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 As a traditional labor-intensive industry, the wooden furniture manufacturing sector has been facing significant occupational health hazards, notably noise exposure. Objective To understand the current status of occupational health management and workplace noise monitoring in the wooden furniture manufacturing industry in Foshan City of Guangzhou Province over the past five years (2020−2024), to clarify the exposure level of occupational noise hazards in this industry, the implementation of prevention and control measures, and their dynamic changing trends, and to provid a reference basis for formulating and optimizing targeted occupational health supervision strategies. Methods By judgment sampling method, 381 wooden furniture manufacturing enterprises in Foshan City from 2020 to 2024 were selected. Through document review, on-site investigation, and on-site testing, the basic information of the enterprise, key indicators of occupational health management (declaration of projects with occupational disease hazards, occupational health training, the setting and effect of occupational disease prevention facilities, the allocation and use of personal protective equipment, occupational health examinations, etc.) and monitoring data of noise intensity in the workplace were systematically collected. Descriptive statistical analysis was adopted to present the characteristics of enterprises and various indicators, and trend tests were used for dynamic changes of occupational health management indicators and noise intensity monitoring results between each year. Results Among the 381 enterprises, small and micro enterprises accounted for 94.0% (358/381), the overall occupational hazard exposure rate of workers was 56.7% (15199/26798), and the noise exposure rate was 45.6% (12221/26798). The report rate of projects with occupational disease hazards was 100%, the occupational health training rate of exposed workers was 69.6%, the setting rate and effectiveness rate of noise prevention facilities were 24.9% and 95.8% respectively, the distribution rate and effective wearing rate of noise protection earplugs/earmuffs were 77.6% and 87.1% respectively, and the rate of occupational health examinations for noise-exposed workers and the abnormal rate were 55.4% and 2.5% respectively. The trend analysis results showed that the rates of occupational health training, setting and effectiveness of noise prevention facilities, distribution and effective wearing of noise protection earplugs/earmuffs, occupational health examinations for noise-exposed workers, and abnormal health examination results all showed an overall upward trend (P values were all<0.05). The proportion of workplace noise intensity greater than 85 dB(A) and the rate of noise exceeding standards at work positions both showed an overall upward trend (P values were both<0.01). Conclusion During the period from 2020 to 2024, the occupational health management in the wooden furniture manufacturing industry in Foshan City has achieved certain positive progress, particularly in areas such as the installation of protective facilities, the use of personal protective equipment, and the implementation of occupational health examinations. However, workplace noise hazards have not been effectively controlled. Moving forward, regulatory efforts must consolidate existing management achievements while strengthening mandatory requirements and support for the technical transformation of high-noise processes and the widespread adoption of noise reduction facilities. This approach is essential to fundamentally curb occupational noise hazards.

ObjectiveTo assess the availability of bronchodilators for treatment of chronic obstructive pulmonary disease (COPD) in community health service centers (CHCs) in Shanghai. MethodsOn the basis of previous research, the questionnaire was updated, and surveys were conducted from April to May 2023 in CHCs in Shanghai, with a focus on the availability of medications for COPD treatment. According to the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug List (2023 Edition), a total of 24 types of bronchodilators for COPD treatment were identified. The availability rates were used to assess the accessibility of specific drugs in CHCs, and the dispensing rates were used to evaluate the variety of these medications in CHCs. ResultsA total of 248 CHCs responded, with a response rate of 100.0%. Among them, a total of 232 CHCs (93.5%) were equipped with bronchodilators. In terms of availability rates, the availability rates for β₂ adrenoreceptor agonists, muscarinic antagonists, combination drugs, and xanthines drugs were 86.3%, 52.0%, 52.4%, and 85.1%, respectively. Regional differences were observed, in that salbutamol/levalbuterol and budesonide-formoterol were less available in suburban CHCs, ipratropium bromide had lower availability in urban CHCs, and aminophylline was more available in suburban CHCs. Regarding the dispensing rates of the 24 types of bronchodilators for COPD treatment, the median of types equipped by CHCs was 5, with a total of 200 CHCs (80.6%) equipped with fewer than 7 types of bronchodilator drugs. ConclusionThe proportion of CHCs in Shanghai equipped with bronchodilators for COPD is relatively high. However, there exist problems such as limited variety of stocked medications, significant differences in the availability of different drugs, and regional imbalances in drug stocking. To improve the standardized diagnosis, treatment, and management of COPD patients, it is recommended to enhance the availability of COPD treatment medications in CHCs.

