1.Epidemiological characteristics and pathogenic analysis of hand,foot,and mouth disease in Hebei province
Zehao LIU ; Le WANG ; Yanyan CAO ; Xiaotong YAN ; Xin ZHAO ; Wenhui LI ; Shengwang GE
Basic & Clinical Medicine 2024;44(9):1279-1283
Objective To identify epidemiological characteristics and pathogen distribution of hand,foot,and mouth disease(HFMD)in Hebei Children's Hospital in order to support prevention and treatment of HFMD.Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected.Real-time PCR was used to detect the specific classification of HFMD.Statistical analysis was performed according to the year,season,age,and sex and enterovirus type of HFMD in the children.Results From 2016 to 2023,the ratio of male to female patients among the 1 698 children admitted to Hebei Children's Hospital was 1.72∶1.Among them,the highest incidence rate in summer was 778 cases,accounting for 45.8%of all cases,followed by autumn,with a total of 614 cases,accounting for 36.2%of cases.The highest incidence was recorded in age group of 1-3 years,with a total of 1 032 cases(60.8%).The lowest incidence was 38 cases in age group>6 years old(2.2%);There were 988 cases of HFM(58.2%)caused by different strains of enterovirus undefined(EVU)except enterovirus 71(EV71)and coxsackievirus A16(CA16).Conclusions HFMD found in Hebei Children's Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16.High morbid-ity is found in children aged 1-3 years,and summer and autumn are the main epidemic seasons.This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.
2.Identification of Q-Markers Associated with the Anti-Inflammatory Effects of Salvia plebeia
Qingxin KONG ; Qixuan WANG ; Xiaoling JI ; Xueqin LIU ; Zehao LI ; Zhongyuan QU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1242-1253
Objective To clarify the anti-inflammatory quality markers(Q-markers)of Salvia plebeia and determine their contents,so as to provide a reference for the quality control of Salvia plebeia.Methods The main components of Salvia plebeia were characterized by high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS).According to the fragmentation information of the secondary mass spectrometry and the literature data,the analysis and identification were carried out.Further,the active components with high oral bioavailability(OB)and in line with the five principles of drug-like(DL)were screened from the identified chemical components through the SwissADME platform.The SwissTargetPrediction database was used to find and predict the component targets of Salvia plebeia.Disease targets were screened through online Mendelian Inheritance in Man(OMIM),GeneCards database,etc.String11.5 database and Cytoscape3.7.2 software were used to construct the PPI network and screen core targets.Gene Ontology(GO)annotation and KEGG pathway enrichment analysis were performed using DAVID6.8,and the enriched pathways were verified by experiments to clarify their mechanism of action.Reverse traceability was used to analyze the potential pharmacodynamic material basis of key pathways,experimental verification was carried out,and high-performance liquid chromatography(HPLC)content determination method was established.Results 36 main components were identified,including flavonoids and terpenoids.Further screening of 190 active ingredients and disease intersection targets;through network topology screening,18 core targets were obtained;enrichment analysis showed that the primary pathways involved in the anti-inflammatory effect of Salvia plebeia include:NF-κB signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway.Four related components including homoplantaginin,hispidulin,luteolin and isorhamnetin were obtained by reverse traceability of the NF-κB signaling pathway.Molecular docking demonstrated excellent docking activities of the 4 components to PTGS2 with the binding energies of-9.5,-9.7,-9.4,and-9.4 kcal·mol-1,respectively.According to the measurability of quality markers,it was determined that homoplantaginin and hispidulin could be used as anti-inflammatory quality markers of Salvia plebeia.Western Blot results showed that homoplantaginin and hispidulin could significantly reduce the expression of COX-2 and NF-κB p-p65(P<0.05,P<0.01).Conclusion The anti-inflammatory quality markers of Salvia plebeia are homoplantaginin and hispidulin,which can exert anti-inflammatory effects through the NF-κB pathway.
