1.Mechanisms of Shenmai Injection in Improving Cisplatin Resistance in Non-small Cell Lung Cancer
Hanyu DONG ; Chun WANG ; Chunying LIU ; Wenjun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):131-142
ObjectiveTo investigate whether Shenmai injection (SMI) improves cisplatin resistance in non-small cell lung cancer (NSCLC) by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups: Blank group, cisplatin group (23.3 μmol·L-1 cisplatin), SMI group (20 g·L-1 SMI), cisplatin combined with SMI group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI), cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin), and cisplatin combined with SMI and Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin). Network pharmacology, transcriptomics and metabolomics, Cell Counting Kit-8 (CCK-8) assay, transmission electron microscopy (TEM), colorimetric assays, and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability, lipid droplet formation, lipid metabolite levels, mitochondrial function, lipid peroxidation, glutathione (GSH) content, total and ferrous iron content, and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells, affecting tumor cell lipid metabolism via autophagy, ferroptosis, and glycerophospholipid metabolism pathways. Compared with the cisplatin group, the cisplatin combined with SMI group showed significantly decreased cell viability (P<0.01), increased lipid droplet accumulation (P<0.01), and reduced mitochondrial maximal respiration, basal respiration, mitochondrial membrane potential, GSH content, total iron, and ferrous iron (all P<0.01). Mitochondrial reactive oxygen species (ROS) was significantly elevated(P<0.01), and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 (SLC7A11) and p62 (P<0.05,P<0.01) and upregulation of ferritin heavy chain (FTH) and microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ) (P<0.05,P<0.01). Compared with the cisplatin combined with SMI group, addition of Ferrostatin-1 significantly increased cell viability (P<0.05), decreased mitochondrial ROS levels (P<0.05), alleviated mitochondrial shrinkage, and reduced lipid peroxidation. Conversely, addition of Erastin further decreased cell viability (P<0.01). ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress, which may trigger ferroptosis through upregulation of lipophagy.
2.Study on Infrared Thermal Characteristics of Meridian Points for Diminished Ovarian Reserve
Hanyu LIU ; Haomin SUN ; Siqi CHEN
Journal of Zhejiang Chinese Medical University 2025;49(6):674-683
[Objective]To discover the changes in the thermal characteristics of meridian points in patients with diminished ovarian reserve(DOR)under pathological conditions,and to filter possible optimal acupoints for diagnosis of DOR.[Methods]There was a cross-sectional survey with 50 DOR patients and 50 healthy participants included,to detect the infrared thermal characteristics of certain acupoints,by observing the skin temperature and regional local temperature of 27 certain acupoints that were used to diagnose and treat DOR.The relative temperature was the acupoint's temperature minus regional local temperature.Calculate the relative temperature of acupoints and compare the difference between two groups.Logistic regression analysis of acupoints that showed significant difference were used to examine whether DOR related acupoint temperature was the risk of DOR in women.Prediction model for increased DOR risk was constructed and evaluated by using the receiver operating characteristic curve(ROC)and the area under curve(AUC).Using Spearman's test to analyze the correlation between the temperature of DOR-related and modified Kupperman Index(KI).[Results]Comparing with control group,the relative temperature of Zhongwan(CV12),Guanyuan(CV4),Qixue(KI13),right Siman(KI14)and right Shangliao(BL31)showed a significant decrease in DOR patients(P<0.05).Right Shangliao(BL31)was significantly negatively correlated with KI(P<0.05).According to the results of binary logistic regression,the relative temperatures of Zhongwan(CV12),right Siman(KI14)and right Shangliao(BL31)were closely bound up with DOR risk(P<0.05).The ROC curve was constructed basing on the temperature of the above three acupoints and the AUC of the prediction model was 0.775.[Conclusion]The acupoints related to DOR exhibit specific thermal radiation changes,demonstrating potential predictive value as an auxiliary diagnostic tool for DOR risk.
