1.Renal Protective Mechanism of Danggui Shaoyaosan in db/db Mice Based on RhoA/ROCK/NF-κB Signaling Pathway
Luyu HOU ; Yuanyuan ZHANG ; Wenjing SHI ; Shilong GUO ; Zixuan WANG ; Linlin ZHENG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):30-38
ObjectiveTo investigate whether Danggui Shaoyaosan (DSS) inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway, thereby delaying the progression of diabetic kidney disease (DKD) and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group, and forty 8-week-old db/db mice were randomly divided into the model group, DSS low-dose group (8.39 g·kg-1), DSS medium-dose group (16.77 g·kg-1), DSS high-dose group (33.54 g·kg-1), and irbesartan group (0.025 g·kg-1), with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration, changes in body weight, fasting blood glucose (FBG), and 24 hour urinary protein (24 h UTP) were observed. After 12 consecutive weeks of administration, hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species (ROS) in renal tissue were detected using the dihydroethidium (DHE) method. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were determined. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of RhoA, ROCK1, and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of fibronectin (FN), Collagen Ⅳ(Col Ⅳ), transforming growth factor-β1 (TGF-β1), RhoA, ROCK, and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed significantly increased body weight, FBG, and 24 h UTP levels (P<0.01), elevated serum IL-1β and IL-6 levels, enlarged glomerular volume, diffuse mesangial expansion, increased mesangial matrix, and marked collagen fiber proliferation in renal tissues. SOD activity was decreased, while MDA, ROS, RhoA, ROCK1, and NF-κB p65 mRNA expression levels were increased (P<0.01), and the protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 were also elevated (P<0.01). Compared with the model group, the DSS low-, medium-, and high-dose groups and the irbesartan group showed reductions in body weight, FBG, and 24 h UTP, decreased serum IL-1β and IL-6 levels, varying degrees of improvement in renal histopathology, increased SOD activity, decreased MDA levels, reduced ROS expression, and significantly downregulated RhoA, ROCK1, and NF-κB p65 mRNA expression (P<0.05, P<0.01), as well as reduced protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 (P<0.05, P<0.01). ConclusionDSS can alleviate oxidative stress and inflammation, reduce extracellular matrix deposition, and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway, thereby exerting a therapeutic effect on DKD.
2.Surgical strategies for osteotomy correction of severe lower limb deformities in hypophosphatemic rickets.
Shaofeng JIAO ; Sihe QIN ; Zhenjun WANG ; Yue GUO ; Hongsheng XU ; Zhijie LIU ; Shilong WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(6):701-707
OBJECTIVE:
To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets.
METHODS:
A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients.
RESULTS:
All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%.
CONCLUSION
For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans
;
Male
;
Osteotomy/instrumentation*
;
Female
;
Adult
;
Retrospective Studies
;
Tibia/abnormalities*
;
Adolescent
;
Femur/abnormalities*
;
Middle Aged
;
Fibula/surgery*
;
Rickets, Hypophosphatemic/complications*
;
Young Adult
;
Treatment Outcome
;
External Fixators
;
Bone Plates
;
Lower Extremity Deformities, Congenital/etiology*
3.Segmented Time Study and Optimization Strategy for Clinical Application of Ethos Online Adaptive Radiotherapy.
Dandan ZHANG ; Yuhan KOU ; Shilong ZHU ; Xiaoyu LIU ; Meng NING ; Peichao BAN ; Jinyuan WANG ; Changxin YAN ; Zhongjian JU
Chinese Journal of Medical Instrumentation 2025;49(2):134-140
OBJECTIVE:
To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy.
METHODS:
The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type.
RESULTS:
Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume.
CONCLUSION
The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans
;
Radiotherapy Planning, Computer-Assisted/methods*
;
Neoplasms/radiotherapy*
;
Female
4.A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis.
Haofan WANG ; Yihang HAO ; Wenrui GAI ; Shilong HU ; Wencheng LIU ; Bo MA ; Rongjia SHI ; Yongzhen TAN ; Ting KANG ; Ao HAI ; Yi ZHAO ; Yaling TANG ; Ling YE ; Jin LIU ; Xinhua LIANG ; Bowen KE
Acta Pharmaceutica Sinica B 2025;15(11):5854-5866
Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.
5.BnaNRT1.5s mediates nitrate transporter to regulate nitrogen use efficiency in Brassica napus.
