved satisfactory and effective long-term clinical outcomes for single-level lumbar degenerative diseases. However, OLIF resulted in less tissue damage, reduced bleeding, better short-term clinical outcomes, and improved recovery of segmental lordosis compared to Mis-TLIF. Therefore, OLIF appears to be the preferable option over Mis-TLIF.

Uncovering the mechanisms of diosmin in treating obesity-related kidney injury based on network pharmacology, molecular docking, and in vitro validation.

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

Modern Instrumental Methods of Diagnostics and Risk Assessment of Developing Antitumor Therapy Cardiovasculotoxicity.

The most important component of cardio-oncology is the assessment of the risk of development and diagnosis of cardiovascular toxicity of the antitumor therapy, the detection of which is largely based on visualization of the cardiovascular system. The article addresses up-to-date methods of non-invasive visualization of the heart and blood vessels, according to the 2022 European Society of Cardiology Clinical Guidelines on cardio-oncology. Also, the article discusses promising cardiovascular imaging techniques that are not yet included in the guidelines: assessment of coronary calcium using multislice computed tomography and positron emission computed tomography with 18F-labeled 2-deoxy-2-fluoro-d-glucose.

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery.

INTRODUCTION: Sixty to eighty percent of oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. The purpose of this study was to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with higher risk of lymph node metastasis at the time of surgery. MATERIALS AND METHODS: A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: mid-epithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing mid-epithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. RESULTS: We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), while 40 of 79 p53-abnormal cases had positive lymph nodes (p<0.001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; p=0.008). CONCLUSION: p53-abnormal OSCCs were significantly more likely to be associated with positive lymph node status compared to p53 wild-type OSCCs at time of surgery. Further investigation with long-term follow-up is required to determine its clinical application prior to surgery planning.

Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

[Traditional Chinese medicinal compress combined with herbal fumigation for acute epididymitis: A clinical observation].

OBJECTIVE: To observe the clinical efficacy of traditional Chinese medicinal (TCM) compress combined with herbal fumigation in the treatment of acute epididymitis. METHODS: This study included 74 cases of acute epididymitis treated in our hospital from December 2021 to December 2023. Using the single blind and random number methods, we divided the patients into a trial (n = 37) and a control group (n = 37). On the basis of routine medication with antibiotics, we treated the patients in the trial group by TCM compress combined with herbal fumigation and those in the control group by dyed pure water compress combined with herbal fumigation. At 3, 7 and 14 days of treatment, we obtained the pain scores and maximum epididymal diameters from the patients and compared them between the two groups before and after treatment. RESULTS: There were no statistically significant differences between the control and trial groups in the baseline pain scores (6.79 vs 6.85, P>0.05) and maximum epididymal diameters of the patients (ï¼»1.61 ± 0.39ï¼½ vs ï¼»1.59 ± 0.42ï¼½ cm, P>0.05) or in the pain scores after 3 days of treatment (4.63 ± 0.95 vs 4.45 ± 1.87, P>0.05). Compared with the controls, the patients of the trial group showed significantly lower pain scores (3.78 ±1.03 vs 1.02±0.36, P<0.05) and a higher overall effectiveness rate (75.68% vs 91.89%, P<0.05) at 7 days, and markedly shorter maximum epididymal diameters at 3 days (ï¼»1.45 ± 0.38ï¼½ vs ï¼»1.23 ± 0.72ï¼½ cm, P<0.05) and 7 days (ï¼»1.21 ± 0.29ï¼½ vs ï¼»0.98 ± 0.15ï¼½ cm, P<0.05). No statistically significant differences were observed between the control and trial groups in the pain scores (0.79 ± 1.12 vs 0.67 ± 0.86, P>0.05), maximum epididymal diameters (ï¼»0.94 ± 0.33ï¼½ vs ï¼»0.92 ± 0.21ï¼½ cm, P>0.05) or overall effectiveness rate (91.89% vs 97.30%, P>0.05) after 14 days of treatment. CONCLUSION: On the basis of routine medication with antibiotics, TCM compress combined with herbal fumigation can effectively relieve pain, reduce local swelling, accelerate recovery and shorten the course of treatment in patients with acute epididymitis, and is therefore worthy of clinical promotion and application.

Machine learning-based analysis identifies and validates serum exosomal proteomic signatures for the diagnosis of colorectal cancer.