3.A survey of natural radionuclide contents in agricultural soils in Hexi area, Gansu province
Fang WANG ; Yanjun WANG ; Hanyu ZHANG ; Yun WANG ; Jialong WU ; Xiaoyun LIU ; Wei SUN ; Qin CHEN
Chinese Journal of Radiological Medicine and Protection 2025;45(3):211-215
Objective:To investigate the contents of natural radionuclides in agricultural soils in some of Gansu Hexi area to accumulate the relevant basic data.Methods:A stratified sampling method was used to collect 146 soil samples in the area. ORTEC P-type HPGE gamma spectrometry system was used to measure radionuclides. The measurement data were collated and analyzed.Results:The activity concentrations measured were 232Th 18.94-108.39 Bq/kg, 226Ra 14.37-79.20 Bq/kg and 40K 440.03-1 358.18 Bq/kg, in turn with the mean values of (68.22±16.32), (47.90±11.12) and (763.90±133.93) Bq/kg, respectively. The difference in activity concentrations of 232Th, 226Ra and 40K in agricultural soils in different areas was statistically significant( H=50.87, 45.14, 40.28, P<0.05). Conclusions:The study on the activity concentrations of natural radionuclides in agricultural soils provides basic information for the transfer of radionuclides to crops, which needs further investigation, monitoring and analysis.
4.Three-dimensional CT reconstruction analysis of correlation between anatomical variations of anterior ethmoidal artery and anterior skull base
Xing YUAN ; Rong LIAN ; Guozheng ZHANG ; Bo PANG ; Hanyu ZHAO ; Jixiang CHANG ; Yue LIU ; Wenfa YU
Journal of Clinical Medicine in Practice 2025;29(8):12-16
Objective To investigate the correlation between the anterior ethmoidal artery(AEA)and anatomical variations of the anterior cranial base,and to analyze the predictive factors for AEA suspension.Methods Sinus CT imaging data of 159 patients undergoing endoscopic sinus sur-gery(ESS)were retrospectively analyzed.Mimics 21.0 software was utilized for three-dimensional reconstruction,measuring parameters of AEA and anterior cranial base anatomy and performing classi-fication.Pearson and Spearman correlation analyses were used to evaluate the correlations among vari-ous anatomical parameters and their classifications.Multivariate binary logistic regression analysis was performed to screen for independentpredictive factors of AEA suspension.Results The rates of AEA suspension differed significantly across different Keros classifications(P<0.001),with an increase rate as the Keros classification level increased(P<0.001).The transverse diameter,height and vol-ume of supraorbital ethmoid cells(SOEC),olfactory fossa depth,lateral lamella of the cribriform plate(LLCP)length and frontal sinus pneumatization classification grade were positively correlated with the distance from AEA to the cranial base(P<0.05).Multivariate binary Logistic regression analysis showed that the presence of SOEC(OR=4.178,95%CI,2.517 to 6.935,P<0.001),in-creased olfactory fossa depth(OR=1.433,95%CI,1.197 to 1.715,P<0.001),and higher frontal sinus pneumatization classification grade(OR=1.621,95%CI,1.121 to 2.345,P=0.01)were independent predictive factors for AEA suspension.Conclusion Detailed preoperative CT imaging assessment,especially the analysis of SOEC,olfactory fossa depth and frontal sinus pneumatization classification,aids in accurately assessing the anatomical position of AEA,thereby effectively reduc-ing the risk of AEA injury,and improving the safety and success rate of surgery.
