1.Effect mechanism of LncRNA MALAT1 on doxorubicin resistance in osteosarcoma cells
Fudong LIANG ; Shufang DI ; Wei LUO ; Jianghua QI ; Libing LIU
China Pharmacy 2025;36(6):698-703
OBJECTIVE To investigate the relationship of long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and doxorubicin (DOX) resistance in osteosarcoma (OS) cells. METHODS MG-63 and MG-63/DOX cells were treated with different concentrations of DOX (0, 0.01, 0.05, 0.1, 1 μmol/L), and survival rates and half maximal inhibitory concentration were determined using CCK-8 assay. The expressions of LncRNA MALAT1 in MG-63 and MG-63/ DOX cells were detected by real-time quantitative fluorescence PCR. MG-63/DOX cells were divided into Control group, knocking down LncRNA MALAT1 negative control (sh-NC) group, sh-MALAT1 group, sh-MALAT1+anti-NC group, and sh-MALAT1+ anti-miR-154-5p group. The expressions of LncRNA MALAT1, miR-154-5p and cyclin D1 (CCND1) mRNA in MG-63/DOX cells of each group were detected. The effects of knocking down LncRNA MALAT1 on the proliferation, migration, invasion, and apoptosis of MG-63/DOX cells were detected by CCK-8 assay, scratch test, Transwell experiment and flow cytometry, respectively. The expression of proliferating cell nuclear protein (PCNA) and CCND1 protein in MG-63/DOX cells was detected by Western blot assay. Interactions between LncRNA MALAT1 and miR-154-5p, miR-154-5p and CCND1 were detected by dual luciferase reporter gene experiment. RESULTS Compared with 0 μmol/L DOX, 0.01, 0.05, 0.1 and 1 μmol/L DOX could reduce the survival rates of MG-63 and MG-63/DOX cells (except for 0.01 μmol/L DOX) (P<0.05), IC50 were 0.07 and 0.13 μmol/L, respectively. The survival rate, cell migration number and invasion number of MG-63/DOX cells, scratch closure rate, mRNA expressions of LncRNA MALAT1, mRNA and protein expressions of CCND1, and PCNA protein expression in sh-MALAT1 group were significantly lower than sh-NC group and Control group; the apoptosis rate and miR-154-5p expression were significantly higher than sh-NC group and Control group (P<0.05). sh-MALAT1+anti-miR-154-5p group was able to reverse the aforementioned biological effects in sh-MALAT1 group (P<0.05). In MG-63/DOX cells transfected with both MALAT1-wild type (WT) and CCND1-WT, the luciferase activity in the miR-154-5p mimic group was significantly lower than mimic negative control group (P< 0.05). CONCLUSIONS Knocking down LncRNA MALAT1 can inhibit the DOX resistance of OS cells, and its mechanism may be targeting the miR-154-5p/CCND1 axis.
2.Development and evaluation of nomogram prediction model for refractory chemotherapy-induced nausea and vomiting
Bo SUN ; Shufang LI ; Xun LIU ; Lu CHEN ; Erfeng ZHANG ; Huipin WANG
China Pharmacy 2025;36(9):1105-1110
OBJECTIVE To construct and evaluate nomogram prediction model for refractory chemotherapy-induced nausea and vomiting (CINV). METHODS The data of malignant tumor patients who received chemotherapy at the Third People’s Hospital of Zhengzhou from January 2017 to December 2023 were collected. These patients were categorized into the occurrence group and the non-occurrence group according to the occurrence of refractory CINV. Multivariate Logistic regression analysis was employed to screen predictive factors for refractory CINV and constructing a nomogram prediction model. Model performance was assessed via receiver operating characteristic curve analysis. Model calibration was evaluated using Bootstrap resampling. Decision curve analysis (DCA) was used to determine the clinical net benefit of three strategies under different risk thresholds. Clinical impact curves were utilized to assess the clinical value of the model at different risk thresholds. Shapley additive explanations (SHAP) analysis was performed to evaluate individual factor contributions to the predictive model. RESULTS A total of 388 patients were included, with 219 experiencing refractory CINV. Multivariate Logistic regression identified 11 predictive factors for refractory CINV, including gastrointestinal disease history, anticipated nausea and vomiting, chemotherapy-induced emetic risk classification, and electrolyte levels, etc. The model’s area under the curve was 0.80 [95% confidence interval (0.76, 0.84)], with a mean error of 0.036. DCA demonstrated the prediction model had higher clinical net benefit when the risk threshold was between 0.05 and 0.85. SHAP analysis revealed the top three predictive factors as gastrointestinal disease history (0.924), chemotherapy- induced emetic risk classification (0.866), and electrolyte levels (0.581). CONCLUSIONS Eleven factors, including gastrointestinal disease history, anticipated nausea and vomiting, chemotherapy-induced emetic risk classification, and electrolyte levels, are identified as predictors of refractory CINV. The model based on these factors has good predictive ability, which can be used to predict the risk of refractory CINV.
