1.The effects and mechanisms of silica on alveolar epithelial cell apoptosis
Yali LAN ; Wenyao SU ; Zhiming HU ; Ping WANG ; Bizhu ZHANG ; Na ZHAO
China Occupational Medicine 2025;52(1):10-16
Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.
2.A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response
Qing SHAO ; Ningning ZHANG ; Xianjun PAN ; Wenqi ZHOU ; Yali WANG ; Xiaoliang CHEN ; Jing WU ; Xiaohua ZENG
Cancer Research and Treatment 2025;57(1):126-139
Purpose:
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods:
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results:
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.
3.Optimal regimen screening of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome.
Yuqiang SONG ; Yuanbo FU ; Sanfeng SUN ; Yali WEN ; Yinxia LIU ; Jie SUN ; Xin DU ; Xueting ZHANG ; Linbo SHEN ; Baijie LI ; Han YU ; Qingdai LI
Chinese Acupuncture & Moxibustion 2025;45(2):242-248
OBJECTIVE:
To screen the optimal regimen of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome (OSAHS), so as to provide the evidences for clinical decision-making.
METHODS:
From 7 databases in Chinese and English i.e. the Full-Text Database of China Journal Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), VIP Information Chinese Journal Service Platform (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Web of Science (WOS) and Cochrane Library, randomized controlled trial (RCT) articals of OSAHS treated with acupuncture and moxibustion were searched. The quality of evidence was evaluated with the modified Jadad scale, the evaluation index was established and the optimal regimen of acupuncture and moxibustion for OSAHS was screened by multi-index decision analysis.
RESULTS:
A total of 10 RCTs were included, and the filiform needling therapy was optimal in treatment of OSAHS. The acupoints included Lianquan (CV23), Danzhong (CV17), Zhongwan (CV12), and bilateral Kongzui (LU6), Pishu (BL20), Fenglong (ST40), Zusanli (ST36), Yinlingquan (SP9) and Zhaohai (KI6). Zusanli (ST36) received the reinforcing method, Pishu (BL20) and Fenglong (ST40) were stimulated with the reducing technique, and the rest acupoints with the uniform reinforcing-reducing. Each acupoint was manually manipulated once every 10 min during the needle retention for 30 min. Acupuncture was delivered once a day, 5 times a week and for consecutive 4 weeks. Among the included literature, the severity of disease was not reported in detail, the filiform needling was the dominant intervention, the local acupoints such as Lianquan (CV23) and Panglianquan (Extra) were mainly selected. The apnea-hypopnea index and the minimum oxygen saturation were taken as the evaluation indexes, and the effect was evaluated in reference to the generally accepted standards. The attention to safety evaluation was insufficient, the report on methodology was not adequate and the quality was low.
CONCLUSION
Filiform needling is the dominant therapy of acupuncture and moxibustion for OSAHS, and the local acupoints are considered specially. But the quality of clinical research should be improved.
Humans
;
Moxibustion
;
Acupuncture Therapy
;
Sleep Apnea, Obstructive/therapy*
;
Acupuncture Points
;
Randomized Controlled Trials as Topic
4.Expert consensus on clinical protocol for treating herpes zoster with fire needling.
Xiaodong WU ; Bin LI ; Baoyan LIU ; Lin HE ; Zhishun LIU ; Shixi HUANG ; Keyi HUI ; Hongxia LIU ; Yuxia CAO ; Shuxin WANG ; Zhe XU ; Cang ZHANG ; Jingsheng ZHAO ; Yali LIU ; Nanqi ZHAO ; Nan DING ; Jing HU
Chinese Acupuncture & Moxibustion 2025;45(12):1825-1832
The expert consensus on the clinical treatment of herpes zoster with fire needling was developed, and the commonly used fire needling treatment scheme verified by clinical research was selected to form a standardized diagnosis and treatment scheme for acute herpes zoster and postherpetic neuralgia (PHN), so as to answer the core problems in clinical application. The consensus focuses on patients with herpes zoster, and forms recommendations for 9 key clinical issues, covering simple fire needling and TCM comprehensive therapy based on fire needling, including fire needling combined with cupping, fire needling combined with Chinese herb, fire needling combined with cupping and Chinese herb, fire needling combined with filiform needling, fire needling combined with moxibustion, and provides specific recommendations and operational guidelines for various therapies.
