1.Discovery of E0199:A novel compound targeting both peripheral Nav and Kv7 channels to alleviate neuropathic pain
Boxuan ZHANG ; Xiaoxing SHI ; Xingang LIU ; Yan LIU ; Xuedong LI ; Qi WANG ; Dongyang HUANG ; Weidong ZHAO ; Junru CUI ; Yawen CAO ; Xu CHAI ; Jiahao WANG ; Yang ZHANG ; Xiangyu WANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(1):244-261
This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.
2.A comparative study of novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique and traditional 2-lobe technique HoLEP in BPH patients
Qifeng CAO ; Ning SHAO ; Jian KANG ; Xingang CUI ; Ding XU
Chinese Journal of Urology 2025;46(5):383-388
Objective:To compare the safety and efficacy of novel en-bloc Holmium laser enucleation of the prostate(HoLEP)with complete membranous urethral mucosa sparing technique with traditional 2-lobe technique HoLEP in benign prostatic hyperplasia(BPH)treatment.Methods:The data of BPH patients treated with HoLEP from January 2023 to May 2024 in Xinhua Hospital,School of Medicine,Shanghai Jiaotong University were retrospectively reviewed. Seventy-two patients received novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique(novel en-bloc group),while 79 patients received traditional 2-lobe technique HoLEP(traditional 2-lobe technique group).There was no significant difference between novel en-bloc group and traditional 2-lobe technique group in the age[(71.0 ± 7.1)years vs.(69.8 ± 6.5)years],body mass index[(24.5 ± 2.8)kg/m 2 vs.(23.9 ± 3.5)kg/m 2],international prostate symptom score(IPSS)[26.0(22.0,28.0)vs. 25.0(22.0,28.0)],quality of life(QOL)score[5.0(5.0,6.0)vs. 5.0(5.0,6.0)],prostate sepcific antigen(PSA)[4.98(2.40,11.11)ng/ml vs. 4.38(1.62,7.54)ng/ml]and prostate volume[(74.06 ± 42.67)ml vs.(70.10 ± 33.94)ml](all P > 0.05). The incidence of acute urinary retention in novel en-bloc group was significantly higher than that in traditional 2-lobe technique group[31.94%(23/72)vs. 17.72%(14/79), P = 0.042].The procedure of novel en-bloc was shown as followed:expose the prostatic capsule near the verumontanum and expand the initial capsule plane on both sides. The prostatic urethral mucosa was cut off in a circular pattern medial to the external urethral sphincter,which could form a complete “circular mucosal pad”. Seperate the apical gland along the capsule plane at 12 o’clock and expand the capsule plane until the bladder neck was reached.The bladder neck was then used as a marker so as to separate the glands on both sides along the capsule plane and merge with the initial plane. The entire lobe of the prostate was finally removed along the surgical capsule of the prostate. The procedure of traditional two lobe method was shown as followed:expose the prostatic capsule near the verumontanum and then divide the prostate into two lobes by longitudinal incision at 6 and 12 o’clock. The mucosa was horizontally cut at 12 o’clock,medial to the external urethral sphincter in order to preserve the apical urethral mucosal flap. The twp lobes were then removedd respectively along the capsule layer. The surgery-related indicators,perioperative complications and other data were compared between the two groups,as well as IPSS,QOL score,lower urinary tract symptoms,and the incidence of stress urinary incontinence in the two groups 1 month after surgery. Results:Compared with the patients underwent 2-lobe technique HoLEP,the patients underwent novel en-bloc HoLEP had lower hemoglobin loss[0.50(-5.50,7.50)g/L vs. 7.00(1.00,13.25)g/L, P = 0.003],lower operation time[(72.06 ± 34.37)min vs.(85.42 ± 40.35)min, P = 0.030],higher surgical efficacy[(0.72 ± 0.31)g/min vs.