1.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.
2.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
3.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
4.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
5.Status of wearable flexible monitoring devices based on organic field effect transistors in biomedical field
Kai GUO ; Cui-Zhi TANG ; Bo SUN ; Duan-Qiang XIAO ; Yuan-Biao LIU ; En-Xiang JIAO ; Jie GONG ; Hai-Jun ZHANG
Chinese Medical Equipment Journal 2024;45(1):93-100
The working principle and development of flexible semiconductor devices based on organic field effect transistor(OFET)technology were introduced.The current research status of OFET-based wearable flexible monitoring devices were reviewed,including biomechanical monitoring devices,tattoo biomonitoring devices and cellular detection devices and etc.The deficiencies of OFET-based wearable flexible monitoring devices were analyzed,and it's pointed out that miniaturization,personalization and diversification were the directions for the development of the future OFET-based wearable flexible moni-toring devices.[Chinese Medical Equipment Journal,2024,45(1):93-100]
6.Preparation and in vivo pharmacokinetics of nanosuspensions of naringenin phospholipids complex
Xiao-Meng LI ; Wu-Mei ZHENG ; Zhi-Qiang ZHANG
Chinese Traditional Patent Medicine 2024;46(1):41-48
AIM To prepare the nanosuspensions of naringenin phospholipids complex,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was applied to preparing the nanosuspensions of phospholipids complex.With stabilizer type,stabilizer-phospholipids complex consumption ratio,homogeneous pressure and homogeneous frequency as influencing factors,particle size,PDI and Zeta potential as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which X-ray powder diffraction analysis was performed,solubility,oil-water partition coefficient,dissociation rate of phospholipids complex and accumulative release rate were determined.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of naringenin and its phospholipids complex,nanosuspensions and nanosuspensions of phospholipids complex(30 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 50 mg for naringenin consumption,PVP K30+TPGS(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-phospholipids complex consumption ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,respectively.The obtained spherical-like or oval nanosuspensions of phospholipids complex demonstrated the average particle size,PDI and Zeta potential of(260.53±25.86)nm,0.160±0.024 and(-31.08±1.37)mV,respectively.Naringenin existed in the nanosuspensions of phospholipids complex in an anamorphous state,along with increased solubility,oil-water partition coefficient and dissociation rate of phospholipids complex,and the accumulative release rate reached more than 90%within 4 h.Compared with raw medicine and nanosuspensions,the nanosuspensions of phospholipids complex displayed shortened tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.38 times.CONCLUSION The nanosuspensions of phospholipids can enhance naringenin's solubility and dissolution rate,and promote its in vivo absorption.
7.Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology
Jin Zi ZHAO ; Ping Xiao CHEN ; Wei Shao HUA ; Yu Feng LI ; Meng ZHAO ; Hao Chen XING ; Jie WANG ; Yu Feng TIAN ; Qing Rui ZHANG ; Na Xiao LYU ; Qiang Zhi HAN ; Xin Yu WANG ; Yi Hong LI ; Xin Xin SHEN ; Jun Xue MA ; Qing Yan TIE
Biomedical and Environmental Sciences 2024;37(4):387-398
Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.
8.Application of different transbronchoscopic biopsies in the diagnosis of senile central lung cancer
Pei ZHAN ; Yu ZHANG ; Fei-Yan LAN ; Wei YANG ; Xiao-Shuang LIAO ; Zhi-Qiang TIAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1081-1084
Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.
9.Application of single-port thoracoscopic surgery for non-small cell lung cancer in the elderly
Zhi-Qiang WU ; Yong-Qiang WEI ; Hong-Li WAN ; Xiao-Fei ZENG ; Hong WANG ; Xian-Bo WANG
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1089-1092
Objective To investigate the clinical efficacy and safety of single-port thoracoscopic surgery for elderly patients with non-small cell lung cancer(NSCLC).Methods The clinical data of 93 patients with NSCLC who underwent thoracoscopic lobectomy or segmentectomy was collected,the patients were divided into uniportal operation group(40 cases,received single-port thoracoscopic surgery)and single-operation port operation group(53 cases,received single-operation port thoracoscopic surgery)according to the operation methods.The operation time,the amount of blood loss,the number of lymph node dissection,chest drainage volume 3 days after surgery,duration of indwelling drainage tube,postoperative hospital stay,visual analogue scale(VAS)score of postoperative pain,and incidence of postoperative complications of patients between the two groups were compared.The cumulative survival rate between the two groups was compared.Results The operation were successfully completed in both groups.There was no statistically significant difference in terms of operation time,the amount of blood loss,the number of lymph node dissection,chest drainage volume 3 days after surgery,duration of indwelling drainage tube,or postoperative hospital stay of patients between the two groups(P>0.05).There was significant difference in VAS score of postoperative pain of patients between the two groups(P<0.05).There was no early death within 1 months after surgery in both groups.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 4 to 30 months of follow-up,there was no significant difference in the cumulative survival rate between the two groups(P>0.05).Conclusion Single-port thoracoscopic lobectomy or segmentectomy for elderly patients with NSCLC has high safety and feasibility,with less trauma,faster recovery and less postoperative pain.
10.Chemical constituents from Rhinacanthus nasutus and their in vitro antitumor and lipid-lowering activities
Zhi-Qiang GONG ; Yang XIAO ; Sha HAN ; Ying LIU ; Jin QI ; Yu HUO ; Yan-Hong HUANG ; Li-Fang YANG
Chinese Traditional Patent Medicine 2024;46(8):2630-2637
AIM To study the Chemical constituents from Rhinacanthus nasutus(L.)Kurz and their in vitro antitumor and lipid-lowering activities.METHODS The ethyl acetate fraction from R.nasutus was isolated and purified by normal phase,reverse phase silica gel column and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-tumor activity was determined by MTT assay,and the in vitro lipid-lowering activity was evaluated by oleic acid-induced HepG2 high-fat cell model.RESULTS Twenty compounds were isolated and identified as rhinacanthin A(1),rhinacanthin B(2),rhinacanthin C(3),rhinacanthin D(4),rhinacanthin E(5),rhinacanthin M(6),rhinacanthin N(7),rhinacanthin Q(8),rhinacanthin T(9),rhinacanthone(10),β-sitosterol(11),gallic acid(12),vanillic acid(13),syringic acid(14),lapachol(15),umbelliferone(16),sambucunlin A(17),17α,21-dihydroxy-1,4-pregnadiene-3,11,20-trione,21-acetate(18),1,8-dihydroxyanthraquinone(19),2,6-dimethoxy-1,4-benzoquinone(20).Compounds 3 and 7 inhibited the proliferation of HepG2,Hela,A549 and H22 tumor cells with IC50 values of(0.66±0.17)-(3.22±0.49)μmol/L in a time-and concentration-dependent manner.Compounds 3,7 and 9 had a lipid clearance rate of more than 50%in oleic acid-induced HepG2 high-fat cells.CONCLUSION Compounds 16-20 are isolated from this plant for the first time.Compounds 3 and 7 have good in vitro anti-tumor activities,and 3,7,9 have good in vitro lipid-lowering activities.

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