3.Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes
Xin LI ; Zehao LI ; Lin LI ; Tong LIU ; Cheng QIAN ; Yanlv REN ; Zhigao LI ; Kejin CHEN ; Dongchen JI ; Ming ZHANG ; Jinsong WANG
Cancer Research and Treatment 2024;56(1):134-142
Purpose:
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods:
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results:
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.
4.Preliminary study on high throughput screening small molecules targeting Gram-negative bacilli outer membrane protein BamA
Pengfei SHE ; Zehao LI ; Shasha LIU ; Yimin LI ; Linhui LI ; Yifan YANG ; Linying ZHOU ; Yong WU
Chinese Journal of Laboratory Medicine 2023;46(6):597-603
Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.
5.Influence of effects of transarterial chemoembolization before liver transplantation on the prognosis of hepatocellular carcinoma
Xiongwei ZHU ; Ziqiang LI ; Yan TIAN ; Bo YOU ; Yang YANG ; Bin LU ; Zehao WU ; Qing ZHANG ; Qingming SHU
Chinese Journal of Digestive Surgery 2022;21(2):256-264
Objective:To investigate the influence of effects of transarterial chemoembo-lization (TACE) before liver transplantation on the prognosis of hepatocellular carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted. There were 276 males and 35 females, aged from 47 to 59 years, with a median age of 52 years. All the 311 patients underwent TACE before liver transplantation. Observation indicators: (1) effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors; (2) follow-up; (3) influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation. Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017. The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation, and once every 1 to 3 months thereafter. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the nonparametric rank sum test. The COX regression model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors. Of the 311 patients undergoing TACE, 57 cases had pathologic complete response (pCR) and 254 cases had pathologic partial response (pPR), respectively. Cases with alpha fetoprotein (AFP) <20 μg/L,20?400 μg/L, >400 μg/L, cases with microvascular invasion, cases with tumor number as single nodule, cases with tumor distribution at right lobe of liver, cases with tumor caliber of feeding artery (CFA) >1 mm were 26, 26, 5, 51, 6, 43, 46 in patients with pCR, versus 87, 64, 103, 158, 59, 125, 159 in patients with pPR, showing significant differences in the above indicators ( Z=3.35, χ2=4.54, 15.71, 12.89, 6.79, P<0.05). (2) Follow-up. All the 311 patients were followed up for 47.0 to 59.0 months, with a median follow-up time of 44.6 months. There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR, and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR. The 1-, 3-, 5-year tumor recurrence free rates were 98.2%, 91.1%, 80.3% in the 311 patients, respectively. The 1-, 3-, 5-year tumor recurrence free rates were 100.0%, 91.1%, 80.3% in the 57 patients with pCR, versus 82.0%, 68.4%, 59.4% in the 254 patients with pPR, showing significant differences in the above indicators ( χ2=13.47, P<0.05). Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR, respectively, showing a significant difference ( χ2=7.06, P<0.05). (3) Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation. Results of univariate analysis showed that gender, basic diseases as viral hepatitis C, AFP (20?400 μg/L, >400 μg/L), Milan criteria, microvascular invasion, tumor number, tumor distribution, tumor CFA, times of TACE, effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.49, 3.97, 1.78, 1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95% confidence interval as 0.30?0.81, 2.23?7.05, 1.03?3.06, 1.18?2.85, 1.63?3.56, 1.28?3.01, 2.04?4.40, 1.20?2.59, 0.13?0.28, 1.28?3.14, 1.63?5.76, P<0.05). Results of multi-variate analysis showed that AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=1.59, 2.06, 1.99, 2.05, 95% confidence interval as 1.22?2.07, 1.35?3.13, 1.29?3.07, 1.02?4.10, P<0.05) and tumor CFA >1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.10, 95% confidence interval as 0.05?0.19, P<0.05). Conclusions:The effects of TACE are related to AFP, microvascular invasion, tumor number, tumor distribution and tumor CFA. AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA >1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.