Shilong CHEN ; Lei YAO ; Rumeng WANG ; Jian ZENG ; Jianghe LI ; Shiyao CUI ; Xu WANG ; Haixing SONG ; Zhenhua ZHANG ; Pan GONG
Chinese Journal of Biotechnology 2025;41(7):2954-2965
Improving the nitrogen use efficiency (NUE) of Brassica napus is of significant importance for achieving the national goal of zero growth in chemical fertilizer application and ensuring the green development of the rapeseed industry. This study aims to explore the effects of the nitrate transporter gene BnaNRT1.5s on the nitrogen transport and NUE of B. napus, providing excellent genetic resources for the development of nitrogen-efficient B. napus varieties. The spatiotemporal expression of BnaA05.NRT1.5 as a key nitrogen responsive gene was profiled by qRT-PCR at different growth stages and for different tissue samples of B. napus 'Westar'. Subcellular localization was employed to examine its expression pattern in the cells. Additionally, CRISPR/Cas9 was used to create BnaNRT1.5s knockout lines, which were subjected to hydroponic experiments under high nitrogen (12.0 mmol/L) and low nitrogen (0.3 mmol/L) conditions. After the seedlings were cultivated for 21 days, root and shoot samples were collected for weighing, nitrogen content determination, xylem sap nitrate content assessment, and calculation of total nitrogen and NUE. The B. napus nitrate transporter BnaA05.NRT1.5 was localized to the cell membrane. During the seedling and early bolting stages, BnaA05.NRT1.5 was predominantly expressed in roots, while it was highly expressed in old leaves and mature silique skin during the reproductive stage. Compared with the wild type, the mutant BnaNRT1.5s showed significant increases in the dry weight and total nitrogen of seedlings under both high and low nitrogen conditions. Under low nitrogen conditions, NUE in the roots of BnaNRT1.5s significantly improved. Notably, under both high and low nitrogen conditions, the nitrate content in the shoots of BnaNRT1.5s decreased significantly, while that in the roots increased significantly, resulting in a significantly decreased shoot-to-root nitrate content ratio. BnaNRT1.5s is involved in regulating the transport of nitrate from the roots to the shoots, and its mutation enhances nitrogen absorption and utilization in B. napus seedlings, promoting seedling growth. This study not only provides references for understanding the physiological and molecular mechanisms by which BnaNRT1.5s regulates NUE but also offers valuable genetic resources for improving NUE in B. napus.
Brassica napus/genetics*
;
Anion Transport Proteins/metabolism*
;
Nitrogen/metabolism*
;
Nitrate Transporters
;
Plant Proteins/metabolism*
;
Nitrates/metabolism*
;
Gene Expression Regulation, Plant
;
Biological Transport
6.Analysis of the relationship between serum ATX,Adropin and inflammatory factors and poor prognosis in patients with dilated cardiomyopathy
Meiying WU ; Shilong SUN ; Lizhen WANG
International Journal of Laboratory Medicine 2024;45(15):1793-1798
Objective To investigate the relationship between serum autotaxin(ATX),energy balance re-lated protein(Adropin)and inflammatory factors and poor prognosis in patients with dilated cardiomyopathy(DCM).Methods A total of 105 DCM patients admitted to Qingdao Huangdao District Traditional Chinese Medicine Hospital from June 2017 to February 2020 were selected as the DCM group,and 100 healthy volun-teers who came to the hospital for physical examination during the same period were selected as the control group.The levels of serum ATX,Adropin and inflammatory factors[hypersensitive C-reactive protein(hs-CRP)and interleukin-6(IL-6)]in the two groups were detected,and the correlation between serum ATX,Adropin and inflammatory factors was analyzed by Pearson correlation analysis.Patients in DCM group were divided into good prognosis group and poor prognosis group according to the occurrence of endpoint events during follow-up.Logistic regression was used to analyze the risk factors of poor prognosis in DCM patients,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum ATX and Adropinfor poor prognosis in DCM patients.Results The serum levels of ATX,hs-CRP and IL-6 in DCM group were higher than those in control group,and the level of Adropin was lower than that in control group,with statistical significance(P<0.05).Pearson correlation analysis showed that serum ATX level was posi-tively correlated with hs-CRP and IL-6,and serum Adropin level was negatively correlated with hs-CRP and IL-6(P<0.05).New York Heart Association(NYHA)functional classification m to Ⅳ and serum ATX lev-el in the poor prognosis group were higher than those in the good prognosis group,the heart failure duration and left ventricular end-diastolic diameter were higher than those in the good prognosis group,the left ventric-ular ejection fraction(LVEF)and serum Adropin levels were lower than those in the good prognosis group,the difference was statistically significant(P<0.05).Logistic regression model analysis showed that NYHA functional classification Ⅲ to Ⅳ and high ATX were risk factors for poor prognosis in DCM patients,and high Adropin and high LVEF were protective factors for poor prognosis in DCM patients(P<0.05).ROC curve a-nalysis showed that the area under the curve(AUC)of serum ATX and Adropin in predicting poor prognosis of DCM patients was 0.841 and 0.793,respectively,and the AUC of combined prediction of poor prognosis of DCM patients was greater than that of single prediction.Conclusion Serum ATX is abnormally elevated and serum Adropin is abnormally decreased in DCM patients,both of which are closely related to inflammatory factors.Detection of serum ATX and Adropin levels can provide reference for prognosis assessment of DCM patients.
