OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

ObjectiveTo explore the possible action mechanism of Qingshi Anti-itch Ointment （青石止痒软膏， QAO） in the treatment of psoriasis. MethodsForty mice were randomly divided into four groups， blank group， model group， calcipotriol group and QAO group， with 10 mice in each group. Except for the blank group， psoriasis was induced by applying imiquimod cream to the dorsal skin. After modeling for 6 hours daily， the calcipotriol group and QAO group were treated with 0.5 g of calcipotriol ointment or 0.5 g of QAO， respectively， applied to the treated dorsal skin. The blank group and the model group received no treatment. The skin lesions were observed， and the psoriasis area and severity index （PASI） score was assessed every other day. After 7 days， Hematoxylin and Eosin （HE） staining was performed on dorsal skin tissue to observe pathological changes. The levels of interleukin 1β （IL-1β） and interleukin 18 （IL-18） were determined by enzym-linked immunosorbent assay （ELISA）. The protein levels of Caspase-1，Pro-Caspase-1， gasdermin D （GSDMD） and gasdermin-D-N （GSDMD-N） were detected by Western Blot （WB）. The protein levels of GSDMD were observed by immunohistochemistry. ResultsCompared with the blank group， the model group mice showed redness， erythema， and white scales on their skin， with histological observations indicating epidermal thickening， elongated spines， and infiltration of inflammatory cells. The PASI scores of the skin tissue on days 1， 3， 5， and 7 were elevated； the IOD and AOD values of GSDMD protein increased； the protein levels of Caspase-1， Pro-Caspase-1，GSDMD， GSDMD-N， and IL-1β and IL-18 were significantly elevated （P＜0.05 or P＜0.01）. Compared with the model group， the QAO group and calcipotriol group showed lighter skin lesions； the PASI scores on day 5 and day 7 in the QAO group， and on day 3， 5， and 7 in the calcipotriol group， were reduced； the IOD and AOD values of GSDMD protein， and the protein level of Caspase-1， GSDMD， and GSDMD-N， as well as level of IL-18 and IL-1β decreased in both groups； in the calcipotriol group， Pro-Caspase-1 protein level also decreased （P＜0.05 or P＜0.01）. Compared with the calcipotriol group， the QAO group showed slightly redder skin， more obvious thickening of the stratum corneum， and less capillary dilation； the PASI scores on day 3 and day 7 increased， while the score on day 5 was reduced； the protein level of Pro-Caspase-1， GSDMD， GSDMD-N， and the level of IL-18 and IL-1β were increased in the QAO group （P＜0.05）. ConclusionQAO can effectively relieve psoriasis dermatitis in mice. Its potential mechanism may be related to the regulation of the Caspase-1/GSDMD protein pathway， down-regulation of IL-18 and IL-1β levels， and alleviation of pyroptosis.

Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.