ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

Background Benzothiazoles and benzotriazoles are ubiquitously detected in drinking water, posing potential health risks. Developing a reliable and sensitive analytical method is critical for assessing their exposure levels and associated risks. Objective To establish an automated solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry method for the simultaneous determination of benzothiazole, 2-aminobenzothiazole, benzotriazole, and 5-chlorobenzotriazole in drinking water. Methods Key parameters were systematically optimized. Three mobile phase systems were compared to evaluate their effects on chromatographic peak shape and separation; three SPE cartridges were tested for extraction efficiency; the influences of water pH on extraction recoveries and matrix effects were investigated; the contributions of pretreatment steps to benzothiazole blank were analyzed, and control measures were established; nitrogen evaporation temperatures were tested to ensure analyte stability. The optimized parameters were used to develop the method, validate its performance, and analyze drinking water samples. Results Drinking water samples were first adjusted to pH 6.0 with formic acid, and then extracted using HLB cartridges. After elution with 6 mL methanol, the eluate was concentrated under nitrogen evaporation at 45 °C, followed by separation on a C18 column using a gradient elution of acetonitrile-0.1% formic acid solution, and tandem mass spectrometry detection. Avoiding nitrogen blow-drying during SPE and eliminating the use of polypropylene materials during nitrogen evaporation can effectively minimize benzothiazole contamination. Good calibration linearity was obtained for the target analytes in the concentration range of 5.0-250 μg·L⁻¹, with a correlation coefficient of r > 0.995. The method detection limits were in the range of 1.0-5.0 ng·L⁻¹. The recoveries of the target analytes in pure water and tap water were 80.2%-119.5% and 72.2%-115.6%, respectively, with relative standard deviations of were 3.2%-12.8% and 2.3%-11.6%, respectively. When applying this method to actual water samples, benzotriazole was detected in 100% of treated and tap water samples, with median concentrations of 79.4 ng·L⁻¹ and 114 ng·L⁻¹, respectively. Benzothiazole was detected in 83.3% of treated water samples and 100% of tap water samples, with median concentrations of 48.3 ng·L⁻¹ and 65.4 ng·L⁻¹, respectively. In addition, 5-chloro-benzotriazole exhibited low detection rates and concentrations, while 2-amino-benzothiazole was undetected. Conclusion The developed method demonstrates high accuracy, reliability, and sensitivity, making it suitable for the analysis of trace levels of benzothiazoles and benzotriazoles in drinking water.

Background/Aims: We examined the association between diabetes duration and hyperuricemia in Korean subjects based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). Methods: This cross-sectional study included 4,575 subjects aged 30 years and older with type 2 diabetes mellitus based on data from the KNHANES from 2016 to 2021. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL. Univariable and multivariable logistic regression models were used calculate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The mean age of subjects was 61.0 years, 56.5% were male, and the mean body mass index (BMI) was 25.6 kg/m2. Compared to those with diabetes duration 5 to < 10 years, those with shorter or longer diabetes duration had higher serum uric acid levels and higher prevalence of hyperuricemia. In multivariable logistic regression models, a U-shaped association between diabetes duration and hyperuricemia was observed after adjusting for age, sex, income, smoking status, alcohol consumption, regular exercise, and presence of hypertension, dyslipidemia, or chronic kidney disease. Compared to those with new-onset diabetes mellitus, the adjusted OR (95% CI) for hyperuricemia was 0.55 (0.38–0.82) in those with diabetes duration 5 to < 10 years. The results were consistent in subgroup analysis according to age, sex, BMI, and chronic kidney disease. Conclusions The U-shaped association between diabetes duration and hyperuricemia was observed in a representative sample of Korean adults.