3.Differences in gut microbiota among primary school students with different levels of sugar sweetened beverage consumption
Chinese Journal of School Health 2024;45(3):335-340
Objective:
To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies.
Methods:
In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared.
Results:
Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05).
Conclusions
There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.
4.Metanephric stromal tumor in children with BRAF V600E gene mutation: a case report and literature review
Shuting MAO ; Dao WANG ; Bai LI ; Shanshan LIU ; Linlin WEI ; Shufang SU ; Yan XU ; Ya′nan MA ; Ge ZHOU ; Yufeng LIU
Chinese Journal of Applied Clinical Pediatrics 2024;39(4):306-310
The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.
5.Correlation analysis of ICAM-1 and NF-κB expression with hepatic inflammatory activity and degree of fibrosis in liver tissues of chronic hepatitis B patients
Tao LI ; Rilin LI ; Zongshu XIE ; Xiuzhen YANG ; Dongming SHE ; Zhijuan LIU ; Shufang YUAN
Chongqing Medicine 2024;53(1):98-101
Objective To detect the expressions of intercellular adhesion molecule-1(ICAM-1)and nu-clear factor(NF)-κB in hepatic tissues of the patients with chronic hepatitis B,and to analyze their correlation with the hepatic inflammatory activity and fibrosis degree.Methods The liver biopsy specimens from 66 pa-tients with hepatitis B and 10 non-hepatopathic controls were selected,and immunohistochemistry and in situ hybridization were used to detect ICAM-1 and NF-κB expression levels in different liver tissues.Results The positive rate of ICAM-1 and NF-κB expression in liver tissues of the patients with chronic hepatitis B was higher than that in normal liver tissues,and the difference was statistically significant(P<0.05).The expres-sion of ICAM-1 and NF-κB in the patients with hepatitis B was positively correlated with the inflammatory ac-tivity and fibrosis degree(r=0.493,0.496,P<0.01;r=0.580,0.519,P<0.01).Conclusion ICAM-1 and NF-κB in the patients with chronic hepatitis B are highly expressed,which is useful in judging the hepatic in-flammatory activity and fibrosis degree.
6.Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer
Shufang ZHANG ; Yan LI ; Lun LIU ; Xiaoning GENG ; Bo ZHOU ; Zhongtao ZHANG ; Fulei LIU
China Pharmacy 2024;35(10):1254-1259
OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase,the Cochrane Library, PubMed, CNKI, and Wanfang databases, cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature, extracting data and evaluating quality, meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included, involving 1 321 patients. There was no correlation between the three genotypes and effective rate, the incidence of myelosuppression, the incidence of neurotoxicity (except for the allele and recessive model of ABCB1 C1236T), and the incidence of hypersensitivity reactions (P>0.05). The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes (P<0.05), there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab (P<0.05). ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens; recessive model with sample size <100 and the African region were correlated with the incidence of peripheral neuropathy; recessive model was correlated with cutaneous adverse reactions (P<0.05). ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100; the incidence of white blood cell count reduction with sample size <100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model; the incidence of infections was correlated with the dominant model (P<0.05). The incidence of neutrophil count reduction with the sample size <100 was correlated with allele model of ABCB1 G2677T/A; the incidence of edema with sample size ≥100 was correlated with allele model and recessive model; the incidence of infection was correlated with allele model and dominant model, especially in patients with neutrophil count complicated with fever (P<0.05). CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer, but ABCB1 C3435T genotype is associated with decreased neutrophil counts, decreased white blood cell counts and infections; ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions; ABCB1 G2677T/A genotype is associated with decreased neutrophil counts, infections, and edema.