The potential of serum extracellular vesicles (EVs) as non-invasive biomarkers for diagnosing colorectal cancer (CRC) remains elusive. We employed an in-depth 4D-DIA proteomics and machine learning (ML) pipeline to identify key proteins, PF4 and AACT, for CRC diagnosis in serum EV samples from a discovery cohort of 37 cases. PF4 and AACT outperform traditional biomarkers, CEA and CA19-9, detected by ELISA in 912 individuals. Furthermore, we developed an EV-related random forest (RF) model with the highest diagnostic efficiency, achieving AUC values of 0.960 and 0.963 in the train and test sets, respectively. Notably, this model demonstrated reliable diagnostic performance for early-stage CRC and distinguishing CRC from benign colorectal diseases. Additionally, multi-omics approaches were employed to predict the functions and potential sources of serum EV-derived proteins. Collectively, our study identified the crucial proteomic signatures in serum EVs and established a promising EV-related RF model for CRC diagnosis in the clinic.

Profiles and interactions of gut microbiome and intestinal microRNAs in pediatric Crohn's disease.

Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn's disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD. IMPORTANCE: Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

The Role of Inflammation and Psycho-Behavioral Factors as Mediators Between Acculturation and Time to Incident Dementia Among Older Mexican Americans.

Background: The mechanisms through which acculturation influences the onset of cognitive impairment and dementia are not well understood, especially among older Hispanics. Objective: To investigate whether inflammation and psycho-behavioral factors mediate the relationship between acculturation and incident dementia among older Mexican Americans. Methods: We analyzed the Sacramento Area Latino Study on Aging (1998-2007, SALSA), a longitudinal study (N = 1,194) with 10 years of follow-up, and used g-computation for mediation analysis with pooled logistic regression to evaluate whether acculturation (assessed by the Revised Acculturation Rating Scale for Mexican Americans [ARSMA-II]) affected dementia or cognitive impairment but not dementia (CIND) through inflammation (i.e., interleukin 6 [IL-6], tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein [hs-CRP]), smoking, alcohol consumption, and depressive symptoms. The potential mediators were assessed at baseline. Results: The 10-year average adjusted risk ratio (aRR) for the effect of high U.S. acculturation and dementia/CIND was 0.66, 95% CI (0.36, 1.30). The indirect effects were: IL-6 (aRR = 0.98, 95% CI (0.88, 1.05)); TNF-α (aRR:0.99, 95% CI (0.93, 1.05)); hs-CRP: (aRR = 1.21, 95% CI (0.84, 1.95)); current smoking: aRR = 0.97, 95% CI (0.84, 1.16); daily/weekly alcohol consumption (aRR = 1.00, 95% CI (0.96, 1.05)); and depressive symptom score (aRR = 1.03, 95% CI (0.95, 1.26)). Hs-CRP yielded a proportion mediated of -26%, suggesting that hs-CRP could suppress the potential effect of high U.S. acculturation. The other factors explored resulted in little to no mediation. Conclusions: The effect of acculturation on time to incident dementia/CIND varied over time. Our study suggests that inflammation could suppress the effect between high U.S. acculturation and dementia risk.

Drivers and collaborative governance of public health emergency response in the context of digital city.

Introduction: With the frequent occurrence of public health events, the government inevitably makes many mistakes in emergency management. In modern emergency management, it is particularly important to promote the diversification of emergency management subjects and improve the government's emergency management ability. Methods: In order to make up for the deficiency of government's participation in public health emergency management, this paper analyzes the driving factors and driving effects of enterprises' participation in public health emergency response under the background of digital city. A fully explained structural model is used to analyze the relationship between the different drivers. In addition, the spatial and temporal distribution characteristics of public health events were analyzed through spatial auto-correlation. On this basis, the government cooperative governance strategy is discussed. Results and discussion: The results show that in the context of digital cities, there are 14 driving factors for enterprises to participate in public health emergency response. The most important factors are the company's own development needs, relative technical advantages and so on. The driving efficiency is mainly concentrated in three aspects: psychology, resources and structure. Public health events have periodicity in time distribution and regional differences in spatial distribution. The significance of this study is to help the government improve the emergency management ability from different angles.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Shijiazhuang in Spring].

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O3） and PM2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 µg·m-3 and 122.18 µg·m-3, respectively. Meanwhile, the OFP was 361.23 µg·m-3 during the polluted period and 266.96 µg·m-3 during the clean period, whereas the SOAFP was 1.98 µg·m-3 and 1.61 µg·m-3, respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM2.5 and O3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Osteoporosis in Relation to a Bone-Related Aging Biomarker Derived from the Urinary Proteomic Profile: A Population Study.

