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Identification of characteristic genes ofanddeficiency constitutions: an integrated analysis based on bioinformatics and machine learning

J Tradit Chin Med. 2025 Aug;45(4):909-921. doi: 10.19852/j.cnki.jtcm.2025.04.021.

ABSTRACT

OBJECTIVE: To utilize the Traditional Chinese Medicine constitution (TCMC) as a complementary and alternative approach for early disease detection and treatment, with a focus on Yin and Yang deficiency constitutions, which serve as key references for disease prevention and management.

METHODS: The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database. This database was used for differential expression genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA), and the characteristic genes were then obtained in the dataset using a machine learning method. The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods, and the hub genes were enriched and analyzed. Subsequently, the hub genes of Yin and Yang deficiency constitution were validated using external datasets. Receiver operating characteristic (ROC) analysis was used on each hub genes of the two groups to further understand their diagnostic performance. The miRNA-lncRNA-gene network was used to further analyze the hub genes. Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.

RESULTS: The GSE87474 dataset was used for DEGs analysis and WGCNA. Using machine learning analyses, we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions, respectively. The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway, whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis-keratan sulfate. The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1 (SAMTOR, also named C7orf60), cofilin 2 (CFL2), cytohesin 1 interacting protein (CYTIP), G protein-coupled receptor 183 (GPR183), hippocampus abundant transcript 1 (HIAT1), kelch like family member 15 (KLHL15), mitogen-activated protein kinase 6 (MAPK6), and prostaglandin-endoperoxide synthase 2 (PTGS2) in Yin deficiency and fucosy-ltransferase 8 (FUT8), TATA-box binding protein associated factor, RNA polymerase I subunit D (TAF1D), zinc finger protein 24 (ZNF24), MAPK6, and leptin receptor overlapping transcript like 1 (LEPROTL1) in Yang deficiency. The ROC results indicated that these genes have diagnostic value. MAPK6 is a shared hub gene for Yin and Yang deficiencies.

CONCLUSIONS: This study identified C7orf60, CFL2, CYTIP, GPR183, HIAT1, KLHL15, MAPK6, and PTGS2 in Yin deficiency and FUT8, TAF1D, ZNF24, MAPK6, and LEPROTL1 in Yang deficiency as potential biomarkers, providing insights into their pathogenesis. This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.

PMID:40810238 | DOI:10.19852/j.cnki.jtcm.2025.04.021

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Clinical study of Yiqi Liangxue Shengji prescription for improving cardiac function after myocardial ischemia reperfusion injury in patients with acute myocardial infarction: a randomized, double-blind, placebo-controlled trial

J Tradit Chin Med. 2025 Aug;45(4):836-844. doi: 10.19852/j.cnki.jtcm.2025.04.012.

ABSTRACT

OBJECTIVE: To evaluate the effect of Yiqi Liangxue Shengji prescription (, YQLXSJ) on cardiac function and outcomes in acute myocardial infarction (AMI) patients with myocardial ischemia-reperfusion injury (MIRI) and to determine its clinical efficacy.

METHODS: This prospective, randomized, double-blind, placebo-controlled trial enrolled hospitalized patients with AMI who underwent percutaneous coronary intervention and experienced MIRI either intraoperatively or postoperatively. Participants were randomly allocated to the treatment group, which received YQLXSJ, or the control group, which received a placebo, concurrent with standard Western Medicine therapy. The intervention period lasted 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF), determined by echocardiography. Secondary outcomes included N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) levels, left ventricular internal diameter, major adverse cardiovascular events (MACE), angina pectoris scores, and Chinese medicine evidence scores.

RESULTS: Following 8 weeks of intervention, the treatment group demonstrated a significant increase in LVEF and a marked reduction in NT-proBNP when compared to the control group. There was also a significant decrease in peak cTnI levels, Chinese medicine evidence scores, and angina pectoris scores. The control group’s left ventricular end-systolic diameter (LVESD) significantly increased compared to baseline after 8 weeks (P < 0.05), whereas the treatment group’s LVESD showed no significant change from baseline (P > 0.05). Although the treatment group showed a downward trend in MACE incidence compared to the control group, this difference was not statistically significant (P > 0.05).