7.Assessment of dietary exposure to lead, cadmium, mercury, arsenic and aluminum among residents in Henan Province
CHAO Feng ; LIU Bingrui ; FU Pengyu ; ZHANG Shufang ; LI Shan ; YUAN Pu
Journal of Preventive Medicine 2024;36(11):971-975,979
Objective:
To assess the exposure levels of lead, cadmium, mercury, arsenic and aluminum in the diets of residents in Henan Province, so as to provide the basis for strengthening food safety supervision.
Methods:
Six sampling points were selected using stratified random sampling method in Henan Province, including Hebi City, Xiangfu District of Kaifeng City, Jianxi District of Luoyang City, Yuzhou City, Baofeng County and Tanghe County. Food samples were collected and processed into mixed samples of 12 major food categories. The levels of lead, cadmium, mercury, arsenic and aluminum in the samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). Dietary consumption information in Henan Province was collected. The dietary exposure risks of lead, cadmium, mercury, arsenic and aluminum were analyzed using the point estimation method and distribution point estimation method, based on the health guidance values of the Joint FAO/WHO Expert Committee on Food Additives and the margin of exposure (MOE) as the assessment criteria.
Results:
The dietary exposure level of lead among residents in Henan Province was 41.89 μg/d, which was equivalent to 18.62% of its provisional tolerable weekly intake (PTWI), with cereals and vegetables being the main sources; the MOE values of lead among residents aged 2 to <7 years and 7 to <13 years were both less than 1. The dietary exposure level of cadmium was 10.79 μg/d, which was equivalent to 20.55% of the provisional monthly tolerable intake, with cereals and vegetables being the main sources. The dietary exposure level of total mercury was 0.45 μg/d, which was equivalent to 1.25% of its PTWI, with cereals, vegetables, and water and beverage categories being the main sources; the dietary exposure level of methylmercury was 0.04 μg/d, which was equivalent to 0.28% of its PTWI, and it was entirely derived from aquatic products. The dietary exposure level of total arsenic was 26.65 μg/d, which was equivalent to 0.89% of the daily allowable intake, with cereals and vegetables being the main sources; the dietary exposure level of inorganic arsenic was 8.41 μg/d, which was equivalent to 6.23% of its PTWI, with an MOE value of 22.47. The dietary exposure level of aluminum was 8.27 mg/d, which was equivalent to 45.94% of its PTWI, with cereals and tubers being the main sources; the P90 and P97.5 of dietary aluminum exposure among residents aged 2 to <7 years and 7 to <13 years were both greater than PTWI.
Conclusion
The overall dietary exposure risks of lead, cadmium, mercury, arsenic and aluminum among residents in Henan Province are relatively low.
8.Analysis of the characteristics and drug-resistance of childhood intestinal bacterial infection in Kunming area
Cuilian LI ; Shufang XIAO ; Honglin LIU ; Li JIANG ; Mingbiao MA ; Ling LIU
Chinese Pediatric Emergency Medicine 2024;31(9):673-677
Objective:To analyze the situation of intestinal bacterial infections and drug resistance in children,and provide reference for the rational use of drugs in the treatment of bacterial enteritis.Methods:We collected cases of diarrhea in children admitted to the outpatient and inpatient departments of Kunming Children's Hospital from January 2014 to December 2022,whose fecal samples was detected pathogenic bacteria.The drug resistance of pathogenic bacteria was analyzed.Results:A total of 10 233 children with diarrhea were tested for fecal samples,and 595 cases of pathogenic bacteria were detected through fecal culture,with a detection rate of 5.8%.Among them,456 cases of Salmonella were detected,accounting for 76.6%.There were 128(21.5%) cases of Shigella genus,of which Shigella flexneri was the main subset(58.6%).The distribution of departments was most common in the gastroenterology department,followed by the infectious disease wards.The seasonal distribution of bacterial enteritis showed that the incidence was high in summer and autumn.Infants and young children under three years old was found have the highest incidence.The drug sensitivity results showed that Salmonella and Shigella had high resistance to penicillin and aminoglycosides,and were highly sensitive to amoxicillin/clavulanic acid,quinolones,and carbapenems; Cephalosporins had good antibacterial activity against Salmonella,with a resistance rate of 12.9% to 32.7%.However,the overall resistance rate of Salmonella to ceftriaxone and ceftazidime was on the rise.Cefotaxime and cefepime had good antibacterial activity against Shigella,but Shigella had a high resistance rate of 95.0% to ceftriaxone.Conclusion:Salmonella is the main pathogen causing bacterial diarrhea in Kunming region,with the highest incidence in infants and young children under the age of three.The resistance rate of Salmonella to ceftriaxone is on the rise,and it is highly sensitive to amoxicillin/clavulanic acid,quinolones,and carbapenems.This can provide local medication references for primary clinical pediatricians when they cannot obtain the results of bacterial culture drug sensitivity.
