1.Mechanism of Guihuang Formula in Regulating NLRP3 Inflammasome-mediated Pyroptosis in Treatment of Chronic Prostatitis
Qinghe GAO ; Jianhua FU ; Shengjing LIU ; Ziwei ZHAO ; Ming ZHAO ; Boda GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):108-116
ObjectiveTo observe the mechanism of Guihuang formula in regulating the activation of NOD-like receptor protein 3 (NLRP3) inflammasome and inhibiting pyroptosis in the treatment of type Ⅲ prostatitis. Methods(1) In an animal experiment, 50 Sprague Dawley (SD) rats were randomly divided into a blank group, a model group, and low-dose, medium-dose, and high-dose groups of Guihuang formula, with 10 rats in each group. Except for the blank group, the type Ⅲ prostatitis rat model was prepared for the other four groups.After the modeling was successful, the blank group and the model group were given normal saline intragastrically, and the low-dose, medium-dose, and high-dose groups of Guihuang formula were given intragastrically with Guihuang formula (4.9, 9.8, 19.6 g·kg-1). After 30 days of intragastrical administration, samples were taken for detection. Inflammatory cell infiltration in prostate tissue was observed by hematoxylin-eosin (HE) staining, and serum IL-1β and IL-18 levels were measured by enzyme-linked immunosorbent assay (ELISA). Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined by biochemistry. NLRP3 expression in prostate tissue was assessed by immunohistochemistry, and the expression of NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), and gasdermin D (GSDMD) in prostate tissue was measured by Western blot. (2) In a cell experiment, human normal prostate epithelial cells (RWPE-1 cells) were divided into a blank group, a model group, a Guihuang formula group, and an NLRP3 inhibitor group (MCC950 group). Except for the blank group, the other three groups were stimulated by 100 μg·L-1 lipopolysaccharide (LPS) for 4 h and 5 mol·L-1 adenosine triphosphate (ATP) for 30 min to prepare the pyroptosis model. After successful modeling, blank serum was given to the blank group and the model group. 6.25 μg·mL-1 Guihuang formula drug-containing serum was added to the Guihuang formula group, and MCC950 was added to the MCC950 group on the basis of the model group. Propidium iodide (PI) uptake and Caspase-1 expression were detected by flow cytometry, and lactate dehydrogenase (LDH) level in the cell supernatant was measured by biochemistry. Interleukin (IL)-1β and IL-18 levels of the cell supernatant were determined by ELISA, and the expression of NLRP3, Caspase-1, and GSDMD was detected in Western blot. Results(1) For the animal experiment, compared with the blank group, the model group showed significant infiltration of inflammatory cells in prostate tissue, while the low-dose, medium-dose, and high-dose groups of Guihuang formula showed reduced infiltration of acinar inflammatory cells, reduced degree of glandular epithelial degeneration and interstitial edema, and significantly reduced degree of damage. Compared with those in the blank group, the levels of IL-1β and IL-18 in the serum of the model group were significantly increased (P<0.01). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significant decrease in serum IL-1β and IL-18 levels (P<0.01). Compared with that in the blank group, the serum MDA level in the model group significantly increased (P<0.01). Compared with that in the model group, the MDA level in the low-dose, medium-dose, and high-dose groups of Guihuang formula was significantly reduced (P<0.01). Compared with those in the blank group, the levels of SOD and GSH-Px in the serum of the model group significantly decreased (P<0.05). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significantly increase in SOD (P<0.01). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significantly increase in GSH-Px (P<0.05). Immunohistochemistry showed that compared with the blank group, the model group had high expression of NLRP3 molecule in prostate tissue. The expression of NLRP3 in the low-dose, medium-dose, and high-dose groups of Guihuang formula was significantly lower than that in the model group. Compared with those in the blank group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins in the prostate tissue of the model group were significantly increased (P<0.01). Compared with those in the model group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins in the low-dose, medium-dose, and high-dose groups of Guihuang formula were significantly inhibited (P<0.01). (2) For the cell experiment, compared with that in the blank group, the PI uptake rate of RWPE-1 cells in the model group significantly increased (P<0.01). Compared with that in the model group, the PI uptake rate of the Guihuang formula group and the inhibitor group significantly decreased (P<0.01). Compared with that in the blank group, the expression of Caspase-1 in the model group was significantly higher (P<0.01). Compared with that in the model group, the Caspase-1 in the Guihuang formula group and the inhibitor group significantly decreased (P<0.01). Compared with the blank group, the model group showed an increase in LDH release (P<0.01). Compared with the model group, the Guihuang formula group and the inhibitor group showed a significantly decrease in LDH release (P<0.01). Compared with those in the blank group, the levels of IL-1β and IL-18 in the supernatant of the model group were significantly increased (P<0.01). Compared with the model group, the Guihuang formula group and the inhibitor group showed a significantly decrease in the levels of IL-1β and IL-18 (P<0.01). Compared with those in the blank group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins significantly increased in the model group (P<0.01). Compared with those in the model group, the protein expression levels of NLRP3, Caspase-1, and GSDMD were significantly reduced in the Guihuang formula group and inhibitor group (P<0.01). ConclusionGuihuang formula can inhibit the activation of Caspase-1, prevent GSDMD cleavation and lysis, and inhibit cell pyrodeath in the treatment of type Ⅲ prostatitis by inhibiting the activation of NLRP3 inflammasome.
