1.Comparison of bioelectrical impedance analysis and dual energy X ray absorptiometry in measuring body composition among Tibetan children and adolescents
Chinese Journal of School Health 2026;47(4):569-573
Objective:
To compare the consistency between bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) in measuring body composition among Tibetan children and adolescents and to explore the applicability of BIA in plateau region, so as to provide scientific and convenient body composition measurement support among children and adolescents.
Methods:
From May to June, 2022, a total of 344 Tibetan children and adolescents aged 6-17 years were selected from Golmud Municipal National Middle School and Changjiangyuan Nationality Primary School in Qinghai Province by cluster sampling method, and their fat mass, fat mass percentage and lean mass were measured by DXA and BIA. The consistency and correlation between the two methods were assessed by using the Wilcoxon rank-sum test, Spearman correlation analysis, intraclass correlation coefficient (ICC), and Bland-Altman analysis.
Results:
DXA measured fat mass and fat mass percentage were significantly higher than those obtained by BIA (6-12 years old: Z =9.91, 11.28; 13-17 years old: Z =9.02, 10.21), while lean mass and lean mass percentage were significantly lower than BIA results (6-12 years old: Z =-11.60, -11.30; 13-17 years old: Z =-10.77, -10.36) (all P < 0.05 ). The two methods showed strong correlations in fat mass and lean mass (all r >0.80, all ICC >0.90), but exhibited poor agreement in fat mass percentage and lean mass percentage (6-12 years old: Lin s CCC =0.64, 0.41; 13-17 years old: Lin s CCC = 0.79 , 0.35). Bland-Altman analysis showed that the difference between the two methods was negatively correlated with the average value in FM%(6-12 years old: r =-0.75, 13-17 years old: r =-0.79, both P <0.01).
Conclusion
BIA and DXA show high consistency in measuring body fat mass and lean body mass in Tibetan children and adolescents, although some bias is still present in certain individuals.
2.Dual-Center Clinical Study on Detection of Intraoperative Air Leak During Pulmonary Resection Using Nebulized Indocyanine Green
Zhenfan WANG ; Songjing ZHAO ; Ruiheng JIANG ; Zhuoer CUI ; Yingtai CHEN ; Jian ZHOU ; Kezhong CHEN ; Yun LI
Medical Journal of Peking Union Medical College Hospital 2026;17(3):646-651
To evaluate the clinical value of nebulized indocyanine green(ICG) combined with near-infrared fluorescence imaging for intraoperative detection of air leaks during pulmonary resection. This was a two-center randomized controlled trial enrolling patients undergoing thoracoscopic pulmonary resection. After enrollment, patients were randomly divided into an experimental group and a control group. The experimental group received nebulized ICG and fluorescence imaging in addition to the conventional water immersion test, while the control group underwent the water immersion test alone. Intraoperative air leak detection and postoperative air leak incidence were compared between the two groups. Multivariable logistic regression analysis was performed to assess the association between ICG nebulization intervention and postoperative air leaks after adjusting for confounding factors including age, sex, smoking history, history of respiratory disease, surgical procedure, and study center. A total of 181 patients were enrolled(90 in the experimental group, 91 in the control group). The experimental group showed significantly higher intraoperative air leak detection rate(37.8% Nebulized ICG combined with near-infrared fluorescence imaging significantly improves intraoperative detection of air leaks, reduces the incidence of postoperative air leaks, and shortens chest tube duration. This technique is convenient, safe, and holds important clinical value for application.
3.Umbrella decision-making model for diagnosis and treatment of elderly lung cancer patients: Construction and practice
Lunxu LIU ; Jian ZHOU ; Xiang DING ; Nan CHEN ; Jianxin XUE ; Xuelei MA ; Ye WANG ; Weiya WANG ; Liqing PENG ; Xin YOU ; Minggang SU ; Xu CHENG ; Jiao WANG ; Ning GE ; Deying KANG ; Yuchen HUANG ; Jinghan WANG ; Yu TONG ; Yaoxi ZHANG ; Jirong YUE ; Hu LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):833-839
With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.
4.Identification of Alumen and Ammonium alum Based on XRD, FTIR, TG-DTA Combined with Chemometrics
Bin WANG ; Jingwei ZHOU ; Huangsheng ZHANG ; Jian FENG ; Hanxi LI ; Guorong MEI ; Jiaquan JIANG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):178-186
ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FTIR) and thermogravimetric-differential thermal analysis(TG-DTA), and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant, Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum, and the XRD characteristic profiles of Alumen were established, and then the common peaks were screened. Based on hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection(VIP) value>1. FTIR characteristic profiles of Alumen were established, and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile, the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA, and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However, by comparing the PDF standard cards of XRD, 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles, 10 characteristic peaks were confirmed, corresponding to diffraction angles of 14.560°, 24.316°, 12.620°, 32.122°, 17.898°, 34.642°, 27.496°, 46.048°, 40.697° and 21.973°. In the FTIR profiles, 4 wavenumber ranges(399.193-403.050, 1 186.010-1 471.420, 1 801.190-2 620.790, 3 612.020-3 997.710 cm-1) and 12 characteristic wavenumbers(1 428.994, 1 430.922, 1 432.851, 1 434.779, 1 436.708, 1 438.636, 1 440.565, 1 442.493, 1 444.422, 1 446.350, 1 448.279, 1 450.207 cm-1) were identified. In the TG-DTA profiles, there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD, FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum, and combined with the discriminant features selected through chemometrics, the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.