CONCLUSIONS: This study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

PMID:40810229 | DOI:10.19852/j.cnki.jtcm.2025.04.012

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Geographic Trends and Geospatial Analysis of Head and Neck Fellowship-Trained Surgeons

Head Neck. 2025 Aug 14. doi: 10.1002/hed.70016. Online ahead of print.

ABSTRACT

BACKGROUND: Disparities in access to otolaryngology and cancer care exist across the United States. However, little is known about the geographic distribution of fellowship-trained head and neck cancer (HNC) surgeons.

METHODS: A cross-sectional study of American Head and Neck Society (AHNS) fellowship graduates from July 1, 1997 to June 30, 2022 was conducted. Geospatial and statistical analysis was conducted to assess current practice location and correlations with training regions.

RESULTS: Among 688 graduates, 622 practice in the US or Canada. Most graduates remained in the region of their training. Geospatial analysis showed concentration of graduates in urban areas, with 152 of 3142 US counties having higher-than-expected density. Underserved regions were identified in the southeastern US, southern border, and western states.

CONCLUSIONS: Head and neck surgical fellowship graduates predominantly practice in large urban areas, leaving rural and underserved regions with limited access to complex HNC care. Strategic interventions are needed to address these gaps.

PMID:40810214 | DOI:10.1002/hed.70016

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Reducing Medication-related Inappropriateness (MRI) in Older Adults: A Systematic Review and Meta-analysis

J Patient Saf. 2025 Aug 14. doi: 10.1097/PTS.0000000000001406. Online ahead of print.

ABSTRACT

BACKGROUND: Medication-related inappropriateness (MRI) poses a significant risk to elderly patients, particularly in aged care settings, where complex medication regimens and health care challenges increase the likelihood of errors. Addressing MRI is critical to enhancing patient safety and improving health outcomes for older adults. This study aims to evaluate the effectiveness of interventions designed to reduce MRI and improve prescribing practices in elderly populations through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis were conducted following the Cochrane Handbook for Systematic Reviews of Interventions. Databases including MEDLINE, EMBASE, CINAHL, PubMed, and EBSCOhost were searched from April 2020 to November 2023. Randomized controlled trials (RCTs) and nonrandomized controlled studies evaluating interventions for reducing MRI in elderly patients receiving care in various healthcare settings were included. Eight studies involving a total of 33,170 participants across 7 countries qualified for analysis. The pooled odds ratio (OR) with a 95% CI was calculated to measure intervention effectiveness. Statistical heterogeneity was assessed using the Higgins I² statistic, and a random-effects model was applied to account for variability.

RESULTS: Interventions ranged from educational programs and peer reviews to computerised decision-support systems. The meta-analysis demonstrated a significant reduction in MRI, with a pooled OR of 0.43 (95% CI: 0.31-0.60), indicating a 57% reduction in inappropriate prescribing. Educational interventions were particularly effective, fostering improved prescriber behavior and medication safety. However, high heterogeneity (I²=92%) underscored variations in patient demographics, care settings, and intervention designs.

CONCLUSIONS: Educational interventions and decision-support systems are found to significantly reduce the inappropriate prescribing of medication in older patients. More research is required to address variability, determine long-term outcomes, and facilitate broader implementation to improve medication safety.

PMID:40810201 | DOI:10.1097/PTS.0000000000001406

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A Tentative Clinical Study: Colistin Combined with Ceftazidime/Avibactam in the Treatment of Carbapenem-Resistant Gram-Negative Bacilli Infection

Infect Drug Resist. 2025 Aug 9;18:3977-3991. doi: 10.2147/IDR.S542467. eCollection 2025.

ABSTRACT

PURPOSE: The emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB) has led to a critical challenge in antimicrobial therapy. This study aimed to assess the efficacy of colistin (COL) combined with ceftazidime/avibactam (CAZ/AVI) in the treatment of CR-GNB infections.

PATIENTS AND METHODS: A retrospective, single-center observational study was conducted on patients diagnosed with CR-GNB infections who were treated with COL combined with CAZ/AVI (C/C), COL combined with Tigecycline (C/T), and COL combined with meropenem (C/M). The primary outcome measure was the rate of microbiological clearance within seven days, while secondary outcomes included changes in inflammatory markers, severe illness-related scores, length of stay, and survival rates.