9.Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China
Rong LIU ; Zhicai YU ; Changxue XIAO ; Shufang XIAO ; Juan HE ; Yan SHI ; Yuanyuan HUA ; Jimin ZHOU ; Guoying ZHANG ; Tao WANG ; Jianyu JIANG ; Daoxue XIONG ; Yan CHEN ; Hongbo XU ; Hong YUN ; Hui SUN ; Tingting PAN ; Rui WANG ; Shuangmei ZHU ; Dong HUANG ; Yujiang LIU ; Yuhang HU ; Xinrui REN ; Mingfang SHI ; Sizun SONG ; Jumei LUO ; Juan LIU ; Juan ZHANG ; Feng XU
Chinese Journal of Pediatrics 2024;62(3):204-210
Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.
10.Changes of physical fitness before and after regular aerobic exercise in children after radical pulmonary atresia surgery
Xiaowei LI ; Xiaotong LAI ; Yunting LI ; Chenghao ZHANG ; Jiaxin ZHUANG ; Junhao CHEN ; Shufang LIU ; Wenjing LI ; Xiaojuan ZHENG ; Yugong GUO ; Yanqin CUI
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):672-679
Objective:To examine the effect of short-term regular aerobic exercise on physical fitness of children with pulmonary with atresia ventricular septal defect after radical biventricular treatment.Methods:This was a prospective self pre-and post-control observation study. The subjects performed regular aerobic exercise for 10 days according to the exercise prescription. Body composition measurement and cardiopulmonary exercise test[lung ventilation function, maximum oxygen uptake(VO 2max), maximum oxygen pulse(O 2/HR max), ventilation oxygen uptake efficiency(OUES), exercise load time], 6 min walking distance(6MWD), sports psychometric test, motor function screening test and fitness test, were collected. The changes of test parameters and scale scoring before and after exercise were analyzed and compared. Results:A total of 7 children with PA/VSD after biventricular surgery were enrolled. The age ranged 8.2-16.2 years old, and there were 2 males and 5 females. VO 2max[(1 196.71±395.31)ml/min vs.(1 297.43±425.73)ml/min, P=0.031], O 2/HRmax[(82.43±7.53)ml/beat vs.(91.57±6.95)ml/beat, P<0.001]increased after exercise. The exercise load time was significantly increased compared with that before intervention[(476.43±35.73)s vs.(531.43±45.76)s, P=0.002]. Resting heart rate before exercise( P=0.013) and peak respiration exchange ratio(PeakRER, P=0.021) were significantly lower. Body composition tests suggest weight, intracellular water, protein and muscle content of lower limb were higher( P<0.05). The motor function score was higher than before( P=0.015); the score of sports fear was lower than before( P=0.009). There was no significant difference in lung capacity and 6-minute walking distance before and after exercise( P>0.05). There were no cardiovascular events during the study period. Conclusion:Short-term regular aerobic exercise for children with PA/VSD after biventricular surgery can improve exercise tolerance, increase lower limb muscle content, improve exercise fear and exercise function, and has good safety and feasibility.


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