Humans
;
Herpes Zoster/therapy*
;
Acupuncture Therapy/instrumentation*
;
Consensus
;
Clinical Protocols
6.Characteristics and lifestyles of patients with metabolic dysfunction-associated fatty liver disease based on the physical examination population
Haiqing GUO ; Mingliang LI ; Feng LIU ; Yali LIU ; Jing ZHANG
Journal of Clinical Hepatology 2025;41(6):1090-1096
ObjectiveTo screen for the patients with metabolic dysfunction-associated fatty liver disease (MAFLD) among the physical examination population, to observe the characteristics of MAFLD patients, and to compare the differences in lifestyle between the MAFLD population and the non-MAFLD population. MethodsA cross-sectional study was conducted among 6 206 individuals who underwent physical examination in a physical examination institution in Beijing from December 2015 to December 2019, and according to the new diagnostic criteria for MAFLD, the examination population was divided into MAFLD group and non-MAFLD group. Based on body mass index (BMI), the MAFLD group was further divided into lean MAFLD group (BMI<24 kg/m2) and non-lean MAFLD group (BMI ≥24 kg/m2). Related data were compared between groups, including demographic indicators, education level, work pressure, physical measurement indicators, and lifestyles such as sleep, diet, and exercise. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. ResultsOf all individuals in this study, 1 926 (31.1%) had MAFLD and 4 280 (68.9%) did not have MAFLD. Compared with the non-MAFLD group, the MAFLD group had significantly higher age (Z=-14.459, P<0.001), proportion of male patients (χ2=72.004, P<0.001), work pressure (χ2=7.744, P=0.005), body weight (Z=-43.508, P<0.001), BMI (Z=-47.621, P<0.001), waist circumference (Z=-48.515, P<0.001), hip circumference (Z=-42.121, P<0.001), and waist-hip ratio (Z=-43.535, P<0.001), as well as a significantly lower education level (χ2=33.583, P<0.001). In terms of behavior, the MAFLD group had a significantly shorter sleep time (χ2=5.820, P=0.016) and a significantly faster eating speed (χ2=74.476, P<0.001). In terms of diet, the patients in the MAFLD group consumed more high-sodium, high-sugar, and high-calorie diets (χ2=42.667, P<0.001) and low-fiber diet (χ2=4.367, P=0.008). In terms of exercise, the MAFLD group had a significantly higher proportion of patients without exercise habits (χ2=10.278, P=0.001). Further analysis showed that there were 202 individuals (10.5%) in the lean MAFLD group and 1 724 (89.5%) in the non-lean MAFLD group. Compared with the non-lean MAFLD group, the lean MAFLD group had significantly higher age (Z=3.368, P=0.001) and education level (χ2=9.647, P=0.002) and significantly lower proportion of male patients (χ2=27.664, P<0.001), body weight (Z=-18.483, P<0.001), BMI (Z=-23.286, P<0.001), waist circumference (Z=-18.565, P<0.001), and hip circumference (Z=-18.097, P<0.001), and in terms of behavior, the non-lean MAFLD group had a significantly faster eating speed (χ2=4.549, P=0.033). ConclusionThere is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing, with a higher number of people with unhealthy lifestyles compared with the non-MAFLD population.
