1.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
2.Establishment of UPLC characteristic chromatogram and component analysis of the volatile oil in the standard decoction of Qingshang juantong decoction
Zhiying FAN ; Qianqian ZHU ; Xiehe WANG ; Yanjuan ZHAI ; Huimin WANG ; Yangxin GU ; Haiqin ZHOU ; Tulin LU ; Kewei ZHANG ; Song LI
China Pharmacy 2024;35(9):1082-1086
OBJECTIVE To establish the characteristic chromatogram of the volatile oil in the standard decoction of Qingshang juantong decoction, and preliminarily infer the main active components of volatile oil that affect the clinical therapeutic effect. METHODS The volatile oil in the standard decoction of Qingshang juantong decoction was extracted by steam distillation. The ultra-high performance liquid chromatography (UPLC) characteristic chromatograms of 15 batches of samples were established by the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition), and the similarity evaluation was carried out. The volatile oil of standard decoction was identified by UPLC coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then the volatile oil components were analyzed by GC-MS. RESULTS The similarities of UPLC characteristic chromatograms for volatile oil of 15 batches of Qingshang juantong decoction were between 0.949 and 0.997. A total of 12 common peaks were obtained. According to the UPLC-Q-TOF/MS, the main components were methyl eugenol, E-ligustilide, E-butylidenephthalide and so on. A total of 23 components were identified by GC-MS, which were mainly 3,4,5-trimethoxy- methylbenzene, patchouli alcohol, Z-ligustilide and so on. CONCLUSIONS The characteristic chromatograms of the volatile oil in the standard decoction of Qingshang juantong decoction is established, and it is inferred that methyl eugenol, ligustilide, E- butylidenephthalide, patchouli alcohol, 3,4,5-trimethoxy-methylbenzene might be the main active components affecting the clinical therapeutic effect of the volatile oil of Qingshang juantong decoction.
3.Trends and factors associated with overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023
Chinese Journal of School Health 2024;45(8):1176-1180
Objective:
To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies.
Methods:
In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys.
Results:
The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively,showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05).
Conclusions
The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.
4.Clinical observation of tolvaptan in the treatment of heart failure with preserved ejection fraction complicated with hyponatremia
Qing MU ; Zhiying LI ; Jingdi ZHANG ; Zhanhai ZHANG ; Weifeng SONG
China Pharmacy 2024;35(18):2283-2287
OBJECTIVE To explore the therapeutic effect and safety of tolvaptan in the treatment of heart failure with preserved ejection fraction (HFpEF) complicated with hyponatremia. METHODS Overall 106 patients with HFpEF complicated with hyponatremia were collected from the Department of Cardiology in the First Affiliated Hospital of Nanyang Medical College from January 1, 2020 to June 1, 2023. According to the random number table, the patients were divided into conventional treatment group (n=53) and tolvaptan group (n=53). The conventional treatment group was given conventional treatment. Tolvaptan group additionally received Tolvaptan tablets 15 mg on the basis of conventional treatment group, increasing to 30 mg after 24 h, and then adjusting the dosage according to the levels of serum sodium; the maximum dose should not exceed 60 mg/d, and the medication should be stopped when the serum sodium level was≥150 mmol/L. Both groups of patients were treated for 6 months. The levels and changes of cardiac function indexes [left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), N-terminal pro-brain natriuretic peptide (NT-proBNP)], 24 h urine output, serum sodium, blood creatinine and urea nitrogen were compared between 2 groups before and after treatment. The occurrence of adverse drug reaction (ADR) was recorded. RESULTS Before treatment, there was no statistically significant difference in those indexes between 2 groups (P>0.05). After treatment, the levels of LVEF, 24 h urine output and serum sodium in 2 groups were significantly higher than before treatment, and the tolvaptan group was significantly higher than the conventional treatment group; the levels of LVESD, LVEDD and NT-proBNP were significantly lower than before treatment, and the tolvaptan group was significantly lower than the conventional treatment group (P<0.05 or P<0.01). The changes in cardiac function indexes, 24 h urine output and serum sodium levels in the atorvastatin group were more significant than the conventional treatment group (P<0.05). There was no statistically significant difference in the levels and changes of blood creatinine and urea nitrogen before and after treatment, as well as the incidence of nausea and vomiting, dizziness, hypernatremia and frequent urination between 2 groups (P>0.05). CONCLUSIONS Tolvaptan can improve cardiac function and increase the blood sodium levels in patients with HFpEF complicated with hyponatremia, without affecting their renal function or increasing the risk of ADR.
5.Exploration of the Disease Mechanism and Treatment of Colorectal Cancer Based on the "One Qi Circulation"
Zhiying WANG ; Ling XU ; Jialin YAO ; Jiajun SONG ; Yun LI ; Shujuan FU ; Yabin GONG ; Yi ZHONG
Journal of Traditional Chinese Medicine 2024;65(10):1068-1071
Based on the theory of "one qi circulation" founded by HUANG Yuanyu, the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward, which leads to the turbidity assemble in large intestine, forming the carcinoma toxin, and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi, Huangya Decoction (黄芽汤) as the basic formula, the circulation of qi ascending and descending as the base, adjusting ascending and descending together with Xiaqi Decoction (下气汤), and differentiating the syndrome on yin-yang excess-deficiency; for spleen-kidney yang deficiency syndrome, treated with Tianhun Decoction (天魂汤) to supplement liver, kidney and assist yang; for liver-kidney yin deficiency syndrome, treated wtih Dipo Decoction (地魄汤) to supplement lung, kidney, and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.
