1.A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma.
Hu CHEN ; Yongfu XIONG ; Minglei TENG ; Yesen LI ; Deliang ZHANG ; Yongjun REN ; Zheng LI ; Hui LIU ; Xiaofei WEN ; Zhenjie LI ; Yang ZHANG ; Syed Faheem ASKARI RIZVI ; Rongqiang ZHUANG ; Jinxiong HUANG ; Suping LI ; Jingsong MAO ; Hongwei CHENG ; Gang LIU
Acta Pharmaceutica Sinica B 2025;15(10):5022-5035
Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as 131I,177Lu, or 18F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, 18F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).
2.Drug Resistance and Prognosis of 150 Cases of Peritoneal Dialysis-associated Peritonitis
Yueyuan WU ; Xiaohua DAI ; Jie XU ; Xianfeng ZHANG ; Deyu XU ; Kun HU ; Lei SHEN ; Guoyuan LU ; Qiang HAN ; Yongfu HANG
Herald of Medicine 2024;43(2):287-291
Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33%,including 65 cases(70.65%)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39%),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96%)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00%),and were sensitive to linezolid(100.00%),teicoplanin(100.00%)and rifampicin(100.00%).The sensitivity rate to vancomycin was 98.59%.G-strains were sensitive to ceftazidime(86.36%),ceftizoxime(88.89%)and amikacin(100.00%).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33%in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23%vs.36.36%,P<0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.
3.Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus
Zhihui WU ; Mingzhi HU ; Qiaoying ZHAO ; Fengfeng LV ; Jingying ZHANG ; Wei ZHANG ; Yongfu WANG ; Xiaolin SUN ; Hui WANG
Journal of Peking University(Health Sciences) 2024;56(5):860-867
Objective:To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells(UC-MSCs)modified by miR-125b-5p on systemic lupus erythematosus(SLE).Methods:The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells(PBMCs)from SLE patients and health checkers.Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs.MRL/lpr mice in each group were injected with UC-MSCs via tail vein,and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks.The expression levels of interleukin(IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA.Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.Results:miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls(P<0.01).Compared with the UC-MSCs group,the expression of miR-125b-5p in UC-MSCs modified by miR-125b-5p group was increased(P<0.01).The survival rate of UC-MSCs was significantly increased by miR-125b-5p(P<0.01).Compared with the untreated group of MRL/lpr mice,the expression level of IL-4 in serum was increased(P<0.05);the expression level of IL-17A was decreased(P<0.05);the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased(P<0.05);the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.Conclusion:UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.
4.Immunomodulatory effect of miR⁃125b⁃5p modified umbilical cord mesenchymal stem cells mediated JAK2/STAT3 signaling pathway on systemic lupus erythematosus
Zhihui Wu ; Lili Ding ; Mingzhi Hu ; Yongfu Wang ; Hui Wang ; Wei Zhang ; Xiaolin Sun
Acta Universitatis Medicinalis Anhui 2023;58(1):28-36
Objective :
To investigate the imunomodulatory effects of umbilical cord mesenchymal stem cells(UC⁃MSCs) modified by miR⁃125b⁃5p through JAK2/STAT3 pathway on systemic lupus erythematosus(SLE) .
Methods:
UC⁃MSCs were isolated and cultured under aseptic conditions ; Peripheral blood mononuclear cells (
PBMCs)were separated from SLE patients by density gradient centrifugation. The relative expressions of IL⁃17A , Foxp3 ,IFN⁃γ , IL⁃4 genes in PBMCs cultured with UC⁃MSCs for 48 h were detected by RT⁃qPCR; The relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were detected by west⁃ern blot.