2.Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway
Xincui BAO ; Baosheng ZHAO ; Lingling QIN ; Haiyan WANG ; Jing YANG ; You WANG ; Lijia WU ; Yujin LI ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):100-108
ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease (CKD) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsSeventy specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a control group (n=15) and a modeling group (n=55). Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg-1·d-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group, an irbesartan group (20.25 mg·kg-1·d-1), and Bushen Tongluo Jiangzhuo prescription low-, medium-, and high-dose groups (5.82, 11.64, and 23.28 g·kg-1·d-1, respectively), with 10 rats in each group. Each group was administered an equal volume of physiological saline, the corresponding concentration of irbesartan, or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine (SCr), blood urea nitrogen (BUN), urine albumin-to-creatinine ratio (ACR), 24-hour urinary total protein (24 hUTP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry (IHC) was used to detect the expression of PI3K, Akt, phosphorylated Akt (p-Akt), and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K, p-Akt, Akt, phosphorylated mTOR (p-mTOR), and mTOR in renal tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression levels of PI3K, Akt, and mTOR in renal tissues. ResultsCompared with the model group, rats in the irbesartan group and the low-, medium-, and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr, BUN, ACR, 24 hUTP, IL-1β, IL-6, and TNF-α (P<0.01). AST levels were significantly increased (P<0.01), while no significant difference was observed in ALT levels. Histopathological examination revealed that, compared with the model group, renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated, inflammatory cell infiltration was reduced, and interstitial and glomerular fibrosis was markedly improved in all treatment groups, with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K, Akt, and mTOR were significantly downregulated in the high-dose group (P<0.01). IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group (P<0.01). Western blot analysis further confirmed that the expression levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly reduced in the high-dose group (P<0.01). ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats, reduces collagen deposition in renal tissues, and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway, thereby alleviating renal fibrosis.