7.Correlation of serum 25 (OH) D3 and IGF-1 levels with glycolipid metabolism and predictive value of retinopathy in elderly patients with type 2 diabetes mellitus
Yanling ZHANG ; Jingjin ZHANG ; Shilong WANG ; Zongying XU ; Juan TAN ; Aihua TONG ; Fangjiang XU
Chinese Journal of Endocrine Surgery 2024;18(3):346-351
Objective:To investigate the correlation between 25-hydroxyvitamin D3 (25 (OH) D3), insulin-like growth factor 1 (IGF-1) and glycolipid metabolism in patients with diabetes 2 mellitus (T2DM), as well as their predictive value in retinopathy.Methods:A total of 120 T2DM patients admitted to Linyi Central Hospital of Shandong Province from Oct. 2020 to Oct.r 2023 were selected as the study objects (defined as the study group). Another 120 healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. Serum 25 (OH) D3, IGF-1, fasting blood glucose (FBG), 2 h plasma glucose (2 hPG) ) and lipid levels (triglycerides) were compared between the two groups. The levels of TG, total cholesterol (TC) and serum 25 (OH) D3 and IGF-1 were analyzed by Pearson correlation analysis. At the same time, the patients in the study group were divided into diabetic group with retinopathy (DR Group, 40 cases) and non-retinopathy group (NDR group, 80 cases) according to the status of retinopathy. Multivariate analysis was used to analyze the risk factors affecting the occurrence of retinopathy in T2DM patients, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of serum 25 (OH) D3 and IGF-1 levels in the occurrence of retinopathy in T2DM patients.Results:The level of serum 25 (OH) D3 was (36.15±4.25) nmol/L in the study group, lower than that in the control group (51.24±5.32) nmol/L ( P<0.05), and the level of IGF-1 was (30.26±4.52) mg/L was in the study group, higher than that in the control group ( P<0.05). The levels of FBG, 2 hPG, TG and TC in the study group were (8.67±2.52) mmol/L, (11.36±2.43) mmol/L, (2.05±0.72) mmol/L, (5.05±1.54) mmol/L respectively, higher than those in the control group [ (5.02±0.42) mmol/L, (6.32±0.54) mmol/L, (1.21±0.32) mmol/L, (3.42±0.68) mmol/L] ( P<0.05). Pearson correlation analysis showed that serum 25 (OH) D3 levels were negatively correlated with FBG, 2 hPG, TG and TC levels in T2DM patients ( r=-0.762, -0.782, -0.736, -0.721, P<0.05). Serum IGF-1 levels were positively correlated with the levels of FBG, 2 hPG, TG and TC in T2DM patients ( r=0.741, 0.756, 0.715, 0.698, P<0.05). Family history of diabetes in DR group, FBG, 2 hPG, TG, TC, IGF-1 levels was 35.00%, (9.31±2.49) mmol/L, (12.52±2.34) mmol/L, (2.76±0.61) mmol/L, (5.92±1.42) mmol/L, (37.89±4.41) mg/L respectively, higher than those in NDR group [16.25%, (8.35±2.15) mmol/L, (10.78±1.75) mmol/L, (1.69±0.52) mmol/L, (4.62±1.31) mmol/L, (26.45±4.06) mg/L] ( P<0.05). 25 (OH) D3 in DR group was (30.21±3.51) nmol/L, lower than that in NDR group (39.12±3.85) nmol/L ( P<0.05). Logistic regression analysis showed that family history of diabetes mellitus, duration of diabetes mellitus, 25 (OH) D3, IGF-1, FBG, 2hPG, TG and TC levels were all risk factors for the occurrence of retinopathy in elderly T2DM patients ( P<0.05). ROC curve analysis showed that AUC and sensitivity of 25 (OH) D3 and IGF-1 combined to predict retinopathy in elderly T2DM patients were 0.854 and 92.50%, respectively, higher than that of 25 (OH) D3 and IGF-1 alone ( P<0.05) . Conclusion:Serum 25 (OH) D3 and IGF-1 levels are abnormally expressed in elderly patients with T2DM, and there is a close relationship between glucose and lipid metabolism in elderly patients with T2DM, and the combined detection of these indicators has a higher predictive value for the occurrence of DR In elderly patients with T2DM.