(0.55 ± 0.29)g/min, P = 0.002]and lower incidence of stress urinary incontinence one month after operation[2.78%(2/72)vs. 10.13%(8/79), P = 0.070]. There was no significant difference in the incidence of postoperative gross hematuria[0 vs. 2.53%(2/79)],postoperative sepsis[1.39%(1/72)vs. 1.27%(1/79)],postoperative dysuria[4.17%(3/72)vs. 5.06%(4/79)],postoperative IPSS improvement[12.0(11.0,13.0)vs. 12.0(10.0,14.0)]and postoperative QOL improvement[3.0(2.0,3.0)vs. 3.0(2.0,3.0)]between the two groups( P > 0.05). The patients were further divided into 2 sub-groups according to whether prostate volume ≥ 60 ml or not. In the patients of prostate volume < 60 ml,surgical efficacy was significantly higher in novel en-bloc HoLEP group than that in traditional 2-lobe technique group[(0.55 ± 0.25)g/min vs.(0.41 ± 0.19)g/min, P = 0.028]. In the patients of prostate volume ≥ 60 ml,the surgical efficacy of novel en-bloc HoLEP was also higher[(0.88 ± 0.28)g/min vs.(0.66 ± 0.31)g/min, P = 0.006]. Conclusions:Novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique was demonstrated to has lower blood loss,shorter operation time,higher surgical efficacy and lower incidence of stress urinary incontinence,which is suitable of all sizes of prostate.
3.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
4.Discovery of E0199: A novel compound targeting both peripheral NaV and KV7 channels to alleviate neuropathic pain.
Boxuan ZHANG ; Xiaoxing SHI ; Xingang LIU ; Yan LIU ; Xuedong LI ; Qi WANG ; Dongyang HUANG ; Weidong ZHAO ; Junru CUI ; Yawen CAO ; Xu CHAI ; Jiahao WANG ; Yang ZHANG ; Xiangyu WANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(1):101132-101132
This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both NaV1.7, NaV1.8, and NaV1.9 and KV7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited NaV1.7, NaV1.8, and NaV1.9 channels with a particularly low half maximal inhibitory concentration (IC50) for NaV1.9 by promoting sodium channel inactivation, and also effectively increased KV7.2/7.3, KV7.2, and KV7.5 channels, excluding KV7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.
5.Preliminary study on the biological characteristics of heat shock cognate protein 20 of Schistosoma japonicum
Xingang YU ; Kaijian YUAN ; Yilong LI ; Xuanru MU ; Hui XU ; Qiaoyu LI ; Wenjing ZENG ; Zhiqiang FU ; Yang HONG
Chinese Journal of Schistosomiasis Control 2025;37(3):294-303
Objective To clone and express the heat shock cognate protein 20 (SjHsc20) of Schistosoma japonicum, and to preliminarily investigate its biological characteristics. Methods The target fragment of the SjHsc20 gene was amplified using PCR assay and cloned into the pET-28a(+) expression plasmid to generate the recombinant expression vector pET-28a(+)-SjH-sc20, which was then transformed into Escherichia coli BL21 (DE3) competent cells. The recombinant SjHsc20 (rSjHsc20) protein was induced with isopropyl β-D-thiogalactopyranoside (IPTG) and purified, and the expression of the rSjHsc20 protein was checked with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The immunogenicity of the rSjHsc20 protein was detected using Western blotting, and the transcriptional levels of SjHsc20 were quantified in S. japonicum worms at different developmental stages and in male and female adult worms using real-time quantitative PCR (RT-qPCR) assay. Thirty female BALB/c mice at ages 6 to 8 weeks were divided into three groups, including the rSjHsc20 immunization group, the PBS control group, and the ISA 206 adjuvant group, of 10 mice in each group. Mice in the rSjHsc20 immunization group were subcutaneously immunized with 20 μg rSjHsc20 on days 1, 15 and 31, and animals in the PBS control group were subcutaneously injected with the same volume of PBS on days 1, 15 and 31, while mice in the ISA 206 adjuvant group were subcutaneously immunized with the same volume of ISA 206 adjuvant on days 1, 15 and 31, respectively. All mice in each group were infected with (40 ± 2) S. japonicum cercariae via the abdomen 14 day following the last