3.Mechanism of Bushen Kaixuan Tongluo Prescription in Improving Diabetic Nephropathy Based on cAMP Signaling Pathway
Miao XU ; Baosheng ZHAO ; You WANG ; Yuzhuo CHANG ; Zehao LIU ; Lingling QIN ; Haiyan WANG ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):87-96
ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease (DKD) by regulating the cyclic adenosine monophosphate (cAMP) signaling pathway. MethodsThirty specific pathogen-free (SPF) male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L-1 and urinary albumin-creatinine ratio (ACR) ≥ 30 mg·g-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group: the model group, the low-, medium-, and high-dose Bushen Kaixuan Tongluo prescription groups (administered at doses of 7, 14, 28 g·kg-1·d-1 respectively), and the positive drug irbesartan group (administered at a dose of 20 mg·kg-1·d-1). Additionally, six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations, irbesartan, or an equal volume of pure water, and the intervention lasted for 12 weeks. During the experiment, the general conditions, body weight changes, and renal function indicators of the mice were dynamically monitored. After the intervention, a blood glucose meter was used to measure the fasting blood glucose (FBG) of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine (SCr), blood urea nitrogen (BUN), urinary microalbumin (uALB), ACR, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), leptin (LEP), glycosylated serum protein (GSP), and insulin (INS) in the mice. Renal tissues were collected for hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry (IHC) was used to detect the expressions of protein kinase A (PKA) and cAMP response element-binding protein (CREB) in the mice. Western blot analysis was performed to determine the expression levels of PKA, phosphorylated protein kinase A (p-PKA), CREB, phosphorylated cAMP response element-binding protein (p-CREB), and B-cell lymphoma-2 (Bcl-2) proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of PKA, CREB, and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group, the mice in the model group showed listlessness, decreased activity, and a significant increase in body weight (P<0.01). Biochemical indicators revealed that the levels of BUN, uALB, ACR, AST, ALT, TC, TG, FBG, LEP, GSP, and INS were significantly increased (P<0.01), while SCr showed an increasing trend with no statistically significant difference. Compared with the model group, the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN, uALB, ACR, TC, GSP, and INS were significantly decreased (P<0.05), while SCr, AST, ALT, TG, and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, and deposition of collagen fibers in the renal tubulointerstitium, and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group, the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased (P<0.01), while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group, the expression levels of p-PKA/PKA, p-CREB/CREB, and Bcl-2 in the model group were significantly decreased (P<0.05). Compared with the model group, the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased (P<0.01). Real-time PCR results showed that compared with the blank group, the mRNA expressions of PKA, CREB, and Bcl-2 in the model group were significantly down-regulated (P<0.05). Compared with the model group, the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated (P<0.05). ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice, correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress, thereby protecting renal function.
4.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
5.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
6.Construction of backpack-based field emergency medical rescue equipment system
Chen-xi LU ; Xin ZHAO ; Ming YU ; Shu-tian GAO ; Jing YUAN ; Yu-chen GUO ; Yun-dou WANG
Chinese Medical Equipment Journal 2025;46(10):17-22
Objective To establish a backpack-based field emergency medical rescue equipment system to enhance emergency rescue efficiency.Methods A backpack-based field emergency medical rescue equipment system was preliminarily constructed with the concept of medical treatment in echelons and prolonged field care(PFC)and the method of capability-based equipment need analysis;with the Delphi method 15 experts from relevant fields were invited to execute two rounds of questionnaire consultations,and the final equipment system was determined after the equipment varieties and quantities were revised based on the expert opinions.Results The response rate for the two rounds of expert questionnaire surveys was 100%.The experts'authority coefficients were 0.8734 and 0.87,respectively;Kendall coefficients were 0.232 and 0.345(both P<0.001),indicating statistically significant results.Ultimately,a backpack-based field emer-gency medical rescue equipment system comprising 15 backpacks and 158 individual pieces of equipment was established.Conclusion The established system demonstrates a certain degree of specificity and practicability,providing references for the equipment allocation and utilization of emergency medical rescue teams.[Chinese Medical Equipment Journal,2025,46(10):17-22]
7.Screen of Disulfidptosis-related Colorectal Cancer Diagnostic and Therapeutic Target:Integrated Single-cell and Bulk RNA Sequencing Data
Yang YANG ; Yi-Xuan MA ; Xin-Yue FAN ; Wen-Xue ZHAO ; Yi-Ming QI ; Ning GAO ; Ju-Mei ZHAO ; Juan DU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1529-1540
Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.
8.Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
Run-min MAO ; Hai-xia ZHAO ; Hai-li DUAN ; Zi-hui GAO ; Ya-nan QU ; Guo-qing FU ; Jian-min MAO ; Jian-ming SUN ; Chang-cheng ZHANG
Chinese Pharmacological Bulletin 2025;41(11):2134-2142
Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.
