1.Improvement effects and mechanism of urinastatin on cisplatin-induced myocardial injury
Jiafu REN ; Pengfei CHEN ; Rong A ; Jing LI
China Pharmacy 2025;36(8):920-925
OBJECTIVE To investigate the improvement effects and potential mechanism of ulinastatin (UTI) on cisplatin (CP)-induced myocardial injury. METHODS Rabbits were used as study subjects and randomly divided into blank group (normal saline 2 mL/d, for consecutive 7 d), CP group (150 mg/m2, on the 1st and 4th day), UTI low-dose/high-dose group (UTIL/UTIH group, UTL 25 000 or 50 000 IU/kg, once a day, for consecutive 7 d), c-Jun N-terminal kinase (JNK) inhibitor group (JNKi group, SP600125 15 mg/kg, on the 1st and 4th day+CP 150 mg/m2, on the 1st and 4th day+normal saline 2 mL/d, on the other 5 days). Except for the blank group, rabbits in the other groups were injected with relevant medicine and/or normal saline via a marginal ear vein on one side. The serum level of cardiac troponin Ⅰ (cTnⅠ) in rabbits on the 1st and 8th days of the detection experiment, as well as the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in myocardial tissue on the 8th day of the experiment, were all measured in each group. The pathological changes and myocardial cell apoptosis in myocardial tissue were observed, and the protein expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), JNK, phosphorylated JNK (P-JNK), mitochondrial fission factor (Mff), and dynamin-related protein 1 (Drp1) in myocardial tissue were all determined. RESULTS Compared with the blank group, the CP group showed significant myocardial injury. The cell apoptotic rate, the levels of cTnⅠ in serum and MDA in myocardial tissue, as well as protein expressions of Bax, JNK, p-JNK, Mff, and Drp1, were all significantly increased or up-regulated, SOD level and protein expression of Bcl-2 significantly reduced or down+regulated(P<0.05). Compared with the CP group, the myocardial injury in rabbits from each drug treatment group showed improvement. The cell apoptosis index, the levels of cTnⅠ in serum and MDA in myocardial tissue, as well as protein expressions of Bax, JNK, p-JNK, Mff (except for UTIL group), and Drp1, were all significantly reduced or down-regulated, while SOD, GSH level and protein expression of Bcl-2 significantly increased or up-regulated (P<0.05); moreover, the improvement in some indicators was significantly better in the UTIH group and the JNKi group compared to the UTIL group (P<0.05). CONCLUSIONS UTI may ameliorate CP-induced myocardial injury, the potential mechanism of which may be associated with antagonizing oxidative stress and inhibiting the JNK/Mff signaling pathway.
2.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
3.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
4.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
5.Measles, rubella, and mumps antibody seroprevalence among the children aged 18 years and younger in Karamay City, Xinjiang Uygur Autonomous Region
Meili WU ; Xia LI ; Ling ZUO ; Liping RONG ; Jing WANG ; Feng WANG
Shanghai Journal of Preventive Medicine 2025;37(3):239-243
ObjectiveTo understand the measles, rubella, and mumps antibody seroprevalence among the children aged 18 years and younger in Karamay City, and to evaluate the effectiveness of vaccination. MethodsA stratified whole cluster random sampling method was used to investigate the antibody seroprevalence of measles, rubella, and mumps among the healthy children aged 18 years and younger in Karamay City, and to further analyze the positive antibody rates and the geometric mean concentration (GMC) of antibodies. ResultsA total of 620 people were investigated, and the positive rates of IgG to measles, rubella, and mumps were 72.74%,62.26%, and 86.45%, respectively, with a GMC of308.94 mIU·mL-1, 21.81 mIU·mL-1, and 249.10 U·mL-1. There were statistically significant differences in the positive rates of antibodies to measles, rubella, and mumps among different age groups (χ2measles=76.707, P<0.001; χ2rubella=60.804, P<0.001; χ2mumps=35.407, P<0.001). The differences in positive rates were statistically significant among individuals with different intervals from the time of their last dose vaccination (χ2measles=60.533, P<0.001; χ2rubella=46.331, P<0.001; χ2mumps=22.825, P<0.001). ConclusionThe antibody levels of measles, rubella and mumps among the people aged 18 years and younger in Karamay City are found to be low. Two doses of measles-mumps-rubella (MMR) vaccine should be given to children born before 2020, and if necessary, supplementary immunization with MMR vaccine should be carried out before they are enrolled in nursery and kindergarten. Additionally, regular population-based antibody surveillance should be conducted to promptly identify the people with weak immunity, which is conducive to effectively reducing and controlling the epidemic situation of measles, rubella and mumps in schools.