5.Mechanism of Modified Shengjiangsan in Improving Diabetic Kidney Disease by Activating Mitochondrial Autophagy Based on PINK1/Parkin Signaling Pathway
Jiaxin LI ; Liya ZHOU ; Yishuo ZHANG ; Ziqiang CHEN ; Yijun HOU ; Jian SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):121-128
ObjectiveTo investigate the mechanism by which modified Shengjiangsan (MSJS) improves diabetic kidney disease (DKD) by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). After successful modeling, the rats were randomly divided into six groups: a normal control group, a model group, low-, medium-, and high-dose MSJS groups (7.7, 15.4, 30.8 g·kg-1, respectively), and an irbesartan group (0.384 g·kg-1). Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose, body weight, and kidney weight were recorded. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to determine urinary microalbumin (mALB), and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Histopathological changes in renal tissues were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy (TEM). The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta (LC3B) and cytochrome c oxidase subunit Ⅳ (COX Ⅳ). ResultsCompared with the normal control group, the model group exhibited significant increases in renal index, blood glucose, and 24-hour urinary microalbumin (24 h mALB) (P<0.05, P<0.01). The levels of serum SCr and BUN were significantly elevated (P<0.01), and the serum levels of TNF-α, IL-1β, and IL-6 were markedly upregulated (P<0.01). Histopathological examination revealed glomerular hypertrophy, mesangial expansion and increased deposition, podocyte foot process flattening and fusion, a decreased number of autophagosomes accompanied by mitochondrial swelling, vacuolar degeneration of renal tubular epithelial cells, and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B, PTEN-induced putative kinase 1 (PINK1), and E3 ubiquitin-protein ligase (Parkin) were significantly decreased (P<0.05, P<0.01), while expression of the selective autophagy adaptor protein p62 was significantly increased (P<0.01). Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group, the MSJS treatment groups and the irbesartan group showed significant reductions in renal index, blood glucose, and 24 h mALB (P<0.05, P<0.01). The serum SCr and BUN levels decreased significantly (P<0.05) and TNF-α, IL-1β, and IL-6 levels were significantly downregulated (P<0.05, P<0.01). Histopathological damage was alleviated, including reduced glomerular hypertrophy, decreased mesangial deposition, and attenuated podocyte foot process fusion. The number of autophagosomes increased, and mitochondrial swelling was improved. The expression levels of LC3B, PINK1, and Parkin in renal tissues were significantly upregulated, whereas p62 expression was significantly downregulated (P<0.05, P<0.01) in MSJS groups. Immunofluorescence signal intensity was enhanced, and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.
6.Identification of Alumen and Ammonium alum Based on XRD, FTIR, TG-DTA Combined with Chemometrics
Bin WANG ; Jingwei ZHOU ; Huangsheng ZHANG ; Jian FENG ; Hanxi LI ; Guorong MEI ; Jiaquan JIANG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):178-186
ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FTIR) and thermogravimetric-differential thermal analysis(TG-DTA), and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant, Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum, and the XRD characteristic profiles of Alumen were established, and then the common peaks were screened. Based on hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection(VIP) value>1. FTIR characteristic profiles of Alumen were established, and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile, the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA, and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However, by comparing the PDF standard cards of XRD, 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles, 10 characteristic peaks were confirmed, corresponding to diffraction angles of 14.560°, 24.316°, 12.620°, 32.122°, 17.898°, 34.642°, 27.496°, 46.048°, 40.697° and 21.973°. In the FTIR profiles, 4 wavenumber ranges(399.193-403.050, 1 186.010-1 471.420, 1 801.190-2 620.790, 3 612.020-3 997.710 cm-1) and 12 characteristic wavenumbers(1 428.994, 1 430.922, 1 432.851, 1 434.779, 1 436.708, 1 438.636, 1 440.565, 1 442.493, 1 444.422, 1 446.350, 1 448.279, 1 450.207 cm-1) were identified. In the TG-DTA profiles, there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD, FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum, and combined with the discriminant features selected through chemometrics, the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.