Results :
Compared with the PBMCs culture group , the expression of IFN⁃γ and IL⁃17A and the propor⁃tion of Th17/Treg cells were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group , UC⁃MSCs + miR⁃NC group and UC⁃MSCs group(P < 0. 01) , the expression of the proportion of Th1/Th2 cells (P < 0. 05) was down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group and UC⁃MSCs + miR⁃NC group ; Compared with the untreated group of MRL/lpr mice , the relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group (P < 0. 01) , and the rela⁃tive expressions of IL⁃18 proteins was significantly
down⁃regulated in UC⁃MSCs + miR⁃NC group and UC⁃MSCs group (P < 0. 01) .
Conclusion
miR⁃125b⁃5p plays a synergistic role in UC⁃MSCs ,which regulates the differenti⁃ation of Th2 cells in PBMCs of SLE patients and the relative expressions of p ⁃JAK2/JAK2 , p ⁃STAT3/STAT3 , and IL⁃18 proteins in kidney tissues of MRL/lpr mice. UC⁃MSCs modified by miR⁃125b⁃5p may play
immunomodulato⁃ry effect on SLE by JAK2/STAT3 signaling pathway.
5.Establishment of whole-process intelligent pharmaceutical care model for peritoneal dialysis patients
Yongfu HANG ; Yan XU ; Xiaohua DAI ; Tiantian WU ; Yinyin DUAN ; Deyu XU ; Kun HU ; Xingxing LIU ; Jianguo ZHU ; Liyan MIAO ; Lin LI
China Pharmacy 2023;34(21):2644-2648
OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis (PD) patients, and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University (hereinafter referred to as “our hospital”), with “home→PD center outpatient→ inpatient department” as the main node, the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems (DRPs) classification tool, developing the corresponding pharmaceutical care process, and presenting specific cases. RESULTS Based on the medication therapy management (MTM) platform, our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care (building document)-PD outpatient MTM-home pharmaceutical care (online App management)”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients, and can reduce DRPs.
6.Progress and perspective on development of non-model industrial bacteria as chassis cells for biochemical production in the synthetic biology era.
Yongfu YANG ; Binan GENG ; Haoyue SONG ; Mimi HU ; Qiaoning HE ; Shouwen CHEN ; Fengwu BAI ; Shihui YANG
Chinese Journal of Biotechnology 2021;37(3):874-910
The development and implement of microbial chassis cells can provide excellent cell factories for diverse industrial applications, which help achieve the goal of environmental protection and sustainable bioeconomy. The synthetic biology strategy of Design-Build-Test-Learn (DBTL) plays a crucial role on rational and/or semi-rational construction or modification of chassis cells to achieve the goals of "Building to Understand" and "Building for Applications". In this review, we briefly comment on the technical development of the DBTL cycle and the research progress of a few model microorganisms. We mainly focuse on non-model bacterial cell factories with potential industrial applications, which possess unique physiological and biochemical characteristics, capabilities of utilizing one-carbon compounds or of producing platform compounds efficiently. We also propose strategies for the efficient and effective construction and application of synthetic microbial cell factories securely in the synthetic biology era, which are to discover and integrate the advantages of model and non-model industrial microorganisms, to develop and deploy intelligent automated equipment for cost-effective high-throughput screening and characterization of chassis cells as well as big-data platforms for storing, retrieving, analyzing, simulating, integrating, and visualizing omics datasets at both molecular and phenotypic levels, so that we can build both high-quality digital cell models and optimized chassis cells to guide the rational design and construction of microbial cell factories for diverse industrial applications.