RESULTS: Among the 95 patients analyzed, the C/C treatment regimen resulted in a higher rate of microbiological clearance (64.7%) compared to C/T (24.1%) and C/M (25.0%) (P=0.002 and P=0.001). In the subgroup analysis for treating infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), the 7-day microbial clearance rates in the C/C, C/T, and C/M groups were 57.9%, 25.0%, and 29.4%, respectively (P = 0.122). Inflammatory markers, including white blood cell count, c-reactive protein, and procalcitonin, showed improvements in three groups. The decrease of some indicators was statistically significant. However, no significant differences in mortality rates were observed across the treatment groups. Furthermore, the survival curve analysis indicates that the survival time of the C/M treatment regimen is significantly longer than that of the C/C treatment regimen.

CONCLUSION: The C/C treatment regimen appears to be more effective in achieving microbiological clearance and improving inflammatory parameters in patients with CR-GNB infections. While the impact on survival rates and survival duration requires further investigation, the C/C regimen warrants consideration as a potent therapeutic option for CR-GNB infections.

PMID:40810173 | PMC:PMC12348888 | DOI:10.2147/IDR.S542467

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Optimization and Evaluation of Complementary Degrader Discovery Assays for Application in Screening

ACS Pharmacol Transl Sci. 2025 Jul 20;8(8):2600-2611. doi: 10.1021/acsptsci.5c00195. eCollection 2025 Aug 8.

ABSTRACT

Targeted protein degradation (TPD) mediated by molecular glues is an innovative pharmaceutical paradigm. By binding to and modulating the surface of an E3-ligase component, molecular glue degraders can facilitate the recruitment of a specific target protein (or vice versa) and ultimately invoke target degradation. This mode of action results in specific challenges for the development of rational discovery strategies, and complex hit validation workflows may be required to reliably eliminate compounds that elicit nonspecific effects. With the aim to guide screening efforts, we optimized two orthogonal cell-based, target-centric assays for degrader discovery: (1) a time-resolved FRET assay directly quantifying the levels of a target protein and its degradation (signal inhibition) and (2) an assay coupling TPD to cell growth (signal rescue). To enable a deeper understanding of the individual assays’ strengths and limitations, we compared their statistical performance as well as respective hit populations by screening a specifically designed collection of about 1000 compounds containing well-annotated reference compounds and known frequent hitters (FHs). We found that the signal rescue format reliably and specifically captured active target degraders while efficiently filtering out interfering or FH compounds. Importantly, this format achieved to retrieve lower potency hits, which might be desirable in order to confidently include as many diverse chemical starting points as possible at the start of a drug discovery project.

PMID:40810141 | PMC:PMC12340641 | DOI:10.1021/acsptsci.5c00195

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Characteristics of meconium impaction/retention in newborn foals: From 2006 to 2024

Equine Vet Educ. 2025 Jan 29. doi: 10.1111/eve.14109. Online ahead of print.

ABSTRACT

BACKGROUND: Meconium impaction/retention is a significant cause of colic in foals. Historically, limitations of both medical and surgical treatment are noted. Outcomes of meconium impaction/retention have not recently been reported.

OBJECTIVE: To describe case characteristics and outcomes in foals with meconium impaction/retention.

STUDY DESIGN: Retrospective, single referral hospital.

METHODS: Medical records from 2006 to 2024 were searched for foals ≤3 days old with a history of straining to defecate, abdominal distention, colic, weakness and/or tail flagging. Signalment, presenting complaint, treatment, outcome and comorbidities were summarised and compared between groups based on sex and survival. Associations between comorbidities and survival were evaluated by zero-inflated Poisson regression.

RESULTS: Forty-three foals met the inclusion criteria. Male foals dominated (30/43; 70%). All foals were managed with enemas; phosphate (11/43; 30%), water with soap/lube (25/43; 58%), not specified 9/43 (21%), multiple types (8; 19%), acetylcysteine retention (1; 2%). Forty foals (93%) survived to discharge, and three (7%) were humanely euthanised. Of surviving foals, 37/40 (93%) responded fully to medical treatment. Surgical treatment was required in 4 foals (9%); 3/4 (75%) survived. Comorbidities were common including sepsis (10/43; 23%), pneumonia (10/43; 23%), failure of passive transfer (6/43; 14%) and hypoxic-ischaemic encephalopathy (5/43; 12%). Non-survivors (3/43; 7%) were euthanised due to sepsis, limb malformation and pneumonia.