immunization. Levels of serum specific IgG and its subtypes IgG1 and IgG2 antibodies against rSjHsc20, and the serum titers of anti-rSjHsc20 antibody were detected in mice using indirect enzyme-linked immunosorbent assay (ELISA). All mice were sacrifice 42 days post-infection, and S. japonicum worms were collected from the hepatic portal vein and counted. The eggs per gram (EPG), worm burden reductions and egg burden reductions were estimated to evaluate the protective efficacy of the rSjHsc20 protein. Results The SjHsc20 gene had an open reading frame (ORF) with 756 bp in length and encoded 252 amino acids, and the rSjHsc20 protein had a relative molecular mass of approximately 29 kDa. The rSjHsc20 protein was recognized by the serum of mice infected with S. japonicum and the serum of mice immunized with the rSjHsc20 protein, indicating that rSjHsc20 had a good immunogenicity. There was a significant difference in the transcriptional levels of the SjHsc20 gene among the 7-day (1.001 4 ± 0.065 7), 12-day (2.268 3 ± 0.129 2), 21-day (1.378 5 ± 0.160 4), 28-day (1.196 4 ± 0.244 0), 35-day (1.646 3 ± 0.226 1), 42-day worms of S. japonicum (1.758 0 ± 0.611 1) (F = 38.45, P < 0.000 1), and the transcriptional level of the SjHsc20 gene was higher in the 12-day worms than in worms at other developmental stages (all P values < 0.000 1). The serum levels of anti-rSjHsc20 IgG antibody were 0.106 6 ± 0.010 7, 0.108 3 ± 0.010 4, and 0.553 2 ± 0.069 1 in the PBS control group, ISA 206 adjuvant group, and rSjHsc20 immunization group following the last immunization, respectively, and the serum levels of IgG1 antibody were 0.137 3 ± 0.054 0, 0.181 1 ± 0.096 8, and 1.765 8 ± 0.221 1, while the levels of IgG2a antibody were 0.280 3 ± 0.197 6, 0.274 0 ± 0.146 3, and 1.560 4 ± 0.106 0, respectively. There were significant differences in the serum levels of anti-rSjHsc20 IgG (F = 397.70, P < 0.000 1), IgG1 (F = 401.00, P < 0.000 1) and IgG2a antibodies (F = 229.70, P < 0.000 1) among the three groups, and the serum levels of anti-rSjHsc20 IgG, IgG1 and IgG2a antibodies were higher in the rSjHsc20 immunization group than in the PBS control group and the ISA 206 adjuvant group (all P values < 0.000 1). There was a significant difference in the IgG1/IgG2a ratio among the rSjHsc20 immunization group (1.177 2 ± 0.143 6), the PBS control group (0.428 4 ± 0.199 8) and the ISA 206 adjuvant group (0.559 9 ± 0.181 1) (F = 43.97, P < 0.000 1), and the IgG1/IgG2a ratio was > 1 in the rSjHsc20 immunization group, which was higher than in the PBS control group and the ISA 206 adjuvant group (both P values < 0.000 1). The titers of serum anti-rSjHsc20 antibody were all above 1∶16 384 in the rSjHsc20 immunization group following immunizations on days 1, 15 and 31, indicating that the rSjHsc20 protein had a strong immunogenicity. The mean worm burdens were (16.60±5.75), (15.80±5.58) worms per mouse and (14.40±5.75) worms per mouse in the PBS control group, the ISA 206 adjuvant group and the rSjHsc20 immunization group 42 days post-infection with S. japonicum cercariae (F = 0.50, P > 0.05), and the EPG were 68 370 ± 22 690, 67 972 ± 19 502, and 41 075 ± 13 251 in the PBS control group, the ISA 206 adjuvant group and the rSjHsc20 immunization group (F = 4.55, P < 0.05), with lower EPG in the PBS control group and the ISA 206 adjuvant group than in the rSjHsc20 immunization group (both P values < 0.05). Immunization with the rSjHsc20 protein resulted in a worm burden reduction of 13.25% and an egg burden reduction of 39.92% relative to the PBS control group. Conclusions SjHsc20 is successfully cloned and expressed, and the rSjHsc20 protein induces partial immunoprotective effects in mice, which provides a basis for deciphering the biological functions of SjHsc20 and assessing the potential of SjH-sc20 as a vaccine candidate.