8.Research progress on the involvement of macrophages in myocardial ischemia reperfusion injury mediated by NF-κB signaling pathway
Shilong LI ; He WANG ; Yingjie CAO
Chinese Journal of Comparative Medicine 2024;34(4):139-146
Myocardial ischemia reperfusion injury(MIRI)has become one of the most serious complications affecting the clinical outcome of patients with cardiovascular diseases.The immune inflammatory response of macrophages is closely related to the occurrence and development of MIRI.Many studies have shown that the NF-κB signaling pathway can participate in MIRI regulation by influencing the polarization and inflammatory state of macrophages,pyrodeath,infiltration and other functions,and is a potential target for MIRI therapy.Therefore,this article will review the research progress of NF-κB signaling pathway between macrophage function and MIRI regulation.
9.A clinical study on the treatment of refractory tennis elbow with arc-edge needle therapy based on zaodian theory
Xuejian MA ; Dongzhe ZHANG ; Chaoyang NIU ; Shuaigang DU ; Wuyang WANG ; Shilong CHENG ; Yingyuan XIAO ; Xuechang WANG
The Journal of Practical Medicine 2024;40(15):2161-2165
Objective To explore the clinical efficacy of arc-edge needle therapy based on Zaodian theory in the treatment of refractory tennis elbow.Methods 64 patients with refractory tennis elbow were collected and randomly divided into a control group and an observation group using a random number table method.Among them,32 cases in the control group were treated with local pain point injection.32 patients in the observation group were treated with arc-edge needle therapy once a week,with two treatments per group.The Number rating scale(NRS)Mayo,elbow joint performance score(MEPS)and Disabilities of the arm,shoulder and hand(DASH)score were recorded and compared between the two groups before treatment and at 1,2,4 and 24 weeks of follow-up after treatment,disease efficacy score(WDES)at 24 weeks of follow-up.Results During the treat-ment process,neither group of patients experienced serious adverse reactions.At each stage after treatment,two groups of NRS MEPS,DASH,and WDES at 24 weeks of follow-up all improved compared to before treatment.After one week of treatment,there was no statistically significant difference in NRS scores between the two groups(P>0.05).At follow-up visits at weeks 2,4,and 24,the NRS scores in the observation group were lower than those in the control group.After 1,2,4,and 24 weeks of follow-up after treatment,the DASH score was lower in the observation group than in the control group,and the MEPS score was higher in the observation group than in the control group,with statistically significant differences(P<0.05).After 24 weeks of treatment,the WDES of the observation group was better than that of the control group,and the difference was statistically significant(P<0.05).Conclusion Local pain point injection and arc-edge Zaodian release can alleviate pain and improve elbow joint function in the early stage of refractory tennis elbow.However,the long-term effect of local pain point injection treatment is not good,and the treatment effect of the observation group gradually improves.
10.Research progress in the pathogenesis, diagnosis and treatment for posttraumatic acute diffuse brain swelling
Shilong FU ; Liang XIAN ; Shousen WANG
Chinese Journal of Trauma 2023;39(3):283-288
Posttraumatic acute diffuse brain swelling (PADBS) is a relatively common severe traumatic brain injury (TBI). Since it can lead to acute intracranial hypertension in a short time, the illness can be acute and critical, with a high disability and fatality rate. The pathogenesis of PADBS is still unclear, with the current theory consisting of acute cerebral vasodilation, cerebral edema and intracranial venous circulation disorder. For PADBS, there is still a lack of unified diagnostic criteria, and the indications and timing of decompression craniectomy remain controversial. The authors review the research progress in the pathogenesis, diagnosis and treatment of PADBS, hoping to provide some new ideas for its treatment.

Result Analysis
Print
Save
E-mail