6.Research on CD147 inhibiting oxidative stress in prostate cancer cells
Haiyue Xu ; Zehao Li ; Yongqi Han ; Liguo Wang ; Fang Fang
Acta Universitatis Medicinalis Anhui 2022;57(1):144-147, 152
Objective :
To investigate the effect of CD147 on reducing hydrogen peroxide - induced oxidative stress injury in prostate cancer LNCaP cells.
Methods :
The lentiviral system was used to establish a CD147 ⁃silencing prostate cancer cell model (LNCaP/shCD147 cells) and a negative control cell (LNCaP/Scramble cell) , and RT⁃qPCR was performed for verification. By detecting the activity of reactive oxygen species ( ROS) , superoxide dismutase (SOD) , glutathione peroxidase ( GSH⁃PX) and malondialdehyde ( MDA) in LNCaP/shCD147 and LNCaP/Scramble cells to verify the changes of oxidative stress and antioxidant enzymes in prostate cancer cells after silencing CD147 ; hydrogen peroxide( H2 O2 ) was added to the cells and the cell growth was detected by CCK⁃8 ; Western blot was used to detect the expression changes of nuclear factor E2 related factors (Nrf2) and heme oxygenase⁃1 (HO⁃1) to verify the relationship between the oxidative stress that occurs in prostate cancer cells after silencing CD147 and the PI3K/AKT signaling pathway.
Results :
Successfully constructed a CD147⁃silencing prostate cancer cell model. Compared with LNCaP/Scramble cells , the expression of CD147 in mRNA was reduced (P <0. 01) . The results of oxidative stress showed that the content of ROS and MDA in cells increased after silencing CD147 (ROS , P < 0. 01 ; MDA , P < 0. 05) , while the activities of SOD and GSH⁃PX decreased(P < 0. 01) , indicating that after silencing CD147 , LNCaP/shCD147 cells undergo oxidative stress. In addition , with the increase of H2O2 concentration , the survival rate of LNCaP/shCD147 group cells decreased (P < 0. 01) . After inhibiting the PI3K/AKT signaling pathway , the expressions of Nrf2 and HO⁃1 in the LNCaP/shCD147 group were reduced (P < 0. 01) , indicating that CD147 inhibits the oxidative stress injury of prostate cancer cells through the PI3K/AKT pathway.
Conclusion
CD147 can reduce the oxidative stress damage of PCa cells , and its inhibitory mechanism
may be related to the PI3K/AKT signaling pathway.
7.Changes in peripheral blood lymphocyte subsets in children with active tuberculosis
Shuo YANG ; Xiaotong YAN ; Teng LIU ; Mengchuan ZHAO ; Zehao LIU ; Guixia LI ; Zhishan FENG ; Le WANG
Chinese Journal of Microbiology and Immunology 2021;41(1):30-35
Objective:To analyze the changes in T lymphocyte subsets, B lymphocytes and NK cells in children with active tuberculosis (TB) and their clinical significance.Methods:T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood samples of 106 patients with acute TB (TB group) and 106 healthy children (healthy control group) were detected by flow cytometry and compared between different groups.Results:The percentages of CD3 + T, CD4 + T and NK cells as well as the CD4 +/CD8 + T cell ratio were significantly lower in the TB group than in the healthy control group ( Z=-3.783, P=0.000; Z=-5.401, P=0.000; Z=-3.434, P=0.001; Z=-2.014, P=0.044). The percentages of double negative T (DNT) and B cells in the TB group were significantly higher than those in the healthy control group ( Z=2.765, P=0.006; Z=6.880, P=0.000). No significant difference in the percentage of CD8 + T or double positive T (DPT) cells was observed between the two groups ( P>0.05). The expression of peripheral lymphocyte subsets varied in TB children of different age groups (0-<3, 3-<6, 6-<10 and 10-<16 years old). There were significant differences in CD3 + T, DNT and B cells among the four age groups ( H=10.081, P=0.018; H=14.583, P=0.002; H=8.498, P=0.037). The percentage of CD4 + T cells was significantly lower in children with extrapulmonary TB than in those with pulmonary TB ( Z=-3.068, P=0.002). No statistically significant difference in other lymphocyte subsets was found between children with extrapulmonary and pulmonary TB ( P>0.05). Conclusions:Tuberculosis could lead to immune dysfunction in children. Dynamic monitoring of the changes in peripheral lymphocyte subsets in children with TB could be conducive to better assessment of immune status and providing personalized treatment.
