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.

Objective: To analyze the epidemiological characteristics of leptospirosis in Jinhua City, Zhejiang Province, from 2007 to 2024, so as to provide a basis for improving the prevention and control strategies of leptospirosis. Methods: Data pertaining to leptospirosis cases in Jinhua City from 2007 to 2024 were collected through the Monitoring and Reporting Management System of the Chinese Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the distribution characteristics of leptospirosis in terms of time, region, population, interval from the onset of the disease to diagnosis and the outbreak of the epidemic. Results: A total of 81 cases of leptospirosis were reported in Jinhua City from 2007 to 2024, with an average annual reported incidence of 0.08/100 000. The peak incidence occurred from August to September, with 57 cases accounting for 70.37%. Leptospirosis cases were reported in 9 counties (cities, districts) in Jinhua City. Pan'an County reported the most cases, with 52 cases accounting for 64.20%. There were 54 male cases and 27 female cases, with a male-to-female ratio of 2∶1. The majority of cases were aged over 40 years, with 73 cases accounting for 90.12%. The average reported incidence of leptospirosis showed an upward trend with the increase of age (P<0.05), and the highest incidence of leptospirosis was at the 60-<80 age group (0.21/100 000). The majority of patients were farmers, with 77 cases accounting for 95.06%. The median interval from onset to diagnosis was 4.00 (interquartile range, 6.00) days. There were significant differences in the interval from onset to diagnosis among cases in Dongyang City compared with Pan'an County, Wuyi County, and Wucheng District, between Pan'an County and Jindong District, Wucheng District, and between Wuyi County and Wucheng District (all P<0.05). In 2007, one outbreak of leptospirosis was reported, which occurred in Jiuhe Township, Pan'an County, with 36 reported cases. Conclusions The reported incidence of leptospirosis in Jinhua City from 2007 to 2024 is generally low. The high-incidence period is from August to September, and Pan'an County is the high-incidence area. Males over 40 years and farmers are the key populations for prevention and control. It is recommended to strengthen epidemic surveillance and health education for high-risk populations.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications. In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner. However, existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes, thereby hindering a comprehensive understanding of their interactions. Here, we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria, respectively. Using a key oral pathobiont, Fusobacterium nucleatum, as the primary test bed, we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes. Compared to conventional models, this system enhanced bacterial invasion, elevated intracellular bacterial loads, and elicited more robust host pro-inflammatory responses, including increased secretion of CXCL10, IL-6, and IL-8. In addition, the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens. Finally, we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont, Porphyromonas gingivalis. These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics, offering a physiologically relevant approach to advance oral and systemic health research.
Coculture Techniques/methods* ; Humans ; Fusobacterium nucleatum/physiology* ; Gingiva/microbiology* ; Keratinocytes/microbiology* ; Host Microbial Interactions ; Mouth/microbiology* ; Host-Pathogen Interactions ; Epithelial Cells/microbiology* ; Cells, Cultured ; Porphyromonas gingivalis

Objective:To investigate anti-inflammatory effects of celastrol as pulp capping agent on experimental pulpitis in rats and to explore its mechanism.Methods:Rat model of experimental pulpitis was established by lipopolysaccharide(LPS).A total of 28 rats were randomly divided into 4 groups(model group,calcium hydroxide group,celastrol group,drug mixture group).After 5 days,the rats were sacrificed and the maxillary and molar specimens were obtained.Pathological changes of pulp tissue were observed by HE staining,as well as the inflammation level was evaluated by a modified histological scoring system.Relative mRNA expression levels of TNF-α and IL-β in dental pulp were detected by qRT-PCR.Western blot was used to assess phosphorylation level of NF-κB p65 in dental pulp.Results:Histological scores of celastrol group and drug mixture group were significantly lower than those of model group and calcium hydroxide group(P<0.01),while there was no significant statistical differences between celastrol group and drug mixture group(P>0.05).Compared with model group,levels of TNF-α and IL-1β mRNA in pulp tissue of calcium hydroxide group,celastrol group and drug mixture group were decreased(P<0.05).Western blot showed that treatment of celastrol and mixed drugs could considerably reduce phosphorylation level of NF-κB p65 in rat pulp tissue.Conclusion:Celastrol can relieve experimental pulpitis in rats,and its mechanism may be related to the inhibition of NF-κB p65 activation and reduce the expressions of TNF-α and IL-1β.

Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length＜5 mm with concentric or moderately eccentric stenosis;type B,lesion length＜10 mm with severely eccentric stenosis;type C,lesion length＞10 mm or arterial angulation＞90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis＜50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as＞50%stenosis within the stent or within5mm of its edges,or＞20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P＜0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

Objective:To explore the effectiveness of digital management platform led by outpatient specialist nurses among patients with type 2 diabetes in outpatient settings.Methods:From March 2024 to March 2025, adult patients with type 2 diabetes who visited the Endocrinology Clinic at Peking Union Medical College Hospital were selected using convenience sampling. Patients were randomly assigned to the control group and intervention group using the random number table method. Patients in control group received routine education on type 2 diabetes during their clinic visits after enrollment. Intervention group was managed by nurses through a digital management platform, establishing long-term connections with patients. Based on the platform, nurses regularly provided patients with knowledge updates, promptly responded to patient inquiries, reviewed daily dietary records, monitored blood glucose data, conducted weekly telephone follow-ups, and scheduled regular clinic visits to precisely intervene in patients' lifestyles. The glycated hemoglobin (HbA1c) and self-management behavior scores were compared between two groups of patients before and after three months of intervention.Results:A total of 46 patients were enrolled and completed the 3-month follow-up, including 25 in control group and 21 in intervention group. There were no statistically significant differences in HbA1c or self-management behavior scores between the two groups of patients before intervention ( P>0.05). At three months of intervention, the HbA1c reduction in intervention group was greater than that in control group, with a statistically significant difference ( P<0.05). There was no statistically significant difference in Summary of Diabetes Self-Care Activities Scale scores between the two groups ( P>0.05). The difference in changes in diabetic foot self-screening scores between intervention group and control group was statistically significant ( P<0.05) . Conclusions:Specialist nurse-led precision health care management utilizing digital platforms can improve HbA1c and enhance self-management behaviors for diabetic foot in patients with type 2 diabetes, which is expected to be promoted and applied in the outpatient management of diabetes patients.