1.YTHDF1 regulation of Fis1 on the activation and proliferation and migration ability of hepatic stellate cells
Lin Jia ; Feng Sun ; Qiqi Dong ; Jingjing Yang ; Renpeng Zhou ; Wei Hu ; Chao Lu
Acta Universitatis Medicinalis Anhui 2025;60(1):49-58
Objective:
To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1).
Methods:
The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential.
Results:
Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05).
Conclusion
YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.
2.Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.
Dan FENG ; Jian ZHANG ; Huanmin NIU ; Xiaoxue ZHENG ; Mengqi JIA ; Qiqi LU ; Jing WANG ; Wenxue GUO ; Qi SUN ; Huiqing YUAN ; Hongxiang LOU
Acta Pharmaceutica Sinica B 2025;15(4):2095-2113
The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe2+ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe2+, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
3.Rapid Analysis of Chemical Constituents in Shenxianshengmai Oral Liquid by UHPLC-Q Exactive Focus MS/MS
Shiyu ZONG ; Zhibiao DI ; Qiqi LIU ; Zhuangzhuang HUANG ; Hong ZHANG ; Ye LI ; Feng LIU ; Yang LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):218-228
Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.
4.Herbal Textual Research on Huoxiang in Famous Classical Formulas
Qiqi REN ; Yangyang LIU ; Jian FENG ; Wenlan LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):1-13
By reviewing ancient materia medica, medical books and modern literature, the name, origin, quality evaluation, producing area and processing methods of Huoxiang herbs were systematically investigated and researched, so as to provide reference and basis for the development and utilization of famous classical formulas containing Huoxiang herbs. Through the herbal textual research, it can be seen that most of materia medica in past dynasties have taken Huoxiang as the nominal rectification, and the mainstream base used is Pogostemon cablin. In order to distinguish another plant of the same family, Agastache rugosa, which has been widely used in Chinese folk since the Ming dynasty, and respect geo-authentic region, Pogostemonis Herba is also named Guanghuoxiang. Pogostemonis Herba is native to Vietnam and other Southeast Asian countries, and was introduced to China as a spice through Guangdong and other places in the early days, and has been successfully cultivated in the south of China since the Song dynasty. The medicinal parts are mostly dried aboveground parts, and the leaves and stems are also separated for medicine sometimes. The geo-authentic region of Pogostemonis Herba is Guangdong in the past dynasties, and it is currently cultivated in Guangzhou, Zhaoqing, Zhanjiang of Guangdong province and Hainan province, with the most famous one cultivated in Shipai. Pogostemonis Herba is mainly planted by cutting propagation. It usually sprouts in February and is harvested in June. The main processed method in region is stuffy dry, which is placed in the sun and repeatedly suffocated until it has an aromatic smell and the color turns yellow. The processing method is mostly to use the raw product as medicine after being selected. Based on the research results, it is suggested that the leaves of P. cablin are used in Yangweitang, for Huopo Xialingtang, it is recommended to choose the raw product of A. rugosa that is removed the roots and old stems.
5.Mortality of drowning and road traffic injury among children aged 5-14 in China from 2008 to 2019.
Jian Hui ZHENG ; Guo Shuang FENG ; Xi Feng WU ; Shicheng YU ; Qiqi WANG
Chinese Journal of Preventive Medicine 2022;56(9):1244-1250
Objective: To analyze the trajectory of drowning and road traffic injury mortality among children aged 5-14 years in China from 2008 to 2019. Methods: Mortality data of unintentional injuries were from the Mortality Surveillance Data Set of National Disease Surveillance System from 2009 to 2018 and grouped by regions, urban and rural areas, genders, and age groups. The trajectory model was used to analyze the trend of drowning and road traffic injury mortality with years. Results: The mortality of drowning and road traffic injury showed a similar trend. In the trajectory model of drowning mortality, east, middle and west rural boys and western urban boys of all ages belonged to the high mortality group. The moderate mortality group included eastern urban boys and western girls aged 5-9 years and also contained eastern and middle urban boys and western urban girls aged 10-14 years. The other combinations belonged to the low mortality group. In the trajectory model of road traffic injury mortality, western urban boys, all rural boys and western rural girls aged 5-9 years, middle and western rural boys and western urban boys aged 10-14 years belonged to the high mortality group. Eastern urban girls aged 5-9 years and 10-14 years belonged to the low mortality group. The other combinations belonged to the moderate mortality group. Conclusion: There are different groups in the trajectory model of drowning and road traffic injury mortality among children in China. Identifying the trajectory of injury mortality is helpful to carry out more targeted prevention in China.