5.Research progress on the clinical application and mechanism of com-monly used traditional Chinese medicine in the treatment of breast cancer
Shanshan LI ; Dandan WEI ; Hanyu KANG ; Xiaopeng LIU ; Shuxun YAN ; Shiqing JIANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):977-983
Breast cancer is a common clinical gy-necological tumor.According to the 2022 global cancer data statistics,breast cancer ranks second in terms of incidence among newly diagnosed cancer cases worldwide.Modern medicine often adopts surgical operation,chemotherapy,and other meth-ods,which have certain efficacy but also many problems such as high drug resistance rates and sig-nificant adverse reactions.Chinese patent medi-cines exhibit extensive anticancer effects.The study found that Shenyi Capsule,Pingxiao Capsule,and Zhenqi Fuzheng Granules were widely used in the treatment of breast cancer,exerting therapeu-tic effects on breast cancer by inhibiting cell prolif-eration,invasion,and metastasis,suppressing an-giogenesis,reversing cellular drug resistance,and inhibiting precancerous lesions.Meanwhile,the oral administration of Chinese patent medicines in combination with other traditional Chinese medi-cine(TCM)compounds,TCM decoctions,or mod-ern medical treatments can improve patients' quali-ty of life and reduce adverse reactions.Currently,there are numerous studies on the treatment of breast cancer with Chinese patent medicines,but a systematic summary is lacking.Therefore,this study conducted a systematic review of the mecha-nisms of action and clinical applications of Chinese patent medicines as adjuvant therapy for breast cancer,aiming to provide guidance for clinical medi-cation.
6.The predictive factors and the short-term outcome of extubation in the operating room after non-ECMO-assisted single lung transplantation in adult patients with interstitial lung diseases
Yanran ZHOU ; Mengyang LIU ; Hanyu YANG ; Hui LIU ; Lan LAN ; Yaoliang ZHANG ; Guilin PENG ; Chao YANG ; Xin XU
Chinese Journal of Organ Transplantation 2025;46(4):292-299
Objective:To explore the predictive factors for extubation in the operating room after single lung transplantation without the assistance of extracorporeal membrane oxygenation (ECMO) in adult patients with end-stage interstitial lung disease (ILD), as well as their short-term (1-year postoperative) prognosis.Methods:A retrospective analysis was conducted on the clinical data of 78 adult ILD recipients who underwent single lung transplantation without ECMO assistance at the First Affiliated Hospital of Guangzhou Medical University from June 2018 to June 2023. Based on whether extubation was completed in the operating room (OR), patients were divided into the OR group (19 cases) and ICU group (59 cases). Baseline characteristics of donors and recipients, as well as intraoperative events, were compared between the two groups. Univariate logistic regression analysis was used to identify potential predictors, and variables with P<0.2 were included in multivariate logistic regression to determine independent predictors for OR extubation. Receiver operating characteristic (ROC) curves were plotted to evaluate predictive performance. The Kaplan-Meier method was used to analyze survival, and short-term prognosis between groups was compared. Results:The rate of OR extubation after single lung transplantation in ILD recipients was 24%(19/78). Compared with the ICU group, the OR group had shorter operation times, lower fluid volumes, reduced transfusions of red blood cells and plasma, less intraoperative bleeding, and lower lactate levels 15 minutes after pulmonary artery reperfusion (all P<0.05). Univariate logistic regression analysis identified the following factors as significantly associated with OR extubation: recipient age ( P=0.100), operative time ( P=0.001), fluid infusion volume ( P=0.005), red blood cell transfusion volume ( P=0.037), plasma transfusion volume ( P=0.039), blood loss ( P=0.004), oxygenation index at 15 minutes after reperfusion ( P=0.174), and blood lactate at 15 minutes after reperfusion ( P=0.041). Multivariate analysis revealed that intraoperative blood loss was an independent predictor of OR extubation ( OR=0.993, 95% CI: 0.986 - 0.999, P=0.026). ROC curve analysis showed that blood loss had an area under the curve (AUC) of 0.822 in predicting OR extubation, with a sensitivity of 64.4% and specificity of 89.5%. Postoperatively, patients in the OR group had significantly shorter durations of mechanical ventilation [0 vs 5 (3,11) days, P<0.001], ICU stay [7(4,8) vs 9(6,20) days, P=0.012], and overall postoperative hospitalization [19 (15,23) vs 25 (19,39) days, P=0.015]. Within one year after surgery, 2 patients (11%) in the OR group and 19 patients (32%) in the ICU group had died, but the difference in 1-year survival rates between the two groups was not statistically significant. Conclusions:Intraoperative blood loss is an independent predictor of extubation in the operating room. Early extubation in non-ECMO-assisted single lung transplantation for ILD patients is associated with improved short-term outcomes.
