Neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), and cardiovascular diseases (CVDs), including heart failure (HF) and coronary artery disease (CAD), are major chronic disorders associated with population aging. Their frequent coexistence in clinical practice suggests that they may not progress independently, but may instead be linked through bidirectional pathological communication within the brain-heart axis. Epidemiological evidence underscores this clinical burden: systematic reviews and meta-analyses have reported pooled relative risks for dementia of approximately 1.27 among individuals with a history of CAD and 1.60 among those with HF, while the pooled prevalence of cognitive impairment and dementia in patients with HF has been estimated at approximately 41.42% and 19.79%, respectively. This review synthesizes current evidence on the mechanistic links, disease-state manifestations, biomarkers, and potential therapeutic strategies involved in the comorbidity between NDs and CVDs from the perspective of the brain-heart axis. The brain and heart communicate through autonomic, neuroendocrine, neuroimmune, vascular, and humoral pathways. Sympathetic activation, parasympathetic withdrawal, vagal dysfunction, cerebral hypoperfusion, endothelial injury, blood-brain barrier (BBB) alterations, peripheral immune activation, and circulating inflammatory mediators may jointly contribute to cross-organ pathological signaling. Oxidative stress and inflammatory response are not specific to the brain-heart axis; rather, they may act as candidate amplifying processes within this network. Mitochondrial dysfunction and NADPH oxidase activation can increase the generation of reactive oxygen species and reactive nitrogen species, which may activate nuclear factor-κB, the NLRP3 inflammasome, and mitogen-activated protein kinase/c-Jun N-terminal kinase signaling. These pathways can promote the release of interleukin-1β, interleukin-6, tumor necrosis factor‑α, and other inflammatory mediators, which may in turn aggravate mitochondrial injury, endothelial dysfunction, immune cell activation, and further oxidant generation. Cytokines, chemokines, oxidized lipids, mitochondrial DNA, damage-associated molecular patterns, and extracellular vesicles may transmit these signals between the cardiovascular and central nervous systems, whereas autonomic reflexes provide an additional route for bidirectional amplification. Distinct disease states illustrate different manifestations of this network. The association between AD and CVDs may involve vascular risk factors, impaired amyloid-β clearance, abnormal cholesterol homeostasis, cerebral microvascular injury, neuroinflammation, and endothelial dysfunction. HF-related cognitive impairment may be linked to reduced cardiac output, recurrent cerebral hypoperfusion, hypoxia-related signaling, BBB dysfunction, circulating inflammation, and impaired autonomic feedback. In PD, cardiovascular autonomic dysfunction and abnormalities in heart rate and blood pressure regulation may interact with vascular injury, reduced cerebral perfusion, inflammation, and oxidative stress. However, the relationship between PD and CAD remains heterogeneous and may be modified by age, ethnicity, medication use, metabolic factors, and coexisting diseases. Biomarker evaluation should therefore move beyond isolated indicators. Traditional markers, including malondialdehyde, superoxide dismutase, glutathione, C-reactive protein, and interleukin-6, reflect systemic oxidative or inflammatory burden but lack sufficient specificity to distinguish primary neurodegeneration, cardiovascular injury, or a comorbid state involving both. Greater clinical value may be obtained from cross-system panels that combine oxidative stress and inflammatory markers with cardiac stress or injury biomarkers, such as N-terminal pro-B-type natriuretic peptide; glial or neuronal biomarkers, such as glial fibrillary acidic protein and neurofilament light chain; BBB- or endothelial injury-related biomarkers; and omics-derived candidates, including microRNAs, long non-coding RNAs, DNA methylation signatures, metabolites, and proteins. Multi-omics integration and artificial intelligence-assisted analysis may support risk stratification, disease monitoring, and prediction of treatment response. However, these approaches require standardized analytical platforms, validation in independent cohorts, and careful distinction between associative findings and causal mechanisms. Potential interventions include antioxidant, anti-inflammatory, mitochondria-targeted, and multi-target combination strategies, together with emerging approaches such as nanodelivery, CRISPR/Cas9- or CRISPR/dCas9-based regulation, mesenchymal stem cell-mediated mitochondrial transfer, and ergothioneine supplementation. Nevertheless, most available evidence is indirect, preclinical, or derived from other disease indications, and no single drug or technology can currently be regarded as specific to brain-heart axis comorbidity. The clinical relevance of these strategies will depend on whether they can be matched to dominant pathological phenotypes and improve both neurological and cardiovascular outcomes. Overall, comorbidity between NDs and CVDs is more appropriately understood as a heterogeneous cross-organ regulatory network than as a disorder driven by a single pathway. Future research should prioritize multicenter longitudinal cohorts, standardized clinical phenotyping, validation of cross-system biomarker panels, and mechanism-guided interventions in clearly defined patient subgroups, with integrated assessment of cognitive function, cardiovascular events, quality of life, long-term safety, and treatment response.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of coronavirus disease 2019. Diagnostic methods based on the clustered regularly interspaced short palindromic repeats (CRISPR) have been developed to detect SARSCoV-2 rapidly. Therefore, a systematic review and meta-analysis were performed to assess the diagnostic accuracy of CRISPR for detecting SARS-CoV-2 infection. Materials and Methods: Studies published before August 2021 were retrieved from four databases, using the keywords “SARS-CoV-2” and “CRISPR.” Data were collected from these publications, and the sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic curve was plotted for analysis with MetaDiSc 1.4. The Stata 15.0 software was used to draw Deeks’ funnel plots to evaluate publication bias. Results: We performed a pooled analysis of 38 independent studies shown in 30 publications. The reference standard was reverse transcription-quantitative PCR. The results indicated that the sensitivity of CRISPR-based methods for diagnosis was 0.94 (95% CI 0.93–0.95), the specificity was 0.98 (95% CI 0.97–0.99), the PLR was 34.03 (95% CI 20.81–55.66), the NLR was 0.08 (95% CI 0.06– 0.10), and the DOR was 575.74 (95% CI 382.36–866.95). The area under the curve was 0.9894. Conclusion Studies indicate that a diagnostic method based on CRISPR has high sensitivity and specificity. Therefore, this would be a potential diagnostic tool to improve the accuracy of SARS-CoV-2 detection.