Bacteria/genetics*
;
Metabolic Engineering
;
Synthetic Biology
7.Chinese consensus on surgical treatment of traumatic rib fractures (2021)
Lingwen KONG ; Guangbin HUANG ; Yunfeng YI ; Dingyuan DU ; Baoguo JIANG ; Jinmou GAO ; Lianyang ZHANG ; Jianxin JIANG ; Xiangjun BAI ; Tianbing WANG ; Xingji ZHAO ; Xingbo DANG ; Zhanfei LI ; Feng XU ; Zhongmin LIU ; Ruwen WANG ; Yingbin XIAO ; Qingchen WU ; Chun WU ; Liming CHENG ; Bin YU ; Shusen CUI ; Jinglan WU ; Gongliang DU ; Jin DENG ; Ping HU ; Jun YANG ; Xiaofeng YANG ; Jun ZENG ; Haidong WANG ; Jigang DAI ; Yong FU ; Lijun HOU ; Guiyou LIANG ; Yidan LIN ; Qunyou TAN ; Yan SHEN ; Peiyang HU ; Ning TAO ; Cheng WANG ; Dali WANG ; Xu WU ; Yongfu ZHONG ; Anyong YU ; Dongbo ZHU ; Renju XIAO ; Biao SHAO
Chinese Journal of Trauma 2021;37(10):865-875
Traumatic rib fractures are the most common injury in thoracic trauma. Previously,the patients with traumatic rib fractures were mostly treated non-surgically,of which 50%,especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities,being unable to retain a full-time job. In the past two decades,thanks to the development of internal fixation material technology,the surgical treatment of rib fractures has achieved good outcomes. However,there are still some problems in clinical treatment,including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans,and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore,the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association,in conjunction with national multidisciplinary experts,formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures(2021)following the principle of evidence-based medicine,scientific nature and practicality. This expert consensus puts forward some clear,applicable,and graded recommendations from aspects of preoperative imaging evaluation,surgical indications,timing of surgery,surgical methods,rib fracture sites for surgical fixation,internal fixation methods and material selections,treatment of combined injuries in rib fractures,in order to provide references for surgical treatment of traumatic rib fractures.
8.Effect of terlipressin on hepatic and renal function in cirrhotic patients undergoing hepatectomy
Hongtao HU ; Hao REN ; Zhe TANG ; Renrui WAN ; Xiangyang LI ; Yang WU ; Yongfu ZHAO
International Journal of Surgery 2016;43(4):231-235
Objective To investigate the effect of terlipressin on hepatic and renal function in cirrhotic patients undergoing hepatectomy.Methods Aanlyze the clinical data of 57 patients following irregular hepatectomy for hepatocellular carcinoma with cirrhosis,according to whether use terlipressin or not after operation,which were divided into terlipressin group (A group,n =27) and control group (B group,n =30).Liver function parameters (ALT,AST,TB),ascites,urine volume and renal function parameters (Cr,BUN) preoperatively and on postoperative day(POD) 1,3,5 and 7 were compared between the two gruops.Results Compared with those of POD 1,the levels of ALT,AST and ascites on POD 3,5,7 were significantly lower in two groups (P < 0.05),urine volume was significantly increased (P < 0.05),Cr of POD 7 was significantly lower (P <0.05),but it is more remarkable in group A than group B.The levels of ALT in terlipressin group on POD 5,7 were (144.9 ±76.3) U/L,(100.5 ±61.5) U/L,which were lower than those of (267.2±91.2) U/L,(199.3 ±70.5) U/L in control group.On POD 3,5,7,the levels of AST,BUN,Cr and peritoneal fluid in terlipressin group,which were respectively(211.1 ±99.8) U/L,(80.4 ±54.6) U/L,(50.6 ±46.5) U/L,(6.6 ± 1.9) mmol/L,(6.5 ± 1.7) mmol/L,(6.3 ± 2.1) mmol/L,(74.3 ± 10.9) μmol/L,(71.5 ± 8.9) μmol/L,(58.7 ±4.1) μmol/L,(247.6±60.3) ml,(58.8±54.3) ml,(40.2±31.8) ml,were significantly lower than those in control group which were (298.7 ±131.2) U/L,(201.1 ±93.4) U/L,(114.7 ±70.3) U/L,(7.3 ± 1.9) mmol/L,(7.2±1.8) mmol/L,(7.1±1.7) mmol/L,(79.5±15.1) μmol/L,(76.9±16.2) μmol/L,(69.4±11.4) μmol/L,(275.2±88.1) ml,(191.7±71.6) ml,(93.2±50.2) ml.while urine volume of (2232.3±409.8) ml,(2270.5 ±395.8) ml,(2179.0±301.4) ml was much more than that of (1921 ± 510.4) ml,(2019.1 ±411.2) ml,(1978.7±323.7) ml in the control group,the differences in the two groups were statistically significant (P < 0.05).There were 11 (36.7%) patients with hepatic and renal dysfunction and hepatorenal syndrome after operation in group B,while only 2 (7.4%) patients in group A.Conclusions The use of terlipressin after partial liver resection has a protective effect on hepatic and renal function in patients with cirrhosis,and can reduce postoperative ascites and prevent hepatorenal syndrome.