7.Fer-1 Alleviates Diabetic Nephropathy Injury by Inhibiting Ferroptosis Through HSF-1/HO-1 Pathway
Yu WANG ; Hanyu WANG ; Liu YANG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(3):305-311
Objective To elucidate the mechanistic role of ferrostatin-1(Fer-1)in the pathogenesis of diabetic nephropathy(DN).Methods Twenty spontaneous diabetic mice and ten negative control mice were used for in vivo experiments.The for-mer were randomly divided into a model group and a Fer-1 treatment group,with the treatment group receiving intraperitoneal injections of Fer-1(1 mg/kg).Levels of BUN,Scr,glucose,microalbuminuria,GSH,and iron were measured in the mice.Renal histopathological staining was performed to observe renal morphology.Western blot and immunohistochemistry were used to detect the expression of ferroptosis marker proteins,heat shock factor 1(HSF-1),and heme oxygenase-1(HO-1)in renal tis-sues.Human renal cortical proximal tubular epithelial cells(HK-2)were cultured and divided into three groups during in vitro experiments:control group,high glucose group(30 mmol/L),and Fer-1 treatment group(1μmol/L).Levels of GSH,MDA,4-HNE,and iron content were measured.Immunofluorescence experiment was used to assess the level of reactive oxygen species(ROS).Western blot was performed to detect the expressions of ferroptosis marker proteins,kidney injury molecule-1,neutro-phil gelatinase-associated lipocalin,HO-1,and HSF-1 in HK-2 cells.Results In the model group,renal pathological changes,in-cluding glomerular hypertrophy,mesangial matrix expansion,glycogen accumulation,and fibrosis,were observed.Compared with the control group,levels of BUN,Scr,glucose,and urinary microalbumin were increased,GSH content was decreased,and iron level was elevated in the model group(all P<0.05).The expression of HSF-1 protein in the kidneys of the model group was lower than that in the control group,while HO-1 protein expression was higher.The Fer-1 treatment group exhibited the oppo-site trend.(both P<0.05).GSH expression was decreased,and iron content,MDA,and 4-HNE levels were increased in the high glucose group(all P<0.05).Immunofluorescence result revealed that,compared with the control group,ROS level was higher in the high glucose group(all P<0.05).Additionally,the high glucose group showed increased expressions of KIM-1,NGAL,and HO-1,along with reduced HSF-1 expression,whereas the Fer-1 treatment group exhibited the opposite trend.(all P<0.05).Conclusion Both in vivo and in vitro experiments have demonstrated that ferroptosis plays a significant role in the de-velopment and progression of DN.Fer-1 may alleviate DN injury by upregulating ferroptosis through the HSF-1/HO-1 signaling pathway.
8.Exploration on the Effects of"Three Methods and Three Acupoints"on Motor Function in Sciatic Nerve Injury Rats Based on Skeletal Muscle α-Actin
Jiayue LIU ; Yingqi ZHANG ; Tianyuan YU ; Hanyu ZHANG ; Jiawei SUN ; Jinping CHEN ; Zhenjie YANG ; Chula SA ; Runlong ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):99-104
Objective To observe the effects of tuina of"three methods and three acupoints"on skeletal muscle α-actin,myostatin(MSTN)and atrophy gene 1(Atrogin1)expression of sciatic nerve injury(SNI)rats;To explore the mechanism of tuina therapy on motor dysfunction.Methods Male SD rats were randomly divided into blank group,sham-operation group,model group and tuina group,with 9 rats in each group.SNI model was established by clamp method in rats of the model group and tuina group.The sciatic nerve was exposed without clamping in rats of the sham-operation group,the blank group was not intervened.7 days after the operation,the intelligent tuina manipulation simulator was used to simulate the point method,dial method and knead method,which were applied to the"Yinmen"(BL37),"Chengshan"(BL57)and"Yanglingquan"(GB34)of rats in the tuina group,once a day,for 20 times.The rats in the sham-operation group and the model group were only grasped and restrained.Rats in the blank group did not receive any intervention.The hind limb muscle strength were evaluated by inclined plate test before modeling,after 10 interventions and 20 interventions.After the intervention,the rats were euthanized.The expressions of α-actin in gastrocnemius muscle tissue were detected by immunofluorescence staining,the expressions of MSTN,Atrogin1 mRNA and protein in gastrocnemius muscle tissue were detected by RT-PCR and Western blot.Results Compared with the blank group and sham-operation group,the model group showed a decrease in hind limb muscle strength(P<0.01),a significant decrease in α-actin expression in gastrocnemius muscle tissue(P<0.01),and a significant increase in MSTN,Atrogen1 mRNA and protein expression(P<0.05,P<0.01).Compared with the model group,the hind limb muscle strength in tuina group significantly increased(P<0.01),the expressions of α-actin significantly increased(P<0.01),and the expressions of MSTN,Atrogin1 mRNA and protein significantly decreased(P<0.05,P<0.01).Conclusion"Three methods and three acupoints"tuina can improve hind limb muscle strength and restore motor function of SNI rats,which is related to the down-regulation of MSTN and Atrogin1 as well as increasing the expression of α-actin in gastrocnemius muscles.
