For a long time， simple asymptomatic renal hematuria has not been taken seriously. Current studies have confirmed that renal hematuria is a risk factor for the progression of renal function， but there is no effective treatment available. Because asymptomatic renal hematuria is highly concealed and lacks typical symptoms， individualized syndrome differentiation in traditional Chinese medicine （TCM） is difficult， making it a challenge in clinical diagnosis and treatment. Although TCM has a long history and solid theoretical basis in the treatment of hematuria， it urgently needs to break through the bottleneck of traditional syndrome differentiation. Based on classical TCM theories， research achievements in modern constitution studies， and relevant clinical and pathological evidence， this article focuses on the decisive influence of age on constitution distribution and its regular association with the evolution of core syndromes， and constructs a three-dimensional diagnostic and therapeutic system of "age-constitution-syndrome". It reveals that the syndrome manifestations of asymptomatic renal hematuria are profoundly shaped by constitution， and that constitution shows a group distribution pattern with age-children often present with deficiency of lung and spleen Qi combined with wind-heat， young and middle-aged individuals often present with deficiency of liver and kidney Yin combined with deficient fire and stasis heat， and elderly individuals often present with deficiency of spleen and kidney combined with cold-dampness and stasis obstruction. By analyzing the common pathogenic mechanisms， outcome characteristics， and internal mechanisms among different age groups， this study provides a basic syndrome framework and core intervention strategies for specific populations in clinical practice， offering a new evidence-based approach to addressing the dilemma of “no identifiable syndrome”.

According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine （TCM） and mitochondria in modern cellular biology， it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation， playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly， mitochondria are vital for maintaining physiological functions such as cellular energy supply， cell survival， and overall human metabolism. Furthermore， spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly， mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease （COPD）， with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore， the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi， while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function， regulate energy metabolism， and reduce oxidative stress levels to alleviate COPD symptoms， slow down disease progression， and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine， this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic， complex age-related diseases.

According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine （TCM） and mitochondria in modern cellular biology， it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation， playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly， mitochondria are vital for maintaining physiological functions such as cellular energy supply， cell survival， and overall human metabolism. Furthermore， spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly， mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease （COPD）， with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore， the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi， while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function， regulate energy metabolism， and reduce oxidative stress levels to alleviate COPD symptoms， slow down disease progression， and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine， this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic， complex age-related diseases.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

BACKGROUND:The analgesic effect of stagnant moving needle on myofascial pain syndrome is remarkable,but the analgesic mechanism is still unclear.OBJECTIVE:To investigate the analgesic mechanism of stagnant moving needle acupuncture in the treatment of myofascial pain syndrome.METHODS:Fifty-four SD rats were randomly divided into a blank group(n=16)and a modeling group(n=38).The models of leftmyofascial pain syndrome in the modeling group were prepared by using the method of"striking combined with centrifugal movement".Twelve weeks after modeling,six mice were randomly selected to verify the success of the modeling.The rest of the 32 rats were randomly divided into the model group and the stagnant moving needle group,with 16 rats in each group.The stagnant needle moving group was treated by stagnant moving needle into the local excitation point nodule of the left medial vastus muscle fascia in rats,twice a week,for 4 weeks.The mechanical foot contraction reflex threshold of the leftfoot were measured weekly in the pre/post modeling and post-intervention groups of rats.At 4 weeks after treatment,hematoxylin-eosin staining was used to observe the morphological changes in the muscle tissue of the leftmedial femoral muscle of rats,ELISA was used to detect the levels of substance P and β-endorphin in the serum and the gray matter around the midbrain aqueduct.Immunohistochemistry was used to detect positive expression of microglia markers(Iba-1)and c-fos in the gray matter around the midbrain aqueduct.Western blot assay was used to detect the expression level of brain-derived neurotrophic factor protein in the periaqueductal gray.RESULTS AND CONCLUSION:Compared with the blank group,the mechanical pain threshold of the rats in the model group and the stagnant moving needle group decreased after modeling(P<0.05).After 4 weeks of treatment,the mechanical pain threshold of the rats in the stagnant moving needle group was higher than that in the model group(P<0.05).Hematoxylin-eosin staining results showed that in the model group,the muscle fibers of the leftlower limb medial femoral muscle of rats were disorganized,unequal in thickness,myocytes were enlarged,with inward movement of the nucleus,rounded contracture nodules and tension bands;whereas in the stagnant moving needle group,the muscle fibers were arranged in a neat way,the myocytes were angular,and the contracture nodules were occasionally seen.Compared with the blank group,the expression of substance P in the serum of the model group was significantly higher(P<0.05),while the levels of β-endorphin in serum and substance P and β-endorphin in brain were decreased(P<0.01).Compared with the model group,the level of serum substance P in the stagnant moving needle group was decreased(P<0.05),and the levels of serum β-endorphin and brain substance P and β-endorphin were increased(P<0.05).Compared with the blank group,the positive expression of c-fos and Iba-1 and the protein of brain-derived neurotrophic factor in the model group were increased(P<0.05).Compared with the model group,the positive expression of c-fos in the stagnant moving needle group was increased(P<0.05),and the positive expression of Iba-1 and the protein of brain-derived neurotrophic factor were decreased(P<0.05).These findings suggest that stagnant moving needle may indirectly promote the release of β-endorphin by microglia polarized to the M2 phenotype and increase the excitability of c-fos neurons by inhibiting the activity of microglia in the gray matter around the periaqueductal gray and downregulating the expression of brain-derived neurotrophic factor protein,thereby reducing the degree of central sensitization and effectively relieving myofascial pain syndrome.

Objective To explore clinical application value of fetal heart quantification(HQ)technology in evaluating morphology and function of fetal heart in gestational hypertension pregnancy patients.Methods A total of 85 women with gestational hypertension(GH)during gestational age of 20-40 weeks from March 2020 to March 2024 had been selected as experimental group.According to blood pressure,urine protein,and symptoms of pregnant women,experimental group was divided into GH group(n=35),mild preeclampsia(MPE)group(n=28),and severe preeclampsia(SPE)group(n=22).Additionally,150 normal pregnant women with matched gestational age were randomly selected as control group.Fetal HQ technique was adopted to obtain cardiac morphological and functional indicators of groups,and statistical analysis was conducted.Results There was statistically significant difference in global spherical index(GSI)in each group(P＜0.05).Patients in SPE group had rounder fetal hearts.Bariance analysis was performed on fractional area change(FAC),Tei index,and global longitudinal strain(GLS)for each group of patients.There were statistically significant differences in right ventricular GLS and right ventricular Tei index(P＜0.05).The absolute value of right ventricular GLS in SPE group and MPE group was lower than that in control group,while right ventricular Tei index in SPE group was higher than that in control group.Conclusion Fetal HQ technique provides quick and easy quantitative assessment of fetal heart shape and function.Gestational hypertension not only changes the fetal heart morphology,but also affects the fetal heart function,and the fetal right heart system is more affected than the fetal left heart.