MAIN LIMITATIONS: Small sample size and low number of non-survivors prevented meaningful statistical analysis.

CONCLUSION: Medical management of meconium impaction/retention is successful in the great majority of cases. Prognosis depends on the comorbidities present.

PMID:40810138 | PMC:PMC12341383 | DOI:10.1111/eve.14109

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All-Inside Versus Inside-Out Suture Techniques in Athletes Undergoing Arthroscopic Meniscal Repair: A Systematic Review and Meta-analysis

Orthop J Sports Med. 2025 Aug 12;13(8):23259671251361488. doi: 10.1177/23259671251361488. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Meniscal tears are a common knee injury in athletes, necessitating effective repair techniques. Despite the prevalence of meniscal tears, there is limited literature comparing the efficacy of the 2 primary suture methods-all-inside and inside-out-in the athletic population.

PURPOSE: To evaluate the postoperative outcomes and failure rates of the all-inside versus inside-out suture techniques in meniscal repairs among athletes.

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a comprehensive search was conducted across the PubMed, Cochrane, and Embase databases on July 26, 2023, yielding 245 studies, of which 7 were included in this review. Studies reporting postoperative outcomes and failure rates of both suture techniques were included. Failure was defined as the need for subsequent surgery due to a persistent meniscal tear. Outcome measures included the Tegner, Lysholm, and International Knee Documentation Committee scores. Differences between groups and subgroups were assessed using the Welch t test and the odds ratio. Wilcoxon tests were used as a sensitivity analysis to confirm the results of the Welch t tests. Heterogeneity was assessed with the I 2 statistic and the Bartlett test. All statistical analyses were done using R.

RESULTS: Seven studies-published between 2009 and 2023-met the inclusion criteria, including 469 operations in 458 patients. A total of 199 operations used the all-inside technique, and 270 operations used the inside-out technique. Of the 469 operations, 377 had documentation on laterality (medial meniscal repair versus lateral meniscal repair), with 167 patients undergoing medial meniscal repair and 210 patients undergoing lateral meniscal repair. Each all-inside repair was done with the Fast-Fix device. The all-inside technique showed a statistically significant increase in failure rate compared with the inside-out technique (23.1% vs 12.2%; P = .003). This trend was exaggerated in all-inside repairs for the medial meniscus versus the lateral meniscus (58.1% vs 11.8%; P = 2.6 × 10-5). When excluding all radial tears, the all-inside technique again had an increased rate of failure compared with the inside-out repairs (20.7% vs 8.3%; P = .01). No significant difference was found in postoperative Tegner scores between all-inside and inside-out repairs (5.9 vs 6.5; P = 0.45).

CONCLUSION: Our review demonstrated that medial meniscal repairs with the all-inside technique using the Fast-Fix device had a higher failure rate compared with those with the inside-out technique; this trend is not seen for lateral meniscal repairs. Based on the findings of this study, surgeons should consider the inside-out technique first for athletic patients presenting with medial meniscal tears who want to return to their sport. Given the limited scope of existing studies combined with more recent utilization of novel all-inside meniscal repair devices that may not be captured in the present study, additional high-quality, prospective studies in this area are needed to validate these findings.

PMID:40810129 | PMC:PMC12344347 | DOI:10.1177/23259671251361488

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The Current State of American Flag Football Injuries Among Female Athletes: A 10-Year Epidemiological Review of National Injury Data

Orthop J Sports Med. 2025 Aug 12;13(8):23259671251360345. doi: 10.1177/23259671251360345. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Flag football, a noncontact variant of American football, has gained significant interest in the United States and globally, which has been attributed to its accessibility, low cost, and perceived safety compared with traditional tackle football.

PURPOSE: To identify the trends, primary mechanisms, and distributions of American flag football injuries among female athletes to better inform prevention and safety measures.

STUDY DESIGN: Descriptive epidemiology study.