Screening for and prevention of osteoporosis and osteoporotic fractures is imperative, given the high burden on individuals and society. This study constructed and validated an aging-related biomarker derived from the urinary proteomic profile (UPP) indicative of osteoporosis (UPPost-age). In a prospective population study done in northern Belgium (1985-2019), participants were invited for a follow-up examination in 2005-2010 and participants in the 2005-2010 examination again invited in 2009-2013. Participants in both the 2005-2010 and 2009-2013 examinations (n = 519) constituted the derivation (2005-2016 data) and time-shifted validation (2009-2013 data) datasets; 187 participants with only 2005-2010 data formed the synchronous validation dataset. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. Analyses focused on 2372 sequenced urinary peptides (101 proteins) with key roles in maintaining the integrity of bone tissue. In multivariable analyses with correction for multiple testing, chronological age was associated with 99 urinary peptides (16 proteins). Peptides derived from IGF2 and MGP were upregulated in women compared to men, whereas COL1A2, COL3A1, COL5A2, COL10A1 and COL18A1 were downregulated. Via application of a 1000-fold bootstrapped elastic regression procedure, finally, 29 peptides (10 proteins) constituted the UPPost-age biomarker, replicated across datasets. In cross-sectional analyses of 2009-2013 data (n = 706), the body-height-to-arm-span ratio, an osteoporosis marker, was negatively associated with UPPost-age (p&;lt0.0001). Over 4.89 years (median), the 10-year risk of osteoporosis associated with chronological age and UPPost-age (53 cases including 37 fractures in 706 individuals) increased by 21% and 36% (p ≤ 0.044). Among 357 women, the corresponding estimates were 55% and 60% for incident osteoporosis (37 cases; p ≤ 0.0003) and 42% and 44% for osteoporotic fractures (25 cases; p ≤ 0.017). In conclusion, an aging-related UPP signature with focus on peptide fragments derived from bone-related proteins is associated with osteoporosis risk and available for clinical and trial research.

Evaluation of end-organ protection in newborns and infants after surgery of aortic arch hypoplasia: A prospective randomized study.

INTRODUCTION: Surgical repair of aortic arch hypoplasia in children requires a "dry" surgical field with reliable end-organ protection. Perfusion strategies commonly involve deep hypothermic circulatory arrest (DHCA) and variations of the continuous perfusion techniques, such as selective antegrade cerebral perfusion (SACP) and full-flow perfusion with double aortic cannulation (DAC). We aimed to evaluate the end-organ protection in the surgery of aortic arch hypoplasia in newborns and infants using DHCA and DAC. MATERIALS AND METHODS: 66 newborns and infants with aortic arch hypoplasia and biventricular anatomy were enrolled in this prospective study. Patients were randomly assigned into two groups according to the perfusion strategy - DHCA (n = 33); and DAC (n = 33). Primary endpoint: acute kidney injury (AKI), graded according to the KDIGO score. Secondary endpoints: neurological sequelae (pre- and postoperative MRI), in-hospital mortality. RESULTS: The lowest temperature was 32 (28; 34)°Ð¡ in the DAC group and 23 (20; 25)°Ð¡ in the DHCA group. The patients with DAC had lower incidence of AKI (6 patients (18.2%) versus 19 patients (57.6%); p = .017). In the multivariate analysis, the inotropic index at 48 h was identified as a risk factor, increasing the risk of AKI by 4%. The DHCA group was associated with a 3.8-fold increase in the risk of AKI. There was no difference in hospital mortality between the DAC and DHCA groups (1 patient (3%) versus 3 patients (9.1%); p = .61). Neurological sequelae by MRI scan were observed in 18 patients (54.5%) in the DHCA group compared to 5 patients (15.15%) in the DAC group (p = .026). The only risk factor identified in the multivariate analysis for neurological lesions on MRI scan was the DHCA group, which increased the risk by 8.8 times. CONCLUSIONS: Surgical reconstruction of the aortic arch hypoplasia using the method of full-body perfusion reduces the incidence of neurological lesions and renal complications requiring renal replacement therapy compared with the deep hypothermic circulatory arrest in neonates and infants.

Assessment of the efficacy and safety of anlotinib for the treatment of recurrent epithelial ovarian cancer.

OBJECTIVE: The current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: Patients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile. RESULTS: This study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%). CONCLUSION: Anlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC.

[The integrated programs in medical education: modern trends and development prospects].

The article considers possibilities of forming integrated educational programs of personnel training. The integration supposes interdisciplinary approach and inclusion within curricula, besides medical subjects, disciplines from different fields of science. As practice demonstrates, this approach provides larger spectrum of professional knowledge, skills and competencies and contributes into better career guidance and subsequent employment of graduates.