6.Effect of Spraying Nano-calcium Carbonate and Calcium Nitrate Tetrahydrate on Characters, Carbohydrate Components and Endogenous Hormones of Dendrobium officinale
Jing LI ; Rong ZHOU ; Yingyue HOU ; Wei CAI ; Xiaoyan ZHANG ; Shuang ZHANG ; Guangying DU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):208-216
ObjectiveTo investigate the effects of foliar fertilizer of nano-calcium carbonate and calcium nitrate tetrahydrate on the agronomic traits, carbohydrate and endogenous hormone contents of Dendrobium officinale planted for 1 year under greenhouse cultivation, in order to provide scientific basis for fertilization to improve the yield and quality of D. officinale. MethodsSingle-factor experimental design was adopted. Starting from early spring, D. officinale was treated with foliar spraying according to corresponding fertilizers. Three treatment groups were established based on different fertilizers, namely, a blank group(clear water), a nano-calcium carbonate group(0.727 g·L-1 nano-calcium carbonate water-soluble fertilizer), and a calcium nitrate tetrahydrate group(1.091 g·L-1 calcium nitrate tetrahydrate water-soluble fertilizer). The frequency of spraying was three times per month, and the entire treatment process lasted for nine months. The effects of various treatments on the traits and relative chlorophyll content of D. officinale were dynamically monitored. Sampling was conducted at three specific time points:August 2, 2023, September 8, 2023, and November 1, 2023, respectively. The contents of glucose and mannose in D. officinale stems were determined by high performance liquid chromatography(HPLC), the content of soluble sugars in D. officinale stems and leaves was determined by phenol method, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of cytokinin and auxin. ResultsCompared with the blank group, the treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could significantly increase stem length, stem node number, leaf number, and tiller number. Among them, during the harvesting period in November, the stem length and tiller number, which are indicators related to the yield of D. officinale, increased by 60.85% and 19.23% after treatment with calcium nitrate tetrahydrate, and by 32.54% and 28.85% after treatment with nano-calcium carbonate, respectively. Compared with the blank group, treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could promote the accumulation of sucrose in the stems and leaves of D. officinale to varying degrees, as well as the accumulation of polysaccharides, mannose, and glucose in the stems. In addition, nano-calcium carbonate treatment also facilitated the accumulation of fructose in the stems and leaves of D. officinale. Specifically, during the harvesting period in November, polysaccharides and mannose, which were the main active ingredients in D. officinale stems, increased by 28.48% and 29.36% after treatment with calcium nitrate tetrahydrate, and by 39.91% and 82.62% after treatment with nano-calcium carbonate, respectively. In addition, compared with the blank group, the concentrations of auxin in the stems and leaves of D. officinale were significantly increased after treatment with calcium nitrate tetrahydrate(P<0.05). Similarly, the concentrations of cytokinin and auxin in the stems of D. officinale were also elevated after treatment with nano-calcium carbonate. Correlation analysis further indicated that elongation growth and tillering of D. officinale stems after foliar spraying of nano-calcium carbonate and calcium nitrate tetrahydrate might be related to the accumulation of carbohydrates in the stems and leaves and the synergistic effect of auxin and cytokinin. ConclusionIn production practice, spraying nano-calcium carbonate and calcium nitrate tetrahydrate can promote the accumulation of cytokinin, auxin, and carbohydrate contents in the stems and leaves of D. officinale, and promote tillering and elongation growth of the stems.
7.Prevalence trends of elevated blood pressure and its association with nutritional status among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2025;46(9):1342-1345
Objective:
To analyze the prevalence trends of different types of elevated blood pressure and their association with nutritional status among primary and secondary school students in Inner Mongolia from 2019 to 2024, providing references for targeted prevention strategies.
Methods:
From September 2019 to 2024, a stratified random cluster sampling method was used to select 12 primary and secondary schools from each league city in Inner Mongolia Autonomous Region. A total of 177 108, 137 758, 190 182, 180 084 , 188 056, 180 351 primary and secondary school students (excluding grades one to three of primary school) were included for physical examination. The correlation between their nutritional status and high blood pressure was analyzed based on the basic situation of 129 821 primary and secondary school students who completed a questionnaire survey at the same time in 2024. Statistical analysis was conducted using a Chi-square test and multiple Logistic regression model.