METHODS: Data analyzed in this study were extracted from the National Electronic Injury Surveillance System (NEISS), a public database representing approximately 100 US emergency departments (EDs) that provides national injury estimates. NEISS was queried for all flag football injuries in female patients from January 1, 2014, to December 31, 2023. Descriptive statistics were used to analyze the distribution of injury by age, mechanism, diagnosis, and body region. Linear regression was used to analyze changes in injury rates over time.

RESULTS: Across the study period, 605 female patients with flag football injuries were evaluated at US EDs, extrapolating to a national estimate (NE) of 22,666 injuries from 2014 to 2023. The highest frequency of injuries occurred in 2023 (NE = 3531; 15.6%) and the lowest in 2020 (NE = 436; 1.9%). The most common injury diagnosis was found to be strain/sprain (NE = 6835; 30.2%), with adolescents aged 11 to 20 years sustaining the greatest number of injuries across all diagnoses. The most commonly affected body part was the finger (NE = 137; 22.6%). When analyzing the mechanism of injury, the most common cause was fall, including fall on an outstretched hand (NE = 4321; 19.1%). In addition, the majority of patients were treated and released (NE = 22,253; 98.2%).

CONCLUSION: This study demonstrated that from 2014 to 2023, female flag football injuries reported to US EDs remained relatively stable, dropping in 2020 during the COVID-19 pandemic and peaking in 2023. The most common injuries sustained by female athletes playing flag football were strains/sprains and fractures. Given the high prevalence of injuries sustained in the adolescent population, the use of appropriate protective gear should be emphasized to prevent a precipitous rise in injuries as the sport continues to grow in popularity throughout the country.

PMID:40810127 | PMC:PMC12344343 | DOI:10.1177/23259671251360345

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Efficacy of Infliximab Versus Vedolizumab in the Management of Immune Checkpoint Inhibitor-Induced Colitis: A Systematic Review and Meta-Analysis

World J Oncol. 2025 Jul 26;16(4):331-341. doi: 10.14740/wjon2613. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe gastrointestinal immune-related adverse events (irAEs), often leading to treatment interruption and increased morbidity. Immune-mediated colitis (IMC) ranges from mild diarrhea to life-threatening colitis, sometimes requiring urgent intervention. While corticosteroids are the first-line treatment, selective immunosuppressive therapy (SIT) with either infliximab or vedolizumab is used for steroid-refractory or dependent cases. However, standardized practices are lacking, and treatment decisions are largely left to provider discretion. This study compares infliximab and vedolizumab for IMC, focusing on remission rates, recurrence, SIT dosing, and systemic steroid exposure duration.

METHODS: We identified six retrospective cohort studies that compared infliximab with vedolizumab in the treatment of IMC through a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, CINAHL, Google Scholar, and Web of Science in English from inception until October 2024. From the identified literature, we extracted pertinent data such as remission and recurrence of IMC. Pooled analysis and heterogeneity analysis were performed using R Studio version 4.4.1. The risk of bias was assessed using the Newcastle-Ottawa Scale.

RESULTS: A total of six studies with 645 patients were included. In ICI-associated colitis, vedolizumab was associated with lower recurrence rates (odds ratio (OR): 0.29, 95% confidence interval (CI): 0.15 – 0.54) and shorter systemic steroid exposure (mean difference (MD): -16.88 days, 95% CI: -20.47 to -13.30) compared to infliximab. While vedolizumab showed improved remission, there was no statistically significant difference in remission rates between vedolizumab and infliximab monotherapy (OR: 3.16, 95% CI: 0.29 – 34.01). Remission was achieved with fewer doses of infliximab than vedolizumab (MD: 1.16, 95% CI: 0.09 – 2.22). The mean number of vedolizumab doses was 2.57 (raw mean score (MRAW): 2.57, 95% CI: 1.43 – 2.71), while the mean number of infliximab doses was 1.36 (MRAW: 1.36, 95% CI: 0.69 – 2.02).

CONCLUSIONS: Among patients with ICI-induced colitis, vedolizumab demonstrated superiority over infliximab by being associated with lower rates of colitis recurrence and decreased systemic steroid exposure, although it required a higher number of doses compared to infliximab.

PMID:40810084 | PMC:PMC12339259 | DOI:10.14740/wjon2613