Psoriasis vulgaris is notoriously difficult to treat and prone to recurrence. Traditional Chinese medicine （TCM）， however， has shown considerable efficacy in mitigating or suppressing such recurrence. The underlying reason lies in the TCM concept of "latent pathogens"， which are prone to be reactivated by external pathogenic factors， thereby triggering relapse. At the early stage of recurrence， manifestations of "latent fire" often appear externally. If treatment is not thorough， the condition may shift into a state of "stalemate between healthy Qi and pathogenic factors"， in which the disease appears on the skin but is rooted in deeper pathological layers， remaining unresolved and accumulating internally. Over time， blood stasis arises from fire， and the fire further congeals due to stasis， leading ultimately to recurrent flare-ups. This aligns with the modern immunological concept of "immunological memory" mediated by tissue-resident memory T cells （T_RM） in the skin， which corroborates the TCM view of "latent fire inducing blood stasis". The interaction between T_RM and keratinocytes （KC） parallels the entanglement of latent fire and latent stasis， both of which are deeply entrenched and difficult to resolve. The core pathogenesis of recurrent psoriasis vulgaris lies in "latent fire causing blood stasis". The hallmark is the deep concealment and persistence of latent fire and stasis， which linger and await an opportunity to reemerge. Based on this understanding， Xijiao Dihuangtang is employed to cool the blood， resolve stasis， and eliminate latent pathogens， and treatment is tailored according to the disease stage through three-phase syndrome differentiation. In the progressive stage， both exterior and interior are treated， with emphasis on clearing latent fire. In the stationary stage， the focus shifts to dispelling latent stasis and simultaneously regulating the Zang-fu organs. In the regressive stage， efforts are made to prevent the retention of latent pathogens and to strengthen healthy Qi. Accordingly， drugs effective in dispersing wind and clearing heat， pungent-moistening and dredging the collaterals， and tonifying deficiency and moistening dryness are often employed to achieve optimal outcomes. The precise mechanisms by which Xijiao Dihuangtang treats recurrent psoriasis vulgaris remain to be fully elucidated. Current research suggests it may intervene in the recurrence process through inhibiting KC proliferation via the PI3K/Akt/mTOR signaling pathway and glycolysis， regulating the Th1/Th2 and Th17/Treg cell balances to restore immune homeostasis， suppressing inflammatory cytokine production to alleviate the inflammatory response， modulating angiogenesis-related factors， such as vascular endothelial growth factor A （VEGF-A） and matrix metalloproteinase-9 （MMP-9）， to control disease progression， and restructuring the gut microbiota to modulate systemic immunity and thereby influence the course of disease recurrence.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

BACKGROUND:Graphene oxide,with its excellent physical and chemical properties and biocompatibility,can promote the differentiation of osteoblasts and inhibit the proliferation of bacteria,which will hopefully improve the success rate of implant restoration.OBJECTIVE:To summarize the research progress of graphene oxide in the field of dental implant restoration.METHODS:The related articles published by CNKI,WanFang Database,ScienceDirect,and PubMed from January 2000 to June 2024 were searched by computer.The keywords were"graphene oxide,dental implantation,biocompatibility,antibacterial mechanism,osteoblasts,mechanical properties,chemical properties"in Chinese and English.By reading the titles and abstracts,we preliminarily screened out the documents irrelevant to the topic of the article.According to the inclusion and exclusion criteria,65 documents were finally included for analysis.RESULTS AND CONCLUSION:Graphene oxide can increase the innate immune protection response of the body through its own antibacterial and drug-loaded antibacterial abilities,thus inhibiting the occurrence and development of periimplant inflammation.Graphene oxide can promote the proliferation and differentiation of bone marrow mesenchymal stem cells,enhance the proliferation of osteoblasts and vascular endothelial cells,inhibit the proliferation of osteoclasts,increase the rate of bone bonding between implants and alveolar bones,and contribute to the formation and stability of bone around implants.Graphene oxide can promote the combination of implant and gingival tissue,and reduce the occurrence of inflammation.Graphene oxide has low toxicity,and its biological safety needs further study.Graphene oxide coating endows the surface of titanium implant with excellent physical and chemical properties,which can greatly reduce the occurrence of complications such as implant fracture and prolong the survival time of implant.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To investigate the predictive value of serum interleukin-6(IL-6)and procalcitonin(PCT)levels on the prognosis of patients with acute respiratory distress syndrome(ARDS).Methods A total of 99 ARDS patients admitted to Lianyungang Hospital affiliated to Xuzhou Medical University from January 2021 to December 2023 were included in the study.According to the Berlin definition,the patients were divided into mild group(n=22),moderate group(n=42)and severe group(n=35)groups.Based on their 28-day outcomes,they were also divided into survival group(n=65)and death group(n=34).The levels of IL-6 and PCT in each group were compared.The predictive value of IL-6 and PCT for the prognosis of ARDS patients was analyzed using receiver operat-ing characteristic(ROC)curve and the area under the curve(AUC).The Kaplan-Meier method was used to plot survival curves for ARDS patients with different levels of IL-6 and PCT.Results Among the three groups with varying severity of ARDS,the severe group had the highest IL-6 and PCT levels,followed by the moderate group,and the mild group had the lowest levels.The differences among the groups were statistically significant(P＜0.05).The levels of IL-6 and PCT in the death group were significantly higher than those in the survival group,and the difference was statistically significant(P＜0.05).The AUC of IL-6 and PCT in predicting the prognosis of ARDS patients were 0.793 and 0.776,with the sensitivity of 79.4％and 94.1％,and the specificity of 70.8％and 61.5％,respective-ly.Kaplan-Meier survival curve analysis showed that when IL-6 was ≥110.700pg/ml and PCT was ≥ 1.700ng/ml,the 28-day sur-vival rate of ARDS patients was significantly lower than that of patients with IL-6＜110.700pg/ml and PCT＜1.700ng/ml(P＜0.001).Conclusion PCT and IL-6 levels have good value in predicting the short-term prognosis of ARDS patients,and can be used as effective indicators for prognosis evaluation in ARDS patients.