7.Comparison of the diagnostic value of ultrasound-derived fat fraction, controlled attenuation parameter, and hepatic/renal ratio in the grading of hepatic steatosis in metabolic associated fatty liver disease
Xinge CAO ; Yali ZHANG ; Lizhuo JIA ; Jianghong CHEN ; Yi DONG
Journal of Clinical Hepatology 2025;41(9):1788-1794
ObjectiveTo investigate the diagnostic accuracy and grading capability of ultrasound-derived fat fraction (UDFF), controlled attenuation parameter (CAP), and hepatic/renal ratio (HRR) in assessing hepatic steatosis in metabolic associated fatty liver disease (MAFLD) with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as the gold standard. MethodsA total of 150 patients with MAFLD who attended The First Hospital of Hebei Medical University from January 2023 to December 2024 were enrolled, and 148 healthy volunteers were recruited. All subjects underwent MRI-PDFF, UDFF, CAP, and HRR examinations. Hepatic steatosis was graded based on MRI-PDFF (S0:148 cases; S1:92 cases; S2:21 cases; S3:37 cases), and the MAFLD patients with different grades of hepatic steatosis were compared in terms of UDFF, CAP, HRR, and clinical features. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups and the Tukey HSD test was used for further comparision between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between UDFF, CAP, HRR, and MRI-PDFF in different grades of MAFLD; the receiver operating characteristic (ROC) curve was used to investigate the efficacy of UDFF, CAP, and HRR in the diagnosis of different degrees of hepatic steatosis in MAFLD; the Bland-Altman difference plot was used to analyze the consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ResultsUDFF measurement gradually increased with the increase in the grade of fatty liver (H=201.52,P0.001). The Spearman correlation analysis showed that there was a strong correlation between any two indicators of UDFF, CAP, HRR, and MRI-PDFF in S1, S2, and S3 MAFLD (all P0.001), with the strongest correlation between UDFF and MRI-PDFF (rs1=0.884,rs2=0.962,rs3=0.929, all P0.001). The ROC curve analysis showed that UDFF had a larger area under the ROC curve (AUC) than CAP and HRR in the graded diagnosis of S1 and S3 (all P0.05), while in the diagnosis of S2 MAFLD, UDFF had a significantly larger AUC than HRR (P0.05) and a similar AUC to CAP (P0.05). The Bland-Altman difference plot showed good consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ConclusionCompared with CAP and HRR, UDFF can accurately measure liver fat content and has good efficacy in identifying varying degrees of hepatic steatosis in MAFLD.
8.Mechanism of action of energy metabolism in hepatic ischemia-reperfusion injury and related targeted therapies
Tiantian YANG ; Lu HUANG ; Xiao ZHANG ; Yali REN ; Weitian XU ; Song ZHANG
Journal of Clinical Hepatology 2025;41(9):1956-1960
Hepatic ischemia-reperfusion injury (HIRI) is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy, and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies, in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.
9.Establishment and Evaluation of Rat Model of Acute Myocardial Infarction in Coronary Heart Disease with Qi and Yin Deficiency Syndrome Based on Sleep Deprivation Combined with Coronary Artery Ligation
Yali SHI ; Yunxiao GAO ; Qiuyan ZHANG ; Yue YUAN ; Xiaoxiao CHEN ; Longxiao HU ; Junguo REN ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):30-40
ObjectiveTo explore the construction and evaluation methods of a rat model of acute myocardial infarction(AMI) with Qi and Yin deficiency syndrome established by sleep deprivation combined with coronary artery ligation. MethodsThirty-six SD rats were randomly divided into a normal group(n=6), a myocardial infarction group(model A group, n=10), an acute sleep deprivation+myocardial infarction group(model B group, n=10), and a chronic sleep deprivation+myocardial infarction group(model C group, n=10) according to body weight. Rats in the normal group were not treated, rats in the model A group underwent only ligation of the left anterior descending coronary artery, rats in the model B group were sleep deprived for 96 h and then underwent ligation of the left anterior descending coronary artery, and rats in the model C group were sleep deprived for an additional 48 h each week with a 24 h rest period as one cycle for three weeks on the basis of the model B group. After coronary artery ligation in the model C group, the first week was defined as the starting point of the first sleep deprivation cycle, and indexes were tested weekly for rats in each group for 3 weeks. Electrocardiogram was used to determine the ligation of the left anterior descending coronary artery in rats, and small animal echocardiography was used to evaluate the cardiac function. The levels of serum creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), cardiac troponin T(cTnT), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by biochemical assays, and hematoxylin-eosin(HE) staining was used to evaluate the pathological changes of myocardial tissue in rats. The syndrome indicators of Qi and Yin deficiency were evaluated by general state and body weight, grip strength, facial temperature, paw