6.Transcriptomics-Based Investigation of the Effects of Job's Tears Oral Solution on Lung Cancer Mice
Lang LANG ; Wenge LI ; Yao CAI ; Siyu YIN ; Xu YAN ; Qi CHEN ; Zhanlan SONG ; Xingang JIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2712-2727
Objective To investigate the anti-tumor effect of Job's tears oral solution on lung cancer mice.Methods Observe the histopathological morphology of the tumor;Flow cytometry detected the changes in the levels of CD4+T and CD8+T in splenic lymphocytes;Elisa detected the contents of immunoglobulins IgA,IgG,IL-2 and IFN-γ;Blood routine was detected;the kit determined the levels of liver and kidney glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)content;Serum alanine aminotransferase(ALT),alkaline phosphatase(ALB),azelaic transaminase(AST),urea nitrogen(BUN),and blood creatinine(CRE)were measured in each group of mice.The transcriptome was found differential genes and pathway enrichment was performed.Western blot was used to detect the expression of proteins related to IL-17 signaling pathway(STAT3,NF-κB,VEGF)and TNF signaling pathway(PI3K/AKT,MAPK,JNK).Results Tumor histopathological and morphological changes were obvious in each administration group,and the heterogeneity was gradually reduced.Compared with the cisplatin group,the levels of CD4+T,CD8+T,CD4+T/CD8+T,IL-2,IFN-γ,and IgG in the Job's tears group were significantly increased(P<0.01).The blood routine results:compared with the model group,WBC,RBC,HGB,PLT,Lym%and GR%in the Job's tears group decreased significantly(P<0.01);Compared with the cisplatin group,WBC,RBC,PLT,HGB and Lym%in the Job's tears group increased significantly(P<0.01).The antioxidant indexes of liver and kidney showed that the levels of GSH and SOD in the liver and kidney tissues of the Job's tears group increased significantly(P<0.01),and the level of MDA decreased significantly(P<0.01).Effects on liver and kidney function indexes in mice AST,ALT,BUN and CRE decreased significantly in the Job's tears group(P<0.01),and ALB level increased significantly in the Job's tears group(P<0.01).Transcriptome results,Job's tears high-dose group mainly exerted anti-tumor effects by affecting TNF signaling pathway and IL-17 signaling pathway.Western blot results,in the IL-17 signaling pathway,S-TAT3 and VEGF decreased in the cisplatin group and the Job's tears group compared with the model group(P<0.01),and NF-κB decreased in the Job's tears high-dose group(P<0.01);Compared with the cisplatin group,STAT3 and NF-κB were decreased in the Job's tears group(P<0.01);VEGF was decreased in the Job's tears low-dose group(P<0.01);In the TNF signaling pathway,PI3K and MAPK were decreased in the cisplatin group and Job's tears group(P<0.01);AKT and P-AKT were decreased in the Job's tears group(P<0.01).Compared with the cisplatin group,the Job's tears group AKT,PI3K,and MAPK decreased(P<0.01);P-AKT decreased in the high dose group of Job's tears(P<0.01).Conclusion High-dose Job's tears oral solution inhibits tumor proliferation,attenuates inflammatory response,enhances immunity,improves blood routine and reduces liver and kidney injury in lung cancer mice mainly by inhibiting IL-17 and TNF signaling pathway.