OBJECTIVE: To analyze characteristics and related factors of the plantar pressure during the level walking and single leg standing in the chronic ankle instability (CAI) individuals. METHODS: From April 2019, 75 CAI individuals and 40 healthy individuals were enrolled in this study. Both of the static and dynamic plantar pressure were measured during six times level walking and three times single leg standing testing. The data including peak force, time to peak force in various foot contact areas and the time to boundary (TTB) and velocity of center of pressure (COP) were measured and compared between the affected side and the unaffected side and between the CAI cases and the healthy individuals. The correlations between the plantar pressure and the gender, Beighton score, affected side and body mass index (BMI) were analyzed. RESULTS: The characteristics of plantar pressure distribution in the CAI individuals included: (1) During the level walking, the affected side showed the similar pressure contribution as the unaffected side (P>0.05). While compared with healthy individuals, there was a significantly higher peak force in the 5th metatarsal area (t=-3.86, P=0.03) of the affected side, lower peak force in the 1st (t=2.99, P=0.02), 2nd metatarsal head areas (t=2.09, P=0.01) of the affected side, medial hindfoot areas of both sides (affected, t=2.33, P=0.01; unaffected, t=3.74, P=0.02) and toes areass of both sides (affected, t=2.23, P=0.01; unaffected, t=3.28, P=0.02) and a delay to peak force in the 4th metatarsal head area (t=3.33, P=0.01) of the affected side. (2) During the single leg standing, the CAI individuals showed significantly worse balance control in the anterior/posterior direction (P < 0.05) and lateral/medial direction (P < 0.05) compared with the healthy controls, and the affected side had more severe balance control deficit in the lateral/medial direction (P < 0.05). (3) The women (P < 0.05) and the individuals with higher Beighton scores (P < 0.05) showed worse balance control deficit in the lateral/medial direction. CONCLUSION CAI individuals showed significantly a more lateral shifted plantar distribution during the level walking compared with the healthy individuals and the tendency was worse on the affected sides, and showed worse balance control in the anterior/posterior direction and lateral/medial direction during the single leg standing. The women and those with generalized ligament laxity showed significantly worse balance control.
Ankle ; Ankle Joint ; Case-Control Studies ; Female ; Foot ; Humans ; Joint Instability