temperature, rectal temperature, salivary flow rate, open field test, tongue color[red(R), green(G), and blue(B)] values, pulse amplitude changes, and enzyme-linked immunosorbent assay(ELISA) for the detection of expression levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), rat serum corticotropin-releasing factor(CRF), adrenocorticotropic hormone(ACTH), triiodothyronine(T3), tetraiodothyronine(T4), and corticosterone(CORT) in serum. ResultsIn terms of disease indicators, compared with the normal group, the ST segment of the electrocardiogram in each model group was significantly elevated, the echocardiographic parameters were decreased, the contents of myocardial enzymes and inflammatory factors were increased(P<0.01), and the myocardial tissue in the infarcted area was significantly damaged. In terms of syndrome indicators, compared with the normal group, the body weight of rats in the model B and C groups decreased at each time point, the grip strength of each model group decreased, the total distance traveled and the number of entries into the center in the open field test decreased, the immobility time increased, the facial and rectal temperatures of rats in the model B and C groups increased, the salivary flow rate of each model group decreased, the tongue color was bright red or light, the tongue body was dry or smooth like a mirror, lacking of moisture sensation, the R, G and B values of the tongue surface increased, the pulse amplitude changes decreased, and the contents of T3 and T4 increased, while the expressions of cAMP, CRF, ACTH and CORT in the model B and C groups increased(P<0.05, P<0.01). ConclusionContinuous sleep deprivation for 96 h in a multi-platform method combined with coronary artery ligation can construct a rat model of AMI with Qi and Yin deficiency syndrome, and the syndrome manifestations can be maintained for 3 weeks.
10.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
ObjectiveTo explore the feasibility, evaluation methods and metabolic differences of high-fat diet(HFD) combined with myocardial ischemia-reperfusion injury(MIRI) to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome(PBSBCS). MethodsThirty-two SD rats were randomly divided into the sham operation, HFD, MIRI, and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet(regular chow), while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery, while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography, including left ventricular ejection fraction(EF), left ventricular fractional shortening(FS), cardiac output(CO), and stroke volume(SV). Serum levels of creatine kinase(CK), CK-MB, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), lactate dehydrogenase(LDH), endothelin-1(ET-1), endothelial nitric oxide synthase(eNOS), tumor necrosis factor-α(TNF-α), interleukin-18(IL-18), oxidized LDL(ox-LDL), and cardiac troponin T(cTnT) were measured by biochemical assays and enzyme-linked immunosorbent assay(ELISA). Myocardial histopathology was evaluated via hematoxylin-eosin(HE) staining, while myocardial infarction and no-reflow area were assessed using 2,3,5-triphenyltetrazolium chloride(TTC), Evans blue, and thioflavin staining. Changes in syndrome characteristics[body weight, tongue surface red-green-blue [RGB] values, and pulse amplitude] of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). ResultsCompared with the sham operation group, the HFD and MIRI+HFD groups showed significant increases in body weight(P<0.01), RGB values and pulse amplitude decreased in the HFD, MIRI and MIRI+HFD groups, TC, TG, LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups, while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased, serum eNOS level decreased, and CK-MB, LDH, and cTnT activities increased in the HFD, MIRI and MIRI+HFD groups(P<0.05, P<0.01). Whole blood viscosity was increased in the HFD group at medium shear rate, and in the MIRI and MIRI+HFD groups at low, medium and high shear rates(P<0.05, P<0.01). Platelet aggregation rate increased in the MIRI and MIRI+HFD groups, accompanied by elevated ET-1, TNF-α, and IL-18 levels, reduced cardiac function indices, expanded myocardial no-reflow and infarction areas, and increased serum CK, CK-MB, LDH, and cTnT activities(P<0.05, P<0.01). Compared with the MIRI group, the HFD and MIRI+HFD groups showed significant increase in body weight, TC, TG, LDL-C and ox-LDL levels, and significant decrease in HDL-C content(P<0.01). The MIRI+HFD group showed decrease in RGB values and pulse amplitude, and an increase in whole blood viscosity, platelet aggregation, blood perfusion peak time, myocardial no-reflow and infarction areas, elevated ET-1, TNF-α and IL-18 levels, decreased eNOS content, EF and SV, increased serum CK, CK-MB and cTnT activities, and worsened myocardial pathology(P<0.05). Compared with the HFD group, the MIRI+HFD group showed similar aggravated trends(P<0.05, P<0.01). Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury, and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices, effectively simulating clinical features of coronary heart disease(CHD), which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

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