7.Comprehensive Clinical Evaluation of Injectable Anti-inflammatory and Hepatoprotective Drugs for the Treatment of Drug-induced Liver Injury
Jing XIE ; Bin XU ; Yu CHEN ; Hongwei YU ; Xingang LI ; Pengfei JIN ; Jing TANG ; Wei LIU
Herald of Medicine 2025;44(10):1671-1677
Objective To conduct comprehensive clinical evaluation of injectable anti-inflammatory and hepatoprotective drugs with different mechanisms of action,and to provide a basis for drug selection and rational drug use in medical institutions.Methods Twenty-two experts in clinical and pharmacological fields were organized to construct a quantitative rating scale for the comprehensive clinical evaluation of drugs by applying the literature research method,expert interview method,and Delphi method,through seminars and interviews,and by referring to the real-world clinical data and evidence-based medical evidence such as the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs,so as to conduct a comprehensive evaluation of eight injectable anti-inflammatory and hepatoprotective drugs in terms of six dimensions:effectiveness,safety,economy,appropriateness,accessibility and maturity.Results A comprehensive clinical evaluation index system of injectable anti-inflammatory and hepatoprotective drugs for the treatment of drug-induced liver injury was constructed,including 6 first-level indexes,14 second-level indexes,and 27 third-level indexes,with a total of 100 points.The scoring results showed that among the evaluated varieties,the scores were,in descending order,magnesium isoglycyrrhizinate injection,compound glycyrrhizin injection,polyene phosphatidylcholine injection,reduced glutathione for injection,thiopronin injection,compound ammonium glycyrrhizinate injection,acetylcysteine injection and diammonium glycyrrhizinate injection.Conclusion The constructed quantitative rating scale for comprehensive clinical evaluation of drugs is operable,and the evaluation process can provide academic guidance for exploring the standardized path of comprehensive clinical evaluation of drugs,which needs to be applied in combination with the actual drug varieties of the medical institutions as well as the specific conditions of the patients to make individualized therapeutic choices.
8.Transcriptomics-Based Investigation of the Effects of Job's Tears Oral Solution on Lung Cancer Mice
Lang LANG ; Wenge LI ; Yao CAI ; Siyu YIN ; Xu YAN ; Qi CHEN ; Zhanlan SONG ; Xingang JIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2712-2727
Objective To investigate the anti-tumor effect of Job's tears oral solution on lung cancer mice.Methods Observe the histopathological morphology of the tumor;Flow cytometry detected the changes in the levels of CD4+T and CD8+T in splenic lymphocytes;Elisa detected the contents of immunoglobulins IgA,IgG,IL-2 and IFN-γ;Blood routine was detected;the kit determined the levels of liver and kidney glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)content;Serum alanine aminotransferase(ALT),alkaline phosphatase(ALB),azelaic transaminase(AST),urea nitrogen(BUN),and blood creatinine(CRE)were measured in each group of mice.The transcriptome was found differential genes and pathway enrichment was performed.Western blot was used to detect the expression of proteins related to IL-17 signaling pathway(STAT3,NF-κB,VEGF)and TNF signaling pathway(PI3K/AKT,MAPK,JNK).Results Tumor histopathological and morphological changes were obvious in each administration group,and the heterogeneity was gradually reduced.Compared with the cisplatin group,the levels of CD4+T,CD8+T,CD4+T/CD8+T,IL-2,IFN-γ,and IgG in the Job's tears group were significantly increased(P<0.01).The blood routine results:compared with the model group,WBC,RBC,HGB,PLT,Lym%and GR%in the Job's tears group decreased significantly(P<0.01);Compared with the cisplatin group,WBC,RBC,PLT,HGB and Lym%in the Job's tears group increased significantly(P<0.01).The antioxidant indexes of liver and kidney showed that the levels of GSH and SOD in the liver and kidney tissues of the Job's tears group increased significantly(P<0.01),and the level of MDA decreased significantly(P<0.01).Effects on liver and kidney function indexes in mice AST,ALT,BUN and CRE decreased significantly in the Job's tears group(P<0.01),and ALB level increased significantly in the Job's tears group(P<0.01).Transcriptome results,Job's tears high-dose group mainly exerted anti-tumor effects by affecting TNF signaling pathway and IL-17 signaling pathway.Western blot results,in the IL-17 signaling pathway,S-TAT3 and VEGF decreased in the cisplatin group and the Job's tears group compared with the model group(P<0.01),and NF-κB decreased in the Job's tears high-dose group(P<0.01);Compared with the cisplatin group,STAT3 and NF-κB were decreased in the Job's tears group(P<0.01);VEGF was decreased in the Job's tears low-dose group(P<0.01);In the TNF signaling pathway,PI3K and MAPK were decreased in the cisplatin group and Job's tears group(P<0.01);AKT and P-AKT were decreased in the Job's tears group(P<0.01).Compared with the cisplatin group,the Job's tears group AKT,PI3K,and MAPK decreased(P<0.01);P-AKT decreased in the high dose group of Job's tears(P<0.01).Conclusion High-dose Job's tears oral solution inhibits tumor proliferation,attenuates inflammatory response,enhances immunity,improves blood routine and reduces liver and kidney injury in lung cancer mice mainly by inhibiting IL-17 and TNF signaling pathway.