Objective: To retrospectively analyze the distribution of non-fermentative bacteria causing bloodstream infection in hospitalized patients in Sichuan Province and their drug susceptibility to common antibiotics for better understanding their epidemiological characteristics. Methods: From January 1, 2015 to December 31, 2017, all of the non-fermentative bacteria isolated from patients with bloodstream infection in nine hospitals in Sichuan Province were collected. Species distribution and drug resistance test results were retrospectively analyzed. Results: A total of 6 291 strains of pathogenic bacteria were isolated, including 3 674 strains of gram-negative bacteria (58.4%) and 2 617 strains of gram-positive bacteria (41.6%). The gram-positive bacteria were 1 895 strains of Staphylococcus (30.1%), 372 strains of Streptococcus (5.9%), 317 strains of Enterococcus (5.1%) and 33 strains of other gram-positive bacteria (0.5%). The gram-negative bacteria were 3 191 Enterobacteriaceae strains (50.7%), 389 non-fermentative strains (6.2%) and 94 other gram-negative strains (1.5%). The isolated non-fermentative bacteria were mainly Pseudomonas aeruginosa (136 strains, 35.0%), Acinetobacter baumannii (126 strains, 32.0%) and Stenotrophomonas maltophilia (33 strains, 8.5%). There were 167 (42.9%), 112 (28.8%) and 82 (21.1%) non-fermentative bacteria isolated in internal medicine departments, ICUs and surgery departments, respectively. The drug resistance rates of Pseudomonas aeruginosa to cefepime, ciprofloxacin and gentamicin were 16.5%, 10.7% and 9.9%, respectively. Carbapenems-resistant Pseudomonas aeruginosa (CR-PA) accounted for 13.6%. No polymyxin-resistant Pseudomonas aeruginosa was found. The resistance rates of Acinetobacter baumannii to all antibiotics were over 30% except for minocycline and polymyxin and 75.7% of carbapenem-resistant Acinetobacter baumannii (CR-AB) were isolated. The drug resistance rates to levofloxacin, trimethoprim/sulfamethoxazole and ceftazidime were 0%, 0% and 37.0% in Stenotrophomonas maltophilia isolates and 10.5%, 4.2% and 19% in Burkholderia cepacia isolates, respectively. Conclusions Non-fermentative bacteria causing 6.2% of bloodstream infection in Sichuan, mainly by Pseudomonas aeruginosa and Acinetobacter baumannii. There were significant differences in the isolation rate of non-fermentative bacteria in different departments and most of the strains were isolated in internal medicine departments. The detection rate of Acinetobacter baumannii with multiple drug resistance was high, while other non-fermentative bacteria had good sensitivity to antibiotics.

Objective:To evaluate the effect of parecoxib sodium on the incidence and severity of postoperative hoarseness and sore throat in general anaesthesia patients.Methods:One hundred and twenty patients,with ASA physical status Ⅰ or Ⅱ,aged 20-60 yr,weighing 45-80 kg,undergoing general anesthesia were randomly allocated to parecoxib sodium group or normal saline group equally.In parecoxib sodium group,parecoxib sodium 40 mg was infused during induction of anesthesia,while the equal volume of 0.9％ normal saline was given instead in normal saline group.Anesthesia was intravenously induced with midazolam (0.05 mg/kg),sufentanyl (0.2-0.3 μg/kg),rocuronium (0.7 mg/kg) and propofol (2.0 mg/kg) and mechanical ventilation was applied after tracheal intubation in both groups.The incidence and severity of postoperative hoarseness and sore throat were evaluated 1,2,6,and 8 h after surgery.Results:Compared with normal saline group,the incidence and severity of postoperative hoarseness were significantly reduced by parecoxib sodium at 1,2,and 6 h time points in parecoxib sodium group (P＜0.05),except for time point of 8 h.The incidence and severity of postoperative sore throat was significantly reduced at 1,2,6,and 8 h time points in parecoxib sodium group,compared with normal saline group (P＜0.05).Conclusions:Parecoxib sodium provides efficacy in reducing the incidence and severity of postoperative hoarseness and sore throat in short term after surgery.

Interferon (IFN)-mediated pathways are a crucial part of the cellular response against viral infection. Type III IFNs, which include IFN-λ1, 2 and 3, mediate antiviral responses similar to Type I IFNs via a distinct receptor complex. IFN-λ1 is more effective than the other two members. Transcription of IFN-λ1 requires activation of IRF3/7 and nuclear factor-kappa B (NF-κB), similar to the transcriptional mechanism of Type I IFNs. Using reporter assays, we discovered that viral infection induced both IFN-λ1 promoter activity and that of the 3'-untranslated region (UTR), indicating that IFN-λ1 expression is also regulated at the post-transcriptional level. After analysis with microRNA (miRNA) prediction programs and 3'UTR targeting site assays, the miRNA-548 family, including miR-548b-5p, miR-548c-5p, miR-548i, miR-548j, and miR-548n, was identified to target the 3'UTR of IFN-λ1. Further study demonstrated that miRNA-548 mimics down-regulated the expression of IFN-λ1. In contrast, their inhibitors, the complementary RNAs, enhanced the expression of IFN-λ1 and IFN-stimulated genes. Furthermore, miRNA-548 mimics promoted infection by enterovirus-71 (EV71) and vesicular stomatitis virus (VSV), whereas their inhibitors significantly suppressed the replication of EV71 and VSV. Endogenous miRNA-548 levels were suppressed during viral infection. In conclusion, our results suggest that miRNA-548 regulates host antiviral response via direct targeting of IFN-λ1, which may offer a potential candidate for antiviral therapy.
3' Untranslated Regions ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; Base Sequence ; Down-Regulation ; drug effects ; Female ; Hep G2 Cells ; Hepatitis B, Chronic ; drug therapy ; metabolism ; pathology ; Humans ; Interferon Regulatory Factor-3 ; metabolism ; Interferon Regulatory Factor-7 ; metabolism ; Interleukins ; antagonists & inhibitors ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; MicroRNAs ; metabolism ; Middle Aged ; NF-kappa B ; metabolism ; Poly I-C ; pharmacology ; therapeutic use ; Promoter Regions, Genetic ; RNA Interference ; RNA, Small Interfering ; metabolism

