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”.

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”.

ObjectiveThis paper aims to investigate the effect and mechanism of Runmu Xiaoyao powder on mice with dry eye and the syndrome of liver depression-heat syndrome based on the toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty-six C57BL/6J female mice were randomly divided into a normal group， a model group， a sodium hyaluronate group， and high-， medium-， and low-dose Runmu Xiaoyao powder groups， with 11 mice per group. Except for those in the normal group， mice in the other groups were subjected to mouse models with dry eye and liver depression-heat syndrome by instilling a benzalkonium chloride solution and applying chronic pain stimulation in a dry environment. After modeling， mice in the high-， medium-， and low-dose Runmu Xiaoyao powder groups were administered intragastrically with 29.7， 14.85， 7.43 g·kg^-1， respectively， twice a day for 14 consecutive days. The mice in the sodium hyaluronate group received 5 μL of sodium hyaluronate eye drops in each eye twice daily. The mice in the normal and model groups were administered intragastrically with an equal volume of deionized water. Measurements were taken of tear secretion in mice， irritability scores， corneal fluorescein staining， and histopathological changes in the cornea， lacrimal glands， meibomian glands， and liver tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and tumour necrosis factor-α （TNF-α） in serum. Immunohistochemistry （IHC） was used to detect the protein expression of IL-1β and TNF-α in corneal and lacrimal gland tissues. Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were employed to detect the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues. ResultsCompared with those in the normal group， mice in the model group exhibited significantly reduced tear secretion， significantly higher irritability scores， and more pronounced corneal fluorescence staining， with marked pathological damage observed in the cornea， lacrimal glands， meibomian glands， and liver tissue. IL-1β and TNF-α levels in serum were significantly elevated. The protein expressions of IL-1β and TNF-α in corneal and lacrimal gland tissues， as well as the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues， were all significantly increased （P<0.01）. Compared with the model group， the sodium hyaluronate group and Runmu Xiaoyao powder groups with different doses exhibited increased tear secretion to varying degrees， alleviated corneal fluorescence staining and histopathological damage， reduced IL-1β and TNF-α levels in serum， and downregulated protein expressions of IL-1β and TNF-α in corneal and lacrimal gland tissues， as well as the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues. The high-dose Runmu Xiaoyao powder group demonstrated a more pronounced effect， with multiple indicators showing superior results compared to those in the sodium hyaluronate group （P<0.05， P<0.01）. ConclusionRunmu Xiaoyao powder down-regulates the TLR4/MyD88/NF-κB signaling pathway activity in the cornea， lacrimal glands， and meibomian glands of model mice with dry eye and liver depression-heat syndrome， thereby suppressing inflammatory responses and mitigating ocular surface tissue damage. The therapeutic effect is dose-dependent， and the high-dose group exerts the most prominent effect.

ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis， as well as independent risk factors for the degree of calcium salt deposition in lesions， and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025， and according to the volume of calcium salt deposition， they were divided into non-deposition group with 16 patients， mild deposition group with 52 patients， moderate deposition group with 16 patients， and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups， and the χ² test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group （no/mild deposition） and the high deposition group （moderate/severe deposition）. A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition， and a predictive model was established. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model， and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution， involvement of other sites， white blood cell count， lymphocyte percentage， fibrinogen， uric acid， sodium ion， chloride ion， and calcium ion （all P<0.05）. The univariate analysis showed that there were significant differences between the four groups in sex， involvement of other sites， white blood cell count， lymphocyte percentage， fibrinogen， alanine aminotransferase， albumin， creatinine， uric acid， sodium ion， chloride ion， and calcium ion （all P<0.1）. The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760， suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex， involvement of other sites， calcium ion， lymphocyte percentage， and uric acid. The multivariate analysis showed that lymphocyte percentage （odds ratio ［OR］=1.106， 95% confidence interval ［CI］： 1.041 — 1.174， P=0.001） and blood calcium level （OR=0.005， 95%CI： 0.000 —0.230， P=0.007） were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit（P）=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716， with a Youden index of 0.353， a sensitivity of 1.000， and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration （χ²=20.688， P=0.008）. The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage （OR=1.106， 95%CI： 1.049 — 1.186， P=0.002） and calcium ion （OR=0.005， 95%CI： 0.000 — 0.214， P=0.010） were consistent with the original model， and the confidence intervals did not include 1， which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis， and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Objective To investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital, Fudan University. According to the treatment plan, patients were divided into the conventional treatment group and the Huangkui combination treatment group (Huangkui capsules combined with conventional treatment), and the clinical efficacy between the two groups was compared. The logistic regression analysis was used to identify the main factors affecting treatment efficacy. Results The Huangkui combination treatment group (n＝29) showed a significantly higher overall effective rate (79.3% vs 42.3%, P＝0.005), and an earlier proteinuria improvement (median time: 3 months vs 6 months, P＝0.008) than the conventional treatment group (n＝26) . The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB) using (OR＝0.190, 95%CI 0.045-0.808, P＝0.025), targeted drug adjustment (OR＝0.132, 95%CI 0.030-0.581, P＝0.007), and Huangkui capsules using (OR＝0.168, 95%CI 0.039-0.730, P＝0.017) were protective factors for treatment efficacy of targeted drug-related proteinuria. Conclusions On the basis of conventional treatment, additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.

Diseases of the central nervous system have become a growing global health concern. At present， there are many adverse reactions in the treatment with Western medicine. In contrast， traditional Chinese medicine has shown unique efficacy and rich clinical practice accumulation in diseases of the central nervous system. As a traditional Chinese medicine， Bupleuri Radix has played an important role in the treatment of neurological diseases through multi-target regulation， multi-pathway intervention， and multi-pathway mechanism of action. In recent years， with the in-depth study of the pharmacological effects of Bupleuri Radix， it has been found that the active ingredients such as saikosaponin， baicalin， quercetin， and kaempferol in Bupleuri Radix can be used as the main material basis for the treatment of neurological diseases. The results of this study showed that in neurodegenerative diseases， active ingredients of Bupleuri Radix can inhibit β-amyloid （Aβ） deposition and abnormal phosphorylation of microtubule-associated protein （Tau protein） in Alzheimer's disease， regulate the nuclear factor-κB/nuclear factor E₂ related factor 2 （NF-κB/Nrf2） pathway to play the anti-inflammatory role， and alleviate α-Synuclein （α-Syn） aggregation and mitochondrial damage in Parkinson's disease. In epilepsy， depression， and cerebral ischemia， they can improve symptoms by regulating neurotransmitters， oxidative stress， and apoptosis pathways， and inhibit brain glioma proliferation. However， the mechanism of action has not been fully elucidated， and the complexity of compound components and poor blood-brain barrier penetration limit their clinical application. In the future， it is necessary to integrate multi-omics， network pharmacology， and nano-delivery technologies， focus on the optimization of active ingredient group compounds and the precise guidance of biomarkers， accelerate the development of innovative therapies for Alzheimer's disease， Parkinson's disease， and other diseases for laying a solid theoretical foundation for further development and application and inspiring new research ideas.

OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.