9.Comprehensive Clinical Evaluation of Injectable Anti-inflammatory and Hepatoprotective Drugs for the Treatment of Drug-induced Liver Injury
Jing XIE ; Bin XU ; Yu CHEN ; Hongwei YU ; Xingang LI ; Pengfei JIN ; Jing TANG ; Wei LIU
Herald of Medicine 2025;44(10):1671-1677
Objective To conduct comprehensive clinical evaluation of injectable anti-inflammatory and hepatoprotective drugs with different mechanisms of action,and to provide a basis for drug selection and rational drug use in medical institutions.Methods Twenty-two experts in clinical and pharmacological fields were organized to construct a quantitative rating scale for the comprehensive clinical evaluation of drugs by applying the literature research method,expert interview method,and Delphi method,through seminars and interviews,and by referring to the real-world clinical data and evidence-based medical evidence such as the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs,so as to conduct a comprehensive evaluation of eight injectable anti-inflammatory and hepatoprotective drugs in terms of six dimensions:effectiveness,safety,economy,appropriateness,accessibility and maturity.Results A comprehensive clinical evaluation index system of injectable anti-inflammatory and hepatoprotective drugs for the treatment of drug-induced liver injury was constructed,including 6 first-level indexes,14 second-level indexes,and 27 third-level indexes,with a total of 100 points.The scoring results showed that among the evaluated varieties,the scores were,in descending order,magnesium isoglycyrrhizinate injection,compound glycyrrhizin injection,polyene phosphatidylcholine injection,reduced glutathione for injection,thiopronin injection,compound ammonium glycyrrhizinate injection,acetylcysteine injection and diammonium glycyrrhizinate injection.Conclusion The constructed quantitative rating scale for comprehensive clinical evaluation of drugs is operable,and the evaluation process can provide academic guidance for exploring the standardized path of comprehensive clinical evaluation of drugs,which needs to be applied in combination with the actual drug varieties of the medical institutions as well as the specific conditions of the patients to make individualized therapeutic choices.