9.Clinical value of anti-cyclic citrullinated peptides antibody in diagnosis, treatment and prognosis of rheumatoid arthritis
Wenlan ZHANG ; Tongping HU ; Yongfu WANG ; Fangrui YIN ; Jianbo ZHAO ; Xin WANG
Chinese Journal of Immunology 2015;(11):1541-1544
Objective:To investigate the diagnostic values of anti-cyclic citrullinated peptides antibody ( anti-CCP ) and rheumatoid factor( RF) in rheumatoid arthritis( RA) ,and analyse the clinical relevance of prognosis,drug reaction and bone destruction between anti-CCP and RA.Methods: Serum anti-CCP was detected by enzyme-linked immunosorbent assay ( ELISA ) , and RF was detected by immune rate nephelometry.Results:The sensitivity and specificity of anti-CCP in RA were 83.0%and 96.7%,while the sensitivity and specificity of RF in RA were 76.0%and 70.0%.When joint detect anti-CCP and RF,with anti-CCP or RF positive as a positive determination,with anti-CCP and RF negative as a negative judgment,the combined sensitivity was 87.0%,higher than that of detection alone.The combined specificity was 98.3%, higher than that of single detection.There were big different concentrations of anti-CCP among RA patients before treatment, three months after treatment and six months after treatment.There were significant differences between bone erosion and non-bone erosion in RA patients.And the more serious joint damage,the higher the concentrations of anti-CCP.As for treatment,anti-CCP concentrations declined.Conclusion:Combined detection of anti-CCP and RF can significantly improve the diagnosis and differential diagnosis of RA.The concentration of anti-CCP can change with effective treatment,then dynamic monitoring can be used as study drug efficacy.At the same time,the level of anti-CCP in patients with RA can reflect the degree of bone erosion,and serious bone destruction who was poor treatment effect.
10.Expression and prognostic significance of HLA-F in hepatocellular carcinoma
Yongfu XU ; Wenlong ZHANG ; Peng HU ; Yu ZHU ; Zheping FANG
Chinese Journal of General Surgery 2014;29(8):630-633
Objective To investigate the expression of human leukocyte antigen F (HLA-F) in hepatocellular carcinoma (HCC) tissues and to evaluate its relation to clinicopathological features and prognosis of HCC.Methods HLA-F expression of tumor lesions and their adjacent normal liver tissues from 115 HCC patients were analyzed by immunohistochemistry,and its relationship between HLA-F expression and the clinicopathological features and prognosis of HCC patients was also analyzed.Results HLA-F expression was positive in 47.0% (54/115) of the HCC lesions and in 10.6% (7/66) of the normal liver tissues (x2 =24.799,P < 0.05).HLA-F expression in HCC lesions was significantly correlated with portal vein invasions (x2 =7.644,P =0.006),tumor number (x2 =4.210,P =0.040) and patient sex (x2 =6.759,P =0.009).The mean survival time of the HLA-F positive HCC patients was 34.0 months(95% CI:27.5-40.5 months),which was significantly shorter than that of HLA-F negative HCC patients(44.6 months,95% CI:38.3-50.9months) (x2 =5.148,P =0.023).HLA-F expression was an independent predictor of overall survival of HCC patients.Conclusions Positive HLA-F expression is negatively correlated with the prognosis of HCC patients.


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