8.SingHealth Radiology Archives pictorial essay Part 2: gastroenterology, musculoskeletal, and obstetrics and gynaecology cases.
Mark Bangwei TAN ; Kim Ping TAN ; Joey Chan Yiing BEH ; Eugenie Yi Kar CHAN ; Kenneth Fu Wen CHIN ; Zong Yi CHIN ; Wei Ming CHUA ; Aaron Wei-Loong CHONG ; Gary Tianyu GU ; Wenlu HOU ; Anna Chooi Yan LAI ; Rebekah Zhuyi LEE ; Perry Jia Ren LIEW ; May Yi Shan LIM ; Joshua Li Liang LIM ; Zehao TAN ; Eelin TAN ; Grace Siew Lim TAN ; Timothy Shao Ern TAN ; Eu Jin TAN ; Alexander Sheng Ming TAN ; Yet Yen YAN ; Winston Eng Hoe LIM
Singapore medical journal 2021;62(1):8-15
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.
9.Construction and practice of the golden course "doctor-patient communication skills"
Ying HUANG ; Jing WU ; Wangbin NING ; Meihua XU ; Xinhua LI ; Zehao LIU ; Zongfeng DING ; Weiru ZHANG ; Xiaobin CHEN
Chinese Journal of Medical Education Research 2021;20(4):378-382
Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.
10.Repair of sciatic nerve defect in rats by adipose tissue decellularized matrix hydrogel
Yan LI ; Zhaoyang CHEN ; Youbai CHEN ; Jing REN ; Zehao NIU ; Wenwen PU ; Yan HAN
Chinese Journal of Microsurgery 2021;44(3):292-297
Objective:To observe the effect of adipose tissue decellularized matrix hydrogel (DAT-gel) on the repair of sciatic nerve defect in rats.Methods:From April, 2019 to April, 2020, aseptic granular adipose tissue was collected from healthy adult women who underwent thigh or abdominal liposuction in the Department of Plastic Surgery, the First Medical Centre of the PLA General Hospital. Decellularisation and enzymatic digestion of adipose tissue were performed to prepare DAT-gel. Scanning electron microscope (SEM) was used to observe the ultrastructure of the hydrogel, and rheology was employed to test the gel dynamics and viscoelasticity of the hydrogel. A rat model of sciatic nerve defect was established and randomly divided into 3 groups: simple chitin catheter group (Chitin group), DAT-gel plus chitin catheter group (DAT-gel group) and autologous nerve reverse connection group (Autograft group) with 10 rats in each group. At the 12th week after surgery, the general view, function and morphology of the regenerated nerve were observed to evaluate the repairing status of the injured nerve. One-way analysis of variance (one-way ANOVA) was used for data analysis. If the difference between the groups was statistically significant, the Turkey method was further used for pairwise comparison. P<0.05 was considered as statistically significant. Results:The results of SEM showed that the DAT-gel had a three-dimensional structure in porous fibre network. The results of rheological test results showed that the complex viscosity of the hydrogel at 4 ℃ and 37 ℃ were 148.91 mPa·s and 801.29 mPa·s, respectively. DAT-gel underwent a sol-gel phase transition when the temperature had been increased. The results showed that DAT-gel had a good temperature-sensitive effect, and its critical point of sol-gel phase transition was similar to the internal temperature of rat. The results of animal experiments showed that the morphology and function of the regenerated nerve in the DAT-gel group were superior to Chitin group at 12 weeks after surgery, according to macroscopic view of the regenerated nerve, electrophysiology of the nerve, the morphology of the new axon and the target muscle, etc.. There was statistically significant between groups ( P<0.05). Conclusion:DAT-gel can significantly promote a repair of sciatic nerve defects in rats.


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