Results:
From 2019 to 2024, the detection rates of elevated blood pressure were 13.60%, 13.68%, 17.60%, 17.24%, 14.77% and 15.96%, respectively. The rates for isolated systolic hypertension were 4.24%, 5.83%, 7.26%, 7.19%, 6.24% and 6.93%; isolated diastolic hypertension rates were 6.38%, 4.99%, 6.23 %, 6.41%, 5.39% and 5.66%; and combined systolic and diastolic hypertension rates were 2.97%, 2.86%, 4.11%, 3.65%, 3.14 % and 3.36%. Multivariate Logistic regression analysis showed that girls, junior high school, senior high school, overweight, and obesity were positively associated with elevated blood pressure risk ( OR =1.27, 1.25, 1.32, 1.66, 3.07, all P <0.05); conversely, county residence, Mongolian ethnicity, and other ethnicities showed negative associations ( OR =0.90, 0.93, 0.90, all P <0.05).
Conclusions
Overweight and obesity among children and adolescents are closely related to various types of elevated blood pressure. Prevention strategies should prioritize effectively controlling weight issues among children and adolescents, thereby effectively reducing the incidence of elevated blood pressure.
8.Therapeutic effects of osthol on acute pancreatitis model rats
Hai-Yun GAO ; Li-Jing SHEN ; Hai-Rong LIU ; Xue-Zhen WANG ; Yi-Fei ZHANG ; Jia LI
The Chinese Journal of Clinical Pharmacology 2024;40(3):403-407
Objective To investigate the therapeutic effect of cnithol on acute pancreatitis(AP)rats and its regulatory mechanism on phosphoinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods SPF-grade SD male rats were randomly divided into control group,model group(50 μg·kg-1 hyranin+10 mg·kg-1 LPS),positive control group(2 mg·kg-1 dexamethasone),experimental-L group(20 mg·kg-1 osthol)and experimental-H group(40 mg·kg-1 osthol),experimental-H+740Y-P group(40 mg·kg-1 osthol+2 mg·kg-1 PI3K activator 740Y-P),15 mice in each group.The activities of amylase and lipase in serum of rats were detected by automatic biochemical analyzer 24 h after the last administration.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in pancreas were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic tissue and score the pathological damage.Western blot was used to detect the expression of PI3K/Akt pathway related proteins in rat pancreas.Results The activities of serum amylase in control group,model group,positive control group,experimental-H group and experimental-H+740Y-P group were(135.67±12.89),(1 027.84±32.16),(174.31±15.27),(186.70±17.39)and(835.92±28.78)U·mL-1,respectively;the contents of TNF-α were(35.69±3.10),(223.54±15.23),(48.76±4.25),(52.31±4.68)and(208.46±13.65)pg·mL-1,respectively;the contents of MDA were(2.15±0.14),(6.37±0.42),(2.78±0.17),(2.81±0.15)and(5.96±0.36)nmol·mg-1,respectively;the histopathological injury scores were 1.12±0.07,10.23±0.38,3.14±0.21,3.25±0.23 and 9.68±0.40,respectively;p-PI3K/PI3K ratios were 0.82±0.05,1.96±0.15,1.07±0.06,1.10±0.07 and 1.69±0.14,respectively.The above indexes were compared with the control group in the model group,the positive control group,experimental-H group and the model group,and the above indexes of experimental-H+740Y-P group and experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion Gossetin can play a therapeutic role in AP,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.
9.Role of TGF-β/Smads signaling pathway in myocardial fibrosis of heart failure and research status of traditional Chinese medicine intervention
Yao-Hui HUO ; Jing ZHANG ; Li-Rong ZHOU ; Xiao-Gang ZHANG ; Yong-Ze GAO ; Li-Ming LIU ; Kai LIU
The Chinese Journal of Clinical Pharmacology 2024;40(3):444-448
During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.
10.General considerations for quality control of recombinant protein PEGylation drug production
Rong LIU ; Wu-Chao LI ; Jing-Feng HU ; Xiao-Hong LU ; Qiao-Qiao FENG
The Chinese Journal of Clinical Pharmacology 2024;40(4):629-632
Polyethylene glycosylation(PEGylation)of recombinant protein drugs are modified by PEG.To preserve the biological activity of the prototype recombinant protein,it overcomes the drawbacks of fast metabolism,poor stability,and the need for multiple doses of the prototype protein in vivo,but also has specificity.In the case of limited guidelines for quality control,discussions are conducted on the control of raw materials used in production,process control during production,quality control of intermediate and final products,stability research,and other aspects,in order to provide reference for the control and development of recombinant protein PEGylation drugs.


Result Analysis
Print
Save
E-mail