OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Objective:To compare the prognostic impact of different extents of resection among patients with molecularly defined glioma subtypes.Methods:This retrospective cohort study included 1191 glioma patients who underwent surgical treatment at Beijing Tiantan Hospital, Capital Medical University, between January 2011 and January 2021. The cohort comprised 692 males and 499 females, with an age of (44.5±11.9) years (range: 18 to 75 years). Tumors were classified according to the 2021 WHO Classification of Tumors of the Central Nervous System (5th edition), and the extent of resection was assessed using postoperative MRI. Kaplan-Meier survival analyses and log-rank tests were used to evaluate the effects of resection extent on progression-free survival (PFS) and overall survival (OS) within each molecular subtype. Cox proportional hazards models were applied to identify independent prognostic factors for PFS and OS. Follow-up was completed in January 2024.Results:Among the 1 191 patients, 291 (24.43%) had isocitrate dehydrogenase( IDH)-mutant, 1p/19q-codeleted oligodendroglioma (OG), 338 (28.37%) had IDH-mutant astrocytoma, and 562 (47.19%) had IDH-wild-type glioblastoma (GBM). Patients with IDH-mutant, 1p/19q-codeleted OG had the best prognosis, with median PFS and OS not reached. In IDH-wild type GBM, the median PFS and OS were 12.0 and 24.0 months, respectively; in IDH-mutant astrocytoma, the median PFS and OS were 61.0 and 102.0 months. Differences in PFS and OS among the three groups were statistically significant ( P<0.01). In patients with IDH-wild type GBM, supratotal resection yielded better PFS and OS than gross total resection ( P<0.05). In IDH-mutant astrocytoma, PFS and OS did not differ between supratotal and gross total resection ( P>0.05), while gross total resection was superior to subtotal resection ( P<0.05). In IDH-mutant, 1p/19q-codeleted OG, PFS and OS did not differ significantly across resection categories ( P>0.05). Multivariate analyses identified age, Karnofsky Performance Status, extent of resection, tumor grade, and O 6-methylguanine-DNA methyltransferase promoter methylation status as independent predictors of both PFS and OS ( P<0.05). Conclusions:For IDH-wild type GBM, maximal efforts should be made to achieve supratotal resection. For IDH-mutant astrocytoma, maximal safe resection is recommended with preservation of neurological function. For IDH-mutant, 1p/19q-codeleted oligodendroglioma, a relatively conservative approach may be appropriate to protect neurological function.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Background With China's socio-economic development, the dietary structure of Chinese residents has gradually shifted from a traditional Eastern pattern characterized by high carbohydrate intake to a relatively high-fat Western dietary model, alongside a growing burden of chronic diseases. However, dietary changes may vary across different occupational groups. Objective To analyze the long-term trends in dietary energy and three major macronutrient intake among various occupational groups aged 18-59 years in nine provinces of China from 1989 to 2018, providing a scientific basis for developing occupation-specific dietary intervention strategies. Methods Based on 11 waves of data (1989–2018) from the China Health and Nutrition Survey (CHNS), 57458 employed individuals aged 18-59 years were selected as observation subjects after applying inclusion and exclusion criteria. Joinpoint regression was used to analyze temporal trends by calculating the annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals. The analysis covered the energy supply ratio from the three major macronutrients and the proportion of the participants within the acceptable macronutrient distribution ranges (AMDR) for the total occupational population and specific occupational group. Results From 1989 to 2018, the dietary structure of the occupational population in the nine provinces gradually Westernized. The carbohydrate energy supply ratio showed a decreasing trend (AAPC=−0.77%, 95%CI: −1.00%, −0.55%, P<0.05), while the fat energy supply ratio increased (AAPC=1.42%, 95%CI: 1.07%, 1.77%, P<0.05). The protein energy supply ratio remained largely unchanged (AAPC=−0.19%, 95%CI: −0.08%, 0.46%, P>0.05), and the total energy intake declined (AAPC=−0.62%, 95%CI: −0.94%, −0.30%, P<0.05). Among the occupational groups studied, white-collar workers were the first to show characteristics of dietary Westernization. Using the AMDR as the criterion, their average fat energy supply ratio first exceeded the AMDR upper limit (30%) in 1993, and their average carbohydrate energy supply ratio first fell below the AMDR lower limit (50%) in 2006, both time points being earlier than other occupational groups. Agricultural workers lagged in this transition (their average fat energy supply ratio first reached ≥30% in 2011), but their rate of increase in the fat energy supply ratio was the fastest among all occupational groups (AAPC=1.59%, 95%CI: 0.90%, 2.30%, P<0.05; P for trend comparison between groups<0.05). The other three occupational groups (blue-collar workers, service workers, and others) generally fell between these two extremes. Taking the fat energy supply ratio as an example, their AAPCs of increase were 1.02% (95%CI: 0.73%, 1.32%, P<0.05) for blue-collar workers, 0.85% (95%CI: 0.61%, 1.09%, P<0.05) for service workers, and 0.88% (95%CI: 0.58%, 1.17%, P<0.05) for others. Conclusion From 1989 to 2018, the macronutrient structure of the occupational population aged 18-59 years in nine China provinces is gradually Westernized. The energy supply ratios of carbohydrates and proteins primarily face issues of potential inadequacy, while the fat energy supply ratio is excessively high. Furthermore, the patterns of change vary among different occupational groups. It is recommended to propose personalized dietary advice tailored to specific occupations.