BACKGROUNDAllografts were widely used in anterior cruciate ligament (ACL) reconstruction for patients with ACL rupture of the knee. This study was to approve the feasibility of bone-posterior cruciate ligament-bone (BPCLB) allograft transplantation in ACL reconstruction.

METHODSEight patients underwent ACL reconstructions with BPCLB allografts and were followed up for an average period of 32 months after operation.

RESULTSSubjective parameters including International Knee Documentation Committee (IKDC), modified Larson knee ligament, Lysholm, and Tegner rating scales were much improved and side to side KT-2000 arthrometer difference was much less postoperatively. Pivot shift test was negative in all patients. The reconstructed ACL had satisfactory shape and tension.

CONCLUSIONSBPCLB allograft is an optional choice for ACL reconstruction.

Adult ; Allografts ; Anterior Cruciate Ligament ; surgery ; transplantation ; Anterior Cruciate Ligament Reconstruction ; methods ; Humans ; Male ; Posterior Cruciate Ligament ; surgery ; transplantation ; Young Adult

BACKGROUNDAllograft meniscal transplantation is an increasingly popular treatment option for the symptomatic young patients with meniscus deficiency. However, many questions still surround it. In this research, we studied the anatomical location and histological structure of human meniscal horn bony insertions and to observe the anatomical morphology and histomorphology of peri-meniscal attachments based on meniscal allograft transplantation.

METHODSTwenty-two fresh-frozen adult cadaver knees were dissected. The locations of meniscal anterior and posterior horn bony insertions to tibia were measured. The anatomical morphology of peri-meniscal attachments was observed and the histological structure of meniscal horn bony insertions and peri-meniscal attachment were studied by HE staining.

RESULTSThe anterior horn bony insertion of medial meniscus was (9.19 +/- 1.83) mm inferior to the corresponding anterior border of tibial plateau, and (7.81 +/- 2.25) mm lateral to the axial line of the medial intercondylar eminence. The posterior horn bony insertion of medial meniscus was in the posterior intercondylar fossa of tibia, located between the anterior fibers of the posterior cruciate ligament (PCL) tibial insertion and anterior border of the tibial posterior intercondylar fossa, and was (5.05 +/- 1.18) mm lateral to the axial line of the medial intercondylar eminence. The distance between anterior and posterior horn bony insertions of the lateral meniscus was (13.68 +/- 2.19) mm. Anterior horn bony insertion of the lateral meniscus was (3.99 +/- 1.27) mm medial to the axial line of the lateral intercondylar eminence, and the posterior horn bony insertion of the lateral meniscus was (5.80 +/- 1.36) mm medial to the axial line of the lateral intercondylar eminence. Except for the meniscal horn bony insertions, which is the typical enthesis, we call the attachment of the other parts of menisci as 'peri-meniscal attachment'. The morphological and histological study showed that the main peri-meniscal attachment was the meniscotibial ligament, through which the meniscus attached to the tibia with enthesis structure, and there was only loose connective tissue between menisci and capsule.

CONCLUSIONSIn meniscal allograft transplantation, the traditional meniscal size-matching method which take medial and lateral intercondylar eminences as references is not as accurate as expected. Attention should be taken to locate both anterior and posterior horn tunnels of medial meniscal allograft inferior to the tibia plateau, and to locate anterior and posterior horn tunnels of lateral meniscus close enough (mean 13.68 mm). The best way to reconstruct the peri-meniscal attachment is to suture the allograft to the preserved outer remnant of the original meniscus.

Adult ; Anterior Cruciate Ligament ; anatomy & histology ; cytology ; Cadaver ; Female ; Humans ; Male ; Menisci, Tibial ; anatomy & histology ; cytology ; transplantation ; Transplantation, Homologous