Accidental Injuries
;
Accidents, Traffic
;
Child
;
China/epidemiology*
;
Drowning
;
Female
;
Humans
;
Male
;
Rural Population
;
Urban Population
;
Wounds and Injuries
6. Effect of esketamine and butorphanol on morphine-induced pruritus after cesarean section: A randomized controlled clinical study
Yan FENG ; Gaowei LI ; Qiqi JIN ; Weicha CAI ; Jun LI ; Yan FENG ; Gaowei LI ; Xuezheng LIN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(12):1425-1430
AIM: To evaluation the effects of esketamine and butorphanol on postoperative pruritus induced by epidural morphine injection in cesarean delivery parturients. METHODS: A total of 162 parturients who underwent elective cesarean section under continuous epidural anesthesia in Taizhou Central Hospital (Taizhou University Hospital), were selected and randomly divided into esketamine group (group K), butorphanol group (group B) and blank control group (group C). 5min after umbilicus amputation, parturients in group K was injected with 3 mg morphine diluent through epidural catheter, and esketamine 0.2 mg/kg intravenously. Parturients in groups B and C were given the same dose of morphine,and butorphanol 10 μg/kg or the same volume of normal saline, respectively. The incidence of postoperative pruritus at different times, the degree of pruritus and incidence of other adverse reactions were compared among three groups. RESULTS: The highest incidence of pruritus occurred within 4 hours after operation. The incidence of postoperative pruritus at 4 hours in group K and B was significantly lower than that in group C (3.7% vs. 3.7% vs. 29.6%, P < 0.05), the total incidence of postoperative pruritus within 48 hours was also significantly lower than that in group C (13.0% vs. 11.1% vs. 40.7%, P < 0.05), and the incidence of moderate to severe pruritus was also significantly lower than that of group C (5.6% vs. 3.7% vs. 31.5%, P < 0.05). There was no significant difference between group K and group B (all P > 0.05). There were no significant differences in the incidence of postoperative nausea, vomiting, dizziness and postoperative pain scores among three groups (P > 0.05). CONCLUSION: Both esketamine and butorphanol can reduce the incidence and degree of pruritus caused by epidural morphine injection in parturients, without affecting the analgesic effect of morphine and without increasing the incidence of adverse reactions. Esketamine is as effective and safe as butorphanol in preventing pruritus after cesarean section.
7.Electroacupuncture in the treatment of acute gastrointestinal injury in patients with severe traumatic brain injury: a prospective randomized controlled trial
Xi XING ; Ronglin JIANG ; Shu LEI ; Qiqi XU ; Meifei ZHU ; Yihui ZHI ; Guolian XIA ; Liquan HUANG ; Shihao MAO ; Zheqi CHEN ; Dandan FENG
Chinese Critical Care Medicine 2021;33(1):95-99
Objective:To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI).Methods:A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis.Results:During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH 2O, 1 cmH 2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH 2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH 2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ 2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. Conclusion:Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.
8.Clinical analysis of 1 057 patients with critical illnesses in a dermatological ward
Hai LONG ; Li JIANG ; Yueqi QIU ; Nan YAO ; Licong LIU ; Yuming XIE ; Feng XIONG ; Siqi TAN ; Qiqi KUANG ; Ruixuan YOU ; Ke CHAI ; Xin LUO ; Haojun LONG ; Yue XIN ; Ziyu GUO ; Jiaqi WANG ; Yixin TAN ; Qing ZHANG ; Guiying ZHANG ; Yaping LI ; Yuwen SU ; Rong XIAO ; Qianjin LU
Chinese Journal of Dermatology 2021;54(9):790-797
Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.