6.Comorbidity of myopia and scoliosis in primary and secondary school students and analysis of risk factors in school environment in Tianjin
ZHANG Xianwei, CHEN Lu, LIU Zhonghui, DONG Yanhui, SONG Yi, SUN Zhiying, XU Ke, ZHAO Saisai
Chinese Journal of School Health 2024;45(5):626-629
Objective:
To investigate the comorbidity of myopia and scoliosis among primary and secondary school students in Tianjin, and to analyze the school environment risk factors contributing to these health issues, so as to provide a scientific basis for development effective prevention measures.
Methods:
A total of 41 654 primary and secondary school students from 16 districts of Tianjin were selected by stratified random cluster sampling from September to October 2023 to screen for myopia and scoliosis. Univariate analysis was performed to examine the data, followed by a bivariate multivariate Logistic regression model and cumulative effect analysis to explore the influencing factors of their comorbidity.
Results:
In 2023, the prevalence of comorbidity of screening positive myopia and scoliosis among primary and secondary school students in Tianjin was 2.65%. The prevalence was higher in suburban areas (3.26%) compared to urban areas (2.02%), higher among females (3.81%) compared to males (1.59%), and highest in high school students (6.17%) compared to middle school (4.19%) and primary school students (0.44%) (χ2=62.23, 198.69, 953.19, P<0.01). Logistic regression analysis showed that the number of physical education classes ≥3 per week, the number of eye health exercises at school ≥2 per day, outdoor activities between classes, teachers reminding to pay attention to reading and writing posture and strict eye standing posture were negatively correlated with the comorbidity of screening positive myopia and scoliosis (OR=0.66, 0.77, 0.71, 0.78, 0.74, P<0.05). Reading or electronic screen while lying or lying on the stomach was positively associated with the comorbidity of screening positive myopia and scoliosis (OR=1.77, P<0.05). Cumulative effect analysis showed that the cumulative score (4-7, 7-9, ≥10) was negatively correlated with the comorbidity of screening positive of myopia and scoliosis (OR=0.65, 0.55, 0.52, P<0.05).
Conclusions
The school environment support and students personal behavior habits in school are related to the comorbidity of comorbidity of screening positive myopia and scoliosis. Prevention and control of myopia and scoliosis should improve the environmental factors related to students health in school.
7.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
8.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
9.Research advances in the role of blood metabolic markers in the treatment response and prognosis prediction of primary liver cancer
Zhiying LIU ; Zhihang ZHOU ; Song HE
Journal of Clinical Hepatology 2023;39(10):2470-2475
Primary liver cancer is one of the most severe cancer burdens around the world. Metabolic reprogramming is one phenotype of cancer, and blood metabolic markers are closely associated with metabolic reprogramming and can predict the risk of recurrence and survival or assess the treatment response of liver cancer, with important significance in the stratified management of patients, the development of rational treatment strategies, and the improvement of patient prognosis. By reviewing the recent studies on blood metabolomics in assessing the treatment response or predicting the prognosis of liver cancer, this article summarizes the blood metabolites with predictive significance and their mechanism of action and analyzes the current research status, existing problems, and prospects of this field. It is believed that the metabolites, such as aromatic amino acids, lipids, and bile acids, have an important clinical value in predicting the prognosis of liver cancer, and metabolomics technology has great potential in finding useful metabolites, but there are still many issues to be solved, such as technical limitations, insufficient studies, and multiple influencing factors.
10.A comparative study of three palliative surgical approaches for pulmonary atresia with ventricular septal defect
Zhiying SONG ; Jinghao ZHENG ; Xiaomin HE ; Kai LUO ; Qi SUN ; Huiwen CHEN ; Zhongqun ZHU ; Hao ZHANG ; Zhiwei XU ; Jinfen LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(02):266-272
Objective To compare and investigate the efficacy and differences of modified B-T shunt, central shunt and right ventricle-pulmonary artery (RV-PA) connection in the treatment of pulmonary atresia with ventricular septal defect (PA/VSD). Methods A total of 124 children with PA/VSD underwent initial palliative repair in Shanghai Children's Medical Center from September 2014 to August 2019, including 63 males and 61 females, aged 7 days to 15 years. They were divided into in a modified B-T shunt group (55 patients), a central shunt group (22 patients) and a RV-PA connection group (47 patients). The clinical data of these children were retrospectively analyzed. Results There were 9 early deaths after palliation, with an early mortality rate of 7.3%. The mean follow-up time was 26.5±20.3 months, with 5 patients lost to follow-up, 5 deaths during the follow-up period, and 105 survivors. The 1-year and 5-year survival rates were both 89.7%. The monthly increased Nakata index was 5.2 (–0.2, 12.3) mm2/m2, 9.2 (0.1, 23.6) mm2/m2, 6.3 (1.8, 23.3) mm2/m2 in the modified B-T shunt group, the central shunt group, and the RV-PA connection group, respectively, with no statistical difference among the three groups. The 1-year survival rate was 85.3%, 78.4%, 95.2%, and the 5-year (4-year in the central shunt group) survival rate was 85.3%, 58.8%, 95.2% in the three groups, respectively, with a statistical difference among them (P<0.05). The complete repair rate was 36.5%, 19.0% and 67.4% in the three groups, respectively, with a statistical difference among the three groups (P<0.001). Conclusion All these three palliative surgical approaches can effectively promote pulmonary vascular development. But compared with systemic-pulmonary shunt, RV-PA connection has a lower perioperative mortality rate and can achieve a higher complete repair rate at a later stage, which is beneficial for long-term prognosis.


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