10.A comparative study of novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique and traditional 2-lobe technique HoLEP in BPH patients
Qifeng CAO ; Ning SHAO ; Jian KANG ; Xingang CUI ; Ding XU
Chinese Journal of Urology 2025;46(5):383-388
Objective:To compare the safety and efficacy of novel en-bloc Holmium laser enucleation of the prostate(HoLEP)with complete membranous urethral mucosa sparing technique with traditional 2-lobe technique HoLEP in benign prostatic hyperplasia(BPH)treatment.Methods:The data of BPH patients treated with HoLEP from January 2023 to May 2024 in Xinhua Hospital,School of Medicine,Shanghai Jiaotong University were retrospectively reviewed. Seventy-two patients received novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique(novel en-bloc group),while 79 patients received traditional 2-lobe technique HoLEP(traditional 2-lobe technique group).There was no significant difference between novel en-bloc group and traditional 2-lobe technique group in the age[(71.0 ± 7.1)years vs.(69.8 ± 6.5)years],body mass index[(24.5 ± 2.8)kg/m 2 vs.(23.9 ± 3.5)kg/m 2],international prostate symptom score(IPSS)[26.0(22.0,28.0)vs. 25.0(22.0,28.0)],quality of life(QOL)score[5.0(5.0,6.0)vs. 5.0(5.0,6.0)],prostate sepcific antigen(PSA)[4.98(2.40,11.11)ng/ml vs. 4.38(1.62,7.54)ng/ml]and prostate volume[(74.06 ± 42.67)ml vs.(70.10 ± 33.94)ml](all P > 0.05). The incidence of acute urinary retention in novel en-bloc group was significantly higher than that in traditional 2-lobe technique group[31.94%(23/72)vs. 17.72%(14/79), P = 0.042].The procedure of novel en-bloc was shown as followed:expose the prostatic capsule near the verumontanum and expand the initial capsule plane on both sides. The prostatic urethral mucosa was cut off in a circular pattern medial to the external urethral sphincter,which could form a complete “circular mucosal pad”. Seperate the apical gland along the capsule plane at 12 o’clock and expand the capsule plane until the bladder neck was reached.The bladder neck was then used as a marker so as to separate the glands on both sides along the capsule plane and merge with the initial plane. The entire lobe of the prostate was finally removed along the surgical capsule of the prostate. The procedure of traditional two lobe method was shown as followed:expose the prostatic capsule near the verumontanum and then divide the prostate into two lobes by longitudinal incision at 6 and 12 o’clock. The mucosa was horizontally cut at 12 o’clock,medial to the external urethral sphincter in order to preserve the apical urethral mucosal flap. The twp lobes were then removedd respectively along the capsule layer. The surgery-related indicators,perioperative complications and other data were compared between the two groups,as well as IPSS,QOL score,lower urinary tract symptoms,and the incidence of stress urinary incontinence in the two groups 1 month after surgery. Results:Compared with the patients underwent 2-lobe technique HoLEP,the patients underwent novel en-bloc HoLEP had lower hemoglobin loss[0.50(-5.50,7.50)g/L vs. 7.00(1.00,13.25)g/L, P = 0.003],lower operation time[(72.06 ± 34.37)min vs.(85.42 ± 40.35)min, P = 0.030],higher surgical efficacy[(0.72 ± 0.31)g/min vs.(0.55 ± 0.29)g/min, P = 0.002]and lower incidence of stress urinary incontinence one month after operation[2.78%(2/72)vs. 10.13%(8/79), P = 0.070]. There was no significant difference in the incidence of postoperative gross hematuria[0 vs. 2.53%(2/79)],postoperative sepsis[1.39%(1/72)vs. 1.27%(1/79)],postoperative dysuria[4.17%(3/72)vs. 5.06%(4/79)],postoperative IPSS improvement[12.0(11.0,13.0)vs. 12.0(10.0,14.0)]and postoperative QOL improvement[3.0(2.0,3.0)vs. 3.0(2.0,3.0)]between the two groups( P > 0.05). The patients were further divided into 2 sub-groups according to whether prostate volume ≥ 60 ml or not. In the patients of prostate volume < 60 ml,surgical efficacy was significantly higher in novel en-bloc HoLEP group than that in traditional 2-lobe technique group[(0.55 ± 0.25)g/min vs.(0.41 ± 0.19)g/min, P = 0.028]. In the patients of prostate volume ≥ 60 ml,the surgical efficacy of novel en-bloc HoLEP was also higher[(0.88 ± 0.28)g/min vs.(0.66 ± 0.31)g/min, P = 0.006]. Conclusions:Novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique was demonstrated to has lower blood loss,shorter operation time,higher surgical efficacy and lower incidence of stress urinary incontinence,which is suitable of all sizes of prostate.

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