9.Effects of "hospital-community-family" model in continuous nursing among diabetics
Xiajun FU ; Lingyan ZHOU ; Chunfang LI ; Qiqi LIN ; Xuehua HE ; Zhongying FENG
Chinese Journal of Modern Nursing 2019;25(34):4496-4499
Objective To explore the effects of "hospital-community-family" continuous nursing model in continuous nursing among diabetics. Methods From February 2018 to February 2019, a total of 102 diabetic out-patients at the Third Affiliated Hospital of South Medical University were selected by stratified random sampling. Patients were divided into control group and observation group with the random number table, 51 cases in each group. Control group carried out routine follow-up nursing. Observation group implemented "hospital-community-family" continuous nursing. We compared the fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h PG), glycosylated hemoglobin (HbA1c), scores of the Champion Health Belief Model Scale (CHBMS), Health-Promoting Lifestyle Profile-Ⅱ (HPLP-Ⅱ) and Quality of Life Scale for Patients with Type 2 Diabetes Mellitus (DMQLS) of two groups before and after intervention. Results After intervention, the FBG, 2 h PG and HbA1c of observation group were (7.11±1.25)mmol/L, (9.15±1.24) mmol/L and (8.15±0.59)% respectively lower than those [(8.56±1.31)mmol/L, (11.21±1.35)mmol/L and (10.99±1.12)%]of control group with statistical differences (t=5.719, 8.026, 16.022; P< 0.05). After intervention, the scores of CHBMS, HPLP-Ⅱ and DMQLS of observation group were (4.16±0.34), (4.09±0.35) and (165.24±5.21) respectively higher than those [(3.52±0.42), (3.24±0.41) and (154.18±4.39)]of control group with statistical differences (t=8.458, 11.260, 11.593;P<0.05). Conclusions Application of "hospital-community-family" continuous nursing in patients with type 2 diabetes mellitus helps the glucose control, improves health belief, health behavior and quality of life which is worthy of being used widely in clinical application.
10.The relationship of pathologic classification and prognosis in diabetic nephropathy
Qiqi FENG ; Meijun SI ; Jing ZHOU ; Xun LIU ; Hui PENG ; Tanqi LOU
Chinese Journal of Nephrology 2018;34(9):641-647
Objective To explore the relationship between clinical manifestations and pathological changes in diabetic nephropathy (DN) and to assess the predictive power of the pathologic classification for DN established by the Renal Pathology Society in 2010.Methods Patients with type 1 or type 2 diabetes and biopsy-proven DN in the Third Affiliated Hospital of Sun Yat-sen University between January 2004 to June 2014 were enrolled in the present study and were followed-up until 31 December 2014.The outcome was defined as renal end-points including renal replacement therapy and doubling of serum creatinine as well as all-cause mortality.The laboratory and histologic data were analyzed and outcomes were assessed using survival analysis.Results Fifty-seven people enrolled in this study were categorized into Class Ⅱa (n=9),Class Ⅱb (n=9),Class Ⅲ (n=25) and Class Ⅳ (n=14) while no participants belonged to Class Ⅰ.The changes of Class Ⅱa were slight and those of Class Ⅳ were severe both in the clinical data (diabetic duration,blood pressure,estimated glomerular filtration rate,urine protein excretion rate,albumin and hemoglobin) and the pathological data (percentage of global glomerulosclerosis,percentage and scoring of interstitial fibrosis and tubular atrophy,scoring of interstitial inflammation and incidence of large vessel lesions).There were no significant differences between Class Ⅱb and Ⅲ in the above variables except for the scoring of arteriosclerosis.The mean follow-up duration was 25.9 months.Twenty-five patients (43.9%) reached the renal outcomes and six people (10.5%) reached all-cause mortality.The survival analysis showed that there were significant differences among the renal survival curves of different glomerular classes and of different interstitial and vascular scorings,but not in the survival curves related to all-cause mortality.Conclusions The glomerular classes are not completely associated with renal prognosis.The clinical manifestations and renal outcomes are benign in Class Ⅱa,moderate but similar in Class Ⅱb and Ⅲ and severe in Class Ⅳ.The glomerular classification and interstitial and vascular scorings are associated to renal prognosis while their associations with mortality remain to be verified.


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