9.Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats
Hanyu Zhang ; Yingqi Zhang ; Hourong Wang ; Jiayue Liu ; Jiawei Sun ; Jinping Chen ; Zhifeng Liu ; Tianyuan Yu ; Jian Shu
Journal of Traditional Chinese Medical Sciences 2025;2025(1):125-134
Objective:
To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI).
Methods:
Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF.
Results:
Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001).
Conclusion
TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.
10.Prometive effect of knockdown of KIF3B gene on autophagy in mouse embryonic palatal mesenchymal cells by inhibiting Shh signaling pathway
Zhongzheng LIU ; Shubo LIAN ; Wenxuan FENG ; Xin WEN ; Hanyu LIU ; Wei HE
Journal of Jilin University(Medicine Edition) 2025;51(6):1445-1451
Objective:To discuss the effect of knock down of gene of kinesin family member 3B(KIF3B),an important component of primary cilia(PC)of in mouse embryonic palatal mesenchymal on the autophagy level of cells(mEPMCs)cells,and to clarify its mechanism.Methods:The mEPMCs from gestational day 14.5 C57BL/6J mice cultured in vitro were collected and divided into control group(administered normal saline),empty lentivirus transfected cell group(sh-NC group)(administered lentivirus transfection),KIF3B knockdown group(sh-KIF3B group)(administered KIF3B gene knockdown),and KIF3B knockdown plus Smoothened receptor agonist(SAG)group(sh-KIF3B+SAG group)(administered KIF3B gene knockdown followed by SAG addition),based on whether the KIF3B gene was knocked down and whether the SAG was used to activate the sonic hedgehog(Shh)signaling pathway and its downstream coreceptor Smo,with 5 rats in each group.Transmission electron microscope was used to observe the morphology and the number of autophagosomes/autolysosomes in the mEPMCs in various groups;Western blotting method was used to detect the expression levels of autophagy-related proteins Beclin-1 and p62,and the Shh signaling pathway proteins Shh and Smo in the mEPMCs in various groups.Results:The transmission electron microscope observation results showed that compared with control group,the number of autophagosomes/autolysosomes in sh-KIF3B group was significantly increased(P<0.05);compared with sh-KIF3B group,the number of autophagosomes/autolysosomes in the mEPMCs in sh-KIF3B+SAG group was significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the Beclin-1 protein expression level in the mEPMCs in sh-KIF3B group was significantly increased(P<0.05),and the KIF3B,p62,Shh,and Smo protein expression levels were significantly decreased(P<0.01);compared with sh-KIF3B group,the Shh,Smo,and p62 protein expression levels in the mEPMCs in sh-KIF3B+SAG group were significantly increased(P<0.01),and the Beclin-1 protein expression level was significantly decreased(P<0.01).Conclusion:Knockdown of KIF3B gene can promote autophagy of the mEPMCs,and the mechanism may be related to its inhibition of the Shh signaling pathway.


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