7.Mechanism of Modified Shengjiangsan in Improving Diabetic Kidney Disease by Activating Mitochondrial Autophagy Based on PINK1/Parkin Signaling Pathway
Jiaxin LI ; Liya ZHOU ; Yishuo ZHANG ; Ziqiang CHEN ; Yijun HOU ; Jian SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):121-128
ObjectiveTo investigate the mechanism by which modified Shengjiangsan (MSJS) improves diabetic kidney disease (DKD) by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). After successful modeling, the rats were randomly divided into six groups: a normal control group, a model group, low-, medium-, and high-dose MSJS groups (7.7, 15.4, 30.8 g·kg-1, respectively), and an irbesartan group (0.384 g·kg-1). Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose, body weight, and kidney weight were recorded. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to determine urinary microalbumin (mALB), and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Histopathological changes in renal tissues were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy (TEM). The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta (LC3B) and cytochrome c oxidase subunit Ⅳ (COX Ⅳ). ResultsCompared with the normal control group, the model group exhibited significant increases in renal index, blood glucose, and 24-hour urinary microalbumin (24 h mALB) (P<0.05, P<0.01). The levels of serum SCr and BUN were significantly elevated (P<0.01), and the serum levels of TNF-α, IL-1β, and IL-6 were markedly upregulated (P<0.01). Histopathological examination revealed glomerular hypertrophy, mesangial expansion and increased deposition, podocyte foot process flattening and fusion, a decreased number of autophagosomes accompanied by mitochondrial swelling, vacuolar degeneration of renal tubular epithelial cells, and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B, PTEN-induced putative kinase 1 (PINK1), and E3 ubiquitin-protein ligase (Parkin) were significantly decreased (P<0.05, P<0.01), while expression of the selective autophagy adaptor protein p62 was significantly increased (P<0.01). Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group, the MSJS treatment groups and the irbesartan group showed significant reductions in renal index, blood glucose, and 24 h mALB (P<0.05, P<0.01). The serum SCr and BUN levels decreased significantly (P<0.05) and TNF-α, IL-1β, and IL-6 levels were significantly downregulated (P<0.05, P<0.01). Histopathological damage was alleviated, including reduced glomerular hypertrophy, decreased mesangial deposition, and attenuated podocyte foot process fusion. The number of autophagosomes increased, and mitochondrial swelling was improved. The expression levels of LC3B, PINK1, and Parkin in renal tissues were significantly upregulated, whereas p62 expression was significantly downregulated (P<0.05, P<0.01) in MSJS groups. Immunofluorescence signal intensity was enhanced, and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.
8.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
9.Initial exploration of non-invasive diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps via nasal brush sampling.
Zhipeng CHEN ; Jian GUO ; Wenyi CHEN ; Yuan MENG ; Daxiao LI ; Junhui ZHOU ; Zhongjue WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(7):617-623
Objective:To identify the key epithelial cell characteristics that can accurately diagnose eosinophilic chronic sinusitis with nasal polyps(ECRSwNP) through nasal brush sampling and comparing with the pathological results of nasal polyp tissue sections. Methods:Ninety-one patients underwent surgery in the Ophthalmology and ENT Department of the Second People's Hospital of Longgang District, Shenzhen, from January 2022 to July 2024 were selected. The cohort comprised 58 males and 33 females(mean age: 41.4 years; range: 12.0-71.0). The clinical characteristics of the patients, including gender, age, disease duration, smoking and drinking history, asthma history, subjective symptoms, sinus CT, and nasal endoscopy scores, were recorded. Nasal brush sampling of nasal polyps and inferior turbinate mucosa was performed before surgery to obtain cytological specimens, and nasal polyp tissues were collected during surgery. The demographic and clinical characteristics of patients with eosinophilic and non-eosinophilic nasal polyps were compared, as well as the relationship between nasal brush cytology of nasal polyps and inferior turbinate and nasal polyp histopathology. Statistical analysis was performed using SPSS 23.0 software. Results:Among the 91 patients, no significant differences were observed between ECRSwNP and NECRSwNP patients in terms of age, gender, smoking status, alcohol consumption, and disease duration. The nasal brush cell population in ECRSwNP patients was more likely to contain eosinophils(P<0.001) and less likely to contain lymphocytes and plasma cells(P<0.001). Additionally, the ciliated cells in ECRSwNP patients exhibited larger widths(P=0.036), shorter cilium lengths(P<0.001), and more disordered arrangements(P<0.001) compared to NECRSwNP patients. In nasal brush cells from the inferior turbinate, ECRSwNP patients also showed shorter cilium lengths(P<0.001) and shorter cilia(P=0.024) compared to NECRSwNP patients. Conclusion:There are significant differences in obtaining epithelial cytological information from nasal polyps or inferior turbinates through nasal brush sampling between ECRSwNP and NECRSwNP patients.
Humans
;
Male
;
Female
;
Middle Aged
;
Adult
;
Nasal Polyps/complications*
;
Sinusitis/complications*
;
Aged
;
Chronic Disease
;
Adolescent
;
Nasal Mucosa/pathology*
;
Young Adult
;
Rhinitis/complications*
;
Eosinophilia/pathology*
;
Child
;
Eosinophils/pathology*
;
Rhinosinusitis
10.Design, synthesis and pharmacological evaluation of 1,2,3,4-tetrahydrobenzofuro2,3-cpyridine derivatives as p21-activated kinase 4 inhibitors for treatment of pancreatic cancer.
Yang LI ; Yan FANG ; Xiaoyu CHEN ; Linjiang TONG ; Fang FENG ; Qianqian ZHOU ; Shulun CHEN ; Jian DING ; Hua XIE ; Ao ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):438-466
The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC50 values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.


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