Periodontitis is a chronic inflammatory disease. The heterotopic colonization of periodontal pathogens results in the development of several systemic diseases. Porphyromonas gingivalis (P. gingivalis), a key pathogen for periodontitis, has been linked to the development of various cancers, such as oral squamous cell carcinoma (OSCC), lung cancer, esophageal cancer, pancreatic cancer, colorectal cancer, cervical cancer, and prostate cancer. P. gingivalis promote the progression of tumor through various mechanisms, P. gingivalis regulates proteins targeting cell cycle and apoptosis to promote proliferation of tumor cells directly, enhances tumor stemness by upregulating the expression of cluster of differentiation 44 (CD44) and cluster of differentiation 133 (CD133), activates inflammasome and p38/c-Jun N-terminal kinase 1(JNK) pathways, regulates tumor-associated neutrophil (TAN) polarization to remodel the tumor microenvironment, regulates epithelial-mesenchymal transition (EMT) to promote tumor metastasis, remodel macrophage function to evade host immune response, and regulates multi-communicating with symbiotic bacteria. In addition, P. gingivalis accelerates the progression of esophageal cancer, pancreatic cancer, colorectal cancer, and prostate cancer by promoting cell proliferation, inhibiting apoptosis, inducing chronic inflammation, and escaping immunity. However, the oral microbiome is a complex system, whether the interactions between oral bacteria affect tumor progression needs to be further investigated.

Objective: To evaluate the performance of the left atrial time-to-peak (TTP) derived from time-resolved magnetic resonance angiography (TR-MRA) as a noninvasive indicator of left atrial pressure (LAP) in patients with atrial fibrillation (AF). Materials and Methods: This retrospective study included 92 patients who underwent cardiac TR-MRA and catheter-based LAP measurements prior to catheter ablation for AF between January 2021 and December 2022. TR-MRA–derived TTP was measured in the left atrium using contrast-enhanced time-signal intensity curves. Catheter-based LAP measured during sinus rhythm served as the reference standard, with high LAP defined as ≥15 mmHg. Univariable and multivariable linear regression analyses were performed, with LAP as the dependent variable and echocardiographic parameters as covariates. The diagnostic performance of TTP for high LAP was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Among the 92 patients (mean age ± standard deviation, 60 ± 10 years; 70 male), 70 (76.0%) had low LAP, and 22 (23.9%) had high LAP. Mean TTP was significantly longer in patients with high LAP than in those with low LAP (25.1 ± 6.9 s vs.16.9 ± 5.7 s, P < 0.001). In multivariable linear regression analysis, TTP remained independently associated with LAP (β = 0.46, P < 0.001). ROC analysis demonstrated good discriminative performance of TTP for identifying high LAP, with an area under the curve of 0.834 (95% confidence interval, 0.742–0.904). Using a TTP cutoff of >19.6 seconds, the sensitivity and specificity for identifying elevated LAP levels were 81.8% (18/22) and 75.7% (53/70), respectively. Conclusion TR-MRA–derived TTP showed a significant independent association with invasively measured LAP. It may serve as a reliable noninvasive imaging marker for identifying high LAP in patients with AF undergoing catheter ablation.

Objectives: This pilot study examined the preliminary findings associated with a cognitive-load-controlled structured psychodrama program on affect, fear of negative evaluation, and general psychopathology in long-term psychiatric inpatients, most of whom had schizophrenia spectrum disorders. Methods: A single-group pre-post design was used. A total of 125 stabilized long-term psychiatric inpatients participated in a 25-session structured psychodrama program. To enhance measurement validity in consideration of participants’ cognitive characteristics, self-report measures were administered in small-group sessions with individualized explanation. Primary outcomes (Positive and Negative Affect Schedule [PANAS], Affect Balance Scale [ABS], and Brief Fear of Negative Evaluation [BFNE]) were assessed in 125 participants, and the secondary outcome (Brief Psychiatric Rating Scale [BPRS]) was assessed in a randomly selected subgroup of 53 participants. Results: After the intervention, positive affect significantly increased, whereas negative affect significantly decreased on both the PANAS and ABS (all p＜0.001). BFNE scores significantly decreased from 43.14 to 28.94 (p＜0.001). Total BPRS scores also significantly decreased from 47.49 to 34.76 (p＜0.001), with notable improvements in depressive mood, anxiety, tension, somatic concern, and emotional withdrawal. Conclusion A structured psychodrama program may be a feasible and potentially beneficial psychosocial intervention for long-term psychiatric inpatients. However, given the single-group pre-post design and other methodological limitations, the magnitude of the observed changes should be interpreted cautiously. These findings may serve as preliminary data for future controlled trials.