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective: To identify research priorities on physical and mental comorbidity among children and adolescents in Zhejiang Province, so as to provide a theoretical base for improving their physical and mental health. Methods: In May 2025, 77 experts in the fields of health and education from 11 cities in Zhejiang Province were selected by convenient sampling method to participate in the first round of expert consultation. In June, 2025, snowball sampling was used to expand to 194 experts for the second round of consultation, and it was convenient to select 21 students from primary schools to high schools in Zhejiang Province and 29 parents to empower the evaluation criteria. It applied the Child Health and Nutrition Research Initiative (CHNRI) method in a structured process, which encompassed the definition of the research field, generation of research ideas, scoring, and quantitative ranking of priorities. Research ideas were evaluated against 6 predefined criteria: effectiveness, safety, answerability, feasibility, sustainability, and scientific significance. Results: After 2 rounds of structured consultations, 81 research ideas on physical and mental comorbidity among children and adolescents were established and classified into 7 subthemes: epidemiological characteristics and influencing factors, optimization of primary service systems and policies, comprehensive intervention strategies for physical and mental comorbidity, biological mechanisms and clinical research, the impact of education and environment on physical and mental health, special populations and social support, and digital and technology driven disease prevention and intervention. The top 10 research priorities primarily centered on the subdomain of "epidemiological characteristics and influencing factors" (5 items). The top 3 research priorities were "the association between outdoor activity duration and the incidence of common diseases (including mental disorders) among children and adolescents" "the impact of outdoor activity duration on the physical and mental health of adolescents" "comprehensive intervention strategies for myopia, obesity, and their comorbidities among children and adolescents". Conclusion The framework of priority issues in the field of psychosomatic comorbidity of children and adolescents in Zhejiang Province based on CHNRI method provides a reference for optimizing the allocation of provincial research resources.

Objective:To compare the prognostic impact of different extents of resection among patients with molecularly defined glioma subtypes.Methods:This retrospective cohort study included 1191 glioma patients who underwent surgical treatment at Beijing Tiantan Hospital, Capital Medical University, between January 2011 and January 2021. The cohort comprised 692 males and 499 females, with an age of (44.5±11.9) years (range: 18 to 75 years). Tumors were classified according to the 2021 WHO Classification of Tumors of the Central Nervous System (5th edition), and the extent of resection was assessed using postoperative MRI. Kaplan-Meier survival analyses and log-rank tests were used to evaluate the effects of resection extent on progression-free survival (PFS) and overall survival (OS) within each molecular subtype. Cox proportional hazards models were applied to identify independent prognostic factors for PFS and OS. Follow-up was completed in January 2024.Results:Among the 1 191 patients, 291 (24.43%) had isocitrate dehydrogenase( IDH)-mutant, 1p/19q-codeleted oligodendroglioma (OG), 338 (28.37%) had IDH-mutant astrocytoma, and 562 (47.19%) had IDH-wild-type glioblastoma (GBM). Patients with IDH-mutant, 1p/19q-codeleted OG had the best prognosis, with median PFS and OS not reached. In IDH-wild type GBM, the median PFS and OS were 12.0 and 24.0 months, respectively; in IDH-mutant astrocytoma, the median PFS and OS were 61.0 and 102.0 months. Differences in PFS and OS among the three groups were statistically significant ( P<0.01). In patients with IDH-wild type GBM, supratotal resection yielded better PFS and OS than gross total resection ( P<0.05). In IDH-mutant astrocytoma, PFS and OS did not differ between supratotal and gross total resection ( P>0.05), while gross total resection was superior to subtotal resection ( P<0.05). In IDH-mutant, 1p/19q-codeleted OG, PFS and OS did not differ significantly across resection categories ( P>0.05). Multivariate analyses identified age, Karnofsky Performance Status, extent of resection, tumor grade, and O 6-methylguanine-DNA methyltransferase promoter methylation status as independent predictors of both PFS and OS ( P<0.05). Conclusions:For IDH-wild type GBM, maximal efforts should be made to achieve supratotal resection. For IDH-mutant astrocytoma, maximal safe resection is recommended with preservation of neurological function. For IDH-mutant, 1p/19q-codeleted oligodendroglioma, a relatively conservative approach may be appropriate to protect neurological function.

Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm² in 2020 to 3 894.45 hm² in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm² in 2020 to a peak in 2023 (172.04 hm²), followed by a reduction to 132.36 hm² in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm² in 2020 to a peak in 2022 (78.43 hm²), followed by a reduction to 40.21 hm² in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m² in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m² in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m² in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ² = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ² = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ² = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ² = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ² = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m²] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m²] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.

ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid （NA） and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes. MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe （NA-P） and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8（CCK-8）. The potency of NA and NA-P was evaluated in the safe concentration range， and the effects of 0-100 μmol·L^-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-23 （IL-23）， and interleukin-17A （IL-17A） inflammatory factors were detected by enzyme-linked immunosorbent assay （ELISA）， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the effects of NA on the mRNA expression of keratin 16 （K16） in HaCaT cells， S100 calcium-binding protein A9 （S100A9）， S100 calcium-binding protein A7 （S100A7）， IL-6， IL-17A， and chemokine 1 （CXCL1）. In vitro fluorescence labeling and competition experiments using NA-P were performed， and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry （Pull-down/LC-MS/MS） were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting （Pull down-WB）， cellular heat transfer analysis combined with protein immunoblot （CETSA-WB） experiments， and molecular docking. Finally， Real-time PCR was utilized to detect the effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the mRNA expression of IL-1β， nucleotide-binding oligomeric structural domain-like receptor protein 3 （NLRP3）， apoptosis-associated speckled-like protein （ASC）， and cysteine protease-1 （Caspase-1） in HaCaT cells. Protein immunoblot （Western blot） was used to detect the effects of phosphorylated p65 （p-p65）， p65， phosphorylated human nuclear factor-κB inhibitory protein α （p-IκBα）， human nuclear factor κB inhibitory protein α （IκBα）， and heat shock protein 90 （HSP90） expression. ResultsIn the 200 μmol·L^-1 safe concentration range， HaCaT cell proliferation， increased expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors， and increased mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L^-1 NA and NA-P groups was inhibited， and the expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors was decreased in the NA-L， NA-M， NA-H， and NA-P-H groups. The mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 was decreased （P<0.05）. High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L^-1 NA competing with 100 μmol·L^-1 NA-P. Compared with that in the blank group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1， as well as the expression of p-p65/p65， p-IκBα/IκBα， and HSP90 protein， were increased in HaCaT cells in the M5 group （P<0.05）. Compared with that in the M5 group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1 of cells in the NA-L group， the NA-M group， the NA-H group， and the NA-P-H group was decreased （P<0.05）. p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups （P<0.05）， and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein， and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1， HSP90B1， and HSP90AB1 all resulted in highly stable binding. ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.

ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid （NA） and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes. MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe （NA-P） and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8（CCK-8）. The potency of NA and NA-P was evaluated in the safe concentration range， and the effects of 0-100 μmol·L^-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-23 （IL-23）， and interleukin-17A （IL-17A） inflammatory factors were detected by enzyme-linked immunosorbent assay （ELISA）， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the effects of NA on the mRNA expression of keratin 16 （K16） in HaCaT cells， S100 calcium-binding protein A9 （S100A9）， S100 calcium-binding protein A7 （S100A7）， IL-6， IL-17A， and chemokine 1 （CXCL1）. In vitro fluorescence labeling and competition experiments using NA-P were performed， and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry （Pull-down/LC-MS/MS） were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting （Pull down-WB）， cellular heat transfer analysis combined with protein immunoblot （CETSA-WB） experiments， and molecular docking. Finally， Real-time PCR was utilized to detect the effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the mRNA expression of IL-1β， nucleotide-binding oligomeric structural domain-like receptor protein 3 （NLRP3）， apoptosis-associated speckled-like protein （ASC）， and cysteine protease-1 （Caspase-1） in HaCaT cells. Protein immunoblot （Western blot） was used to detect the effects of phosphorylated p65 （p-p65）， p65， phosphorylated human nuclear factor-κB inhibitory protein α （p-IκBα）， human nuclear factor κB inhibitory protein α （IκBα）， and heat shock protein 90 （HSP90） expression. ResultsIn the 200 μmol·L^-1 safe concentration range， HaCaT cell proliferation， increased expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors， and increased mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L^-1 NA and NA-P groups was inhibited， and the expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors was decreased in the NA-L， NA-M， NA-H， and NA-P-H groups. The mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 was decreased （P<0.05）. High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L^-1 NA competing with 100 μmol·L^-1 NA-P. Compared with that in the blank group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1， as well as the expression of p-p65/p65， p-IκBα/IκBα， and HSP90 protein， were increased in HaCaT cells in the M5 group （P<0.05）. Compared with that in the M5 group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1 of cells in the NA-L group， the NA-M group， the NA-H group， and the NA-P-H group was decreased （P<0.05）. p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups （P<0.05）， and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein， and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1， HSP90B1， and HSP90AB1 all resulted in highly stable binding. ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.