9.Clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma
Ming-yuan WU ; Yun-ke YANG ; Xin-tong GAO ; Zhao-shuo YANG ; Zhen-feng ZHU
Chinese Traditional Patent Medicine 2025;47(3):802-806
AIM To investigate the clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for intervention of RALOX-HAIC regimen,and observation group(46 cases)for intervention of both Cinobufosin Injection and RALOX-HAIC regimen.The changes in short-term effects,survival situation,inflammatory indices(LCN2,NLRP3 inflammasome,NLR,PLR),immune indices(NK cells,CD8+T cells,IL-17,Th17/Treg)and incidence of toxic and side effects were detected.RESULTS Based on mRECIST,the observation group demonstrated higher disease control rate and objective remission rate than the control group(P<0.05),along with lower disease progression(P<0.05).After the treatment,the two groups displayed decreased inflammatory indices,IL-17,Th17/Treg(P<0.05),and increased NK cells,CD8+T cells(P<0.05),especially for the observation group(P<0.05).The observation group exhibited lower incidence of abdominal pain,nausea,vomiting,diarrhea,leukopenia and thrombocytopenia than the control group(P<0.05),and no significant differences in overall survival and incidence of other toxic and side effects were found between the two groups(P>0.05).CONCLUSION For the patients with hepatocellular carcinoma,Cinobufosin Injection combined with RALOX-HAIC regimen can safely and effectively enhance body immune functions,and reduce in vivo immune indices.
10.Relationship between skeletal muscle mass and strength with metabolic syndrome in children
Mengyao CAO ; Wu YAN ; Yanan SHI ; Luting PENG ; Qingqing ZHENG ; Shenghu GAO ; Ming ZHAO ; Li WANG ; Xiaonan LI
Chinese Journal of Pediatrics 2025;63(5):498-504
Objective:To explore the correlation between skeletal muscle mass and strength with metabolic syndrome in children.Methods:This cross-sectional study was conducted involving 383 children aged 10 to 15 years who visited the Department of Child Health Care, Children′s Hospital of Nanjing Medical University from June 2021 to December 2022. Their height, weight, waist circumference, body composition, grip strength and blood pressure were measured. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were calculated. The levels of fasting blood glucose, lipids and insulin were tested. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children were divided into the metabolic syndrome group and the non-metabolic syndrome group. Independent t test or Mann-Whitney U test etc. was used to compare the difference between groups. Spearman correlation analysis and binary Logistic regression were used to investigate the correlation between skeletal muscle mass and strength and metabolic syndrome. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to compare the accuracy of the index of skeletal muscle in predicting metabolic syndrome in children. Results:Among the 383 children, 282 (73.6%) were male, at the age of 11.4 (10.6, 12.5) years. There were 216 children (56.4%) diagnosed with obesity and 90 children (23.5%) diagnosed with metabolic syndrome. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index of the metabolic syndrome group were all lower than those in the non-metabolic syndrome group (all P<0.001). After adjusting for sex and age, relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were all negatively correlated with body mass index ( r=-0.84, -0.38, -0.63), waist circumference ( r=-0.76, -0.36, -0.70), systolic blood pressure ( r=-0.42, -0.21, -0.38), diastolic blood pressure ( r=-0.33, -0.18, -0.24), triglycerides ( r=-0.29, -0.13, -0.23), fasting insulin ( r=-0.28, -0.20, -0.29), and HOMA-IR ( r=-0.26, -0.18, -0.26) (all P<0.05), and positively correlated with high-density lipoprotein cholesterol ( r=0.38, 0.13, 0.31, all P<0.01). After adjusting for sex and age, high relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index all decreased the risks of metabolic syndrome ( OR=0.80, 0.55, 0.90), obesity ( OR=0.53, 0.64, 0.82), hypertension ( OR=0.86, 0.58, 0.92), low high-density lipoprotein cholesterol ( OR=0.83, 0.62, 0.92), hypertriglyceridemia ( OR=0.88, 0.78, 0.96). After adjusting for sex and age, high relative skeletal muscle mass and high grip strength-to-body weight index all decreased the risks of hyperglycemia ( OR=0.93 and 0.95, all P<0.05). ROC curve analysis showed that the relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index all had good predictive accuracy of metabolic syndrome in children (AUC=0.79, 0.71, 0.76), with optimal cutoff values of 40%, 1.2, and 35%, respectively. Conclusions:High relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index are all protective factors for metabolic syndrome in children. Regular measurement of skeletal muscle mass and grip strength can aid in the early identification and prevention of obesity and metabolic syndrome during childhood .


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